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Title: Obstetrics and Gynaecology lecture notes
Description: A very comprehensive and detailed set of notes covering all aspects of Obstetrics and Gynaecology. Complete with a nice set of diagrams to aid learning. Useful for medical students.

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Obstetrics  and  Gynaecology  lecture  notes  
 
Reproductive  lecture  notes:  week  1  
The  human  life  cycle  
 

 
 
 
SPERMATOGENESIS  AND  MALE  INFERTILITY  
Within  our  bodies  are  a  few  types  of  cells:  




 
 
 

Somatic  cells:    A  somatic  cell  (diploid  cell  –  23  pairs  of  chromosomes)  is  any  biological  cell  
forming  the  body  of  an  organism;  that  is,  in  a  multicellular  organism,  any  cell  other  than  a  
gamete,   germ   cell,   or   undifferentiated   stem   cell
...
    There   are   approximately   220   types   of  
somatic  cells  in  the  human  body  
Germ   cells:   germ   cells   are   reproductive   line   diploid   cells   (23   pairs   of   chromosomes)   that  
give   rise   to   haploid   gametes   (reproductive   cells   with   23   chromosomes   –   half   the   genetic  
material  to  form  a  baby)    



Gametes:  gametes  are  haploid  cells  that  fuse  during  sexual  reproduction
...
       Ova  also  contain  mitochondrial  DNA  necessary  
for  foetal  development
...
     



Stem   cells:   stem   cells   are   multipotent/totipotent   cells   are   cells   that   can   divide   through  
mitosis  and  differentiate  into  diverse  specialized  cell  types  

 
 
Germ  cells  


A  germ  cell  (diploid)  is  any  biological  cell  that  gives  rise  to  the  gametes  of  an  organism  that  
reproduces  sexually
...
  There,   they   undergo   cell  
division  of  two  types:  
! Mitosis:  to  produce  more  germ  cells  (so  that  germ  cells  are  not  all  depleted)  –  self  
renew  
! Meiosis:  to  produce  gametes  (haploid  cells)  



Germ  cells  are  diploid  cells  (23  pairs  of  chromosomes:  22  pairs  of  autosomal  +  a  pair  of  sex  
chromosomes   =>   46   in   total)   in   the   reproductive   organs   of   a   multicellular   organism   that  
undergo   division   and   are   the   precursors   of   haploid   gametes   (23   chromosomes   in   total;   22  
autosomal  +  single  sex  chromosome),  such  as  a  spermatogonium  or  oogonium
...
 

 
 
 

! Different   timing   of   maturation:   oogenic   meiosis   is   interrupted   at   one   or   more  
stages  (for  a  long  time)  while  spermatogenic  meiosis  is  rapid  and  uninterrupted
...
g
...
g
...
g
...
      If   Y   is   absent   =>   testicles   absent   =>   testicular   hormones  
absent  =>  then  we  get  development  of  female  external  genitalia  e
...
 vagina  and  
clitoris  +  female  secondary  characteristics  
! Gender:  perceived  genital  sex  +  rearing  of  individual  as  male  or  female  =>    results  
in  gender  identity
...
 Everyone  is  born  with  both  
the   Wolffian   duct   /   Mesonephric   duct   (male   duct   system)   and   the   Mullerian   duct   /  
Paramesonephric  duct  (female  duct  system)
...
 The  SRY  gene  (on  Y  chromosome)  is  what  causes  testis  to  develop
...
    SRY   is   a   sex-­‐determining   gene   on   the   Y   chromosome   (male  
chromosome)  in  the  humans
...
 



Once   the   testis   are   developed   (in   response   to   activation   from   SRY),   the   male   duct  
(Wolffian/mesonephric)   system   begins   to   form
...
   



SRY   results   in   formation   of   testes   =>   production   of   testosterone   from   Leydig   cells   (later  
under  control  of  LSH)  =>  the  formation  of  the  testis,  including  the  seminiferous  tubules,  rete  
testis,   epididymis,   the   vas   deferns,   and   seminal   vesicles   can   develop
...
 



Females   and   males   are   also   born   with   both   the   Mullerian   and   Wolffian   duct   systems  
(bipotential   gonad)
...
      The   Mullerian   duct  
(paramesoneohric  duct)  develops  (as  no  Anti-­‐Mullerian  factor  released  from  Sertollic  cells  of  
testicles)   into   the   female   reproductive   tract   e
...
  the   uterus,   the   fallopian   tubes,   cervix  and  
upper   parts   of   the   vagina
...
     



There  are  two  sex  determination  stages:  One  stage  determines  the  gonadal  sex  internally  
(reproductive   tract   development)   and   one   stage   determines   the   genital   sex   externally  
(external  genitalia  +  secondary  sex  characteristics)
...
  This   is   why   you   could   have  a   person   with   the   outer   appearance  
of  a  female,  but  internally  their  organs  are  male,  and  they  are  not  able  to  produce  because  
they  do  not  have  a  uterus
...
     



Fetal  testes  secretes:  
! Testosterone  from  Leydig  cells  (later  under  control  of  LSH)  
! Mullerian  inhibiting  factors  (anti-­‐Mullerian  factor)  from  Sertolli  cells  (later  under  
control  of  FSH)  

 
 
 



Release   of   Mullerian   inhibiting   factors   (Anti-­‐Mullerian)   from   testes   =>   Mullerian  
(paramesonephric)  ducts  degenerate    



Release  of  testosterone  from  testes  =>  Wolffian  (mesonephric)  ducts  develop  into  the  male  
reproductive    tract  



Without  stimulus  of  male  testicular  hormones  (e
...
 testosterone  and  Anti-­‐Mullerian),  the  
fetus  will  develop  female  internal  genital  tract  (Mullerian  ducts)  



Testosterone   also   results   in   development   of   external   male   genitalia   and   secondary   male  
characteristics  
 

Females      


Absent  of  Y  chromosome  (absence  of  SRY/TDF)  =>    development  of  ovaries  (from  bipotential  
gonad)  



No  testes  =>  lack  of  testosterone  and  lack  of  Mullerian  inhibiting  factor  



Lack  of  Mullerian  inhibiting  factor  =>  Mullerian  ducts  develop  into  the  female  reproductive  
tract  e
...
 uterus,  fallopian  tubes,  vagina    



Absence  of  testosterone  =>  Wolffian  ducts  degenerate  



Absence   of   testosterone   =>   results   in   development   of   external   female   genitalia   +   female  
secondary  sexual  characteristics  

 
 
Differentiation  of  External  Genitalia:  second  stage  of  sex  development  
In  males  the  testicles  release:  


Mullerian   inhibiting   factor   (from   Sertolli   cells)   which   causes   degeneration   of   Mullerian  
ducts  /  Paramesonephric  ducts  (female  reproductive  tract)  



Testosterone  (from  Leydig  cells)  which  is  converted  into  dihydrotestosterone  which:  
! Transforms  Wolffian  ducts  into  male  reproductive  tract  
! Causes  undifferentiated  external  genitalia  to  develop  into  male  genitalia  
! Apprreciate   that   testosterone   is   important   for   both   internal   and   external   sexual  
development  and  secondary  sexual  charachteristics  

In  females:  
 
 
 



Lack   of   Mullerian   inhibiting   factor   causes   Mullerian   ducts   to   develop   into   female  
reproductive  tract  e
...
 oviducts  (fallopian  tube)  and  uterus  



Absence  of  testosterone  causes:  
! Degeneration  of  Wolffian  ducts  (male  reproductive  tract)  
! Undifferentiated  external  genitalia  to  develop  into  female  genitalia  

 
Summary  

 
 
Summary  





 
 
 
 
 

Chromosomal  sex:    46XX  (female)  or  46XY  (male)  
Gonadal  sex:    internal  reproductive  tract  sex  
Genital  sex:    external  reproductive  tract  sex  
“Gender”:    way  the  child  is  raised    
 

Clinical  example:  Androgen  insensitivity  syndrome  (testicular  feminisation  syndrome)  


Congenital   insensitivity   to   androgens   e
...
  condition   that   results   in   the   partial   or   complete  
inability  of  the  cell  to  respond  to  androgens  (male  sex  hormones)  



X-­‐linked  recessive  disorder  which  only  affects  male  karyotypes  (male  chromosomal  sex)  



Disorder  of  male  karyotype  (46XY)  =>  male  chromosomal  sex  =>  testis  develop  



Testosterone   is   secreted,   howeer   the   tissues   of   the   dveelopeing   genital   tract   are  
unrepsonsive  to  it  



The   unresponsiveness   of   the   cells   of   the   developing   genital   tract   to   the   presence   of  
androgenic   hormones   (androgen   resistance)   can   impair   or   prevent   the   development   of  
male   reproductive   tract   and   masculinization   of   the   male   external   genitalia   in   the  
developing   fetus,   as   well   as   the   development   of   male   secondary   sexual   characteristics   at  
puberty  



Testis  develop  due  to  presence  of  SRY  on  Y  choromosome  (but  do  not  descend  –  as  this  is  
under  control  of  testosterone)  =>  testes  release  androgens  (testosterone  from  Leydig  cells)  
and  Mullerian  inhibition  factor  (from  Sertolli  cells)  



Androgen   induction   of   wolffian   duct   does   not   occur   (due   to   androgen   resistance)   =>    
internal  male  reproductive  tract  does  NOT  develop  



Androgen   induction   of   undifferentiated   external   genitalia   is   dysfunctional   =>   external  
female  genitalia  may  develop  



Mullerian   inhibition   does   occur   (as   Anti-­‐Mullerian   released   from   Sertoli   cells)   =>  
degeneration  of  internal  female  reproductive  tract  



Therefore   individuals   with   complete   androgen   insensitivity   are   born   with   male   chromosome  
sex,  phenotypically  external  female  genitalia  (with  short  vagina),  with  an  absent  uterus  and  
ovaries
...
 
They  are:  
! Complete   androgen   insensitivity   syndrome   (CAIS),   where   there   is   total  
insensitivity   to   androgen   and   a   child   (chromosomally   male)   develops   external  
genitals   that   are   entirely   female
...
   Most  children  born  with  CAIS  are   brought  up  
as  girls  (but  have  male  chromosomal  sex)  

 
 
 

!  Partial  androgen  insensitivity  syndrome  (PAIS),  where  there  is  some  sensitivity  
to   androgen;   the   level   of   sensitivity   will   determine   how   the   genitals   develop
...
 


In   summary:     A   child   born   with   androgen   insensitivity   syndrome   (AIS)   is   genetically   male  
(male  chromosomal  sex:  as  X  linked  condition  only  affecting  males),  but  their  genitals  may  
appear  to  be  female  or  somewhere  in  between  male  and  female
...
 The  distal  end  of  the  penis  is  called  the  glans  
penis   and   is   covered   with   a   fold   of   skin   called   the   prepuce   or   foreskin
...
 The  arteries  of  the  penis  are  dilated  while  the  veins  are  passively  compressed  so  
that  blood  flows  into  the  erectile  cartilage  under  pressure
...
   Its  opening,  known  as  the  
external  urethral  meatus,  lies  on  the  tip  of  the  glans  penis
...
  It   holds   and  
protects   the   testes
...
  The   scrotum  
remains  connected  with  the  abdomen  or  pelvic  cavity  by  the  inguinal  canal
...
     
 

Internal  genital  organs  


Testes:  The  testes  are  located  in  the  scrotum
...
 Testosterone  is  produced  in  the  testes  (by  Leydig  cells  in  
response  to  LH)  which  stimulates  the  production  of  sperm  (in  the  seminiferous  tubules;  the  
process  is  helped  by  Sertolli  cells  which  are  stimulated  by  FSH)  as  well  as  give  secondary  sex  
characteristics  beginning  at  puberty
...
     
! Seminiferous   Tubules:   each   testis   contains   lots   of   tightly   packed   seminiferous  
tubules
...
  The   seminiferous   tubules   are   the   functional   units   of   the   testis,   where  
spermatogenisis  takes  place  (with  the  help  from  “nursing”  Sertoli  cells  and  FSH)
...
   It  
is   activated   by   follicle-­‐stimulating   hormone   FSH,   and   has   FSH-­‐receptor   on   its  
membranes
...
  Because   of   this,   it   has   also   been   called   the  
"mother  cell
...
   Sertoli  cells  are  
also  stimulated  by  testosterone
...
    They   are   responsible   for   secreting   the   male   sex   hormones   (e
...
   
testosterone)  in  response  to  LH  stimulation  


The   two   muscles   that   regulate   the   temperature   (essential   for   spermatogenesis)     of   the  
testes  are  the  dartos  and  cremaster  muscles:  
! Dartos   muscle:   the   dartos   muscle   is   a   layer   of   smooth   muscle   fibers   in   the  
subcutaneous   tissue   of   the   scrotum   (surrounding   the   scrotum)
...
    Lowers   testes   away  
from  body  when  they  are  too  warm
...
 This  muscle  is  a  continuation  of  
the  internal  oblique  muscle  of  the  abdominal  wall,  from  which  it  is  derived
...
    Site   of   sperm   travel:    
seminiferous   tubules   =>   rete   testes   =>   epididymis   =>   vas   deferens   =>   ejalucatory   duct   =>  
prostatic  urethra  



Vas  deferens:  The  vas  deferens,  also  known  as  the  sperm  duct,  is  a  thin  tube  approximately  
30   centimetres   long   that   joins   the   epididymis   to   the   seminiferous   tubule   duct   where   they  
fuse  together  to  form  the  ejaculatory  duct
...
     



The   spermatic   cord   is   the   cord-­‐like   structure   in   males   formed   by   the   vas   deferens   and  
surrounding  tissue  that  run  from  the  deep  inguinal  ring  down  to  each  testicle
...
  They   are   the   seminal   vesicles,   the   prostate   gland,   and   the  
bulbourethral  glands
...
 
They   secrete   LOTS   of   fructose   to   provide   an   energy   source   for   sperm   and  
alkalinity  to  enhance  sperm  mobility
...
    Form   most   of   the  
volume  of  semen
...
  The   smooth   muscle   of   the  
prostate   gland   contracts   during   ejaculation   (peristalsis)   to   contribute   to   the  
expulsion   of   semen   from   the   urethra
...
    The  
alkalinity  of  seminal  fluid  helps  neutralize  the  acidic  vaginal  pH  and  permits  sperm  
mobility   in   what   might   otherwise   be   an   unfavorable   environment
...
     
! Bulbourethral   glands:   The   bulbourethral   glands   also   called   Cowper's   glands   are  
located  below  the  prostate  gland  and  empty  into  the  urethra
...
    This   process   is   androgen-­‐dependent   =>   hence   whey   testes   do   not   descend   in  
androgen  insensitivity  syndrome    



The   gubernaculums   (ligament   like   structure)   moves   the   testes   from   retroperitoneal   (near  
kidneys)  to  within  the  scrotum  



Normally  a  boys  testes  have  descended  into  the  scrotum  (“dropped”)  by  birth  



Why  is  it  important  that  testes  descend?    The  testes  require  a  lower  temp  outside  body  to  
facilitate  spermatogenesis
...
g
...
   The  cremaster  muscle  
which  covers  the  testes  and  spermatic  cord  is  also  important  for  this  function
...
 It  is  a  common  birth  
defect  regarding  male  genitalia
...
  Orchiopexy   also   describes   the   surgery   used   to   resolve   testicular   torsion   (twisting  
of   spermatic   cord,   cutting   off   the   testicle's   blood   supply   =>   testicular   ischemia   and   severe  
pain)  



If  undescended  as  adult,  consider  orchidectomy  (surgical  removal  of  testes)  due  to  the  risk  
of  cancer  e
...
 seminoma  (6x  increase)  

 
Function  of  Testis  


Spermatogenesis:  occurs  in  the  seminiferous  tubules  (with  help  of  nursing  Sertollic  cells)  of  
the  testes
...
    Under   the   control   of   LH
...
     
 

 
 
 

 
 
 
The  site  of  spermatogenesis    


Occurs  in  seminiferous  tubules  



Spermatogenesis   is   the   process   by   which   spermatozoa   are   produced   from   male   primordial  
germ  cells  through  mitosis  and  meiosis
...
   In  contrast  the  the  one  ovum  and  
three  polar  bodies  produced  in  meisosis  in  F
...
   
This   is   the   cornerstone   of   sexual   reproduction   and   involves   the   two   gametes   both  
contributing   half   the   normal   set   of   chromosomes   (haploid)   to   result   in   a   chromosomally  
normal  (diploid)  zygote
...
  Otherwise,   the   offspring   will  
have   twice   the   normal   number   of   chromosomes,   and   serious   abnormalities   may   result
...
 



Spermatogenesis  takes  place  within  several  structures  of  the  male  reproductive  system
...
   



Maturation  of  sperm  occurs  in  the  epididymis  
 

 
 
 
A  spermatozoon  


A  spermatozoon  is  a  motile  sperm  cell  e
...
 mobile  male  gamete  (haploid)  



A  spermatozoon  joins  an  ovum  to  form  a  zygote  (a  zygote  is  a  single  cell,  with  a  complete  set  
of  chromosomes,  that  normally  develops  into  an  embryo)  



Features  of  spermatozoon:  
! Acrosome:   containing   enzymes   that   play   an   important   role   in   the   penetration  
through  the  zona  pellucida  of  the  oocyte  

 
 
 

! The   midpiece   has   a   central   filamentous   core   with   many   mitochondria   spiralled  
around   it,   used   for   ATP   production   for   the   journey   through   the   female   cervix,  
uterus  and  uterine  tubes
...
 

 
 
The  roles  of  the  Sertoli  cells  


A  Sertoli  cell  is  a  'nurse'  cell  of  the  testes  that  is  part  of  the  seminiferous  tubule
...
   

 
 
Hormonal  Control  of  Spermatogenesis  
Gonadotrophin  Releasing  Hormone  (GnRH)  



 
 
 

Decapeptide  
Released   from   hypothalmus   in   bursts   every   2-­‐3   hours   (begins   age   8-­‐12   years   e
...
  near  
puberty)  



Released  by  the  hypothalamus  and  travels  to  the  anterior  pituitary  by  the  portal  system      



Stimulates  the  anterior  pituitary  to  produce  and  release  LH  and  FSH    



Under  negative  feedback  control  from  testosterone  

 
Luteinizing  hormone  (LH)  and  follicular  stimulating  hormone  (FSH)  


Glycoproteins  secreted  by  anterior  pituitary  



Secretion  of  LH  and  FSH  is  stimulated  by  gonadotropin-­‐releasing  hormone  (GnRH)  from  the  
hypothalamus  



Secretion  of  LH  and  FSH  is  under  negative  feedback  control  from  testosterone  



Production  is  non-­‐cyclical  in  males  (in  contrast  to  females)  =>  constantly  fertility  in  males  



Luteinizing  hormone  (LH):    
! Acts  on  Leydig  cells  to  stimulate  testosterone  secretion  
! Regulated  by  negative  feedback  from  testosterone  



Follicle  stimulating  hormone  (FSH):    
! Acts  on  Sertoli  cells  to  enhance  spermatogenesis  
!  Regulated  by  negative  feedback  from  inhibin  
! Regulated  by  positive  feedback  from  activin  which  stimulates  FSH  production  
! Regulated  by  negative  feedback  from  testosterone  

 
Testosterone  


Produced  in  Leydig  cells  in  response  to  LH  stimulation  



Steroid  hormone  derived  from  cholesterol  



Secreted  into  blood  and  seminiferous  tubules  for  sperm  production  



Negative   feedback   on   hypothalamus   and   pituitary   gland   =>   high   levels   of   testeosterone  
feedback  the  hypothalamus  to  decrease  GnRH  and  feedback  to  the  pituitary  to  decrease  LH    
and  FSH  



Testosterone  Effects:  
! Before   birth:   masculinises   internal   reproductive   tract,   induces   development   of  
male  external  genitalia,  and  promotes  descent  of  testes  

 
 
 

! Puberty:   promotes   puberty   and   secondary   male   characteristics   +   growth   of  
external  genitalia  
! Adult:   controls   spermatogenesis,   secondary   sexual   characteristics   (male   body  
shape,  deep  voice,  thickens  skin),  libido,  penile  erection,  aggressive  behaviour?  
 
Inhibin  and  Activin  


Peptides  (closely  related)  



Secreted  by  Sertoli  cells  of  the  seminferous  tubules  (testes)  



Feedback  on  FSH:  
! Inhibin  inhibits  FSH  production  
! Activin  stimulates  FSH  production  
 

Spermatozoa  after  ejaculation  


Liquified  (by  enzymes  from  prostate  gland  eg
...
   
Mandatory  process
...
e
...
   
Produce  most  of  the  fluid  in  semen
...
  The   rete   testis   is   an   anastomosing   network   of  
delicate  tubules  that  carries  sperm  from  the  seminiferous  tubules   to  the  efferent  
ducts
...
   
! The   epididymis   is   composed   of   tightly   coiled   ducts   lying   just   outside   each   testis  
connecting   efferent   ducts   to   vas   deferens
...
 



Route   of   sperm:     testes   (seminiferous   tubules)   =>   rete   testes   =>   epididymis   =>   vas  
deferens  =>  ejaculatory  duct  =>  prostatic  urethra  =>  +/-­‐  female  vagina  



Erection:   blood   fills   corpora   cavernosa   (corpus   cavernosum)   -­‐   under   parasympathetic  
control  =>  point    



Emission:  contraction  accessory  sex  glands  and  vas  deferens  (peristalsis)  so  semen  expelled  
to  urethra  



Ejaculation:   contraction   of   smooth   muscles   of   urethra   and   erectile   muscles   (under  
sympathetic    control  =>  shoot)    



Problems   if   premature   or   retrograde  ejaculation  e
...
  neuropathy  (e
...
  DM),   prostate   surgery  
or  anticholinergic  drugs  (blocking  of  parasymepathetic  NS  =>  problems  with  erection)  

 
 
Fertilisation  in  ampullary  region  of  Fallopian  Tube  

 
 
 

 
 
Male  infertility  


Infertility  resulting  from  failure  of  the  sperm  to  normally  fertilise  the  egg  



Usually  associated  with  abnormalities  in  semen  analysis  



Common  cause  of  infertility  



Idiopathic  in  approximately  50%  cases  



Male  infertility  is  increasing  possibly  related  to  environmental  oestrogens  

 
Aetiology  of  Male  Infertility  


Low  sperm  count  or  quality:  usually  idiopathic  



Endocrine  causes  (pre-­‐testicular  failure):    
! Acromegaly  (excessive  GH)  
! Cushings  disease  (excessive  cortisol)  

 
 
 

! Hyperprolactinaemia:    suppreses  LH  and  FSH  resulting  in  decreased  testosterone  
production,  galactorrhoea,  low  libido,  erectile  dysfunction    
! Hypogonadotrophic   hypogonadism:   due   to   hypothalamic   dysfunction   (e
...
 
anorexia,   Kallmans,   excessive   excercise)   or   pituitary   dysfunction   (e
...
  adenoma  
causing   decreased   LH   and   FSH   production)
...
     
! Hyper  or  hypothyriodism  


Non-­‐obstructive  (testicular  failure)  =>  Hypergonadotrophic  hypogonadism:    
! Genetic  (Klienfelters  syndrome  47XXY)  
! Chemotherapy  or  radiotherapy  (DNA  damage)  
! Diseases  that  affect  the  testicle,  including  mumps,  orchitis,  and  testicular  cancer  
! Undescended  testes  
! Idiopathic  



Obstruction  to  vas  deferens  (post-­‐testicular  failure):    
! Congenital  absence  e
...
 cystic  fibrosis  (CF)  
! Infection  e
...
 epididymitis  due  to  Chlamydia  infection  or  orchitis  due  to  mumps  
infection  (can  also  cause  failure  of  sertoli  cells  to  produce  sperm)  
! Vasectomy:   minor   operation,   where   the   vas   deferns   (which   carry   sperm   from   a  
man's  testicles  to  the  penis)  are  cut,  blocked  or  sealed
...
g
...
g
...
  It   is   associated   with   very   low   levels   of  
fertility   or   even   sterility,   but   many   forms   are   amenable   to   medical   treatment
...
 
Azoospermia  can  be  classified  into  four  major  types  as  listed  below
...
 



Pretesticular  azoospermia  (hormonal):    
! Pretesticular  azospermia  is  characterized  by  inadequate  stimulation  of  otherwise  
normal  testicles  and  genital  tract
...
     
! Hypogonadotropic   hypogonadism   can   occur   due   to   hypothalamic   or   pituitary  
dysfunction  e
...
 anorexia,  illness,  pituitary  adenoma
...
     Therefore  lab  results  will  
show  low  FSH,  low  LH  and  low  testosterone
...
g
...
 



Testicular  azoospermia  (testicular  failure)  =>  hypergonadotrophic  hypogonadism:    
! In   this   situation   the   testes   are   abnormal,   atrophic,   or   absent,   and   sperm  
production  severely  disturbed  to  absent
...
   
! Specific   causes   for   testicular   failure   include   congenital   issues   such   as   in   certain  
genetic   conditions   (e
...
  Klinefelter   syndrome   47XXY),   as   well   as   acquired  
conditions  by  infection  (orchitis),  surgery,  cancer,  or  other  causes
...
     
! Generally,  men  with  unexplained  hypergonadotropic  (high  FSH/LH)  azoospermia  
need  to  undergo  a  chromosomal  evaluation  =>  Klinefelters  (47  XXY)  is  a  common  
cause  of  primary  testicular  failure  
! Lab   features:   low   testosterone,   high   LH,   high   FSH   (hypergonadotropic  
hypogonadism)  



Post-­‐testicular  azoospermia:    
! In  post-­‐testicular  azoospermia  sperm  are  produced  but  not  ejaculated
...
  The   most   common   reason   is   a   vasectomy   done   to   induce  
contraceptive   sterility
...
 
! Ejaculatory   disorders   include   retrograde   ejaculation   and   anejaculation   (inability  
to  ejaculate);  in  these  conditions  sperm  are  produced  but  not  expelled  (e
...
 DM)  
! Lab  features  =  normal  hormone  screen  


Idiopathic  azoospermia  
! Idiopathic   azoospermia   is   where   there   is   no   known   cause   of   the   condition
...
   
! For   example,   a   review   in   2013   came   to   the   result   that   oligospermia   and  
azoospermia   are   significantly   associated   with   being   overweight   (odds   ratio   1
...
3)  and  morbidly  obese  (odds  ratio  2
...
   Other  factors  include  alchol,  smoking  and  drugs
...
g
...
g
...
g
...
g
...
g
...
 This  is  the  most  common  type  
of  fertility  testing
...
   FSH/LH  and  testosterone  levels  are  particularly  
useful
...
g
...
g
...
 

 
Treatment  of  Male  Infertility  
Intra-­‐uterine  Insemination  (IUI)  


Indication:  low  sperm  count  (oligozoospermia)  



Procedure:  semen  sample  prepared  to  produce  concentrated  sperm  sample  



Inseminated   into   uterine   cavity   around   time   ovulation   (i
...
  approx   14   days   before  
menstration  is  the  time  of  ovulation)  



Pregnancy  Rate:  15%  per  treatment  cycle  

 
 
Surgical  Sperm  Aspiration  




Procedure:   sperm   aspirated   surgically   (can   be   done   as   diagnostic   procedure   or   at   time   of  
oocyte  recovery  e
...
 in  IVF)
...
g
...
  The   man   can   still  
ejaculate   seminal   fluid   (semen)   but   this   fluid   will   not   contain   any   sperm
...
 



In  cases  of  non-­‐obstructive  azoospermia  (complete  absence  of  sperm  in  semen),  very  small  
amounts   of   sperm   may   be   produced   and   can   be   collected   directly   from   the   testes  
(seminiferous  tubules)
...
 In  
these   cases   a   biopsy   will   normally   be   sent   to   the   laboratory   for   analysis   as   to   the   possible  
cause  of  the  problem
...
g
...
  The   fertilised   egg   (embryo)   is   then  
transferred   to   the   woman’s   uterus
...
 



Type  of  IVF  (in-­‐vitro  fertilisation)  e
...
 an  egg  is  fertilised  by  sperm  outside  the  body  



 
 
 

Indications:   very   low   sperm   count   (severe   oligozoospermia;   if   non   severe   oligozoospermia  
then   can   use   intra-­‐uterine   insemination)   or   azoospermia   (if   collected   by   surgical   sperm  
aspiration)  

Procedure:   Sperm   collected   (e
...
  via   surgical   sperm   aspiration)   and   injected   into   stripped  
oocyte  obtained  during  IVF
...
 



Antepartum   haemorrhage   (APH),   also   known   prepartum   hemorrhage,   is   bleeding   from   the  
vagina  during  pregnancy  from  the  24th  week  gestational  age  to  labour
...
  This   is   because  
many  pregnancies  are  lost  spontaneously  before  a  woman  recognizes  that  she  is  

 
 
 

pregnant,   and   the   clinical   signs   of   miscarriage   are   mistaken   for   a   heavy   or   late  
menses  (menstruation)  
 
Types  of  Spontaneous  Miscarriage  
Threatened  miscarriage  


This  is  when  you  have  bleeding  early  in  your  pregnancy  and  your  cervix  (the  opening  to  your  
uterus)   is   tightly   closed   (os   closed)
...
 



Bleeding  not  profuse  (mild  bleeding)  



Pain  –ve  (usually  little  or  no  pain)  



Cervical  os  is  closed  (as  it  should  be)  



Uterus  size  =  correct  for  gestational  age  



FH  (fetal  heartbeat)  +ve  
 

Inevitable  miscarriage  


Bleeding  early  in  your  pregnancy  and  your  cervix  is  open  =>  pregnancy  will  INEVITABLY  be  
lost
...
 The  miscarriage  may  
happen  quickly  or  take  some  time
...
    When   the  
clinical   examination   reveals   a   dilated   cervix   (open   cervical   os),   spontaneous   miscarriage   is  
inevitable
...
  The   vaso-­‐vagal   effect   of   the  
products  of  conception  passing  through  the  cervix  causes  a  reflex  bradycardia  and  vasovagal  
syncope
...
 The  shock  normally  resolves  spontaneously
...
 



Tenderness  and  pain  +ve  



Cervix  open  (cervical  os  open)  –  this  distuinguishes  from  missed  where  cervical  os  is  closed  



Products  of  conception  (POC)  may  be  present  in  cervix  (cervical  canal)  



FH  –ve  (this  distuinguishes  from  inevitable  miscarriage)  
 

Complete  miscarriage  


This  means  that  you  have  lost  your  pregnancy  and  your  uterus  is  empty  



History  similar  to  incomplete  abortion  followed  by  cessation  of  bleeding  



Uterus  smaller  than  <  gestation  age  =>  as  no  produts  of  conception  in  uterus  



Cervix  closed  (cervical  os  closed)  



FH  –ve  
 

Septic  miscarriage  


Infection  following  a  miscarriage  



Can  cause  septic  shock  (vasogenic  shock  due  to  peripheral  vasodilation)  e
...
 presenting  with  
tachycardia,  hypotension,  cold  clammy  skin,  increased  CRT  etc  

 
Missed  miscarriage  (“silent  miscarriage”)  

 
 
 



Its  called  a  missed  miscarriage  because  you  won't  realise  that  anything  has  gone  wrong
...
 



The  uterus  is  small  for  dates  as  the  foetus  is  not  alive  and  therefore  not  growing  (uterus  <  
gestation  age)
...
   



Fetus  dies  in  uteruo  but  is  not  expelled  



It   may   present   with   a   history   of   threatened   miscarriage   and   persistent,   dirty   brown  
discharge
...
 



FH  –ve  



Cervical  os  closed  
 

 
 
Aetiology  of  Miscarriage  


Most  cases  are  idiopathic  



Chromosomal  (abnormal  conceptus)  
! Chromosomal  (50%)  e
...
 trisomy  15,16,21,22,21  
! Turners  45X  (despite  the  excellent  postnatal  prognosis,  99%  of  Turner-­‐syndrome  
conceptions  are  thought  to  end  in  spontaneous  abortion  or  stillbirth)  
! Hydratiform  mole  (molar  pregnancy):  not  strictly  called  “miscarriage”  

 
 
 



Uterine  abnormalities  
! Uterine  malformations  
! Fibroids  (leiomyoma  growths)  
! Incompetent   cervix   (dilated   cervix):   cervix   dilates   and   effaces   before   pregnancy  
has  reached  term:  can  treat  with  cervical  cerclage  (cervical  stitch  with  sutures)  



Acquired  disease  
! Infections  
! Hypertension  e
...
 Pre-­‐eclampsia  
! Renal  disease  
! Diabetes  mellitus  
! Thyroid  disorders  



Toxins  
! Alcohol  
! Smoking  
! Chemotherapy  
! Anaesthetic  gases  
! Immunological   e
...
  antiphospholipid   syndrome   (lupus   anticoagulant,   anti  
cardiolupin)   –   charachterised   by   recurrent   miscarriages,   antenatal  
complications,  recurrent  arterial  and  venous  thrombosis    



Endocrine  
! Deficient  corpus  luteum  =>  deficient  progesterone  production  
! High  preovulatory  LH  (>  10  IU/l)  



Trauma  
! Amniocentesis:   Amniocentesis   is   a   test   during   which   your   doctor   takes   a   small  
sample   of   amniotic   fluid   from   around   the   baby
...
  This   sample   is   then  
examined  in  a  laboratory  to  check  for  any  abnormalities
...
 
! Chorionic  villous  sampling  (higher  risk  than  amniocentesis)  –  usually  perfomed  at  
earlier  stage  in  pregnancy  (<  15  weeks)
...
g
...
    If   recurrent   miscarriages   =>  
further  Ix
...
 
! History  of  PID,  endometriosis,  or  IUCD/Mirena  



Hydatiform  mole:    large  for  dates,  heavy  bleed  in  early  pregnancy,  very  high  beta-­‐HCG  (can  
cause  beta-­‐HCG  thyrotoxicosis  and  hyperemesis  gravidarium)  



Neoplasia  e
...
 choriocarcinoma  

 
Investigations  


 
 
 

Transvaginal   US:   the   majority   of   women   will   require   a   transvaginal   ultrasound   (TVS)   and  
98%   of   complete   miscarriages   can   be   diagnosed   in   this   way
...
   
A  uterus  found  to  be  empty  on  ultrasound  examination  (+  closed  cervical  os)  may  signal  a  

completed   spontaneous   abortion,   but   the   diagnosis   is   not   definitive   until   ectopic  
pregnancy  is  excluded
...
   Serum  b-­‐hCG  is  preferred  due  to  higher  sensitivity
...
   



hCG   enters   the   maternal   circulation   almost   immediately   after   implantation   of   the   embryo  
(blastocyst)   on   about   day   21   of   the   menstrual   cycle   (approximately   7   days   after   fertilisation)  
e
...
 gestation  =  3  weeks
...
    hCG   takes   over   from   LH   =>   hCG   maintains   the  
corpus   luteum   =>   maintains   progesterone   production   =>   maintains   maternal   endometrial  
decidua  (mucosal  layer  of  endometrium  during  a  pregnancy,  which  forms  the  maternal  part  
of  the  placenta
...
     



Progesterone   enriches   the   uterus   with   a   thick   lining   of   blood   vessels   and   capillaries  
(secretory   phase)   so   that   it   can   sustain   the   growing   fetus
...
     



 
 
 

Beta-­‐hCG  is  produced  by  the  trophoblast  cells  of  the  placenta  (foetal  part  of  placenta)  

The   concentration   of   hCG   rises   in   an   exponential   manner,   doubling   approximately   every  
two  days  in  the  first  few  months  of  pregnancy
...
 



By  day  28  (first  day  of  missed  menses  in  28  day  cycle  =>  4  weeks  gestation)  the  median  hCG  
level   in   serum,   plasma   or   urine   is   about   100   mIU/ml
...
   



In  a  normal  pregnancy  beta  hCG  doubles  every  two  to  three  days  through  to  its  maximum  
level   at   nine   to   10   weeks   gestation
...
 



Remember  that  serum,  plasma  and  urine  hCG  results  can  vary  widely
...
 It  can  take  up  to  three  to  four  
weeks   for   the   HCG   to   drop   to   non-­‐pregnant   levels   after   a   pregnancy,   depending   on   the  
gestation  reached
...
   



If  the  beta  HCG  is  excessively  high,  suspect  molar  pregnancy  (or  multiple  pregnancy)  



However,  remember  that  the  dating  (gestation)  of  the  pregnancy  could  be  wrong
...
   However,  it  is  not  so  reliable  at  detecting  an  ectopic  pregnancy
...
   

 In  a  normal  pregnancy  the  foetal  heart  beat  should  be  seen  on  transvaginal  ultrasound  by  
six  to  seven  weeks’  gestation  (after  only  4-­‐5  weeks  development!!!)  



Sometimes   the   pregnancy   is   of   ‘unknown   location’,   where   the   pregnancy   test   is   positive   but  
there   is   no   sign   of   the   pregnancy   on   ultrasound   scan
...
 



If   ectopic   pregnancy   cannot   be   ruled   out,   consider   referral   to   hospital   for   further  
assessment,   especially   if   the   woman   has   pelvic   pain
...
  Since   the   placenta   isn't   putting   out   hCG,   hCG   levels   will   eventually   drop
...
 



When   hCG   levels   continue   to   rise   or   don't   fall   appropriately   after   miscarriage,   it's  
important  that  the  reason  is  found
...
g
...
g
...
 
Anticoagulation   appears   to   prevent   miscarriage   in   pregnant   women
...
  Prednisolone   can   also   be   used   (dampens   down   the  
immune  mechanism)
...
g
...
g
...
   
Synthetic  oxytocin  can  be  used  to  induce  labour  for  medical  reasons
...
 In  this  case  the  syntocinon  can  be  used  to  stimulate  release  of  products  
of  conception  in  miscarriage  (by  causing  uterus  contraction)  



Evacuation   of   uterus:     It   usually   includes   a   combination   of   vacuum   aspiration,   dilation   and  
curettage,  and  the  use  of  surgical  instruments  (such  as  forceps)
...
 
 

Complete  miscarriage  


Conservation  management  e
...
 bed  rest,  reassurance  and  pain  relief  



Advice  and  reassurance  
 

 
 
 

Septic  miscarriage  


Resuscitation  if  shock  is  present:  ABCDE,  fluids,  vasopressor  e
...
 NA  or  dopamine  



SEPSIS  6  in  one  hour  



Antibiotics  



Evacuation   of   uterus:   It   usually   includes   a   combination   of   vacuum   aspiration,   dilation   and  
curettage,  and  the  use  of  surgical  instruments  (such  as  forceps)
...
    The   antiphospholipid   antibodies,   lupus   anticoagulant  
(misnomer,   cause   anti   coagulation   and   prolonged   APTT   in   test   tubes   not   in   the  
body!),   and   anticardiolipin   antibodies   may   be   associated   with   recurrent  
miscarriage  before  ten  weeks
...
    Thrombophillic   disorder   which   causes  
formation   of   blood   clot
...
    Tx   with  
asprin,  LMWH  and  potentally  steroids
...
g
...
g
...
 It  was  also  found  that  
metformin   therapy   improves   the   chances   of   a   successful   pregnancy   in   patients   with   an  
abnormal  glucose  tolerance  test
...
     



Assessment   for   PCOS:   US   (large   follicles),   raised   testosterone,   decreased   SHBG,   hirsutism  
(excessive  hair  growth  in  male  pattern),  amenorrhoea/oligomenorrhea,  acne,  obesity,  raised  
LH/FSH  ratio  



Hysteroscopy:  where  the  uterus  is  examined  through  the  vagina  using  a  special  endocscope  
called  a  hysteroscope  



Hysterosalpingogram   (HSG):     an   X-­‐ray   test   that   looks   at   the   inside   of   the   uterus   (hystero)  
and   fallopian   tubes   (salpinx)   and   the   area   around   them
...
    During   a   hysterosalpingogram,   a   dye  
(contrast   material)   is   put   through   a   thin   tube   that   is   put   through   the   vagina   and   into   the  
uterus
...
 Pictures  are  taken  using  a  steady  beam  of  X-­‐ray  (fluoroscopy)  as  the  
dye  passes  through  the  uterus  and  fallopian  tubes
...
 A  blockage  also  could  prevent  
sperm  from  moving  into  a  fallopian  tube  and  joining  (fertilizing)  an  egg
...
     



Laparoscopy:   where   the   uterus   is   examined   through   a   small   cut   in   the   abdomen,   using   a  
laparoscope
...
     



IVP  (intravenous  pyelogram)  

 
Treatment  


TLC  +  emotional  support    



Treat  any  underlying  course  

 
Ectopic  Pregnancy  


 
 
 

Implantation  of  the  conceptus  outside  the  uterine  cavity  (uterus)  
Most   occur   in   the   fallopian   tubes   (tubal   ectopic   pregnancies),   however   implantation   can  
also  occur  in  the  cervix,  ovaries,  and  abdomen
...
g
...
   Ectopic  pregnancies  can  cause  fatal  intra-­‐peritoneal  bleeding
...
  It   is   often  used  
synonymously   with   pelvic   inflammatory   disease   (PID),   although   PID   lacks   an  
accurate  definition  and  can  refer  to  several  diseases  of  the  female  upper  genital  
tract,  such  as  endometritis,  oophoritis,  myometritis,  parametritis  and  infection  in  
the  pelvic  peritoneum  
! Previous  tubal  surgery  
! Previous  tubal  ligation  
! Endometriosis   –   adhesions   and   blockages   of   fallopian   tubes   can   presevtn   the  
conceptus  moving  to  the  uterus  
! IUCD  (Mireana  IUS  or  copper  IUCD)  

 
Pathophysiology  




Most  commonly  this  invades  vessels  and  will  cause  bleeding
...
   

This   intratubal   bleeding   hematosalpinx   expels   the   implantation   out   of   the   tubal   end   as   a  
tubal  abortion
...
  The   pain   is   caused   by  
prostaglandins  released  at  the  implantation  site,  and  by  free  blood  in  the  peritoneal  cavity,  
which  is  a  local  irritant
...
  Usually   this   degree   of   bleeding   is   due   to   delay   in   diagnosis,   but   sometimes,  
especially  if  the  implantation  is  in  the  proximal  tube  (just  before  it  enters  the  uterus),  it  may  
invade  into  the  nearby  Sampson  artery,  causing  heavy  bleeding  earlier  than  usual
...
 
! Hypovolaemic  shock  and  syncope  due  to  blood  loss  
! Abdominal  guarding  and  rigidity:  may  mimic  appendicitis  (esp  if  in  right  fallopian  
tube  =>  RIF  pain)  
! Cervical   excitation:   in   gynecology,   cervical   motion   tenderness   or   cervical  
excitation   (chandelier   sign),   is   a   sign   found   on   pelvic   examination   suggestive   of  
pelvic   pathology
...
   It  is  also  colloquially  known  as  "chandelier  sign”
...
"  
! Adnexal  tenderness:  pain  from  the  ovary  and  fallopian  tube  on  bimanual  exam  
! Bulky  uterus  

 
Differential  diagnosis  


 
 
 

Miscarriage  
Early  normal  pregnancy  



PID:   however   the   presence   of   a   positive   pregnancy   test   virtually   rules   out   active   PID  
infection   as   it   is   rare   indeed   to   find   pregnancy   with   an   active   pelvic   inflammatory   disease  
(PID)
...
 



GI  disorders  e
...
 appendicitis  



Urinary  system  problems  



For  abdominal  pain:    GI  history,  Obs  and  Gynae  history,  GU  history,  and  if  upper  GI  also  a  
cardioresp  history  

 
Outcomes  


Tubal   abortion:   In   a   typical   ectopic   pregnancy,   the   embryo   adheres   to   the   lining   of   the  
fallopian   tube   (tubal   ecotopic   pregnancy)   and   burrows   into   the   tubal   lining
...
 This  intratubal  bleeding  hematosalpinx  expels  
the  implantation  out  of  the  tubal  end  as  a  tubal  abortion
...
 Sometimes  the  bleeding  might  be  heavy  enough  to  threaten  the  health  or  life  
of   the   woman
...
 These  are  the  tubal  abortions
...
 

 
Locations  of  ectopic  pregnancy  
Tubular:  


Ampullary  (common  site):  where  fertilisation  normally  occurs  

Non-­‐tubular:  



 
 
 

Periotneal  


 

Ovarian  

Cervical  

 
 
 
 
Diagnosis  of  Ectopic  Pregnancy  


An  ectopic  pregnancy  should  be  considered  and  ruled  out  as  the  cause  of  abdominal  pain  
or   vaginal   bleeding   or   amenorrhoea   in   every   woman   who   has   a   positive   pregnancy   test  
(positive  beta  HCG)
...
   



Ectopic  pregnancy  can  be  diagnosed  if  the  ultrasound  detects  a  fetal  heart  beat  (can  be  seen  
from  6-­‐7  weeks  gestation)  or  an  embryo  that  is  outside  of  the  uterus
...
   
! Since   ectopic   pregnancy   is   a   potentially   life   threatening   gynaecological   problem  
serum  beta-­‐HCG  is  preferred  (as  more  sensitive)  

 
 
 

! NB:   Although   hCG   is   sensitive   to   ectopic   pregnancies,   it   is   clearly   not   selective!  
Beta-­‐hCG   is   raised   in   normal   pregnancies   or   hydratiform   mole   or   rare   germ   cell  
tumours
...
 Not  all  ectopic  pregnancies  are  life-­‐
threatening   or   lead   to   a   risk  to  the  mother
...
 The  pregnancy  often  dies  in  a  way  similar  to  a  miscarriage
...
 You  would  need  to  
have   treatment   if   symptoms   become   worse
...
 



Laparoscopic  salpingotomy:  Surgeons  use  laparoscopy  to  gain  access  to  the  pelvis  and  can  
incise  the  affected  Fallopian  and  remove  only  the  pregnancy  



Laparoscopic   salpingectomy:   surgical   removal   of   the   affected   fallopian   tube   with   the  
pregnancy  



Methotrexate:   Early   treatment   of   an   ectopic   pregnancy   with   methotrexate   is   a   viable  
alternative   to   surgical   treatment
...
 



Laparotomy  if  ectopic  pregnancy  is  ruptured:  A  laparotomy  is  a  surgical  procedure  involving  
a  large  incision  through  the  abdominal  wall  to  gain  access  into  the  abdominal  cavity
...
 



Cure  rates  are  excellent  for  this  condition
...
 


 
 
 

Gestational   trophoblastic   disease   (GTD)   forms   a   group   of   disorders   which   range   from  
hydatidform  mole  to  malignant  conditions  such  as  choriocarcinoma
...
   



It  is  the  result  of  abnormal  conception  (chromosomal)  



Molar   pregnancy   is   an   abnormal   form   of   pregnancy   in   which   a   non-­‐viable   fertilized   egg  
implants  in  the  uterus  results  in  abnormal  development  of  trophoblast  



Can   be   complete   (absence   of   maternal   chromosomes)   or   partial   (maternal   chromosomes  
present)  



Developmental   anomaly   of   the   trophoblast   (foetal   placenta)   in   which   there   is   a   local   or  
general  vesicular  change  in  the  chorionic  villi  (villi  that  sprout  from  the  chorion  in  order  to  
give  a  maximum  area  of  contact  with  the  maternal  blood)  



It   may   cause   bleeding   in   early   pregnancy   and   is   usually   suspected   on   an   early   pregnancy  
ultrasound   scan
...
 
However,   close   follow-­‐up   is   needed   after   a   hydatidiform   mole   because   there   is   a   small  
chance  of  developing  a  type  of  cancer  (choriocarcinoma)
...
 



Incidence:  UK  and  Europe  1  in  1000  to  1  in  2000  



A  pregnancy  that  results  in  a  hydatidiform  mole  is  called  a  molar  pregnancy
...
 They  are  'non-­‐viable'  pregnancies
...
  These   villi   grow   in   clusters   that   resemble   grapes   (snow  
storm)  



They   have   a   risk   of   possibility   of   malignant   change   to   choriocarcinoma,   which   is   a  
malignant,  trophoblastic  cancer,  usually  of  the  placenta
...
  It   belongs   to   the   malignant   end   of   the  
spectrum  in  gestational  trophoblastic  disease  (GTD)
...
 

 
Pathophysiology  

 
 
 



In   complete   molar   pregnancies,   all   the   genetic   material   comes   from   the   father
...
     This  is  an  ovum  not  carrying  any  chromosomes  
or  genetic  material
...
  But   rarely,   the   ovum   doesn't   die   and   implantation   takes   place
...
   
Therefore   there   is   no   maternal   DNA   present   =>   no   fetal   tissue   develops
...
 This  is  a  complete  hydatidiform  mole
...
 



In  partial  molar  pregnancies,  the  trophoblast  cells  usually  have  three  sets  of  chromosomes  
(triploid)
...
   This  means  
that   there   is   too   much   genetic   material   present   =>   also   results   in   the   development   of   too  
much  trophoblastic  tissue
...
   There  is  usually  evidence  of  fetal  
tissue   or   fetal   blood   cells   in   a   partial   molar   pregnancy
...
 



Both   complete   and   partial   molar   pregnancies   (hydratiform   moles)   are   'non-­‐viable'  
pregnancies
...
 



NB:   Trophoblasts   are   cells   forming   the   outer   layer   of   a   blastocyst
...
  They   are   formed   during   the   first   stage   of   pregnancy   and  
are  the  first  cells  to  differentiate  from  the  fertilized  egg
...
  This   is   the   most   common  
symptom
...
   MAY  BE  HEAVY
...
 This  is  
because  a  molar  pregnancy  grows  more  quickly  than  a  normal  pregnancy  would,  due  to  the  
abnormally  developing  trophoblastic  tissue  (placental  tissue)  



‘Doughy’  uterus  



FH  -­‐ve  



Hyperemesis:   Hyperemesis   gravidarum   (HG)   is   a   complication   of   pregnancy   characterized   by  
intractable  nausea,  vomiting,  and  dehydration  (due  to  abnormally  high  hCG)  



Pre-­‐eclampsia:   medical   condition   characterized   by   high   blood   pressure   and   significant  
amounts  of  protein  in  the  urine  of  a  pregnant  woman
...
   
! Levels  of  hCG  may  be  of  value  in  diagnosing  molar  pregnancies  but  are  far  more  
important  in  disease  follow-­‐up
...
 



 
 
 

Definitive  diagnosis  is  made  by  histological  examination  of  the  products  of  conception
...
   Complicated  pathology      



CXR  or  CT  lung:  to  assess  for  lung  mets  

 
Treatment  


Evacuation   of   uterus:   hydatidiform   moles   should   be   treated   by   evacuating   the   uterus   by  
uterine  suction  or  by  surgical  curettage  as  soon  as  possible  after  diagnosis,  in  order  to  avoid  
the  risks  of  choriocarcinoma  



Prolonged   follow-­‐up   with   urinary   and   serum   b-­‐hCG:   Patients   are   followed   up   until   their  
serum  human  chorionic  gonadotrophin  (hCG)  level  has  fallen  to  an  undetectable  level
...
g
...
 It  has  the  ability  to  spread  locally,  
as  well  as  metastasise  (early  metastatic  spread  to  lungs  is  common)  
Note:     molar   pregnancy   =   partial   molar   pregnancies,   where   the   trophoblast   cells   usually  
have  three  sets  of  chromosomes  (triploid)
...
  It   is  
characterized  by  early  hematogenous  spread  to  the  lungs
...
 



 It  is  also  classified  as  a  germ  cell  tumor  and  may  arise  in  the  testis  or  ovary
...
 



Clinical  features  in  females:  
! increased  quantitative  β-­‐hCG  levels    (very  high  levels)  
! Vaginal  bleeding  
! Shortness  of  breath  
! Haemoptysis  (coughing  up  blood)  
! Pleurtitic  chest  pain  
! Chest  X-­‐ray  shows  multiple  infiltrates  of  various  shapes  in  both  lungs  
 

Cervical  Incompetence  




When  you're  not  pregnant,  the  cervical  canal  remains  open  a  tiny  bit  to  allow  sperm  to  enter  
the  uterus  and  menstrual  blood  to  flow  out
...
    During   a   normal   pregnancy,   the   cervix   remains   firm,   long,   and   tightly  
closed  until  late  in  the  third  trimester
...
 
the  neck  of  the  uterus
...
 



If   you   have   cervical   insufficiency,   it   means   that   your   cervix   is   effacing   (shortening   and  
thinning)  and  dilating  prematurely  (before  your  baby  is  full  term  and  ready  to  be  born)
...
 There  are  usually  no  contractions  or  other  symptoms
...
   



Internal   os   opening   more   than   1   cm   is   abnormal   and   cervical   length   less   than   2   cm   is  
considered  diagnostic
...
 



Incidence  1-­‐2%  



Key  clinical  features:  cervical  dilation  in  the  absence  of  any  abdominal  pain  



Aetiology  
! Cervical  dilatation  during  TOP  (termination  of  pregnancy)  
! Cone  biopsy  of  cervix  
! Cervical  amputation  during  Manchester  repair  
! Exposure  to  DES:  Diethylstilbestrol  (DES)  is  a  synthetic  nonsteroidal  estrogen  
! Idiopathic  in  25%  of  cases  

 
Management  




Cervical   incompetence   can   be   treated   using   cervical   cerclage,   a   surgical   technique   that  
reinforces  the  cervical  muscle  by  placing  sutures  (stitches)  above  the  opening  of  the  cervix  
to  narrow  the  cervical  canal
...
   



 
 
 

Cervical   incompetence   is   not   generally   treated   except   when   it   appears   to   threaten   a  
pregnancy
...
 
Transabdominal   cerclage   of   the   cervix   makes   it   possible   to   place   the   stitch   exactly   at   the  
level   that   is   needed
...
   



Cerclages   are   usually   performed   between   weeks   14   and   16   of   the   pregnancy
...
   

 
Cervical  cerclage  


Shirodkar’s  suture  or  McDonald  suture  



Performed  usually  at  14  weeks  of  gestation  (to  prevent  inevitable  miscarriage)  



Risk  of  ROM  (ruptures  of  membranes,  also  known  as  amniorrhexis)  and  infection  



Removed  at  36  weeks  of  gestation  or  in  early  labour,  whichever  is  earlier  

 
 
 
EARLY  EMBRYOLOGY    
Learning  objectives  


Only  know  the  essentials  as  this  is  a  very  complex  area  of  medicine  



Know   what   is   meant   by   gastrulation:   early   phase   in   the   embryonic   development   during  
which   the   single-­‐layered   blastula   is   reorganized   into   a   trilaminar   ("three-­‐layered")  
structure   known   as   the   gastrula
...
 



Name  the  germ  layers  (ectoderm,  mesoderm  and  endoderm)  and  what  they  give  rise  to  
! Ectoderm  (derived  from  epiblast):  epidermis  and  CNS  (neural  tube)  +  neural  crest  
! Endoderm  (derived  from  hypoblast):  GI  tract  lining  and  respiratory  tract  lining  
! Mesoderm   (derived   from   between   epiblast   and   hypoblast):   CV,   GU,   MSK,  
connective  tissue  (mesenchyme)  e
...
 blood,  bones,  tendons,  dermis  etc  





Know   that   the   thoracic   and   peritoneal   cavities   are   formed   by   the   division   of   a   single   body  
cavity  



 
 
 

Know   that   the   respiratory   tract   develops   from   the   gut   tube   as   an   outpouching   (endoderm  
forms  the  lining)  and  how  this  impacts  on  the  congenital  defects  involving  the  trachea  and  
oesophagus  e
...
 tracheooeshageal  fistula  

Know  that  there  are  a  number  of  different  components  that  contribute  to  the  formation  of  
the  diaphragm    



Know  that  embryonic  folding  plays  a  key  role  in  bringing  the  septum  transversum  into  the  
correct  location  to  contribute  to  the  diaphragm  =>  explains  why  diaphragm  is  innervated  by  
C3,4,5  (3,4  and  5  keeps  the  diaphragm  alive)  
 

First  steps  in  development:  Embryogenesis  




The   blastocyst   is   formed   on   approximately   day   5
...
     



Implantation:   the   blastocyst   hatches   out   of   zona   pellucida
...
   Implantation  occur  day  6-­‐9
...
  These   three   germ   layers   are   known   as   the   ectoderm,  
mesoderm,  and  endoderm
...
 



 
 
 

Cleavage:  the  zygote  undergoes  mitotic  divisions  with  no  significant  growth  in  size  (a  process  
known  as  cleavage)
...
    The   first   cleavage   occurs   on   approximately   day   1   =>   resulting   in   2   cells
...
    At   the   end   of   the   fallopian   tube   (usually   day   4)   the   cluster   of   cells   is  
called   the   morula   and   is   still   surrounded   by   zona   pellucida   (glycoprotein   membrane  
surrounding  the  plasma  membrane  of  an  oocyte)
...
   Fertilisation  of  the  egg  cell  (oocyte)  with  sperm  cell  (spermatozoon)  occurs  
within   fallopian   tubes   (commonly   ampullary   region)
...
      This   also   occurs   in   the   third   week   of  
development
...
     



At  least  four  initial  cell  divisions  occur,  resulting  in  a  dense  ball  of  at  least  sixteen  cells  called  
the  morula
...
     



The  morula  then  develops  into  the  blastocyst  (approximately  day  5)  as  it  enters  the  uterus  



Implanation  of  the  blastocyst  then  occurs  (approximately  day  7-­‐10)  



 
 
 

Produces  a  cluster  of  cells  that  is  the  same  size  as  the  original  zygote
...
     

After   implantation   the   blastula   develops   into   the   gastrula   in   which   the   germ   layers   of   the  
embryo   form
...
g
...
 



 It  possesses  an  inner  cell  mass  (embryoblast)  which  subsequently  forms  the  embryo
...
 This  layer  surrounds  the  
inner  cell  mass  (embryoblast)  and  a  fluid-­‐filled  cavity  known  as  the  blastocoels  (cavity  made  
up  of  fluid  which  is  essential  for  the  embryo's  needed  nutrients)
...
 It  is  this  part  of  the  blastocysts  that  
can  give  rise  to  GTD
...
   



 
 
 

The  blastocyst  is  a  structure  formed  in  the  early  development  of  mammals
...
 The  blastocyst  embeds  itself  into  the  endometrium  (implantation  occurs  on  day  7-­‐
10)   of   the   uterine   wall   where   it   will   undergo   later   developmental   processes,   including  
gastrulation
...
  It   can   be   more   a   viable   method   of   fertility  
treatment  than  traditional  IVF
...
 



At  this  stage  of  prenatal  development,  the  embryo  is  a  blastocyst
...
 


 
 
 

Process   in   which   the   conceptus   actively   burrows   into   the   uterine   lining   (decidua   of  
endometrium  –  the  outer  layer  of  the  uterus)  

In   humans,   implantation   of   a   fertilized   ovum   is   most   likely   to   occur   about   7-­‐10   days   after  
ovulation  



The   reception-­‐ready   phase   of   the   endometrium   of   the   uterus   is   usually   termed   the  
"implantation   window"
...
  On   average,   it   occurs   during   the   20th   to   the   23rd   day   after   the   last  
menstrual  period  (e
...
 in  third  gestational  week)  



The  implantation  window  is  characterized  by  changes  to  the  endometrium  cells,  which  aid  in  
the   absorption   of   the   uterine   fluid
...
    Progesterone   released   from   the   corpus   luteum   is   essential
...
     



Progesterone   causes   increased   blood   flow   and   uterine   secretions   and   reduces   the  
contractility   of   the   smooth   muscle   in   the   uterus   to   thicken   and   increase   blood   flow   to  
support  a  developing  embryo  =>  deciduas  forms  (females  side  if  the  placenta)
...
    So   oestrogen   causes   the   endometrium   to  
proliferate  (proliferative  phase),  but  progesterone  makes  it  habitable  (secretory  phase)  and  
reduces  myometrium  activity
...
   
! The  syncytiotrophoblast  also  produces  human  chorionic  gonadotropin  (hCG),  a  
hormone  that  maintains  the  corpus  luteum  (as  very  similar  in  structure  to  LH  its  
sister   molecule)   and   therefore   stimulates   the   release   of   progesterone   from   the  
corpus   luteum
...
   
! The   villi   begin   to   branch   from   the   chorion   (trophoblast   membrane   layer)   and  
contain  blood  vessels  of  the  embryo
...
 
! Projections   (villi)   from   trophoblast   layer   (foetal   placenta   capillaries)   break   down  
connections  of  cells  in  uterine  lining  (endometrium)  
! Blastocyst  becomes  completely  embedded  in  wall  
! Fibrin  plug  covers  area  of  uterine  lining  damage  (coagulation  plug)  


 
 
 

The  placenta  also  begins  to  develop  upon  implantation  of  the  blastocyst  into  the  maternal  
endometrium
...
 This  outer  layer  is  divided  into  two  further  layers:  the  underlying  
cytotrophoblast  layer  and  the  overlying  syncytiotrophoblast  layer
...
  The   inner   cell   mass   is   the   source   of   embryonic   stem   cells,  
which  are  pluripotent  and  can  develop  into  any  one  of  the  three  germ  layer  cells
...
 



Membranes  are  also  beginning  to  form  that  will  support  the  embryo:  
! Chroion:  placenta  membrane  
! Amnion   cells   derived   from   epiblast   cells   start   to   form   the   amniotic   cavity   which  
surrounds  the  foetus  and  holds  amniotic  fluid  (amniotic  fluid  or  liquor  amnii  is  the  
protective  liquid  contained  by  the  amniotic  sac  of  a  pregnant  female)  
! Primitive  yolk  sac:  surrounded  by  Heuser’s  membrane    

 
 
 

 
 
 

 
 
Third  developmental  week  (week  five  of  gestation)  


Three  important  structures  form  during  the  3rd  developmental  week:  the  primitive  streak,  
the  notochord  and  the  neural  tube
...
     
! The   primitive   streak   is   a   structure   that   forms   in   the   blastula   (implanted  
blastocyst)  during  the  early  stages  of  development
...
 
! The  notochord:  The  notochord  forms  during  gastrulation  and  soon  after  induces  
the  formation  of  the  neural  plate  (neurulation),  synchronizing  the  development  
of  the  neural  tube  
! The  neural  tube:  forms  the  CNS
...
     

 
 
Gastrulation  
 
 
 



Critically  important:  gives  3  germ  layers  that  form  all  different  tissues  



The   embryoblast   forms   an   embryonic   disc   which   is   a   bilaminar   disc   (bilaminar   blastocyst)   of  
two   layers,   an   upper   layer   the   epiblast   (primitive   ectoderm),   and   a   lower   layer   the  
hypoblast  (primitive  endoderm)
...
 



During  the  third  week  a  process  called  gastrulation  creates  a  mesodermal  layer  between  
the  endoderm  and  the  ectoderm
...
 



The  primitive  streak,  a  linear  band  of  cells  formed  by  the  migrating  epiblast,  appears,  and  
this   marks   the   beginning   of   gastrulation,   which   takes   place   around   the   sixteenth   day  
(week  3)  after  fertilisation
...
   



A   primitive   node   (or   primitive   knot)   forms   in   front   of   the   primitive   streak   which   is   the  
organiser   of   neurulation   (folding   process   in   vertebrate   embryos,   which   includes   the  
transformation  of  the  neural  plate  into  the  neural  tube)  



The   bilaminar   blastocyst   (epiblast   and   hypoblast)   then   transforms   into   a   trilaminar   structure  
(three  overlapping  flat  discs)  
! The  epiblast  transforms  into  the  ectoderm  
! The  hypoblast  transforms  into  the  endoderm  
! The  mesoderm  occurs  between  the  outer  ectoderm  and  inner  endoderm  



The  three  germ  layers  are  the  ectoderm,  mesoderm  and  endoderm,  and  are  formed  as  three  
overlapping  flat  discs
...
g
...
g
...
g
...
g
...
 



The  notochord  burrows  from  primitive  node  (which  forms  in  front  of  the  primitive  streak)  
between  ectoderm  and  endoderm  



The  notochord  determines  the  longitudinal  axis  of  the  embryo
...
 



Important  in  regulating  development  of  structures  =>  tells  tissues  what  to  become
...
 

Because   of   position   it   is   ideally   placed   for   sending   signals   superior/inferior/lateral   to   the   3  
layers
...
g
...
    The   amnion   is   a   membranous   sac   which  
surrounds  and  protects  the  embryo
...
   


 
 
 

Folding  is  important  for  arrangement  of  membranes  surrounding  embryo  

As   the   volume   of   the   fluid   increases,   the   amnion   expands   and   ultimately   adheres   to   the  
inner  surface  of  the  chorion  (placental  membrane)  



The  chorion  (formed  from  the  two  layers  of  the  trophoblast)  begins  to  form  the  foetal  part  
of  the  placenta  



Increasing  liquor  amnii  (amniotic  fluid)  quantities  allow  free  movements  of  the  fetus  during  
the   later   stages   of   pregnancy,   and   also   protect   it
...
  Will   gradually   fill   the   chorionic   cavity
...
   



Differentiate  into  3  types:  
! Dermatome:  dermis  
! Myotome:  skeletal  muscle  
! Scleratome:  cartilage,  tendons,  and  endothelial  cells,  bones  (contributes  to  axial  
skeleton)  
 

Neural  Tube  Defects  

 
 
 



A  NTD  (neural  tube  defect)  is  an  opening  in  the  spinal  cord  or  brain  that  occurs  very  early  in  
human  development
...
 



Neural   tube   defects   arise   because   of   failure   of   closure   or   failure   of   bony   elements   that  
protect  the  neural  tube  



Spina   bifida:   NTD   congenital   disorder   caused   by   the   incomplete   closing   of   the   embryonic  
neural   tube
...
 If  the  opening  is  large  enough,  this  allows  a  portion  of  the  spinal  cord  to  
protrude  through  the  opening  in  the  bones
...
   Range  of  
severity
...
 This  is  the  mildest  form  of  spina  
bifida
...
    The   splits   in   the   vertebrae   are   so   small   that   the   spinal   cord   does   not  
protrude
...
   AFP  normal
...
  In   this   form,   the   vertebrae   develop   normally,   but   the  
meninges   are   forced   into   the   gaps   between   the   vertebrae
...
    In   individuals   with   meningomyocele,   the   unfused   portion   of   the  
spinal  column  allows  the  spinal  cord  (myo)  to  protrude  through  an  opening
...
 





 
 
 

Rachischisis:  Vertebrae  overlying  the  open  portion  of  the  spinal  cord  do  not  fully  form  and  
remain  unfused  and  open,  leaving  the  spinal  cord  and  neural  tissue  exposed
...
 This  defect  often  occurs  with  anencephaly
...
  It   is   a   cephalic   disorder   that   results   from   a  
neural  tube  defect  that  occurs  when  the  rostral  (head)  end  of  the  neural  tube  fails  to  close,  
usually   between   the   23rd   and   26th   day   of   conception
...
  This   exposure   causes   the   nervous   system   tissue   to   break   down  

(degenerate)  due  to  the  toxic  effects  of  amniotic  fluid
...
  Almost   all   babies  
with  anencephaly  die  before  birth  or  within  a  few  hours  or  days  after  birth
...
 However,  most  of  these  pregnancies  end  in  miscarriage,  so  the  prevalence  of  
this  condition  in  newborns  is  much  lower
...
    The   septum   secundum   grows  
downward  from  the  upper  wall  of  the  atrium  immediately  to  the  right  of  the  primary  septum  
and  ostium  secundum
...
 It  is  an  
arterial   trunk   (the   one   and   only   outflow   tract)   that   originates   from   both   ventricles   of   the  
heart   that   later   divides   into   the   aorta   (attached   to   left   ventricle)   and   the   pulmonary   trunk  
(attached  to  right  ventricle)  



Two  parts:  
! Muscular   part:   muscular   ridge   grows   upwards,   with   expansion   of   ventricles   on  
either  side  of  ridge
...
    This   results   in   separation   of   the   right   ventricle/pulmonary   trunk   from   left  
ventricle/aorta  



Truncal  ridges  grow  downwards  in  spiral  fashion    

 
Cardiac  development  anomalies    




Transposition  of  the  great  vessels:  can  occur  due  to  absent  spiral  movement  of  the  ridges    
(right  to  left  shunt  =>  cyanotic)  



Tetraology  of  Fallot  (right  to  left  shunt  =>  cyanotic)  



Patent  foramen  ovale  (left  to  right  shunt  =>  acyanotic)  



 
 
 

Persistent  truncus  arteriosus:  can  occur  due  to  absent  truncal  ridges  (right  to  left  shunt  =>  
cyanotic)  

Patent  ductus  arteriousus  (left  to  right  shunt  =  acyantoic)  

 

 
 
Congenital  cyanotic  heart  disease  


Truncus   arteriosus:   single   vessel   connected   to   both   right   and   left   ventricles   =>   mixing   of  
deoxygenstaed   blood   into   systemic   circulation   =>   right   to   left   shunt   =>   cyanotic   heart  
disease
...
 



Transposition   of   the   great   vessels:   aorta   is   connected   to   RV   and   pulmonary   trunk   is  
connected  to  LV=>  pumping  of  deoxygenated  blood  in  the  systemic  circulation  (Right  to  left  
shunt)
...
  Branches   into   left   and  
right  lungs
...
g
...
g
...
  Folding  of  the  septum  transversum  carries  
nerves  (C3,4,5)  the  phrenic  nerve  with  it  as  it  moves  downwards    

 
 
Formation  of  Diaphragm  



Vast  majority  innervated  by  cervical  nerves,  but  edges  may  have  local  innervation    



Multiple  parts  need  to  fuse  to  form  diaphragm  =>  many  potential  defects  



 
 
 

Comes  to  rest  in  between  future  throracic  and  abdomen  cavities  

Large  portion  formed  from  septum  transversum  

 
 
 
Congenital  diaphragmatic  hernia  


A   diaphragmatic   hernia   may   result   from   failure   of   fusion   of   its   constituent   parts   (4   parts  
form  the  diaphragm)  



Most  commonly  on  left  side  



Usual  cause  is  a  defect  in  the  formation  of  the  pluroparietal  membrane  



Abdomen  contents  will  herniate  through  into  thoracic  cavity  



Abdomnal   contents   can   compress   on   lungs   =>   severe   impact   on   lung   development   =>  
pulmonary  hypoplasia  =>  small  hypoplastic  lung  =>  decreased  gas  exchange  



Often  on  left  side  =>  left  hypoplastic  lung  and  shifting  of  apex  beat  to  the  right    

 
 
 
 

 
 
INFERTILITY  AND  ASSISTED  CONCEPTION  


Assisted   conception   treatment   (ACT)   is   any   treatment   in   which   involves   gametes   outside  
the  body  



One  in  six  couples  require  assessment  of  infertility  in  UK    



Approximately  half  of  these  will  require  ACT    



2%  of  live  births  in  UK  are  the  result  of  ACT    



Demand  for  ACT  is  rising:    
! increasing  parental  age  
! increasing  Chlamydia:  can  affect  both  male  (orchitis  or  obstruction)  and  female  
(obstruction  to  tubes  due  to  PID)  
! Male  factor  infertility  
! Increasing  range  of  ACT  treatments  and  improved  success  rates  
! Obesity  and  DM  –  common  cause  of  subfertility  
 

Infertility  


Primary  infertility  refers  to  couples  who  have  not  become  pregnant  after  at  least  1  year  of  
unprotected  sex  (intercourse)
...
 



Causes:  
! Tubal  disease  e
...
 PID  (common  cause)  
! Male   factors   e
...
  poor   sperm   counts   (common   cause)   –   oligozoospermia   or  
azospermia;  or  problems  with  erection  or  ejaculations  
! Endometriosis:  can  reduce  number  &  quality  of  eggs,  and  effect  implantation  
! Endocrine  causes  
! Not  having  enough  sex  and/or  having  sex  at  correct  times  of  cycle  
! Lifestyle  factors  e
...
 alcohol,  smoking,  lack  of  exercise  

 
 
 

! Large  number  unexplained  (idiopathic)  
!

Often  multiple  factors:  M  and  F  factors  

 

 
 
Other  Indications  for  Assisted  Conception  Treatment  


Fertility  preservation  in  cancer  patients,  before  treatments  that  may  affect  gametes  



Treatment  to  avoid  transmission  of  blood  born  viruses  between  patients  (e
...
 HIV,  Hepatitis  
B  &  C)  



Prenatal  diagnosis  of  inherited  disorders  (pre-­‐implantation  genetic  diagnosis,  e
...
 muscular  
dystrophy)  



Treatment  of  single  parents  (not  allowed  on  NHS)  or  same  sex  couples  



Others:  cryopreservation  of  gametes  for  social  reasons  e
...
 to  preserve  eggs  when  young  to  
have  babies  when  older  without  increased  risk  of  Down’s  Syndrome  etc
...
  Also   reduces   risk   of  
complications,   e
...
  miscarriage,   pre-­‐eclampisa,   gestational   diabetes
...
4mg/day   preconception   until   12   weeks   gestation   (Some   women   have   an  
increased   risk   of   having   a   pregnancy   affected   by   a   neural   tube   defect,   and   are   advised   to  
take  a  higher  dose  of  5mg/day  of  folic  acid  each  day  until  they  are  12  weeks  pregnant
...
  Causes   severe   congenital  
abnormalities  



Cervical   smears:   check   up   to   date   according   to   national   screening   programme
...
g
...
 Stably  off  all  drugs  (including  methadone)  for  at  least  a  year  to  get  IVF  



Screen   for   blood   born   viruses:   hepatitis   B/C   and   HIV   and   syphilis   (minimise   transmission  
between  male,  female  and  foetus)  

 
OVULATION   INDUCTION   SHOULD   BE   TRIED   BEFORE   IVF   e
...
  clomiphene   citrate   and   GnRH  
analogues    
 
What  treatments  are  available?  


Intra-­‐Uterine  Insemination  (IUI):  for  mild  male  factor  infertility  (e
...
 oligozoospermia)  



IVF  
! In  Vitro  Fertilisation  (IVF)  –  eggs  bathed  in  sperm    
! Intra-­‐Cytoplasmic   Sperm   Injection   (ICSI-­‐IVF):   for   severe   male   factor   infertility  
(azoopsermia  or  severe  oligozoospermia)  



Others:   treatment   with   donor   sperm   or   eggs,   surrogacy   (e
...
  in   Hx   of   hysterectomy,  
congential  abnormality),  cryopreservation  of  sperm  or  eggs  

 
Intra  Uterine  Insemination  (IUI)  


Indications:  
! Unexplained  infertility  
! Mild  or  moderate  endometriosis  
! Mild  male  factor  infertility  e
...
 mild  oligozoospermia  (sperm  can  be  collected  and  
concentrated)  



Method:  
! Can  be  in  natural  (lower  success  rate)  or  stimulated  cycle    

 
 
 

! Prepared   semen   (concentrated)   inserted   via   syringe   into   uterine   cavity   around  
time  of  ovulation  


~  12%  success  rate  per  treatment  cycle  

 
In  Vitro  Fertilisation  (IVF)  


Indications:  
! Unexplained  (>  3  years  durations)  
! Pelvic  disease  (endometriosis,  tubal  disease,  PID,  fibroids)  
! Male  factor  infertility  (severe  oligozoospermia  or  azoospermia  =>  surgical  sperm  
aspiration  with  ICSI  IVF)  
! Anovulatory   infertility   e
...
  PCOS:   1st   line   is   normally   clomifiene   citrate   +/-­‐  
metformin,  then  gonadotrophins  (LH/FSH  analogues),  then  IVF  
! Others  (pre-­‐implantation  genetic  diagnosis)  



In  vitro  fertilisation  (IVF)  is  a  process  by  which  an  egg  is  fertilised  by  sperm  outside  the  
body  e
...
 in  vitro
...
g
...
  The   fertilised   egg   (zygote)   is  
cultured  for  2–6  days  in  a  growth  medium  and  is  then  transferred  to  the  mother's  uterus  
with  the  intention  of  establishing  a  successful  pregnancy
...
 

 
IVF  method  
IVF  Step  1:  Downregulation  


 
 
 

This   step   is   used   in   order   to   "switch   off"   the   womans   own   reproductive   hormone  
production  (LH  and  FSH)  



A  woman’s  reproductive  (menstrual)  cycle  is  controlled  by  the  pituitary  gland  (LH  and  FSH)
...
   



This  is  because  these  drugs  stimulate  the  production  of  a  “follicle
...
  In   IVF   we   want   to   stimulate   as   many  
follicles   to   grow   as   possible
...
     



The   drugs   used   to   switch   off   your   reproductive   cycle   are   called   gonadotrophin-­‐releasing  
hormone   analogues,   or   GnRH   analogues   for   short
...
 You  will  need  to  take  these  drugs  every  day
...
 



High   doses   of   GnRH   analogues   cause   reversible   down   regulation   of   the   pituitary   =>  
suppression  of  LH  and  FSH  



Having  your  reproductive  cycle  turned  off  tricks  your  body  into  thinking  it  is  going  through  
the   menopause
...
 
 

Key  points  

 
 
 

Synthetic   gonadotrophin   releasing   hormone   analogue   (Buserelin)   is   administered     as     a    
spray    or    injection  and  must  be  taken  every  day  



Causes    reversible    “downregulation”  of  pituitary  due  to  overstimualtion  =>  suppression  of  
LH  and  FSH  production  =>  so  that  we  can  take  control  of  the  cycle!  



Begin  buserelin  Tx  on  Day  21  of  cycle  (20  days  after  first  day  of  last  bleed)  



Take  daily  for  3-­‐4  weeks  



Patient  comes  back  for  baseline  US  scan  before  beginning  step  2  

 
IVF  Step  2:  Stimulation  of  Follicle  Production:  Ovarian  hyperstimulation  


Once  LH  and  FSH  is  suppressed  (pituitary  downregulation)  the  patient  will    receive  drugs  to  
encourage  follicle  production  (ovarian  hyperstimualtion)  



The   patient   will   need   to   carry   on   taking   downregulation   drugs   (eg
...
 
Follicles   can   be   found   on   the   outer   wall   of   the   ovaries
...
 A  natural  hormone  called  follicle-­‐stimulating  hormone  
(FSH)  tells  the  ovaries  when  to  produce  follicles
...
 Eventually,  there  is  usually  only  one  dominant  follicle  that  grows  to  the  right  size  
and  bursts  (due  to  LH  surge)
...
 



Drugs   that   are   given   to   encourage   follicle   production   work   in   a   similar   way   to   FSH
...
 As  follicles  contain  eggs,  this  means  that  there  will  hopefully  
be  many  more  eggs  available  for  collection
...
   



Drugs  that  are  used  to  encourage  follicle  production  include:  
! Gonal-­‐F  (synthetic  FSH)  –  stimulates  the  gonads  
! Menopur  (human  menopausal  gonadotropin  or  hMG)  



They   are   all   given   by   daily   injections   which   can   be   self   administered   (remember   Tx   with  
buserelin  must  be  continued  daily)  



Side    effects:  
! Mild    allergic    reactions  
! Ovarian    Hyperstimulation    Syndrome    (OHSS)  

 
 
 



Tx  is  continued  for  approximately  8-­‐9  days  (approx  one  week)  



An  “action  US  scan”  is  then  performed  before  stage  3  

 
Action  US  scan  


The   scan   will   enable   the   ultrasonographer   to   check   that   the   drugs   for   downregulation   have  
worked  (e
...
 no  activity  in  ovaries  e
...
 no  rupture  of  follicles)    



They  will  also  be  able  to  count  and  measure  the  follicles  growing  in  your  ovaries  (to  check  
that   ovary   hyperstimulation   has   worked)
...
 8%  of  cycles  are  
abandoned  due  to  not  enough  follicles)  

 
IVF  Step  3:  Egg  maturation  and  release  of  egg    


When   the   scan   shows   that   your   follicles   have   grown   to   the   right   size   (and   there   are   a  
suitable  number  of  follicles  present),  you  will  be  given  a  drug  to  mature  the  eggs  within  the  
follicles
...
   Remember  hCG  is  a  
sister  molecule  of  LH
...
    We   want   to   be   in   control   of   the   LH   surge
...
     

 
 
 

! Needs   to   be   given   36   hours   before   the   egg   collection   procedure   which   means  
that  it  may  need  to  be  taken  late  at  night
...
 
 
Step  4:  Preparing  the  uterus  to    receive  the  embryos  


The  uterus  needs  to  be  prepared  before  it  can  receive  the  fertilised  eggs  (embryos)
...
 



The  secretory  phase  is  the  final  phase  of  the  uterine  cycle  and  it  corresponds  to  the  luteal  
phase   of   the   ovarian   cycle
...
    Remember   that   in   the   normal   menstrual   cycle,   it   is   the   fall   of  
progesterone,  which  results  in  shedding  of  the  endometrium
...
 

 
IVF  Step  5:  Sperm  collection  


Abstinence    for    72    hours    before  hand  



Collect   in   pot   (in   “mens   room”)   if   male   is   fertile   or   can   use   sperm   aspiration   if   male   has  
fertility  issues  (azoospermia  or  oligozoospermia)  



Assessment:  
! Volume  
! Density  (numbers  of    sperm)  
! Motility:  what    proportion    are    moving  
! Progression:  how    well    they    move    

 
 
 
 

IVF  Step  6:  Egg  collection  


This  procedure  is  also  called  “oocyte  capture”  and  “ovum  retrieval
...
 After  
the  eggs  have  been  collected,  they  will  be  mixed  with  your  partners  sperm  and  allowed  to  
fertilise
...
  A   fine   needle   will   then   be   used   to   collect   the   eggs   from   the   follicles
...
 



Embryologist  observes  under  microscope
...
0C  (body  temp)  



Normal  fertilisation:  
! Two    pronuclei    
! Male    and    female    genetic    information  
! Approx  60%  of  eggs  fertilise  normally  



Embryo  transfer:  
! Day  0:    Egg  collection  
! Day  1:    Pronuclear  stage  
! Day  2:    Average  4  cell  stage  
! Day  3:    Average  8  cell  stage  
! Cryopreserve  good  quality  embryos  

 
 
 

! Day  2  or  3  embryos  are  usually  used  
 
Can  do  standard  IVF  (bathe  eggs  in  sperm)  or  ICSI  IVF  (inject  sperm  into  eggs)
...
”  



Embryos   are   usually   transferred   to   the   uterus   approximately   three   days   after   fertilisation  
has  begun  



Number  of  embryos  to  be  transferred  
! Patients  under  the  age  of  40:  no  more  than  2  embryos  to  be  transferred  
! Patients   aged   40   and   over:   3   may   be   transferred   in   exceptional   circumstances  
only
...
     
! Guidelines  to  reduce  to  one  embryo  in  selected  patients  to  minimise  the  risk  of  
twins  
! Complications  of  twins:  risk  of  lots  of  things  e
...
 cerebral  palsy,  twin  transfusion  
syndrome  
! Complications   of   triplets:   may   selectively   terminate
...
     



LH   maintains   the   corpus   luteum   however   during   the   luteal   phase,   increasing   levels   of  
progesterone   cause   LH   levels   to   decrease   =>   the   corpus   luteum   will   degenerate   unless  
fertilisation   occurs
...
     



In  assisted  reproduction  techniques  (ART)  the  progesterone  or  hCG  levels,  or  both,  are  low  
and  the  natural  process  is  insufficient
...
   



Progesterone  analogues  should  be  given  before  implantation  and  continued  thereafter  



Drug  =  cyclogest  pessaries  (progesterone)  

 
IVF  step  10:  pregnancy  test  


Pregnancy  test  2  weeks  after  embryo  transfer  (hCG  test)  



If  positive  pregnancy  test  =>    transvaginal  scan  5  weeks  after  embryo  transfer  



Artificial  progesterone  for  1st  few  weeks  

 
Summary  of  IVF  

 
 
 

 
 
Intra  Cytoplasmic  Sperm  Injection  (ICSI)  with  IVF  –  ICSI  IVF  


Indications:  
! Severe  male  factor  infertility  e
...
 azoospermia  or  severe  oligozoospermia  
! Previous  failed  fertilisation  with  IVF  
! NB:    In  IVF  without  male  factor  infertility  =>  the  eggs  are  bathed  in  washed  
sperm  =>  standard  IVF  



Method:  
! Form  of  IVF  
! Each  egg  is  stripped  
! Sperm  is  surgically  aspirated  and  then  injected  into  egg  
! Surgical  Sperm  aspiration  is  indicated  for  azoospermia  (or  severe  
oligozoospermia)  
! Sperm  immobilised  
! Single  sperm  injected  into  egg  
! Incubate  at    37
...
   



Most  cases  are  mild,  but  a  small  proportion  are  severe
...
g
...
g
...
  The   risk   is   further   increased   by   multiple  
doses  of  hCG  after  ovulation  and  if  the  procedure  results  in  pregnancy
...
g
...
 
! As   hCG   causes   the   ovary   to   undergo   extensive   luteinization,   large   amounts   of  
estrogens,  progesterone,  and  local  cytokines  are  released  =>  inflammation
...
   
! Overstimulation  =>  leaky  capillary  membranes  =>  proteins  leak  out  =>  fluid  goes  
into  abdominal  cavity  =>  ascites  and  increased  risk  of  thromboembolic  disease  

 
 
 

! Distension   and   IV   depletion   affects   renal   function   =>   increased   urea   and   Cr,  
decreased  eGFR  etc
...
g
...
g
...
   Twins  and  triplets  have  a  long  list  of  complications
...
 

!

COCP  is  the  most  common  –  multiple  other  uses  including  dysmenorrhea,  menorrhagia,  
and  hirsuitism    

!

 Rates  of  each  vary  significantly  with  age
...
 



Pearl   Index   (PI)   =   number   of   unintended   pregnancies   which   occur   if   100   women   use   the  
method  for  1  year
...
 



 High  PI  =>  less  effective  

 
PI  for  no  contraception      
 
 
 



Natural  fertility  declines  with  increasing  age
...
02  

Female  Sterilisation  

                       

0
...
16  

LNG-­‐IUS  (Mirena)  

                 

 

<0
...
2  

IUD  

               

 

 

 

     1
...
9  

Male  condom                

 

 

     3
...
6  

Withdrawel  (“pull  out”)            

 

     6
...
9  

Natural    

 

 

   15
...
   Calendar  



 
 
 

Ovulation   occurs   on   12-­‐16   day   (average)   of   menstrual   cycle   –   usualy   14   days   before  
menstruation  (Luteal  phase  is  usually  14  days)  
Allows  for  survival  time  of  ovum  and  sperm  =>  intercourse  must  be  avoided  between  day  
10  and  20  of  the  menstrual  cycle  (for  28  day  cycle)  



Not  very  effective  

 
 

 

 
2
...
 The  vulva  will  begin  to  feel  slippery  (fertile  phase)
...
 Ovulation  occurs  no  more  than  
48  hours  after  the  peak
...
   Temperature  



 
 
 

Relies  on  the  fact  that  progesterone  released  from  the  corpus  luteum  raises  the  basal  body  
temperature  by  0
...
4  C  after  ovulation  (luteal  phase)  and  maintains  it  until  the  onset  of  
next  menstruation  
Biphasic  pattern
...
 

 
4
...
 
 

5
...
e
...
g
...
   

!

NB:    Female  condoms  (different  from  diaphragm)  can  protect  against  STDs
...
   

!

Provides  alternative  to  hormone  treatments  =>  often  preferred  by  woman  who  do  not  have  
sex  too  frequently  

!

Problems:    
! Loss  of  spontaneity  (as  have  to  insert)  
! Poor  vaginal  tone  
! Patient  motivation  =>  needs  changed  often  (max  time  of  30  hours)  
! Psychological  aversion  

 
 
 
 
 
 

 
Sterilisation  
!

‘Permanent’   (some   forms   may   be   reversed)   method   of   contraception   for   couples   who   are  
certain  their  family  is  complete  

!

Uptake   rates   have   declined   since   advent   of   LARC   (long-­‐acting   reversible   contraception)  
which   provide   surgical-­‐free   alternatives   e
...
  implanon/explanon   (upper   limb   progesterone  
implant  which  lasts  for  3  years),  IUS  (Mirena:  the  levonorgestrel/progesterone  coil  which  last  
for   5   years),   IUCD   (copper   coil   which   lasts   for   5-­‐10   years),   Depo-­‐provera   (progesterone  
injection  which  lasts  for  3  months)  

!

Male  and  female  methods  available  

 

 

Female  Sterilisation    
There  are  two  main  types  of  female  sterilisation:  
!

Laproscopic:  tubal  occlusion  e
...
 fallopian  tubes  are  blocked,  for  example  with  clips  or  rings  
=>  effective  immedialtey  but  more  invasive
...
 The  
presence  of  the  micro-­‐inserts  causes  scar  tissue  to  form  in  the  Fallopian  tubes
...
 

!

Hysteroscopic  sterilisation  is  as  effective  as  laparoscopic  sterilisation  however  the  woman  
should  use  an  additional  form  of  contraception  until  the  implants  have  been  shown  to  be  
in  the  correct  place
...
 

Effectiveness  depends  upon  technique  used,  experience  of  surgeon  and  length  of  follow-­‐up  

 
 
Female  sterilisation:    Pros  and  Cons  
Pros  
!

Effective  immediately  (although  hysteroscopic  methods  need  to  be  confirmed  successful  at  
3/12  with  HSG  before  withdrawal  of  other  forms  of  contraception)  

!

Women  often  more  motivated  than  men  

!

Non  hormonal  

!

Permanent  

 
Cons  
!
!

Requires  specialist  skills  and  facilities  

!

 
 
 

Cannot  always  be  reversed  nor  is  it  always  available  on  the  NHS  

!

 

Risk  of  operative  mortality  and  morbidity  

Higher  failure  rates  than  other  methods  e
...
 Mirena  (levonorgestrel-­‐releasing  intrauterine  
system  e
...
 basically  a  progesterone  coil),  progesterone  implant  (nexplanon/implanon)  and  
vasectomy  (male  sterilisation)  

 
 
Counselling  for  sterilisation  
!

Simple  description  techniques  (diagram  &  leaflet)  

!

Risk  of  laparoscopy    

!

Failure  rate  (1:200  to  2-­‐3  in  1000)  

!

Ectopic  pregnancy  risk  

!

Prospects  of  reversal  

!

Alternatives:  Vasectomy,  Mirena  (levonorgestrel-­‐releasing  intrauterine  system,  5  years)  and  
Nexplanon/Implanon  (progesterone  upper  arm  implant,  3  years)  

!

Implications  of  relationship  breakdown  etc  

!

Dispelling  myths  

 
Female  sterilisation:  Complications  
Short  term  (operative)  
!

Bleeding  

!

Infection    

!

Pain    due  to  tubal  ischaemia    

!

Damage  to  other  organs  e
...
 Bowel  injury  

 
Long-­‐term  
!
 
 
 

Failure/unwanted  pregnancy  

!

Ectopic  pregnancy  

!

Psychosexual    

!

Risk  of  regret  (approx  7-­‐10%)  

!

Infertility/request  for  reversal  

 
Male  Sterilisation  
!

Diathermy  (sealing  with  heat)  or  division  of  the  vas  deferens  (usually  under  LA)  

!

Vas  deferens  are  cut,  blocked  or  sealed  

!

Low  failure  rate  (1  in  2000)  

!

Requires  use  of  reliable  contraception  until  azoospermia  confirmed  =>  two  negative  
semen  samples  at  12  and  16  weeks  (3  and  4  months)  

!

Risks  of  procedure:  
! Haematoma  
! Infection  
! Chronic  testicular  pain  (~20%)  

!

Reversal  has  low-­‐moderate  chance  of  success  and  not  available  on  NHS  

 
 
Male  vs  Female  

 
 
 

 
 
!

Overall   male   is   more   effective   and   less   invasive   and   has   less   complications
...
g
...
g
...
g  cerazette):  not  as  effective  as  “the  COC  pill”  

!

Injection   (Depo-­‐provera):     lasts   3   months   –   can   be   used   with   enzyme   inducers   (e
...
 
rifampicin,  carbamazepine  and  phenytoin)
...
     

!

Implant  (Nexplanon/Implanon):    lasts  3  years  –  cant  be  used  with  enzyme  inducers  

!

Intrauterine   coil   system   (Mirena):   levonorgestrel-­‐releasing   intrauterine   system   (basically   a  
progesterone  coil)  –  lasts  5  years,  can  be  used  with  enzyme  inducers  

 
MIRENA  AND  DEPROPROVERA  CAN  BE  USED  WITH  ENZYME  INDUCING  DRUGS  
 
Mode  of  action  
Oestrogen  
!

Inhibit   ovulation   by   suppressing   secretion   of   LH/FSH   from   pituitary   (due   to  
prolonged  negative  feedback)  

!

Leads   to   failure   of   follicular   maturation   =>   annovulation   (menstrual   cycle   during  
which   the   ovaries   do   not   release   an   oocyte;   may   or   may   not   be   associated   with  
amenorrhoea)  
 

Progestogen  
!

Progestogen  thickens  the  mucus  (secretory  phase)  in  the  cervix,  which  stops  sperm  
penetration  of  cervix  =>  stops  sperm  reaching  egg
...
     

!

In  can  also  stop  ovulation,  depending  on  the  type  of  progestogen  (dose/preparation)  
=>  due  to  –ve  feedback  to  the  hypothalamus  and  pituitary  =>  decrease  LH  and  FSH  

!

Poor  secretory  activity  of  the  endometrium  which  resists  implantation  
! Why  does  the  progesterone  only  pill  inhibit  implantation?    Progesterone  is  
essential   for   implantation!   In   the   absence   of   oestrogen,   progesterone  
does   not   prepare   the   endometrial   wall
...
     

!
 
 
 

Cervical  mucus  is  more  resistant  to  sperm  penetration  

!

Interferes  with  Fallopian  Tube  transport  

 
Combined  Hormonal  Contraception  (CHC)  
Delivery  
!

Pills  (COC):  “the  pill”  or  microgynon  

!

Patch  (Evra)  

!

Vaginal  ring  (Nuvaring)  

 
SHOULD   NOT   BE   USED   WITH   ENZYME   INDUCING   DRUGS   =>   THESE   DRUGS   DECREASE   EFFICACY   OF  
CONTRACEPTION  
 
Contents  
!

Two  eostrogens  (ethinyl  oestradiol  E2  and  mestranol):  many  of  which  have  an  increased  risk  
of  VTE  disease  (and  ER  +ve  breast  cancer  risk,  and  of  cervical  cancer)  

!

Many   progestogens:   three   of   which   have   a  slight   increased   risk   of   venousthromboembolic  
VTE  disease  and  PgR  +ve  breast  cancer  risk  

 
How  to  take  COC  
!

Each  pill  strip  contains  21  active  tablets  taken  consecutively  

!

Followed  by  7  day  pill-­‐free  interval  (or  7  placebo  pills)  =>  induces  withdrawel  bleed  

!

Always  restart  next  strip  on  same  day  

!

Missed  pill  rules  (see  clinical  skills)  

 
Formulations  of  COC  
1
...
Fixed  dose  of  oestrogen  and  progestogen:  21  tablets  +  7  placebo  tablets  
3
...
   
 
 
 
 

CHC:  Advantages  
!

   Effective  (>99%)  and  convenient  method    (more  effective  than  POP)  

!

   Not  related  to  SI  (sexual  intercourse)  

!

   Fully  reversible  (reversibility  is  fast)  

!

   Non-­‐contraceptive  benefits    
! Reduces   menstrual   pain/blood   loss/PMS   =>   usefull   for   dysmenorrhoea,   and  
menorrhagia  (although  Mirena  is  first  line  for  menorrhagia  due  to  DUB)  
! Improves  acne  (some  dual  licensed)  –  can  be  used  for  acne  and  for  hirsutism  in  PCOS  
!  ↓   risk   ovarian/endometrial   cancer   (due   to   suppression   of   the   menstrual   cycle  
which  is  a  risk  factor)  
! ↓  risk  colorectal  cancer    
! ↓  functional  ovarian  cysts  and  benign  breast  disease  
! Can  be  used  for  hirustism    
 

CHC:  disadvantages/risks  
!

Side  effects:    
! headache  
!  weight  gain  
! mood  changes  
!  reduced  libido    
! often  settle  after  3/12  of  use  

!

RIsks  
! VTE  
! Increased  cancer  risk:  breast,  cervical  
! Liver:  metabolic  effects    
! Arterial   disease:   HT,   MI,   stroke   –   higher   risk   in   migraines   with   aura,   BMI   >35,  
smokers  >35  

!
 
 
 

User-­‐dependent  

!

Drug  interactions  e
...
 CANT  be  used  with  certain  enzyme  inducing  drugs    

!

Contraindications  for  use  e
...
 BMI>35,  smoker  >35,  migraine  with  aura,  previous  breast  Ca  

 
 
Drug  interactions  
!

Hormonal  contraceptives  are  metabolised  in  liver  

!

Certain   drugs   (liver   enzyme   inducers)   can   increase   the   rate   of   metabolism   thus   leading   to  
reduced  plasma  levels  =>  ↑  risk  pregnancy  

!

Liver  enzyme  inducers  include  (CRAP  GPs):    
! Carbamezepine  (AED)  
! Rifampicin  (AB)  –  king  of  enzyme  inducers  
! Alcohol  –  chronic  use  
! Phenytoin  
! Griseofulvin  
! Phenobarbitons  
! SUs  and    St  Johns  Wort  
! Many  more  

 
COC  contraindications  (absolute  and  relative)  

 
 
 

 
 
Other  contraindications  include:  


Breast   cancer   and   cervix   cancer   is   also   a   contraindication   (due   to   increased   risk   of   these  
cancers  in  COCP)  



Pregnancy  



Breast  feeding  –  POP  is  preffered  during  breast  feeding  

 
Risk  Factors  for  VTE  
!
!

Genetic  Predisposition  

!

Acquired  predisposition  e
...
 cancer  or  SLE  

!

Immobility    

!

Trauma  

!

Physiological  Factors  e
...
 dehydration  

!

Throbophillic  diseases  e
...
g
...
   Dont  forget  to  ask  about  family  history  as  well
...
g
...
g
...
   The  COC  +  smoking  
=>  very  damaging  to  the  CV  system  

!

Selected,   healthy   non-­‐smoking   women   without   risk   factors   can   be   prescribed   low   dose  
combined  preparations  up  to  age  of  50  years,  provided  they  are  carefully  monitored  

 
Evra  (transdermal  patch)  


COC  transdermal  patch  



Left  on  for  1  week  



Apply  each  week  for  3  weeks  followed  by  patch  free  week  
 

 
 
 

 
 
NuvaRing  
!

Inserted   into   vagina   for   3   weeks   then   removed   for   1   week   (hormone   free   week   induces  
withdrawal  bleed)  

!

New  ring  reinserted  for  next  cycle  

!

Better  cycle  control  than  COCP  (oral)  

!

Overall  lower  levels  of  oestrogen  vs  COCP/patch  =>  decreased  VTE  risk  

 
Progestogen-­‐only  methods  
!

Pill    (“the  minipill”  e
...
 cerazette):  every  day  with  no  break  

!

Injection  (deproprovera):  every  3  months;  can  be  used  with  enzyme  inducing  drugs  

!

Implant  (implanon/nexplanon):  every  3  years,  CANT  be  used  with  enzyme  inducers    

!

Mirena   IUS   (intrauterine   system):   levonorgestrel-­‐releasing   intrauterine   system   e
...
 
progesterone   coil
...
    Can   be   used   for   up   to   5   years
...
     

 
Progestogen  Only  Pill  (POP)  
!
!

Newer  generation:  Desogestrel  (cerazette)  

!

Some   women   taking   the   POCP   continue   to   have   regular   normal   periods
...
  Some   women   also  
have  occasional  'spotting'  between  periods
...
 

 
Indications  for  POP  
!

Contraindications   to   /   or   side   effects   with   oestrogen   e
...
  migraine   with   aura,   HT,   smoker  
over  35,  history  of  VTE  disease,  breast  cancer,  cervical  cancer  

!

Older  women  who  smoke  

!

Lactation  (breast  feeding)  –  can  actually  be  good  for  breast  feeding!  

!

Mild  hypertension  

!

Alternative  to  COC  before  surgery  

!

Sickle  cell  disease    

!

Migraine  with  aura  
 
 

Contraindications  to  POP  
Absolute  
!

Pregnancy  

!

Breast  cancer  (as  may  be  PG  receptor  +ve)  

!

Severe  decompensated  liver  disease  

 
Relative  
!

If   irregular   bleeding   unacceptable   (major   side   effect   of   POP   is   irregular   bleeding;   NOT   a  
side  effect  of  Mirena  and  in  actual  fact  Mirena  is  first  line  Tx  for  DUB)  

!

Severe  CVD/ischaemic  stroke  

!

Drug  interactions  e
...
 EIDs  (enzyme  inducing  drugs)  –  such  as  carbamazepine,  rifampicin  and  
St  Johns  Wort  

 
MIRENA  AND  DEPROPROVERA  CAN  BE  USED  WITH  ENZYME  INDUCERS  
 
 
 
 
 

Injectable  prostogens:  Deproprovera  
!

Long  acting  reversible  contraceptive  (LARC)  =>  given  every  3  months  

!

As   well   as   other   progestogenic   effects   they   inhibit   ovulation   (due   to   pituitary   suppression)  
=>  annovulation  

!

Preperations:  
! Depoprovera   (medroxyprogesterone   acetate)   =>   IM   injection   given   every   12  
weeks  (3  months)  

 
Indications  
!

Unreliable  with  COC  or  POP  eg
...
    Progesterone   counteracts  
estrogen  and  inhibits  the  growth  of  the  ectopic  endometrial  tissue  

 
Contraindications  
!

as  for  POP  e
...
 pregnancy,  breast  cancer  

!

Short  term  contraception  

!

Dislike  of  amenorrhoea  (35%  at  1  year)  

!

Long  term  use  in  those  at  high  risk  for  osteoporosis  –  as  linked  to  osteroporosis    

 
Effect  on  BMD  
!

!

Greatest  concern  at  extremes  of  reproductive  age  

!

 
 
 

Studies   have   demonstrated   that   deproprovera   ↓   BMD   in   chronic   users   =>   can   cause  
osteopenia  (-­‐1  to  -­‐2
...
5  BMD)  

In   all   women   careful   re-­‐evaluation   of   risks   and   benefits   should   be   carried   out   for   those  
wishing  to  take  it  for  more  than  2  years  

!

In  those  with  lifestyle  and/or  medical  risk  factors  for  osteoporosis  other  methods  should  be  
considered  

!

Modify  risk  factors  for  osteoporosis  

!

Perform  DEXA  scan  every  2yrs  in  long  term  users  

 
 
Progestogen  implant:    Implanon/Nexplanon  
!

Etonogestrel   is   a   steroidal   progestin   used   in   hormonal   contraceptives,   most   notably   the  
subdermal  implant  Nexplanon  and  the  vaginal  ring  NuvaRing  (combined  contraceptive)  

!

Progesterone  implant  is  placed  in  upper  arm,  sub  dermal  

!

Lasts  three  years  =>  LARC  

!

Consider  changing  earlier  if  problematic  bleeding  towards  end  

!

Inserted  between  day  1  and  5  of  the  cycle  for  immediate  effect    

!

Not  suitable  for  people  taking  EIDs  (enzyme  inducing  drugs):  Remember  depro-­‐provera  is  
the  Tx  of  choice  for  LARC  in  patients  using  EIDs  (Mirena  also  suitable)  

!

Almost  100%  effective  

!

Not  suitable  for  needle  phobias  as  need  to  give  LA!  

 

 
 
Side  effects  
!
!

Skin  changes  

!
 
 
 

Irregular  bleeding  

Headaches  

!

Weight  gain    

!

Loss  of  libido  

!

Amenorrhoea  

 
The  IUS  ‘Mirena’  (“the  progesterone  coil”)  
!

A  52mg  levonogestrel  (synthetic  progestogen)  containing  Intra-­‐Uterine  System  IUS  (coil)    

!

Lasts    5  years  

!

Mode  of  Action  of  Mirena  
! Local  progestogen  (from  levongestrel)  suppresses  endometrium  secretory  phase  
thus  preventing  implantation  
! Alters  cervical  mucus/intratubal  fluid  preventing  sperm  migration  
! May  be  anovulatory  in  some  

 
Advantages  
!

Highly  effective  (>99%)  

!

Lasts  5  years    

!

Dual  license  for  treatment  of  DUB  menorrhagia  (reduces  pain/flow)    -­‐  first  line  for  DUB  in  
pts  who  want  contraception    

!

High  rate  of  amenorrhoea  

!

Can  be  used  as  progestogenic  component  of  HRT  (4  years)  

!

Fully  reversible  

!

Can  be  used  in  patients  with  epilepsy  on  AEDs  or  on  other  EIDs  

 
Disadvantages  
!
!

Requires  specialist  fitting  

!

Irregular  bleeding    (early  months  of  use)  

!
 
 
 

Not  many!  

‘Lost  threads’  e
...
 threads  from  the  device  lost:  expulsion,  malposition,  perforation  

!

PID  

!

Ectopic  pregnancy  

 
 
The  copper  coil  (IUCD)  
!

Mode  of  action  
! ‘Foreign-­‐body  effect’  within  endometrium    
! Direct  toxicity  of  Cu  (copper)  to  sperm  
! Altered  uterine/tubal  fluid        
! Less  sperm  reaching  upper  genital  tract  

!

Last  5-­‐10  years  depending  on  type  

!

Few  problems/side  effects  

!

Avoids  use  of  hormones  
 

Advantages:  
!

Last  5-­‐10  years  (depending  on  type)  

!

Highly  effective  (>98%)  

!

Fully  reversible  

!

Immediately  effective  

!

Independent  of  SI  (sexual  intercourse)  

!

Avoids  hormones  

!

Also  used  for  EC  (emergency  contraception)  –  up  to  5  days  

!

Long  history  of  use  

 
Disadvantages:  
!
!
 
 
 

Heavy,  painful  periods  
Irregular  menstrual  bleeding  

!

Require  specialist  fitting  

!

Insertion  risks  e
...
 perforation,  infection  

!

‘Lost  threads’    

!

Ectopic  pregnancy    

 
Contraindications  to  IUDs  
Absolute  
!

Pregnancy  

!

Unexplained  vaginal  bleeding  

!

Current  pelvic  inflammatory  disease  

!

Wilson’s  Disease/  Copper  allergy  (only  for  the  copper  coil)  

 
Relative  
!

<4wks  post-­‐partum  

!

History  of  ectopic  pregnancy  

!

Fibroids  (distort  cavity)  

!

Anaemia    (does  not  apply  to  Mirena)  

!

Menorrhagia    (does  not  apply  to  Mirena)  

!

Valvular  heart  disease  

!

High  risk  STI’s/recent  PID  

!

Immunosuppressed      (steroids,  HIV)    

 
Infection  and  the  IUD  
!
!

Inserting  coil  into  patient  with  pre-­‐existing  STI  will  worsen  symptoms  

!

Highest  risk  in  first  20  days  after  procedure  

!
 
 
 

Coils  do  not  cause  pelvic  infection!!  

Therefore  risk  is  related  to  background  risk  of  STI’s  in  population  

!

RCOG  advise  screen  (chlaymidia  CT  and  gonorrhoea  GC)  +  treat  policy  prior  to  insertion  in  
high  risk  populations  such  as  UK  

 
LARC:  Long  Acting  Reversible  Contraception  
!

Cost-­‐effective,  independent  of  SI,  long  acting  and  highly  effective  methods
...
 

!

Types:  
! Depoprovera  (progestogen  IM  injection):  3  months  
! Progestogen  implant:  Implanon  /  Nexplanon:  3  years  
! Mirena  IUS  (levonorgestrel-­‐releasing  intrauterine  system):  5  years  
! Copper  IUCD:  5-­‐10  year  

 
Post-­‐Coital  Contraception  (emergency  contraception)  
!

Also  known  as  emergency  contraception  

!

Midcycle  risk  of  pregnancy  is  30%  

!

Levonelle:  
! Levonorgestrel   LNG   (progestogen)   dose   up   to   72   hours   (3   days)   after  
unprotected  SI  
! Efficacy  decreases  over  time  

!

EllaOne:    
! Ulipristal  acetate  (anti-­‐progestogen)    
! Dose  up  to  120  hours  (5  days)  after  unprotected  SI  
! Twice  as  effective  as  LNG  

!

Copper  IUCD  
! Can   be   fitted   up   to   5   days   after   unprotected   SI   and   up   to   5   days   after   the  
expected  date  of  ovulation  (day  19  of  a  28  day  cycle)  
! MOST  EFFECTIVE  

 
 
 
 

When  to  stop  contraception?  
!

<50  years:  Contraception  for  2yrs  after  LMP  

!

>50  years:  Contraception  for  1yr  after  LMP  

!

Menopause  is  defined  as  1  year  after  LMP  (last  menstrual  period)  

 
 
TERMINATION  OF  PREGNANCY  (TOP)  
The  Abortion  Act  1967  
!

Two   doctors   must   agree   that   termination   is   indicated   under   one   of   the   grounds   (A-­‐G):  
basically  when  pregnancy  would  cause  physical  or  psychological  harm  to  mother  

!

Some  of  these  are  time  limited  

!

Legal  requirements  for  notification    

 
Ethics  
!

Doctors   may   refuse   to   participate   in   terminations   but   are   obliged   to   provide   necessary  
treatment  in  an  emergency  when  the  woman’s  life  may  be  jeopardised  

!

Doctors   with   a   conscientious   objection   may   not   impose   their   views   on   others   but   may  
explain  their  views  to  patients  IF  invited  to    

 
TOP  consultation  
!

Determine  patient’s  wishes/certainty  to  proceed  

!

Perform  USS  (ultrasound  scan)  to  determine  gestation/which  options  available  

!

Explain  what  procedure  involves  including  risks,  anaesthetic,  method,  hospital  stay  

!

Full  medical/drug/social  history  

!

Discuss  current  and  future  contraception    

 
Methods  of  Termination  
Surgical  
 
 
 

!

Vacuum  aspiration:    
! suction  curettage  (GA)    
! manual  vacuum  aspiration  MVA  (outpatient/LA)  
! 6-­‐13  weeks  (NOT  before  6  weeks)  

!

Dilatation  and  evacuation  
! 13-­‐24  weeks  (not  Scotland)  
 

Medical  
!

Early:  up  to  9  weeks  

!

Late:  9-­‐12  weeks  

!

Mid-­‐trimester:  12-­‐24  weeks  

!

Up  to  24  weeks  (0-­‐24  weeks)  

 
Cervical  priming  
!

Used  to  assist  surgical  abortions  or  medical  abortions  

!

This  makes  the  cervix  easier  to  dilate,  reducing  the  later  risk  of  cervical  incompetence
...
   
! Misoprostol  (synthetic  prostaglandin  PG)  
! Cervagem  (synthetic  prostaglandin  PG)  dilates  cervix  

 
Medical  Termination  of  Pregnancy  
!

This  can  be  carried  out  for  all  gestations  (from  0  up  to  24  weeks)  due  to  the  effect  of  the  
anti-­‐progesterone  

!

Treatment:  
! Anti-­‐progesterone   (Mifepristone   –   “missed   one”)   followed   48   hours   later   by  
vaginal    prostaglandin  (Misoprostol)  –  cervical  dilation  and  uterine  contractions  
! MM:    mifeprisotone  and  misoprostol    

!
 
 
 

Action  of  anti-­‐progesterone  Mifepristone:  

! Causes  detachment  of  the  embryo  
! Increases   myometrial   activity   (remember   that   progesterone   decreases  
myometrial  activity  =>  Anti-­‐progesterone  increases  myoemtrial  activity)  
! Makes  the  myometrium  more  sensitive  to  exogenous  prostaglandin  
! Causes  opening  (dilation)  and  ripening  of  the  cervix  
 
 
Complications  of  Termination  
Early:  
!

Uterine  perforation  (Specific  to  surgical  methods)  

!

Anaesthetic  (Specific  to  surgical  methods)  

!

Haemorrhage  

!

Retained  products  

!

Infection  (strategy  for  reducing  risk)  

 
Late  
!

Long  term  psychological  sequelae    

!

Cervical  incompetence  (Specific  to  surgical  methods)  

!

Infertility  (Specific  to  surgical  methods)  

!

Rhesus   isoimmunisation:   if   mother   is   Rh  –ve   she   may   produce   Anti-­‐D   ABs   (IgG)   which   can  
cross   the   placenta   of   any   future   pregnancy   and   cause   damage   to   a   Rh   +ve   foetus
...
 
 

NON  SEXUALLY  AQUIRED  GENITAL  INFECTIONS  
Reminder  of  common  bacteria    
!

Streptococcus  (gram  +ve,  blue,  strips  of  cocci):  
! Alpha   haemolytic:   Strep   viridians   (endocarditis)   and   Strep   pneumonia  
(pneumonia  and  meningitis)  

 
 
 

! Beta   haemolytic   Strep:   Strep   pyogenes   GAS   (throat   and   skin   infections)   and   Strep  
agalactiae  GBS  (neonatal  meningitis)  
! Gamma  haemolytic:  Enteroccoccus  (gut  commensal,  UTI)  
!

Staphyloccocus  (gram  +ve,  blue,  clusters  of  cocci):  
! Cogulase   +ve:   Staph   aureus   (wound,   skin   infections,   bone   infections,  
endocarditis)  
! Coagulase  –ve:    Strep  epidermidis  (skin  commensals,  IV  line  infections)  

 
Normal  vaginal  flora  
!

Lactobacillus  sp
...
 (fungus)  

 
Non-­‐sexually  transmitted  genital  infections  
!

Candida  (albicans)  infection  =>  “Thrush”  (candida  vaginitis)  

!

Bacterial  vaginosis  (B
...
g
...
,  others  incl
...
5)  

!

Treatment  
! Metronidazole  orally  (very  effective  AB  against  anaerobes)  

 
 
 

 
NOTE:     HVS   is   used   to   diagnose   ALL   infections   (sexual   and   non   sexual)   excluding   CT   and   GC
...
     
 
Prostatitis  
Classification:  
!

Acute  bacterial  prostatitis  

!

Chronic  bacterial  prostatitis:  these  account  for  <5%  of  all  prostatitis  diagnoses  

!

 

Chronic  prostatitis/chronic  pelvic  pain  syndrome  (CP/CPPS)  

 
Acute  bacterial  prostatitis  
!

Clinical  features  
! Symptoms  of  UTI  e
...
 dysuria  and  frequency  
! May   have   lower   abdominal/back/perineal/penile   pain   and   tender   prostate   on  
DRE  examination  

!

Rare  complication  of  UTI  

!

Same  organisms  as  UTI:  
! E
...
 (non-­‐haemolytic/gamma  Strep)  

!

Check  for  STI  in  patients  <35years  (gonorrhoea  and  chlamydia)  

!

Diagnosis:  
! Clinical  signs  
! MSSU  (midstream  urine  sample)  for  C&S  (culture  and  sensitivity)  NOT  first  pass  
(as  its  is  effectively  a  UTI)  

!

Rx  (treatment):  
! Ciprofloxacin  for  28  days  (altered  depending  on  culture  result)  as  often  caused  by  
coliforms  (this  is  the  AB  of  choice  for  severe  GI  infections)  
! Trimethoprim  (for  28  days)  if  high  C
...
g
...
  Is   it   a  
diagnosis  of  exclusion  

!

Significant  impact  on  psychological/mental  health  

 
Management:  
!

Important  to  exclude  malignancy  and  reassure  patient  

!

No  good  evidence  for  antibiotic  treatment  

!

Some   limited   evidence   that   α-­‐blockers   (alfuzosin/tamsulosin/prazosin)   may   help   =>   relax  
muscle  of  prostate  (these  drugs  are  also  used  in  BPH)  

!

Longitudinal  studies  suggest  that  for  many  patients,  symptoms  ↓over  2  years  

 
 
SEXUALLY  TRANSMITTED  INFECTIONS  
BACTERIAL  INFECTIONS  
 
 
 

!

Chlamydia  trachomatis  (CT)  infection  causes  =>  chlamydia  (CT)    

!

Neisseria  gonorrhoeae  (gonococcus  GC)  infection  causes  =>  gonorrhoea  (GC)  

!

Non-­‐specific  urethritis  (NSU)  =>  thought  to  be  caused  by  Ureasplasma  and  Mycoplasma  

!

Treponema  pallidum  infection  causes  =>  syphilis  

 
Chlamydia  trachomatis  (CT)  infection:  Chlamydia  


Chalmydia  trachomatis  =  gram  –ve  bacteria  



DOES  NOT  GRAM  STAIN  



Intracellular  organism    



Can  cause  a  range  of  infections  in  human  body  
 

Symptoms  
Females  
!

Asymptomatic:   70%   (hence   why   screening   is   so   important)
...
 

!

Persistent  discharge  (micrpurulent,  but  much  less  so  than  GC),  often  clear  

!

Intermenstrual   bleeding:   vaginal   bleeding   (other   than   postcoital-­‐   after   sex)   at   any   time  
during  the  menstrual  cycle  other  than  during  normal  menstruation
...
g
...
      PID   can   cause   scarring   inside   the   reproductive   organs,   which   can  
later  cause  serious  complications,  including  chronic  pelvic  pain,  difficulty  becoming  pregnant  
(infertility),  ectopic  (tubal)  pregnancy,  and  other  dangerous  complications  of  pregnancy
...
     

!

Symptoms   of   epididymo-­‐orchitis   (swollen   painful   testicle,   pain   relief   on   raising   testes,  
positive  urinalysis)  =>  in  rare  cases  can  cause  infertility  

!

NB:  Remember  that  discharge  is  more  common  in  an  STD  in  comparison  to  UTI  (but  both  
have  similar  presentations,  and  UTIs  can  present  with  discharge)  

 

 
 
Pathophysiology  
!

Bacterial  infection,  but  can  only  reproduce  inside  host  cell  =>  INTRACELLULAR  PATHOGEN  
WHICH  DOES  NOT  GRAM  STAIN  

!

3  types  of  infection  
! Chlamydia  conjunctivitis  or  trachoma  (tropical  eye  infection):  serotypes  A,  B,  C  
! Genital  Chlamydia  CT  infection:  serotypes  D  –  K  

 
 
 

! Lymphogranuloma   venereum:   serotypes   L1,   L2,   L3   (associated   with   MSM   males  
who  have  sex  with  males)
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
M   ceftriaxone   (used   in   bacterial  
meningitis  e
...
 against  Meningoccous,  which  belongs  to  the  same  family  as  Gonoccous;  IM  is  
longer  acting)  and  oral  azithromycin  (single  dose  can  also  be  used  to  Tx  Chlamydia)  

!

Tx  =  IM  Ceftriaxone  +  oral  azithromycin    

!

NB:  IM  ceftriaxone  is  used  as  it  is  much  longer  acting  than  oral  

!

Requires  two  ABs  as  serious  infection  with  increasing  resistance  (plus  azithromycin  will  also  
target  any  potential  comorbid  CT  infection)  

!
 
 
 

Resistance  of  N
...
B
...
B
...
g
...
 Various  other  neurological  deficits  can  occur  
e
...
  tabes   dorsalis   (slow   degeneration   of   the   DCs)   and   general   paralysis   of   the  
insane  
!

Congenital   syphilis:  vertical  transmission   occurs   from   4th   month   onwards   =>  all  mothers  still  
offered  screening  at  1st  antenatal  visit  
 

 

 
 
 

 
 
 
Latent  syphilis  
!

Latent  stage  asymptomatic  but  low-­‐grade  infection  continues  

!

Any  organ  may  be  affected  

!

Patient  becomes  less  infectious  

!

May   have   relapse   of   secondary   stage   symptoms   (in   early   latent   period)   e
...
  syphilis  
generalised  rash,  mouth  ulcers,  condylomata  lata  (flat  wart-­‐like  growths)  

!

Latent  stage  may  last  for  20+  years  

!

60%  will  self-­‐cure  and  some  patients  will  be  treated  by  having  antibiotics  for  something  else  

 
Late  stage  (tertiary)  syphilis  
!
!

Mimics  many  other  diseases  

!
 
 
 

Rarely  seen  now  

Cardiovascular  

! Aneurysm  of  arch  of  aorta  =>  may  rupture  =>  ruptured  aortic  aneurysm  (aortic  
dissection)   which   may   present   with   sudden   onset   excruciating   pain   (severity  
10/10)
...
   
The  pain  will  often  present  with  chest  pain  which  may  radiate  to  the  back
...
 
!

Neurovascular  
! Tabes   dorsalis   (giving   a   wide-­‐based   gait):   syphilitic   myelopathy,   is   a   slow  
degeneration   (specifically,   demyelination)   of   the   nerves   primarily   in   the   dorsal  
columns  of  the  spinal  cord
...
 
! Charcot’s   joints   (progressive   degeneration   of   joint   due   to   loss   of   sensation   and  
proprioception  –  due  to  tabes  dorsalis  =>  causes  chornic  unnoticed  microtrauma)  
! General  paralysis  of  the  insane  (GPI)  =>  chronic  meningoencephalitis  that  leads  to  
cerebral  atrophy  which  can  result  in  a  variety  of  neuropsychiatric  disorders  such  
as  dementia,  seizures,  depression  and  psychosis    
! Argyll-­‐Robertson   pupil   (prostitutes   pupils):   bilateral   small   pupils   which   are  
reactive   focussing   on   a   near   object   (pupil   accommodation)   but   not   reactive   to  
light  
! Syphilis  dementia  
! Many  more  

 
Diagnosis  
!

Clotted  blood  for  syphilis  serology  (diagnostic  identification  of  antibodies  in  the  serum)  

!

Details  of  tests  will  be  given  in  Practical  class  

!

Swab  of  chancre  for  PCR:  test  done  at  Reference  Lab  only  (at  present)  

 
Treatment  
!

IM  Penicillin  (long  acting,  IM)  e
...
 IM  benzylpenicllin  

 
VIRAL  STDs  
!
 
 
 

Genital  warts:    HPV  6  and  11  

!

Genital  herpes:      HSV  

!

Hepatitis  B  &  C  

!

HIV    

 
Genital  warts  
!

Very   common   infection,   caused   by   Human   papilloma   virus   (HPV):   types   6   and   11  
commonest  

!

Few  strains  of  HPV  associated  with  increased  risk  of  cervical  cancer  (Types  16,  18)
...
g
...
g
...
g
...
g
...
g
...
g
...
 

!

If   the   test   is   positive,   a   copy   of   the   lab   result   goes   to   SRH   clinic   and   Health   Advisors   can  
access  patient’s  telephone  number  to  contact  patient  directly  

!

Ideally,  patients  should  be  informed  of  this  BEFORE  the  tests  are  taken  

 
Role  of  Sexual  Health  Advisors  (specially  trained  nurses)  
!

Education  and  prevention  of  STIs  

!

Partner  notification  (contact  tracing)  done  for  
! syphilis,  gonorrhoea,  trichomonas,  chlamydia,  HIV,  hepatitis  
! SRH  clinic  gets  copies  of  all  positive  STI  lab  results  in  Tayside  

!

Partner  notification:  
! By  patients  themselves  
! By  Health  Advisors  
! National  Network  

 
Reminder  of  the  reproductive  cycle  

 
 
 

 

 
 
 

 
 
 
Reproductive  lecture  notes:  week  2  
PATHOLOGY  OF  THE  CERVIX,  VULVA  AND  VAGINA  
Anatomy  review  


Ovaries:  The  ovaries  are  ovum-­‐producing  reproductive  organ  (female  gonads),  often  found  
in   pairs   as   part   of   the   female   reproductive   system
...
     
! Oogenesis  starts  in  the  germinal  epithelium,  which  gives  rise   to  the  development  
of  ovarian  follicles,  the  functional  unit  of  the  ovary
...
 In  women,  fifty  per  
cent  of  testosterone  is  produced  by  the  ovaries  and  adrenal  glands  and  released  
directly  into  the  blood  stream
...
     
! Oestrogen  is  responsible  for  the  appearance  of  secondary  sex  characteristics  for  
females  at  puberty  and  for  the  maturation  and  maintenance  of  the  reproductive  
organs   in   their   mature   functional   state
...
   Oestrogen  stimulates  breast  duct  growth
...
 

 
 
 

Progesterone  functions  with  oestrogen  by  promoting  menstrual  cycle  changes  in  
the  endometrium
...
    When   an   oocyte   is   developing   in   an   ovary,   it   is   encapsulated   in   a   spherical  
collection   of   cells   known   as   an   ovarian   follicle
...
 This  secondary   oocyte   is   then   ovulated  into   the   peritoneal   cavity
...
 The  secondary  oocyte  is  caught  by  
the   fimbriated   end   of   the   fallopian   tube   and   travels   to   the   ampulla   of   the   uterine   tube  
where   typically   the   sperm   are   met   and   fertilization   occurs;   meiosis   II   is   promptly  
completed
...
 After  about  five  days  the  new  embryo  (blastocyst)  
enters   the   uterine   cavity   and   on   about   day   6-­‐9   day   implants   into   the   wall   of   the   uterus  
(endometrium)
...
 
One   end,   the   cervix,   opens   into   the   vagina,   while   the   other   is   connected   to   both   fallopian  
tubes
...
 
! Endometrium:  this  is  the  lining  of  the  uterus  
! Myometrium:  this  is  the  muscular  portion  of  the  uterus  (responsible  for  uterine  
contractions)  





Vagina:  The  vagina  is  a  fibromuscular  elastic  tubular  tract  which  is  a  sex  organ  and  has  two  
main   functions:   sexual   intercourse   and   childbirth
...
 Unlike  
males,   who   have   only   one   genital   orifice,   females   have   two,   the   urethra   (external   urethral  
meatus)  and  the  vagina
...
    The   external   urethral   meatus   is   anterior   to   the  
vaginal  opening
...
 

Vulva:  The  vulva  consists  of  the  external  genital  organs  of  the  female
...
 

 
 
 

 
 

 
 
 

 
 
The  cervix  


The  cervix  is  the  inferior,  narrow  portion  of  the  uterus  where  it  joins  with  the  superior  end  of  
the  vagina
...
   



The  ectocervix's  opening  is  called  the  external  os
...
 
! In   women   who   have   not   had   a   vaginal   birth   the   external   os   appears   as   a   small,  
circular  opening
...
 





 
 
 

The   passageway   between   the   external   os   and   the   uterine   cavity   is   referred   to   as   the  
endocervical  canal  (endocervix)
...
   
The  endocervical  canal  terminates  at  the  internal  os  which  is  the  opening  of  the  cervix  inside  
the  uterine  cavity
...
 When  
the  endocervix  (columnar  cells)  is  exposed  to  the  harsh  acidic  environment  of  the  vagina  it  
undergoes   metaplasia   to   squamous   epithelium,   which   is   better   suited   to   the   vaginal  
environment
...
 



The  original  transformation  zone  is  approximately  at  the  external  os  premenarche  (before  
first  menstruation)  



Times  in  life  when  this  metaplasia  of  the  transformation  zone  occurs:  
! Puberty   (menarche):   the   endocervix   everts   (moves   out)   of   the   uterus   =>  
columnar  epithelium  undergoes  metaplasia  to  squamous  =>  TZ  moves  into  the  
vagina  away  from  external  os  
! Menstrual   cycle:   with   the   changes   of   the   cervix   associated   with   the   normal  
menstrual  cycle  
! Post-­‐menopause:   the   uterus   shrinks   moving   the   transformation   zone   upwards  
(inwards)  towards  the  uterus  



Position  of  TZ  also  alters  during  life  as  physiological  response  to:  
! Menarche  (part  of  puberty  when  the  first  menstrual  cycle  begins)  
! Menstrual  cycle  
! Pregnancy  
! Menopause  




 
 
 

All  these  changes  are  normal  and  the  occurrence  is  said  to  be  physiological
...
g  columnar  cells  of  
the  endocervic  metaplasing  to  squamous  cells)  does  increase  the  risk  of  cancer  in  this  area  
=>  the  transformation  zone  is  the  most  common  area  for  cervical  cancer  to  occur  

               

 

 
Cervical  erosion  (cervical  ectropion/eversion)  



Exposure   of   delicate   endocervical   columnar   epithelium   to   acid   environment   of   vagina  (e
...
 
which   occurs   at   menarche)   leads   to   physiological   squamous   metaplasia   of   the   endocervix  
columnar  epithelium,  and  movement  of  TZ  away  from  the  cervix  



Thus   the   term   cervical   erosion   is   something   of   a   misnomer   =>   Cervical   ectropion   is   more  
commonly  used  



Cervical   ectropion   (or   cervical   eversion)   is   a   condition   in   which   the   central   (endocervical)  
columnar   epithelium   protrudes   out   through   the   external   os   of   the   cervix   and   onto   the  
vaginal  portion  of  the  cervix  (commonly  during  menarche),  undergoes  squamous  metaplasia,  
and  transforms  to  stratified  squamous  epithelium  via  metaplasia
...
g
...
 

 
Nabothian  cyst  


Nabothian   cyst   =   distended   endocervical   gland   (mucus   filled   cyst),   usually   with   overlying  
squamous  metaplasia
...
   



This   tissue   growth   can   block   the   cervical   crypts   trapping   cervical   mucus   inside   the   crypts
...
 

 
Pathology  of  the  cervix  
Inflammatory  pathology  
Cervicitis  


Cervicitis  =  inflammation  of  the  uterine  cervix  



Non-­‐specific  acute  or  chronic  inflammation
...
g
...
g
...
       
! non-­‐use  of  barrier  contraception  



 
 
 
 
 

Smoking:  3  x  risk  
Immunosuppression  

 
Human  Papillomavirus  (HPV)  Infection  
1
...
 



Genital  warts  often  look  “mushroom”  like  



Can  be  itchy    



Clinical  diagnosis  



NB:   A   Koilocyte   is   a   squamous   epithelial   cell   that   has   undergone   a   number   of   structural  
changes,   which   occur   as   a   result   of   infection   of   the   cell   by   human   papillomavirus
...
   Koilocytes  may  have  the  following  cellular  changes:  
! Nuclear  enlargement  (two  to  three  times  normal  size)  
!  Irregularity  of  the  nuclear  membrane  contour  
! A  darker  than  normal  staining  pattern  in  the  nucleus,  known  as  Hyperchromasia  

 
2
...
 Cervical  cancer  


High  risk  HPV  (16  and  18)    



Invasive  squamous  cell  carcinoma  (SCC):  Virus  integrated  into  host  DNA  



The   HPV   produces   oncoproteins   that   can   cause   cancer
...
    The   E6/E7   proteins   inactivate   two   tumor   suppressor  
proteins,  p53  (inactivated  by  E6)  and  pRb  (inactivated  by  E7)
...
   Less  than  1%  of  CIN  
1,  approx  5%  of  CIN  2  and  >12%  of  CIN  III  will  progress  to  malignancy,  

 
Prevalence  of  HPV  Infection  


15-­‐25years:  

 

30-­‐50%  



26-­‐30years:  

 

15-­‐20%  



31-­‐35years:  

 

10-­‐20%  



>35years:  

 

   5-­‐15%  



80%  cumulative  prevalence  in  a  lifetime  



Most  develop  immunity  and  clear  infection  



Persistence  increases  risk  of  disease  (hence  why  HPV  tests  are  very  useful)  

 
Cervical  Intraepithelial  Neoplasia  (CIN)    



Dysplasia   of   Squamous   epithelial   cells   (particulary   at   the   vulnerable   transformation   zone):  
the   ectocervical   columnar   cells   protrude   out   through   the   external   os   and   then   undergo  
metaplasia   to   squamous   cells
...
     



Cervical   intraepithelial   neoplasia   (CIN)   is   the   potentially   premalignant   transformation   and  
abnormal  growth  (dysplasia)  of  squamous  cells  on  the  surface  of  the  cervix    



CIN  is  not  cancer,  and  usually  clears  by  itself
...
 



Most   cases   of   CIN   remain   stable,   or   are   eliminated   by   the   host's   immune   system   without  
intervention
...
 



The   major   cause   of   CIN   is   chronic   infection   of   the   cervix   with   the   sexually   transmitted  
human  papillomavirus  (HPV),  especially  the  high-­‐risk  HPV  types  16  or  18
...
 



Not  visible  by  naked  eye  and  asymptomatic  =>  screening  is  very  important  



Detectable  by  cervical  screening  (ages  20-­‐60,  every  3  years)  

 
Progressive  Degrees  of  Dysplasia  and  Neoplasia  


This  slide  is  a  diagram  of  cervical  epithelium  showing  progressive  degrees  of  dysplasia  and  
neoplasia,  and  the  correlating  terminology
...
 



Dyskaryosis  (dysplasia)  occurs  after  koilocytosis  

 

 
 
Histology  of  CIN  



Koilocytosis  is  very  suggestive  of  high  risk  HPV  infection  (HPV  16,18)  


 
 
 

Dysplasia  and  koilocytosis  

Grade  the  neoplasia  on  the  level  of  dyskaryosis  



Delay  in  maturation/differentiation  (dysplasia)  



Nuclear  abnormalities  
! Hyperchromasia   (A   darker   than   normal   staining   pattern   in   the   nucleus   due   to  
increased  proliferation)  
! Increase  in  nucleocytoplasmic  ratio:  due  to  increased  proliferation  
! Pleomorphism:  variability  in  the  size  and  shape  of  cells  and/or  their  nuclei  



Excess  mitotic  activity  

 
Staging  and  grade  


The   stage   of   a   cancer   is   a   measure   of   how   much   the   cancer   has   grown   and   spread   =>   use  
TNM  classification  



The   grade   of   a   cancer   looks   at   features   of   the   cancer   cells,   using   a   microscope   or   other   tests  
(e
...
  histological   and   cytoscopical),   to   identify   how   abnormal/normal   the   cancer   cells   are  
e
...
 the  level  of  differentiation,  mitotic  figures,  pleomorphism  etc  



 The  stage  and  grade  of  a  cancer  help  to  say  how  advanced  it  is,  and  how  well  it  may  respond  
to  treatment
...
 



CIN  (non  malignant,  but  may  be  premalignant)  is  graded  I-­‐III  depending  on  severity  of:  
! Delay  in  maturation/differentiation        
! Nuclear  abnormalities  e
...
 plemorphism,  increasd  NC  ratio,  hyperchromasia  
! Excess  mitotic  activity  



Grading  classification  
! CIN   I     (mild   dyskaryosis   =>   low   grade)   =>   Repeat   colposcopy   in   3   months   -­‐   6  
months  (may  also  test  for  HPV  and  perform  colposcopy  depending  on  result)  
! CIN  II  (moderate  dyskaryosis  =>  high  grade)  =>  colposcopy  =>  Most  often  should  
be  excised  
! CIN   III   (severe   dyskaryosis   =>   high   grade):   also   known   as   ”carcinoma   in   situ”   =>  
colposcopy  =>  SHOULD  ALWAYS  BE  EXCISED  



Often  koilocytosis  (indicating  HPV  infection)  also  present  

 
Natural  History  of  Cervical  Lesions  
 
 
 



Appreciate  that  most  cases  of  CIN  will  NOT  advance  to  invasive  cancers  (HPV  is  cleared  by  
the  body’s  immune  system  before  this  occurs)  



CIN  3  has  the  highest  risk  of  progressing  to  cervical  SCC  (however  only  12%  will  progress  to  
malignancy!)  
 

 
 
Invasive  Cervical  Squamous  Cell  Carcinoma  (cervical  SCC)  




2nd  commonest  female  cancer  (worldwide)  



Incidence   reducing   in   UK   due   to   screening   (an   hopefully   will   decrease   even   further   soon  
due  to  HPV  vaccination)  



Increasingly  detected  in  younger  women  =>  often  found  in  early  asymptomatic  stage  



Develops  from  pre-­‐existing  CIN,  therefore  most  cases  should  be  preventable  by  screening  



Some  are  rapidly  progressive  tumours  



Appreciate   that   the   highest   incidence   is   between   25   and   45   (cancer   of   the   young!)   =>  
screening  from  20  to  60  every  3  years  


 
 
 

75-­‐95%   of   malignant   cervical   tumours   are   squamous   carcinoma   (commonly   occurring   at  
TZ)  

Pain,  PCB,  and  IMB  

 
Staging  


Stage  1A:  microinvasive  



Stage  1B:  confined  to  the  cervix  



Stage  2:  spread  to  adjacent  organs  (vagina,  uterus,  etc
...
 
 

Grading  of  squamous  carcinoma  


Well  differentiated  (low  grade)  =>  better  prognosis  



Moderately  differentiated  



Poorly  differentiated  (high  grade)  =>  worse  prognosis  



Undifferentiated  /  anaplastic  =>  worse  prognosis  

 
Treatment  

 
 
 
 
 
 

Treatment  and  prognosis  depend  on  stage  and  grade  

Symptoms  of  invasive  carcinoma  


Usually   none   at   microinvasive   and   early   invasive   stages   (detected   at   screening)   =>   hence  
why  screening  is  so  important  



Abnormal  bleeding  (especially  in  younger  woman)  
! Post  coital  (after  sex)  =>  always  perform  cervical  examination  
! Post   menopausal   (vaginal   bleeding   that   happens   at   least   12   months   after   your  
periods  have  stopped):  however  this  is  more  suggestive  of  endometrial  cancer  
! Brownish  or  blood  stained  vaginal  discharge  
! Contact  bleeding  due  to  friable  epithelium  (easily  broken  or  torn)  
! IMB  =>  always  perform  cervical  examination?  



Pelvic  pain  



Haematuria    



Urinary  infections  



Ureteric  obstruction  and  obstructive  renal  failure  (ureters  are  in  close  proximity  to  cervix)  

 
Pathology  of  Squamous  Carcinoma  


Variable  microscopic  appearance  
! Sheets  of  squamous  cells    
! Keratisation  
! Often   well   differentiated   keratinising   tumours
...
g
...
g
...
g
...
 
 

 
 
 

 
 
Vulva  pathology  


Infections:  
! Candida   (particularly   diabetics):   Candidal   vulvovaginitis   (Candidiasis)   or   vaginal  
thrush  due  to  Candida  fungal  infection  (often  Candida  albicans)
...
   May  have  thick  white  discharge
...
       May  be  precipitated  by  ABs
...
   
Mushrooom  like  (“I  don’t  want  to  have  sex  with  a  mushroom”)
...
   Tx  with  cryotherapy,  imiquimod  or  podophyllin  
cream
...
   Most  often  caused  by  HSV  2
...
     
! Bartholin’s  gland  abscess  (blockage  of  gland  duct)
...
  They   secrete  
mucus   to   lubricate   the   vagina   and   are   homologous   to   bulbourethral   glands   in  
males
...
  A   Bartholin's   cyst   is   not   an   infection,   although   it   can  
be   caused   by   an   infection,   inflammation,   or   physical   blockage   (mucus   or   other  
impediment)   to   the   Bartholin's   ducts   (tubes   which   lead   from   the   glands   to   the  
vulva)
...
 

 
 
 
 

 
 


Non  Neoplastic  epithelial  disorders:  
! Squamous  hyperplasia:  Squamous  cell  hyperplasia  is  an  abnormal  growth  of  the  
skin  of  the  vulva
...
 
! Lichen  Sclerosis:  Lichen  sclerosis  is  a  relatively  uncommon  condition  in  which  thin  
white   crinkly   patches   appear   on   the   skin
...
    S   everely  
itchy   or   sore   white   spots
...
 It  helps  to  reduce  the  inflammation  and  keep  symptoms  under  
control
...
g
...
  This   most  
commonly  occurs  after  menopause
...
   
The  vaginal  mucosa  becomes  thinner,  drier,  less  elastic  and  more  fragile
...
    Can   cause   painful   coitus   (dyspareunia)   due   to   dry   and   thin  
vagina
...
g
...
    Can   also   cause   vaginal   discharge  
and  urinary  problems
...
       



Three  grades,  like  CIN  



Neoplasia  of  squamous  cells  



Young  women:  often  multifocal,  recurrent  or  persistent  causing  treatment  problems
...
 



Sometimes  HPV  related
...
 

 
Vulvar  Invasive  Squamous  Carcinoma  


Keratinising  Squamous  Cell  Carcinoma  (SCC)  



Usually  elderly  women  



Can  arise  from  normal  epithelium  or  VIN
...
 



Surgical  treatment:  radical  vulvectomy  and  inguinal  lymphadenectomy
...
   



A  crusting  rash  is  characteristic
...
 May  also  have  cervical  and  vulval  lesions
...
 A  disease  of  
the  elderly
...
 May  appear  as  a  polyp
...
e
...
 



 
 
 

Abnormal  cells,  directly  sampled  from  cervix,  can  be  identified  cytologically  



 

CIN1-­‐CIN3   is   asymptomatic   and   can   persist   for   some   time,   allowing   time   for   detection   in  
preclinical  phase  and  prevention  of  possible  progression  to  cancer
...
 

Organisation  of  the  SCSP  


Three  yearly  invite  



Target  population  
! Women  with  a  cervix    
! Age  20  to  60y    

 
Timelines  


HPV  infection  =>    high  grade  CIN  (6  months  to  3  years)  



High  grade  CIN  =>  invasive  cancer  (5  to  20  years)  



Although   remember   that   must   CIN   HPV   infections   will   be   cleared   by   the   body’s   immune  
system  

 
The  cervical  smear  test  


Obtain   representative   samples   of   cells   from   surface   of   transformation   zone   (the   TZ   is   the  
high  risk  area  for  cervical  cancer)  close  to  the  external  os
...
   Then  place  in  vial  
–  tap  ten  and  rotate  5
...
 



Stain  cells  (Papanicolaou  =>  papa  stain)    



Abnormal  cells  identified  by  cytologist  

 
 
Thin  prep  pap  test  process  
 
 
 



Since   its   introduction   over   50   years   ago,   the   pap   test   has   been   the   single   greatest  
contributor  to  the  overall  decline  in  cervical  cancer
...
  Still,   even   as   total   cervical   cancer   deaths   are   falling,   a   specific   type  
of   cervical   cancer   (adenocarcinoma)   is   on   the   rise,   making   regular   pap   testing   as   vital   as  
ever
...
   Dispersion  (in  liquid)  
! 2
...
   Cell  transfer  onto  slide  
 

 
 
Cautions  



 
 
 
 

Smear  may  underestimate  the  grade  of  underlying  CIN
...
 

Cytological  analysis  


Dyskaryosis:  abnormal  nucleus  (dysplastic  nucleus)  



Dyskaryosis  is  suggestive  of  CIN  or  invasive  cancer
...
 

 
Management  of  abnormal  smears  


High  grade  dyskaryosis  (CIN  II  and  CIN  III)  
! High  specificity  (~90%)    
! Colposcopy  indicated    

 
 
 



Low  grade  dyskaryosis  (CIN  I)  
! Less  specific   (~30%)  
! Repeat   a   further   one   or   two   smears   before   referral   to   colposcopy   e
...
  repeat  
smear  in  6  months  

 
Colposcopy  


Detailed  examination  of  cervix  with  x10  magnification  



A   microscope   (colposcope)   with   a   strong   light   will   be   used   to   look   at   your   cervix
...
 



If  any  abnormal  areas  are  identified  on  STAINING,  a  small  sample  of  tissue  (a  biopsy)  may  be  
removed  for  closer  examination
...
 



Acetic  acid  picks  out  abnormal  epithelium  



If   abnormal   areas   seen   they   are   biopsied   -­‐   removes   cone   of   abnormal   tissue   for  
histological  assessment  



You  may  have  treatment  at  the  same  time  as  your  colposcopy
...
 



Can  also  be  used  to    
! destroy   abnormal   tissue   by   laser   (laser   burns   away   the   abnormal   cells)   or   cold  
coagulation  
! remove  abnormal  tissue  by    LLETZ  (large  loop  excision  of  transformation  zone)  –  
form  of  diathermy  under  local  anaesthetic
...
 

 
 

 
 
 

 
 
 
Management  


Treatment   for   CIN   1,   which   is   mild   dysplasia,   is   not   recommended   if   it   lasts   fewer   than   2  
years
...
   Repeat  smear  in  6  months
...
g
...
g
...
 
! Will  boosters  be  necessary?  Ab  levels  higher  with  vaccine  than  natural  immunity
...
)    found  widely  in  the  sexually  active  population
...
   



Sensitivity  higher  than  cytology    



Test  for  cure  after  treatment  (began  April  2012):  test  for  presence  of  HPV  in  cervical  smear  



Detects  patients  with  infection,  not  disease  (CIN)  =>  no  persistence  =>  unlikely  to  develop  
cancer  



High  predictive  value  of  a  negative  HPV  test  



Planning  for  Primary  HPV  testing    

 
Important  points  




If  vaccinated  young  women  wilfully  refuse  cervical  screening,  the  population  rates  of  cervical  
cancer  will  increase  



Screening  remains  important  for  all  women  as  immunisation  does  not  protect  against  all  
HPV  types  =>  even  HPV  immunised  woman  should  be  screened    


 
 
 

For  unimmunised  women,  screening  remains  the  most  effective  way  to  reduce  their  risk  of  
cervical  cancer
...
g
...
 


Placenta    =>  Chorionic  Villus  Biopsy/sampling  (CVS)  <  15  weeks  



Skin  /  Urine  Cells  =>  Amniocentesis  (“amnio”)  >  15  weeks  



Blood    =>  Fetal  blood  sampling  e
...
 from  umbilical  cord  



Maternal  serum    =>  Free  fetal  DNA  analysis  (non  invasive)  
 

 
Chorionic  villous  sampling  (CVS)  


CVS   is   a   form   of   prenatal   diagnosis   to   determine   chromosomal   or   genetic   disorders   in   the  
fetus
...
g
...
 



It  is  the  preferred  technique  before  15  weeks
...
5  weeks)
...
 



Although  this  procedure  is  mostly  associated  with  testing  for  Down  Syndrome,  overall,  CVS  
can  detect  more  than  200  disorders
...
g
...
   



The  most  common  reason  to  have  an  "amnio"  is  to  determine  whether  a  baby  has  certain  
genetic  disorders  or  a  chromosomal  abnormality,  such  as  Down  syndrome
...
 
Women   who   choose   to   have   this   test   are   primarily   those   at   increased   risk   for   genetic   and  
chromosomal   problems,   in   part   because   the   test   is   invasive   and   carries   a   small   risk   of  
misscarriage
...
     



Viability  of  tissues  =  poor  (as  not  taking  a  direct  tissue  sample)  



Risks:  miscarriage  risk  is  approx  0
...
g
...
 
! check   for   and   treat   severe   fetal   anaemia   or   other   blood   problems   such   as   Rh  
disease
...
 
! check  for  fetal  infection
...
 




Not  commonly  used  technique  



Risks:  1-­‐2%  miscarriage  risk  


 
 
 

Used  from  18+  weeks  gestation  

Viability  of  tissues  =  good  

 
Fetal  DNA  from  maternal  blood  


Completely  non  invasive  



Can  be  used  from  8  weeks  gestation  



No  miscarriage  risk  



“stable”  tissue  viability  



Not   commonly   used   due   to   limited   analysis   available
...
 

 
Summary  
 

 
 
 
Chromosome  analysis  

 
 
 

Array   CGH   (comparative   genomic   hybridization):   whole   genome   analysis   –   rarely   used  
currently    



Standard  Karyotype  (in  metaphase):  whole  genome  analysis  (takes  a  few  weeks)  



Fluorescence  in-­‐situ  Hybridisation  (FISH):  Targeted  e
...
 tags  a  specific  gene  (but  can  also  do  
for  chromosome  analysis)  



Quantitative  Fluorescent  PCR    (QF-­‐PCR):  Targeted    (but  can  also  do  chromosome  analsysis)  



Quantification  of  fetal  DNA  in  maternal  serum:  Targeted  

 
Whole  genome  tests:  the  catch  


Mutation:  Can  be  defined  as  a  genetic  change  that  causes  disease  



Polymorphism:  Genetic  Variation  that  is  not  per-­‐se  disease  causing  (appears  in  at  least  1%  
of  population)  



The   arbitrary   cut-­‐off   point   between   a   mutation   and   a   polymorphism   is   1   per   cent
...
  If   the   frequency   is   lower   that   this,   the   allele   is   regarded   as   a  
mutation
...
g
...
g
...
  For   example,   a   typical  
prenatal   FISH   test   will   tell   you   how   many   number   13,   18,   21,   X   and   Y   chromosomes   are  
present  (i
...
,  whether  there  are  two  copies  or  three)  but  will  not  give  you  any  information  
about   any   of   the   other   chromosomes   or   any   information   about   the   actual   structure   of  
chromosomes
...
g
...
g
...
   



However,  the  cost  of  this  labour  intensive  procedure  has  limited  its  application  mainly  to  
high-­‐risk  pregnancies
...
   It  is  much  cheaper  than  FISH
...
g
...
   If  <15  weeks  
=>  CVS
...
     
 
Non-­‐Invasive  Prenatal  Testing:  Free  Fetal  DNA  in  maternal  circulation  


Cell-­‐free  fetal  DNA  (cffDNA)  is  fetal  DNA  circulating  freely  in  the  maternal  blood  stream
...
   



Analysis  of  cffDNA  provides  a  method  of  non-­‐invasive  prenatal  diagnosis
...
 
 

Currently  (not  routine):  


Sex   determination:   usefull   for   determining   if   further   tests   are   required   e
...
  in   X   linked  
conditions,  if  shows  female  embryo  =>  relax!      



Trisomy  testing  

 
Future  


Chromosome  deletions  



Single  gene  analysis  
 

 
 
 

 


NB:  Cordocentesis  =  fetal  blood  sampling  from  umbilical  cord
...
 She  is  18  weeks  pregnant  (therefore  CVS  is  CI)
...
Reassurance  
2
...
Chorionic  Villus  sample  
4
...
Fetal  Blood  Sampling  
 
In  this  case  we  could  go  straight  to  amnio  due  to  AV  abnormality  found
...
Microarray  CGH  
 
 
 

2
...
Chromosome  analysis  
4
...
DNA  testing  for  a  point  mutation  
 
‘Ideal’  Timeline  for  Management  

 
 



 



At  18  weeks  TOP  would  have  to  be  medical  e
...
 prostaglandin  for  cervical  ripening,  
and  anti-­‐progesterone  (mifepristone)  for  termination  
Medical  TOP  can  be  used  from  0  to  24  weeks:  MM  -­‐  Misoprostone  (anti-­‐
progesterone)  +  misoprost  (progesterone)  
Surgical  TOP  can  be  used  from  6  –  13  weeks:    vaccum  aspiration  +  PGs  

 
RAPID  PRENATAL  DIAGNOSIS  


Rapid  techniques  are  important  e
...
 for  parents  anxiety  levels,  to  make  further  Mx  decisions  
(e
...
 TOP),  to  Dx  within  abortion  limits  etc  



Rapid  techniques  (24-­‐48  hours):  
! Interphase   chromosome   counting   using  FISH   (Fluorescence   In   Situ   Hybridization):  
very  expensive  
! QF-­‐PCR  (Quantitative  Fluorescent  PCR):  simple  and  cheap  

 
 
 

! Karoytping  is  NOT  rapid  
NB:  QF-­‐PCR  and  FISH  have  the  same  limitation  of  detecting  only  selected  chromosome  disorders
...
g
...
 However,  
carriers  of  balanced  reciprocal  translocations  have  increased  risks  of  creating  gametes  with  
unbalanced   chromosome   translocations   leading   to   miscarriages   or   children   with  
abnormalities
...
 
Usually  1  or  3  copies  of  some  of  the  genome
...
 



Other  translocations  occur  but  do  not  lead  to  a  viable  fetus
...
e
...
 

A   Robertsonian   translocation   in   balanced   form   results   in   no   excess   or   deficit   of   genetic  
material  and  causes  no  health  difficulties
...
  She   is   10   weeks   pregnant
...
 
 
What  is  your  best  ‘genetic'  management?  
1
...
Serum  Screening  
3
...
Amniocentesis  
5
...
   Direct  karyotype  or  FISH  may  be  available  
2
...
    Potentially   could   use   FISH
...
 
Don’t   we   know   that   it   could   either   be   trisomy   4   or   trisomy   9?     NOT   AS   SIMPLE   AS   ABOVE!     See  
below
...
   
 

 
 
‘Ideal’  Timeline  for  Management  
 
 
 
 

 
 
Termination  of  Pregnancy  (TOP)  


Surgical  termination:  from  6  weeks  to  13  weeks  (in  Scotland)  –  vaccum  aspiration    



Induction   (medical   abortion)   before   6   weeks   or   to   24   weeks   e
...
  anti   progesterone  
(mifepristone)  +  followed  by  Prostaglandin    (misoprostol)  



No  time  limit  on  TOP  if  there  is  a  risk  of  serious  abnormality  in  the  child  or  to  the  health  of  
the  mother  

 
Ultrasound  Scanning  (USS)  


Booking  Scan:  usually  10-­‐12  weeks:    NT,  size  of  foetus    



Detailed  anomaly  scan  at  20  weeks  



To  detect  specific  anomalies  
! Cardiac  (12-­‐20  weeks)  
! Microcephaly  (Usually  after  22  weeks)  
! Short  Limbs  (Usually  after  22  weeks)    
! Brain  malformations  



A  minor  scan  abnormality  may  be  an  indicator  of  more  severe  disease  

 
DNA  testing,  Screening  and    Pre-­‐Implantation  Genetic  Diagnosis  
 
 
 

Gene  testing  (NOT  chromosome)  in  pregnancy  
Chromosome  Analysis  or  Array  CGH  (Comparative  genomic  hybridization)  


General  Analysis  of  the  Genome  



A  diagnosis  may  be  suspected  

 
For  FISH  or  DNA  analysis  


You  need  to  suspect  a  diagnosis    



Useful  for  common  chromomse  deletions  



This  tells  you  where  to  look    



However  FISH  can  be  used  to  tag  individual  genes  to  assess  for  chromosome  anueploidies  

 
QF-­‐PCR  


You  need  to  suspect  a  diagnosis  



Only  analyses  specific  loci  e
...
 point  mutations  



Result  in  24  hours  (4  hours  is  technically  feasible)    



However  QF-­‐PCR  can  be  used  to  tag  individual  genes  to  assess  for  chromosome  anueploidies  
 

Next  generation  sequencing  



Sequence  whole  genome  (<£1,000)  



Or  just  all  known  exons  (=  £500)  



Will  be  cheaper  by  next  year  



DNA  testing  finds  lots  of  polymorphisms  



 
 
 

Now  available  



 

DNA  testing  (often  via  PCR)  

If   you   sequence   the   whole   genome,   you   will   drown   in   data,   8,000,000   polymorphisms   and  
you   will   REALLY   need   clinical   data   to   tell   you   which   genetic   changes   are   important   =>   Not  
currently  feasible  in  prenatal  diagnosis  

US  scanning  (USS)  


Booking  Scan  :  usually  10-­‐12  weeks  



Detailed  Scan  at  20  weeks  



To  detect  specific  anomalies  
! Cardiac  (12-­‐20  weeks)  
! Microcephaly  (Usually  after  22  weeks)  
! Short  Limbs  (Usually  after  22  weeks)  

 

! Brain  malformations  


A  minor  scan  abnormality  may  be  an  indicator  of  more  severe  disease  

 
 
 
Making  a  diagnosis  

 
 
Autosomal  dominant  


 
 
 

Disease  seen  in  all  generations  (usually)  
50%  risk  of  affected  child  if  parent  is  affected  



Heterozygotes:     nucleus,   cell   or   organism   possessing   two   different   alleles   for   a   particular  
gene
...
g
...
g
...
     



Carrier  females  will  have  a  50%  chance  of  affected  male  and  50%  chance  of  carrier  female  



Affected   men   will   have   100%   chance   of   having   carrier   female   and   0%   chance   of   affected  
male  

 
Genes  and  Maternal  Health  in  Pregnancy  


It  is  not  just  about  risk  to  the  baby!  



Haemophilia   A  or  B:   female   carriers   with   haemophillia   dont   have   full   blown   disease   due   to   X  
linked  inactivation  however   they   may  have  significantly  lower  factor  levels  than  normal  =>  
therefore  during  pregnancy  they  are  at  higher  risk  of  bleeding  complications  



Hereditary   Haemorrhagic   Telangiectasia:   AD   disorders   which   can   cause   abnormal   bleeding  
=>  if  mum  affected  can  cause  bleeding  complications  

 
Antenatal  testing  for  specific  genetic  mutations    
Sampling  method  
 
 
 



Chorionic  Villus  Biopsy  at  11
...
g  point  mutation  


Usually  PCR  based  e
...
 QF-­‐PCR:  results  in  2-­‐3  days  



Appreciate   that   QF-­‐PCR   is   often   used   for   both   detecting   chromosomal   amueploidies  
(unless  high  risk  =>  aneuplodies  or  FISH)    and  specific  genetic  mutations    



Occasionally  southern  blotting:  may  take  2-­‐3  weeks  

 
Example  
Mrs  Smith  comes  to  see  you
...
 
Her  brother  Charles  was  affected  with  duchenne  muscular  dystrophy  (X-­‐linked)  and  died  at  the  age  
of  14
...
 
 
What  is  your  best  ‘genetic'  management  ?  
1
...
Serum  Screening  
3
...
5   weeks,   and   not   before
...
   After  16  weeks  perform  amniocentresis
...
   
4
...
Fetal  Blood  Sampling  
 
Note:    she  will  have  50%  chance  of  being  carrier
...
g
...
   If  girl  =>  relax!  

 
Communicating  Risk  and  Uncertainty  


Sometimes  genetic  testing  gives  you  a  definite  answer  



Sometimes  it  allows  assignment  of  a  precise  probability  



Sometimes  there  is  significant  uncertainty  

 
Does  free  fetal  DNA  help  here  ?  


Yes!   We   can   do   8   week   “sexing”   on   free   detal   DNA   in   maternal   blood
...
    If   boy   =>  
perform  invasive  testing  (CVS  at  11
...
 

 
Screening  for  Genetic  Disorders  


Antenatal  screening  is  a  way  of  assessing  whether  the  unborn  baby  (fetus)  could  develop,  or  
has  developed,  an  abnormality,  or  other  condition,  during  pregnancy
...
 



Tests  assign  a  risk  of  abnormality  in  a  pregnancy  



Subject  to  specificity  and  sensitivity
...
g
...
g
...
 It  consists  of  
making   a   pinprick   puncture   in   one   heel   of   the   newborn   and   soaking   the   blood   into   pre-­‐
printed  collection  cards  known  as  Guthrie  cards  



Tests  for:  
! Cystic  Fibrosis  
! Phenylketonuria    
! Hypothyroidism  
! Others  



Easier  to  define  the  benefit      

 
Pre  Implantation  Genetic  Diagnosis  (PGD)  


Perform  genetic  tesst  on  embryos  before  re-­‐implanting  one  with  the  ‘correct’  genotype
...
g
...
g
...
g  QF-­‐PCR)  based  analysis  for  single  gene  disorders    



PCR  analysis  improved  by  whole  genome  amplification  

 
Preimplantation  genetic  diagnosis:  sex  determination  using  FISH  


Preimplantation  genetic  diagnosis  =  PGD  



Different  coloured  probes  (tags)  to  label  chromosomes  X,  Y  and  18  (control)  



Individual  chromosomes  are  not  visible    



Use  FISH  

 
PGD:  Advantages  and  disadvantages  
Advantages  


Pregnancy  less  likely  to  be  affected  from  outset  



Lower  likelihood  of  requiring  T
...
P
...
g
...
g
...
   ASK  A  GENETICIST!!!!  



 
 
 

Tell  us  (the  geneticists)  early  if  we  are  needed:  if  possible  at  the  pregnancy  planning  stage  

Chorionic   villous   sampling/biopsy   (CVS   or   CVB)   can   be   done   at   11   weeks   (up   until   15  
weeks)  gestation  but  carries  a  risk  of  miscarriage  of  1-­‐2%
...
 Chorionic  villus  is  also  a  slightly  
weird  tissue  to  work  with  genetically,  and  can  result  in  false  +ves  due  to  confined  placental  
mosaicism
...
  Risk   of   miscarriage   is  
lower   (0
...
    Most   DNA   (genes)   tests   only   take   about  
3-­‐4  days  following  amnio,  but  full  chromosomes  can  take  2  weeks  (usually  much  faster  with  
QF-­‐PCR   if   we   are   testing   for   specific   chromosomal   abnormalities;   must   perform   full  
karyotyping  if  we  are  not  testing  for  the  common  aneuploidies)    



Fetal   blood   sampling   is   rarely   done   and   later   in   pregnancy
...
 There  may  be  non-­‐genetic  indications  that  I  am  unaware  of
...
  The   test   varies   on  
indication:  
!

!

Array   CGH   is   coming   in,   but   not   used   antenatally   in   Dundee   (it   is   elsewhere)
...
  In  
two  to  three  years  we  will  do  a  CGH  as  our  first  line  test
...
   In  this  method    you  get  to  count  
each   chromosome   stripe
...
g
...
   PCR  can  also  be  used  
to  look  for  point  mutations  (specific  mutations)  e
...
 Duchennes  

Don’t   forget   the   isolation   of   fetal   DNA   from   maternal   serum,   which   is   about   to  
replace  QF-­‐PCR  and  will  soon  probably  replace  the  others  at  around  8-­‐10  weeks  
gestation  

 
 
 
PRESENTATION  OF  BREAT  CONDITIONS  
Breast  symptoms  not  typically  due  to  cancer  
Breast  pain  (mastalgia)  
Breast  tenderness  
Bilateral  nipple  discharge  
Generalised  lumpiness:  not  definable  as  single  lump  (typical  of  fibrocystic  disease  -­‐  
fibroadenosis)  
• Disparity  in  breast  size  (hardly  any  women  have  symmetrical  breasts)  
• Longstanding  nipple  inversion  (a  condition  where  the  nipple,  instead  of  pointing  outward,  is  
retracted  into  the  breast):  very  common,  often  bilateral,  doesn't  require  assessment
...
 More  than  80%  of  breast  cancer  cases  are  
discovered  when  the  woman  feels  a  lump
...
     
Axillary  lump:  Lumps  (or  swellings)  found  in  lymph  nodes  located  in  the  armpits  can  also  
indicate  breast  cancer
...
g
...
 Peau  d'orange  is  caused  by  cutaneous  lymphatic  edema,  
which  causes  swelling
...
 This  is  a  normal  breast  change  and  nothing  to  worry  about
...
 The  lining  can  also  become  ulcerated  and  painful  as  well,  although  this  is  
not  common
...
   Causes  
mastitis
...
     
 
Most  managed  by  US  guided  drainage  (for  abscesses)  and  antibiotics  (e
...
 fluclox)
...
 If  systemically  well  can  be  treated  as  an  
outpatient  with  oral  Abs
...
g
...
g
...
   The  stroma  is  replaced  with  
fat  as  age  increases  
Lots  of  individual  variation:  may  still  have  dense  breasts  aged  80  =>  US  may  be  preffered  
Don’t  generally  do  mammography  <40  unless  suspicion  of  cancer  (US  is  preferred  as  first  line  Ix  
under  40)  

 
Advantages  of  Mammography  



 

Images  whole  both  breasts  
High  sensitivity  for  detecting  Duct  carcinoma  in  situ  (microcalcifications,  not  breeched  
basement  membrane)  &  invasive  cancer  
Only  screening  modality  known  to  reduce  population  mortality  

Disadvantages  of  Mammography  




 

Non-­‐specific:    only  1  in  5  to  1  in  10  actually  have  breast  cancer  when  detected  (screen  +ve)  
Uses  ionising  radiation  
Can  be  uncomfortable  
~  10  %  of  cancers  are  probably  over  diagnosis  

Ultrasound  





Useful  in  symptomatic  clinic  =>  useful  in  breast  lump  
Indications:  palpable  mass,  work  up  of  a  mammographically  detected  lesion,  image  guided  
biopsy,  breast  inflammation  (can  see  &  drain  abscesses),  breast  problems  during  pregnancy  
(breasts  very  dense  because  of  proliferation  of  breast  tissue  e
...
 oestrogen  stimulates  duct  
growth  and  progesterone  stimulates  lobule  growth)  
Advantages:  
! Useful  for  woman  <40  with  dense  breasts  (or  for  woman  >40  with  dense  breasts)  
! No  ionising  radiation  
! Not  uncomfortable  for  patient  
! Good  sensitivity  and  specificity  for  detecting  invasive  cancer  
! Quick  if  examination  tailored  to  one  area  
! Can  differentiate  cystic  from  solid  
! Cheap  
! Image  guided  biopsy  very  easy  

 
Biopsy  methods  



 
 
 

There  are  four  types  of  biopsies:  
! Fine-­‐needle  aspiration  (FNA):  for  fluid  filled  masses  e
...
 cyst  
!  Core-­‐needle  biopsy:  for  solids  
!  Surgical  biopsy  
! Vaccum  
The  latter  three  are  the  most  commonly  used  on  the  breast
...
g  fluid  filled  cyst)  
Core  needle  biopsy  (image  guided  cone  biopsy):  technique  most  commonly  used,  core  needle  
biopsy  is  the  procedure  to  remove  a  small  amount  of  suspicious  tissue  from  the  breast  with  a  
larger  “core”  (meaning  “hollow”)  needle
...
 Generally  have  to  biopsy  using  
mammogram  machine
...
g
...
g
...
   
Cyclical  change  in  lumpiness  +/-­‐  cyclical  mastalgua
...
 
Though  tell  to  come  back  if  they  get  another  lump
...
 
>  50  =  cancer  

 
Clinical  features  of  Lumps  




Benign:  smooth,  soft,  round/oval,  mobile,  well-­‐defined  
Suspicious:  irregular,  stoney  hard,  ill  defined,  speculated,  fixed,  associated  lymphadenopathy  
(only  ~10-­‐20%)  
Cannot  ever  tell  just  from  physical  charachteristics!  
 

 
Imaging  


 
 
 

US  best:  
! Age  <40  
! Age  >  40  with  dense  breasts  
! Fluid  filled  e
...
 cyst  



 
Mammography  
! Age  >40  
! If  clinical  or  US  findings  are  suspicious    
! Screening:  woman  aged  50-­‐70  every  3  years,  mammography  

 
Spiculate  masses  


 




In  oncology,  a  spiculated  mass  is  a  lump  of  tissue  with  spikes  or  points  on  the  surface
...
e
...
 
Suspect  carcinoma  
Surgical  scar  can  occasionally  look  similar,  as  can  radial  scar  (complex  sclerosing  lesion)  

 
 
Axillary  US  






 
 
 

US  axilla  
Abnormal  nodes  identified  by  cortical  thickness  and  shape  
Core   biopsy   or   FNA   of   abnormal   nodes   identifies   about   40%   of   node   positive   women   pre-­‐
operatively  
Chemo/radio/surgical  
Sentinel   lymph   node   biopsy:   A   sentinel   lymph   node   is   the   first   lymph   node(s)   to   which   cancer  
cells   are   most   likely   to   spread   from   a   primary   tumour
...
    A   surgeon   injects   a  
radioactive   substance,   near   the   tumor   to   locate   the   position   of   the   sentinel   lymph   node
...
    Once   the  


 

sentinel   lymph   node   is   located,   the   surgeon   makes   a   small   incision   in   the   overlying   skin   and  
removes   the   node
...
 If  no  cancer  detected  =>  unlikely  the  cancer  has  spread  
If  spread  to  the  axillary  lymph  nodes  =>  can  do  surgical  clearance  of  axillary  nodes  

MRI  
Used  only  on  those  with  particular  problems  e
...
 lobular  cancer  has  very  diffuse  growth  =>    
difficult  to  size  and  stage  accurately  =>  MRI  can  prevents  multiple  operations  
• MRI  used  to  size  tumour  =>  stage  tumour  size  
 
 
Staging  (TNM)  


Staging  is  important  for  prognosis  and  treatment  decisions  
For  locally  advanced  disease  or  recurrent  breast  cancer  use  CT  chest,  CT  abdo  and  CT  pelvis  to  
look  for  mets  
• Common  sites  of  mets:  bones,  lung,  pleura,  liver,  brain  
• If  liver  or  brain  mets  =>  lucky  to  survive  1  year
...
g
...
     Effective  if  oestrogen-­‐receptor  positive  e
...
 oestrogen  
receptor  protein  measurable  in  primary  tumor
...
   Used  in  premenopausal  woman
...
     
! Aromatase  inhibitors  (AIs)  are  a  class  of  drugs  used  in  the  treatment  of  breast  cancer  
and  ovarian  cancer  in  postmenopausal  women
...
   In  
contrast  to  premenopausal  women,  in  whom  most  of  the  estrogen  is  produced  in  the  
ovaries,  in  postmenopausal  women  estrogen  is  mainly  produced  in  peripheral  tissues  of  
the  body
...
e
...
 
! Oophorectomy  (surgical  removal  of  ovaries)  =>  decrease  oestrogen  (useful  for  ER  +ve  
tumours)  and  decrease  progesterone  (useful  for  PgR  +ve  tumours)  
 
• Immunotherapy  with  monoclonal  ABs:  
! Trastuzumab  (Herceptin):  a  monoclonal  antibody  to  HER2  (human  epithermal    growth  
factor  receptor  2)  for  HER2  +ve  breast  cancers  
 
 
 
Clinical  Decision  Making    
 
• CPC:    Clinical  Pathological  Conference  
• MDT:  Multidisciplinary  Team  Meeting  
• Review  preoperative  decisions  
• Review  operative  pathology  
• Plan  subsequent  management  
• Management  of  recurrent  disease
...
 Benefits  not  shown,  harm  gets  worse  (overdiagnoses  &  shorter  
life  expectancy  &  breast  cancer  less  aggressive  as  you  get  older)  
Some  evidence  that  women  in  40s  should  have  mammography  

BREAST  PATHOLOGY  1  
Assessment  of  a  patient  with  breast  disease  
Triple  assessment:  
 
 
 



Clinical  
! History  
! Examination  



Imaging  
! Mammography  (>40  years)  
! Ultrasound  (<40  years)  
! MRI  



Pathology  
! Cytopathology  (cellular  level)  
! Histopathology  (tissue  level)  

 
Breast  Cytopathology  


Cytopathology=   a   branch   of   pathology   that   studies   and   diagnoses   diseases   on   the   cellular  
level    



Collection  methods:  
! Fine  Needle  Aspiration  (FNA)  
! Fluid  
! Nipple  discharge  
! Nipple  scrape  



Breast  FNA  cytology:  
! C1  -­‐  Unsatisfactory  
! C2  -­‐  Benign  
! C3  -­‐  Atypia,  probably  benign  
! C4  -­‐  Suspicious  of  malignancy  
! C5  –  Malignant  
 

Breast  Histopathology  
 
 
 



Histopathology   refers   to   the   microscopic   examination   of   tissue   in   order   to   study   the  
manifestations  of  disease
...
g
...
 



The  development  stages  of  secondary  sex  characteristics  (breasts,  pubic  hair,  menstruation  
etc
...
 



During   thelarche,   the   developing   breasts   sometimes   are   of   unequal   size,   and   usually   the   left  
breast   is   slightly   larger;   this   asymmetry   is   transitory   and   statistically   normal   to   female  
physical  and  sexual  development
...
 After  
initial   development   of   the   milk   lines   they   go   into   remission
...
  Most   humans   have   two   nipples,   but   in   some   cases   more   than   two   will  
develop
...
 



Hormone   driven:   many   hormones   involved   e
...
  oestrogen   (stimulates   duct   growth),  
progesterone   (stimulates   lobule   growth),   prolactin   (promotes   lactation   e
...
  mik  
production)  and  oxytocin  (stimulates  smooth  muscles  of  ducts  =>  ejection  of  milk)  

 
 
Stages  of  breast  development    




 
 
 

1
...
  By   the   time   a   female  
infant  is  born,  nipples  and  the  beginnings  of  the  milk-­‐duct  system  have  formed
...
   Puberty:  Once  ovulation  and  menstruation  begin,  the  maturing  of  the  breasts  begins  with  
the  formation  of  secretory  glands  at  the  end  of  the  milk  ducts
...
 The  rate  at  
which  breasts  grow  varies  greatly  and  is  different  for  each  young  woman
...
   Adult  “resting”:  Each  month,  women  experience  fluctuations  in  hormones  that  make  up  
the  normal  menstrual  cycle
...
 The  increasing  level  of  
oestrogen   leads   to   the   LH   surge   and   ovulation   halfway   through   the   cycle,   and  
then  the  hormone  progesterone  takes  over  in  the  second  half  of  the  cycle
...
   
! These  hormones  are  believed  to  be  responsible  for  the  cyclical  changes  such  as  
the   swelling,   pain,   and   tenderness   that   many   women   experience   in   their  
breasts  just  before  menstruation  (cyclical  changes)  
!  During   menstruation,   many   women   also   experience   changes   in   breast   texture,  
with   breasts   feeling   particularly   lumpy
...
  If   pregnancy   does   not   occur,   the  
breasts  return  to  normal  size
...
 
! A   breast   lump(s)   that   appears   during   the   menstrual   cycle,   grows   rapidly   and  
shows   spontaneous   regression   with   completion   of   the   menses   is   most  
suggestive   of   fibrocystic   changes   (fibroadenosis)
...
  Fibrocystic   changes   is   most   common   in  
woman  30-­‐50
...
   Involution:  Regression  of  mammary  tissue  to  a  non-­‐secreting  state,  with  disappearance  
of   much   of   the   high   density   epithelial   tissue,   and   replacement   with   low   density   fatty  
tissue
...
     


 
 
 

4
...
 The  areolas  begin  to  swell  
followed  by  the  rapid  swelling  of  the  breasts  themselves  (progesterone  causes  enlargement  
of  lobules)
...
   By  the  fifth  or  
sixth   month   of   pregnancy,   the   breasts   are   fully   capable   of   producing   milk
...
  Many   other   hormones,   such   as   follicle   stimulating   hormone   (FSH),  
luteinizing  hormone  (LH),  prolactin,  oxytocin,  and  human  placental  lactogen  (HPL)  also  play  
vital  roles  in  milk  production  and  secretion  (lactation)
...
  Postmenopausal   atrophy:   By   the   time   a   woman   reaches   her   late   40s   and   early   50s,  
menopause   is   beginning   or   is   well   underway
...
  This   leads   to   many   of   the   symptoms   commonly  
associated   with   menopause
...
   The  connective  
tissue   of   the   breast   becomes   dehydrated   and   inelastic,   and   the   breast   tissue,   which   was  
prepared  to  make  milk,  shrinks  and  loses  shape  =>  atrophy
...
     
 
Tanner  stages  of  female  pubertal  development  


Thelarche  =  breast  development  (usually  occurs  first)  



Pubarche   =   development   of   pubic   hair   (often   the   second   noticeable   change   in   puberty,  
usually  within  a  few  months  of  thelarche)  



Menarche  =  first  menstrual  bleed  (typically  occurs  about  two  years  after  thelarche)  

 

 
 
Normal  breast  anatomy    


 
 
 

2nd  to  6th  rib  
Sternal  edge  to  anterior  axillary  line  +  axillary  tail  (don’t  forget  about  the  axillary  tail  e
...
 on  
examination)  



Lies  on  pectoralis  major  fascia  and  serratus  anterior  fascia  



Blood   supply:   Axillary   artery   (subclavian   artery   becomes   axillary   artery),   internal   thoracic  
artery  &  intercostal  arteries    



Lymphatic  drainage  
! Axillary  nodes→  Supraclavicular  nodes  →  Cervical  nodes  
! Internal  mammary  
! ALWAYS  EXAMINE  LYMPH  NODES  



Glandular  tissues  
! Lobules   (mammary   glands):   produce   milk   during   pregnancy   and   breastfeeding   and  
pathological   states   (e
...
  hyperprolactinaemia)
...
   Stimulated  to  produce  milk  by  prolactin
...
 
! Lactiferous   ducts:   connect   the   lobules   of   the   mammary   gland   to   the   tip   of   the  
nipple
...
   Stimulated  to  grow  by  
oestrogen
...
    Ducts   endocrine  
control  by  OO
...
 The  terminal  lactiferous  ducts  
drain  the  milk  from  TDLUs  into  4–18  lactiferous  ducts,  which  drain  to  the  nipple
...
g
...
    Apocrine   metaplasia   is   a   very   common   finding   in   the   female   breast  
after   the   age   of   25   especially   post   menopausal
...
   May  be  a  risk  factor  for  breast  cancer  (controversial)  
! Microcyst  formation  

 
ANDI  Classification  of  benign  breast  disorders  


Disorders   of   development   e
...
 fibroadenoma   (commonest   breast   lump   in   woman   less   than  
30  years,  breast  mouse,  highly  mobile)  



Disorders   of   cyclical   change   e
...
  mastalgia   and   nodularity   and   fibrocystic   changes  
(generalised  lumpiness,  also  known  as  fibroadenosis)  



Disorders   of   involution:   Fibrocystic   changes   (often   cyclical   as   well)   e
...
  Cysts,   Fibrosis   and    
Sclerosing  adenosis  



NB:   Involution   =   regression   of   mammary   tissue   to   a   non-­‐secreting   state,   with   disappearance  
of  much  of  the  epithelial  tissue
...
   Occurs  from  
approx  30  years  old  



NB:  Fibrocystic  changes  often  occur  cyclically  due  to  hormonal  influences
...
     

 
Gynaecomastia  



Pathophysiology:  the  causes  of  common  gynecomastia  remains  uncertain,  but  is  thought  to  
result   from   an   imbalance   between   the   actions   of   oestrogen   and   androgens   on   the   breast  
tissue
...
 



 
 
 

Breast  development  in  the  male  

Increased   oestrogen   to   testosterone   ratio   leads   to   proliferation   of   breast   ducts   and  
fibroblastic  stroma
...
 



Gynaemocastia   =   ductal   growth   without   lobular   development   (due   to   the   excessive  
oestrogen;  it  is  progesterone  which  causes  lobule  growth)  
 

Causes  of  gynaecomastia  


Physiological:   Newborn,   Adolescence,   Increasing   age     (associated   with   low   testosterone  
levels)  



Lack   of   testosterone:   Congenital   absence   of   testes,   Androgen   resistance   syndrome,  
Klinefelter's  syndrome  (47  XXY)          



Increased   oestrogen   levels:   Testicular   tumours   (e
...
  Leydig's   cell   tumour   which   secrete  
estradiol),  liver  disease  (cirrhosis),  Adrenal  tumours,  other  tumour,  obesity  



Drugs:   Oestrogen   (e
...
  oral   contraceptive   pill),   Inhibitors   of   testosterone   (e
...
  finasteride),  
spironolactone  (commonest  drug  induced  cause)  and  digoxin
...
      Can  
cause  discharge
...
 It  is  a  disorder  of  peri-­‐  or  
post-­‐menopausal  age
...
         



Acute  mastitis/abscess  (infection/inflammation  of  the  breast  tissue)  



Fat  necrosis:  often  associated  with  trauma  to  breast  

 
Duct  ectasia  



Can  cause  periductal  mastitis  



 
 
 

This  is  a  benign  breast  disease  that  can  mimic  invasive  carcinoma  clinically
...
 As  women  reach  the  
menopause  and  the  breasts  age,  the  ducts  behind  the  nipple  get  shorter  and  wider  (due  to  
involution)   =>   this   is   called   ectasia
...
     



Sometimes   a   secretion   can   collect   in   the   widened   ducts   and   their   lining   can   become  
irritated
...
 This  is  a  benign  (not  cancer)  condition  called  duct  ectasia
...
 The  discharge  can  vary  in  colour  and  can  be  either  clear  or  bloodstained
...
  As   the   ducts   shorten   this   can   eventually   pull   the   nipple   inwards   so   it  
becomes   inverted
...
     



The   process   that   causes   the   condition   is   still   being   debated   but   histologically   it   is  
characterised  by  dilation  of  major  ducts  in  the  subareolar  region
...
g
...
 



This   term   is   sometimes   used   interchangeably   with   mammary   duct   ectasia
...
   



 
 
 

Periductal  mastitis  occurs  when  the  ducts  under  the  nipple  become  inflamed  and  infected
...
 

Although   the   aetiological   process   is   still   being   researched,   bacterial   infection   is   involved  
(most   commonly   S
...
  Surgery   is   occasionally   required   if   there   is   a   residual   mass,   to   confirm   the  
benign  nature  of  the  histology  and  prevent  recurrence  of  infection
...
   
! It   occurs   in   a   younger   age   group   than   mammary   duct   ectasia   (mammary   duct  
ectasia  most  commonly  occurs  in  peri-­‐  or  post-­‐menopause  woman)  



Clinical  presentation:  
! Periductal  inflammation  
! Pain  and  inflammation    
! Periareolar  mass    
! Periductal  fibrosis  
! Scarring  and  distortion    
! Pus   discharge   from   the   nipple
...
 
Associated  with  smoking  
! Sub-­‐areolar  duct  dilatation  

 
Management  


Treat   acute   infections   e
...
  ABs   (flucloxacillin   empirically   as   S
...
g
...
  It   does   not  
increase  your  risk  of  getting  breast  cancer
...
 This  is  called  fat  
necrosis  (dead  tissue)  



Associated  with  trauma  to  breast  tissue  



The  damage  to  the  fatty  tissue  can  occur  following  a  needle  biopsy,  breast  surgery  (including  
breast  reconstruction)  or  radiotherapy  to  the  breast
...
 



Aetiology:  
! Local  trauma  e
...
 Seat  belt  injury,  needle  biopsy,  radiotherapy,  surgery  
! Warfarin  therapy  
! Frequently  no  history  
! Link  witn  obesity    



Pathophysiology:  
! Damage  and  disruption  of  adipocytes  
! Infiltration  by  acute  inflammatory  cells  
! “foamy”  macrophages  
! Subsequent  fibrosis  and  scarring  
! Microcalcification  

 
Management  


 
 
 

Confirm  diagnosis:    triple  assessment    
Exclude  malignancy  

 
Fibrocystic  change  (Fibroadenosis)  


Women  aged  30-­‐50  (majority  40-­‐50)  



Very  common  



Characterized   by   noncancerous   breast   lumps   (generalised   lumpiness   or   nodularity)   in   the  
breast   which   can   sometimes   cause   discomfort,   often   periodically   related   to   hormonal  
influences  from  the  menstrual  cycle  (cyclical)  



Often  cyclical  



Not   usually   discrete   masses=   >   nodularity   instead
...
     Up  to  
half   of   women   have   this   problem   at   some   time   during   their   life
...
 



Aetiology:  The  causes  of  the  condition  are  not  fully  understood,  though  it  is  known  that  they  
are   tied   to   hormone   levels,   as   the   condition   usually   subsides   after   menopause   and   is   also  
related  to  the  menstrual  cycle  (cyclical)  



It  is  rare  in  women  after  menopause,  unless  they  are  taking  oestrogen
...
   



 Usually  multiple  cysts
...
)  



Myoepithelioma  (benign  tumour  of  glands  which  may  rarely  originate  in  breasts)  



ID   (intraductal)   papilloma:   small,   noncancerous   (benign)   tumor   that   grows   in   a   milk   duct  
(intraductal)  of  the  breast,  can  cause  nipple  discharge  including  blood  stained    



Adenoma:  benign  tumour  of  glandular  origin  

 
Malignant  tumours  

 
 
 



Ductal   carcinoma:   carcinoma   of   the   epithelium   which   lines   the   ducts   (most   common   breast  
cancer;  associated  with  calcification)  



Lobular   carcinoma:   carcinoma   of   the   epithleium   lining   the   lobules   (unlike   ductal   cell  
carcinoma,  lobular  carcinoma  is  NOT  associated  with  calcification)  



Papillary  carcinoma:  very  rare  type  of  invasive  ductal  breast  cancer  



Squmaous  cell  carcinoma:  rare  



Liposarcoma:  cancer  of  fatty  tissue  



Angiosarcoma:  cancer  of  blood  vessells  



Lymphoma:  cancer  of  lymphoid  tissue  



Myoepithelial  carcinoma  

 
Terminology  


Carcinoma  =  cancer  of  epithelial  origin  



Sarcoma   =   cancer   of   mesenchymal   origin   e
...
  cancer   of   connective   tissues   such   as   blood  
vessels,  blood,  bone  etc
...
    This   is   because   during   the  
reproductive  years  women’s  breasts  are  constantly  going  through  change,  from  the  time  of  
their   development,   through   pregnancy   and   the   menopause
...
 



Fibrocystic  changes  are  the  commonest  cause  of  breast  lumps  in  pre-­‐menopausal  woman    
and  present  with  breast  lumpiness  and  tenderness  which  is  often  cyclical
...
   Fibrocystic  changes  are  
classed   as   aberrations   in   the   Normal   Development   and   Involution   of   the   breast   (ANDI)
...
g
...
   
With  an  estimated  incidence  of  over  60%  of  women,  many  consider  it  a  variation  
of   normal
...
 Majority  occur  aged  40-­‐50
...
 May  present  with  generalised  lumpiness  or  multiple  soft  well  
demarcated   cysts
...
  Fibrocystic   breast   changes   usually   involve   the   entire   breast   but   may   be  
more   severe   in   the   upper,   outer   area   of   the   breast
...
    Occur   due   to   combined   effects   of   involution   and   cyclical  
changes
...
  It  is  usually  found  in  adolescent  girls  
and   women   in   their   twenties
...
  It   is   usually   freely   moveable   (sometimes   called  
“breast   mouse”   as   very   mobile)   and   painless
...
 This  mass  is  solid  and  no  fluid  
will   be   obtained   if   aspiration   is   attempted
...
  The   only   way   to   be   sure   that   a  
solid   breast   lump   is   a   fibroadenoma   versus   a   cancerous   mass   is   to   obtain   cells  
from   the   breast   tissue   to   examine   under   a   microscope
...
g
...
   



Because  breast  cancer  can  also  appear  as  a  lump,  doctors  may  recommend  a  tissue  sample  
(core  needle  biopsy)  to  rule  out  cancer  (esp  in  older  patients)    



Unlike   typical   lumps   from   breast   cancer,   fibroadenomas   are   easy   to   move   (not   tethered),  
with  clearly  defined  edges  



The  typical  case  is  the  presence  of  a  painless,  firm,  solitary,  highly  mobile,  slowly  growing  
lump   in   the   breast   of   a   woman   of   child-­‐bearing   years   (particularly   in   adolescent   woman  
and  women  in  their  20s)  



Generally  non  cyclical  (may  have  a  slight  cyclical  component)  



A   fibroadenoma   is   usually   diagnosed   through   clinical   examination,   ultrasound   or  
mammography,  and  often  a  needle  biopsy  sample  of  the  lump
...
   Doctors  may  recommend  a  tissue  sample  
(biopsy)  to  rule  out  cancer  in  older  patients
...
   



All  forms  of  phyllodes  tumors  are  regarded  as  having  malignant  potential
...
 Sclerosis  is  found  in  these  benign  (not  cancer)  breast  conditions:  



Types:  
! Sclerosing  adenosis  
! Radial  scar  (complex  sclerosing  lesion)  



Combination  of  epithelial  proliferation,  stromal  fibrosis  and  sclerosis  (hardening)  



Can  cause  a  mass  or  calcification  



May  mimic  carcinoma  (ductal  carcinoma  presents  with  calcified  mass)  

 
Sclerosing  adenosis  



Sclerosis   adenosis   is   a   benign   breast   condition   composed   of   small   breast   lumps   caused   by  
enlarged  lobules  which  are  distorted  by  scar  like  fibrous  (thickened)  tissue  



Pain,  tenderness  or  lumpiness/thickening  



Asymptomatic  



Age  20-­‐70  


 
 
 

Adenosis  =  enlarged  lobules  

ANDI  (aberrations  in  the  normal  development  and  involution  of  breast)  



Related  to  fibrocystic  breast  changes  (fibroadenosis)  

 
Radial  scar  


Radial   scars   and   complex   sclerosing   lesions   are   benign   conditions   (not   cancer)   that   are  
essentially  the  same  thing  but  are  identified  by  size,  with  radial  scars  usually  being  smaller  
than  1cm  and  complex  sclerosing  lesions  being  more  than  1cm
...
 



Hsitology:  fibrous  tissue  (forms  scar)  +  epithelial  proliferation  



Wide  age  range  



Common  



Incidental  finding  often  mammographically  detected  



Mimic  carcinoma  radiologically  (due  to  calcification)  



Probably  not  premalignant  per  se  



Often  show  epithelial  proliferation  



In  situ  or  invasive  carcinoma  may  occur  within  these  lesions  

 
Papillary  lesions  


Intraduct  papilloma  



Nipple  adenoma  



Encysted  papillary  carcinoma  

 
Intraduct  papilloma  (IDP)  




Usually  close  to  nipple  



Benign  



 
 
 

Intraductal  papillomas  are  small  growths  (wart  like)  that  occur  in  the  ducts  of  the  breast  and  
can  cause  nipple  discharge  –  which  may  be  blood  stained  

Age  35-­‐60  



They   are   most   common   in   women   over   40   and   usually   develop   as   the   breast   ages   and  
changes
...
g
...
 
 
BREAST  CARCINOGENESIS  
Pathways  of  breast  carcinogenesis  


 
 
 

Breast   cancer   emerges   by   a   multistep   process   which   can   be   broadly   equated   to  
transformation  of  normal  cells  via  the  steps  of  hyperplasia,  premalignant  change  (dysplasia),  
in  situ  carcinoma  and  invasive  carcinoma  



Breast   carcinoegensis   occurs   due   to   progressive   epithelial   proliferation,   dysplasia,   and  
mutations  leading  to  malignant  changes  



Multistep  process  

 
Epithelial  Proliferations  (hyperplasia)  
Ductal  


Epithelial  hyperplasia  of  usual  type  



Atypical  Ductal  Hyperplasia  



Ductal  Carcinoma  in  situ  –  BM  not  been  breached,  microcalcification    

 
Lobular  


Lobular  in  situ  neoplasia  



Atypical  lobular  hyperplasia  



Lobular  carcinoma  in  situ  

 
Intraductal  proliferation:  risk  of  progression  to  invasive  carcinoma  


Risk  of  progression  to  invasive  carcinoma:  
! Epithelial  hyperplasia  of  usual  type  =>  low  risk  
! Atypical  Ductal  Hyperplasia  =>  moderate  risk  
! Ductal  Carcinoma  in  situ  (low  grade)  25%  over  following  10  years  =>  high  risk  

 
Breast  cancer  grades  
Ductal  


DCIS  (ductal  carcinoma  in  situ):    
! Low  grade  
! Intermediate  grade  
! High  grade  

 
 
 

! DCIS   can   progress   in   grade   e
...
  low   grade   DCIS   =>   intermediate   grade   DCIS   =>  
high   grade   DCIS   =>   G3   (high   grade)   ductal   carcinoma
...
g  from  low  grade  DCIS  
to  G1  (low  grade)  ductal  carcinoma
...
g
...
    More   time   for   hormonal  
stimulation  of  breasts
...
 
! Parity:   the   number   of   children   borne   by   one   woman;   childbearing   reduces   the  
risk  of  breast  cancer  (and  ovarian  Ca)
...
 Women  who  have  given  birth  to  five  or  more  children  
have   half   the   risk   of   women   who   have   not   given   birth
...
   That’s  probably  because  
she’s   been   exposed   to   more   oestrogen
...
 So  the  more  menstrual  periods  
a   woman   has,   the   longer   these   tissues   are   exposed   to   oestrogen
...
    Oestrogen   stimulates  
some   breast   cancers   (ER   +ve   breast   cancers)   to   grow   by   triggering   particular  
proteins  (receptors)  in  the  cancer  cells
...
g
...
 Higher  oestrogen  levels  due  
to  conversion  of  androgens  to  eostroens  by  fatty  tissue
...
 
! Alcohol  consumption:  Small  association  with  alcohol  =>  higher  levels  of  oestrogen  
in  alcohol  consumers  
! Diet:  High  fat  intake  associated  with  small  increased  risk
...
 



Genetics:  
! FH:  Affected  first  degree  relative  doubles  risk  
! Also   can   be   associated   with   familial   syndromes   =>   even   higher   risk   e
...
  BRCA   1  
and  BRCA2  plus  other  rarer  mutations  

 
TAKE  A  FULL  OBS  AND  GYNAE  MOSCC  HISTORY  
 
Genetics  and  breast  cancer  


Some  genetic  susceptibility  may  play  a  role  in  most  cases
...
   This  includes  those  who  carry  the  BRCA1  and  BRCA2  gene  
mutation
...
 



BRCA1   and   BRCA   2   mutations:   Associated   with   breast   and   ovarian   cancer,   as   well   as  
prostate  cancer  (in  males)  

 
BRCA  1  and  BRCA  2  


 
 
 

BRCA  1  and  BRCA  2  mutations    
Each  present  in  0
...
g
...
g
...
g
...
 But  even  so,  most  women  with  CIS  never  develop  breast  cancer  



Confined  within  basement  membrane  of  acini  &  ducts  


 
 
 

Majority  of  invasive  carcinomas  originate  from  in  situ  carcinoma  (pre-­‐cancerous  epithelial  
tumour  constrained  within  BM)  

Cytologically  malignant  but  non-­‐invasive  (pre-­‐invasive)  



Non-­‐obligate  precursor  of  invasive  carcinoma  =>  e
...
 if  patients  with  carcinoma  in  situ  were  
followed  for  a  period  of  time,  rather  than  having  the  CIS  treated,  not  all  the  lesions  of  CIS  
will   have   developed   invasive   carcinoma
...
 



Classification  
! Ductal  CIS  (most  common):  associated  with  calcification  
! Lobular  CIS:  not  associated  with  calcification  

 
Ductal  Carcinoma  in  situ  (DCIS)  


15-­‐20%  of  breast  malignancies  are  DCIS    



Arises  in  TDLU  (terminal  ductal  lobular  unit)  



Cytologically  malignant  epithelial  cells  



Confined  within  basement  membrane  of  duct  



May   involve   nipple   skin   (Paget’s   diease   of   the   nipple   and   areola:   eczematous   rash   and  
crusting)  



Associated  with  calcification  (and  microcalcification)  in  contast  to  LCIS  

 
Classification  of  DCIS  


Cytological  grade  (cellular  levels)  



Histological  type  (tissue  level)  



Presence  of  necrosis  (comedo)  

 
Significance  


Risk  factor  for  development  of  invasive  carcinoma  (ductcal  cell  carcinoma)  



True  precursor  lesion  for  invasive  carcinoma    

 
Management  

 
 
 

Diagnosis  



Surgery:  Surgical  excision  aimed  at  excising  all  of  the  abnormal  duct  elements  is  a  common  
treatment
...
 



Chemoprevention  (trial)  

 
Paget’s  Disease  of  the  Nipple  


High  grade  DCIS  extending  along  ducts  to  reach  the  epidermis  of  the  nipple    



Areola  can  also  be  affected  



It  produces  eczema-­‐like  symptoms,  appearing  as  an  itchy,  red  rash,  crusting  on  the  nipple  
that  can  extend  to  the  darker  area  of  surrounding  skin  (the  areola)
...
     



Can  be  DCIS  (ie  non-­‐invasive)  or  invasive  ductal  carcinoma  



Key   features   are   eczema   like   crusty   itchy   red   rash   of   the   nipple   which   can   extend   to   the  
areola  

 
Lobular  in  situ  neoplasia  
Two  major  types:  


Atypical  Lobular  Hyperplasia  (ALH):  <50%  of  lobule  involved  



Lobular  Carcinoma  in  situ  (LCIS):  >50%  of  lobule  involved  

 
Features:  



Frequently  multifocal  and  bilateral  



Incidence   decreases   after   menopause   (due   to   decreased   oestrogen   levels?)   =>   more  
common  in  pre-­‐menopausal  woman  



Not  palpable,  not  visible  grossly  and  usually  an  incidental  finding  


 
 
 

Intra-­‐lobular  proliferation  of  characteristic  cells  

NOT  associated  with  calcification  (in  contrast  to  ducal  cell  carcinoma  and  DCIS)  

 
Significance  


Marker  of  subsequent  risk  (10-­‐20%  risk  of  malignancy)  



Also  a  true  precursor  lesion  

 
Management:  


Core  biopsy  =>  Excision  or  vacuum  biopsy  to  exclude  higher  grade  lesion  



Vacuum  or  excision  biopsy:  Follow  up  and  clinical  trials  

 
Invasive  carcinoma  


Malignant  epithelial  cells  which  have  breached  the  BM  (basement  membrane)  



Infiltration  of  normal  tissues  



Risk  of  metastasis  and  death  

 
Microinvasive  Carcinoma  


Rare  



DCIS  (high  grade)  with  invasion  of  <1mm  



Treat  as  high  grade  DCIS  

 
 
Invasive  Carcinoma  Types  



 
 
 

Ductal  most  common  (70%)  
Lobular  second  most  common  (10%)  

 
 
 
Pathological  assessment  of  invasive  carcinoma  


Staging  (TNM):    CT  head,  abdo,  chest  and  pelvis  



Grade  (1-­‐3)  



Completeness  of  excision  



Prognostic  factors  



Predictive  factors  

 
Prognostic  factors  of  breast  cancer  


Grade  (1-­‐3)  depending  on  histological  and  cytological  features  
! Tubular  differentiation  (1-­‐3)  
! Nuclear  pleomorphism  e
...
 degree  of    nuclear  shape  and  size  variation  (1-­‐3)    
! Mitotic  activity  (1-­‐3)  



Stage  (TNM):  
! Tumour:  size,  type,  invasive  versus  situ  
! Node:  lymph  node  metastasis:  number  involved,  sentinel  node  biopsy  
! Mets:  in  distant  parts  of  body  excluding  local  lymphatics  


 
 
 

Completeness  of  excision  



We  test  for  the  following  receptors  on  tumour  cells:  
! ER   (oestrogen   receptor):   helps   to   predict   response   to   treatment   e
...
  with  
tamoxifen   (anti   oestrogen   in   breast)   in   premenopausal   woman,   and  
oophrorectomy  (surgical  removal  of  ovaries)  
! HER  2  (Human  Epidermal  growth  factor  Receptor  2):  helps  to  predict  response  to  
treatment  e
...
g
...
  Also   used   to   determine   need   for   systemic   therapies
...
   They  grow  in  response  to  the  hormone  oestrogen
...
”   They   grow   in   response   to   another   hormone,  
progesterone
...
 
ER  expression  predicts  response  to  anti-­‐oestrogen  therapy:  



Tamoxifen:   antagonist   of   the   estrogen   receptor   in   breast   tissue   (prolonged   use   is   a   risk  
factor  for  endometrial  hyperplasia  and  cancer)  



Aromatase   inhibitors   (Letrozole):   block   the   conversion   of   androgens   to   oestrogen   =>  
decrease  oestrogen  effects  in  breast  tissue
...
 



 
 
 
 

Oophorectomy:  surgical  removal  of  ovaries  

GnRH  agonists  (Goserilin  and  buserelin):  cause  down  regulation  of  pituitary  secretion  of  LH  
=>   down   regulation   =>   decreased   oestrogen   production   (can   also   be   used   for   Tx   of   prostatic  
cancer)
...
     

Human  Epidermal  growth  factor  receptor  2  (HER  2)  
HER2:  


HER  2  overexpression  and  amplification  seen  in  ~15%  



HER  2  overexpression  or  amplification  predict  response  to  Trastuzamab  (Herceptin)  



Trastuzamab   (Herceptin)   is   a   MAB   (monoclonal   AB)   which   can   be   used   against   certain   HER   2  
+ve  breast  cancers  

 
Hormone  receptors  status  


80%  ER  positive  



67%  PgR  positive  



14%  HER2  positive  

 
 
Summary  



Breast   cancer   pathology   predicts   response   to   specific   therapies   e
...
  endocrine   and   MAB  
therapies  


 
 
 

Breast  cancer  pathology  predicts  outcome  

All  rational  management  of  breast  cancer  depends  on  the  Pathology  



Nottingham  prognostic  score  

 
 
Breast  conditions:  presentation,  surgery  and  reconstruction  
Presentation  of  breast  conditions  


Patients   either   present   symptomatically   through   GP   (e
...
  with   lump,   pain,   nipple  
abnormality  etc)  or  the  abnormality  is  found  on  screening  (mammography  is  recommended  
for  woman  50  to  70  every  3  years)    



Patients   with   an   unexplained   abnormality   are   referred   to   the   one   stop   breast   clinic   where  
triple  assessment  occurs:  
! Clinical   (history   and   examination):   FH,   risk   factors,   nipple   changes,   indrawing,  
lump,  skin  changes,  arm  changes                                            
! Radiology:  mammograms  esp  >40  years  (as  less  dense  breast  tissue),  ultrasound  
<40  years  (as  more  dense  breast  tissue)  
! Pathology   (cytology   and   histology):   fine   needle   aspiration,   core   biopsy,   surgical  
biopsy  



Results   can   be   discussed   at   the   clinical   pathological   conference   =>   decide   on   Mx   e
...
  no  
further  Mx,  follow  up,  surgery,  chemo,  radio  etc  

 
Management  of  benign  breast  problems  
Benign  conditions:  
h Fibroadenoma:  possibly  excise  (vaccuum)  
h Sclerosing  lesions  and  radial  scar:  excise  
h Intraductal  papilloma:  excise  (as  can  be  pre-­‐malignant)  
h Cysts:  drain  if  needed  
h Breast  sepsis  (duct  ectasia,  mastitis,  abscess,  fistula):    drain  if  antibiotics  fail  
h Gynaecomastia:  possibly  excise                                                                
 
Clinical  pathological  conference  (CPC)                        

 
 
 

For  breast  cancer  the  following  are  discussed:  

! Triple  assessment  
! Tissue  diagnosis  (e
...
 subtype  of  cancer)  
! Grade  
! Receptor   status:   ER   (oestrogen   receptor),   PgR   (progesterone   receptor),   HER2  
(human  epidermal  growth  factor  receptor  2)  
! Staging:  TNM  (important  for  Mx  and  prognosis)  
! General  fitness  of  patient  
! Patients  concerns  and  preferences  


Management  options:  
! surgery  
! radiotherapy  
! chemotherapy  
! endocrine  therapy  (tamoxifen,  oophorectomy,  buserelin  or  goserelin,  letrozole)  
! immunotherapy  with  MABs  e
...
 Herceptin  (trastuzumab)  
! palliative  care  

 
Breast  cancer  management  


Surgery:    
! Breast:  lumpectomy  (wide  local  excision)  or  mastectomy    
! Axillary:  sentinel  node  biopsy,  sample,  node  clearance      
! reconstruction    




Endocrine  therapy  



Immunotherapy  



 
 
 

Chemotherapy  



 

Radiotherapy  –  for  all  pts  with  breast  conserving  surgery  (wide  local  excision)  

Bisphosphonates  for  prophylactic  bone  protection  (e
...
  One   or   more   lymph   nodes   may   be   biopsied   during   the   surgery;  
increasingly  the  lymph  node  sampling  is  performed  by  a  sentinel  lymph  node  biopsy
...
 
! Quadrantectomy:  Removal  of  one  quarter  of  the  breast
...
   Breast  
conserving   surgery,   however   higher   risk   that   all   the   cancer   will   not   have   been  
removed
...
     



Once   the   tumor   has   been   removed,   if   the   patient   desires,   breast   reconstruction   surgery,   a  
type  of  plastic  surgery,  may  then  be  performed  to  improve  the  aesthetic  appearance  of  the  
treated  site
...
  Nipple/areola   prostheses   can   be   used   at   any   time   following   the  
mastectomy
...
 


Why?    For:    
! local  control  of  cancer  
! prognostic  information  
! to  guide  additional    (adjuvant)  therapy
...
g
...
g
...
  The   most   common   donor   site   for   this   tissue   is   the   abdomen,   but   there   are  
several  other  choices
...
 
‘Gold-­‐standard’  for  breast  reconstruction  

 
 
DIEP  flap  


Latest  variation  in  TRAM  flap  reconstruction  



Relies  on  two  or  three  perforators  from  the  deep  inferior  epigastric  artery  



Leaves  muscle  and  fascia  intact  



No  problems  with  abdominal  wall  closure
...
 

 
 
Complications  of  breast  reconstruction  


 
 
 

Necrosis:  skin,  fat  (fat  necrosis)  
Flap  failure  



Implant  exposure  



Infection  



Scarring  



Capsular  contracture  



Lymphoedema  

 
BREAST  ONCOLOGY  


Commonest  cancer  in  women  



Increasing   incidence   =>   due   to   ageing   population   (in   contrast   to   cervical   SCC   which   is  
decreasing)  



2nd  commonest  cause  of  death  from  cancer  in  women  



Survival  improving:  5  year  survival  improved  from  56%  in  1970  to  81%  in  2003-­‐7    

 
Presentation    


Screening:   age   50-­‐70   (screened   every   3   years   via   mammography)   =>   small,   impalpable  
lump,  microcalcifactions  (if  ductal  carcinoma)  



Symptomatic:  most  often  lump  in  breast  
! 84%  operable  
! 8%  with  distant  metastases  =>  uncurable  
! 8%  locally  advanced/inoperable  

 
Treatment  


Surgery  



Radiotherapy  



Systemic  therapy  
! hormonal  therapy  
! cytotoxic  chemotherapy  
! immunotherapy  

 
 
 

 
 
Radiotherapy  


Postoperatively  to  breast/chest  wall  and  to  nodal  areas  (axilla,  supraclavicular  fossa,  internal  
mammary  nodes)  =>  used  to  kill  any  remaining  cancer  cells  



Primary  radical  for  locally  advanced    



Palliatively  to  painful  bony  mets,  skin  deposits,  brain  mets  etc
...
g
...
g  large  tumour,  extensive  nodal  involvement,  
involved  margins  etc
...
g
...
g
...
g
...
   



Deep  venous  thrombosis  (oestrogen  can  increase  thrombosis  risk)  

 
Chemotherapy  side  effects  



Infertility  



Alopecia  



Neutropenia  (sepsis):    NE  <  0
...
 



Drainage  of  pleural  or  peritoneal  effusions  



Optimise  quality  of  life  and  survival  



Endocrine   therapy   may   be   used   for   elderly   patietns   with   metastatic   disease   unsuitable   for  
chemo    
 

 
BREAST  PALLITIVE  CARE  


Palliative   care   is   an   area   of   healthcare   that   focuses   on   relieving   and   preventing   the   suffering  
of  patients  



Palliative  care  is  an  approach  that  improves  the  quality  of  life  of  patients  and  their  families  
facing  the  problem  associated  with  life-­‐threatening  illness,  through  the  prevention  and  relief  
of   suffering   by   means   of   early   identification   and   impeccable   assessment   and   treatment   of  
pain  and  other  problems,  physical,  psychosocial  and  spiritual  



Common  targets  for  palliative  care:  
! Back   pain   due   to   back   mets   =>   NSAIDs,   opioids,   radiotherapy   can   be   used   +/-­‐  
Dexa  (if  suspect  spinal  cord  compression  –  holding  measure)  
! Neurological  deficits  due  to  brain  mets  =>  radiotherapy  can  be  used  
! Respiratory   problems   due   to   pleural   effusion   =>   drainage   +/-­‐   pleurodesis   (if  
recurrent)  
! General  pain  =>  analgesia    
! Nausea  and  vomiting  =>  domperidone    

 
Back  mets  


 
 
 

Back   pain:   is   it   the   cancer?   Metastatic   back   pain   is   usually   constant   unremetting   pain
...
   Commonly  spine,  pelvis  or  proximal  long  bones
...
 
! Radio  isotope  bone  scan:  more  sensitive  but  does  not  show  structure  or  confirm  
it  is  cancer
...
5,   wedge   fracture   and   excessive   thoracic  
kyphosis  (kyphosis)  in  post  menopausal  women  
! Metastases:   bone   destruction   and   other   lesions   in   skeleton   –   often   osteolytic   but  
can  be  osteosclerotic  (e
...
 prostate  Ca)  
! Disc  herniation:  loss  of  disc  space  

 
IF   SUSPECT   CORD   COMPRESSION   OR   CES   =>   GIVE   DEXA   AS   HOLDING   MEASURE   BEFORE   SCAN
...
     
 
Treatment  of  bone  pain  



Chemotherapy    eg  breast  cancer  &  myeloma  



Analgesics:    WHO  cancer  pain  guidelines  


 
 
 

Radiotherapy:  effective  in  1-­‐2  weeks  

Bisphosphonates  e
...
C  via  syringe  driver)  



By  the  clock  (adminster  next  dose  BEFORE  pain  comes  back)  



By  the  ladder  (follow  the  WHOs  pain  ladder)  

 
By  the  clock  


Give  analgesic  before  the  pain  comes  back  =>  REGULAR  prescribing    



Paracetamol  

 

 

 

4  hours  (but  max  4  grams/day)  



Codeine  

   

 

 

4  hours  



Tramadol  

 

 

 

4hours  



Morphine    

 

 

 

4  hours:  can  also  give  SC  



MST  (sustained  release  morphine)                    12hrs  

 
By  the  ladder  


Stage   1   =   Simple   REGULAR   analgesic   e
...
  paracaetamol   or   NSAID   +/-­‐   adjuvant   (e
...
 
amitriptyline,  pregabalin,  or  gabapentin  for  neuropathic  pain)  



Stage  2  =    Mild  opioid  (e
...
 tramadol,  codeine  or  co-­‐codamol)  +  stage  1  



Stage   3   =     Strong   opioid   e
...
  morphine   or   MST   (ideally   long   acting   MST   twice   daily)   +/-­‐   stage  
1  

 
 
Specific  uses  of  analgesics  



 
 
 

Paracetamol:   don’t   forget   this   drug!     Very   effective   with   minimal   side   effects,   NSAID   and  
opiate  sparing
...
   



The  lymph  glands  especially  the  axillary  groups  but  also  the  internal  mammary  chain  clear  
tissue  fluid
...
  Breast   morphology   is   influenced   by   these   steroid   hormones   and  
changes  with  the  normal  menstrual  cycle
...
   



Both  benign  and  malignant  conditions  cause  breast  symptoms
...
 

 

 
Age  and  presentation  
The  benign  disorders  are  particularly  found  in  pre-­‐menopausal  women  whereas  some  80  per  cent  of  
breast  cancers  occur  in  patients  who  have  passed  the  menopause  
The  age  of  a  woman  suggests  the  likely  diagnosis  of  a  breast  lump:  


<30  years:  normal  lumpiness,  fibroadenoma,  rarely  cancer  



30-­‐45  years:  normal  lumpiness,  cyst  (often  fibrocystic  e
...
 fibroadenosis),  sometimes  cancer  



45-­‐60  years:  cyst,  cancer,  normal  lumpiness  



>60  years:  cancer  until  proven  otherwise  

 
Evaluation  
 
 
 

There  are  three  methods  of  assessing  benign  and  malignant  breast  disorders  which  together  make  
up  the  ‘triple  assessment’
...
   



The  majority  of  patients  presenting  with  breast  cancer  in  Britain  are  operable  -­‐  that  is  the  
staging  tests  do  not  reveal  evidence  of  metastases
...
g
...
 
 

Treatment  of  breast  cancer:  summary  
Treatment  is  thought  of  in  two  categories:  


Local  or  loco-­‐regional  treatment  (treatment  given  to  the  affected  breast,  chest  wall  
and   the   first   line   lymph   nodes   in   the   axilla   and   along   the   internal   mammary   node  
chain)   =>   Surgery   +/-­‐   radiotherapy   (i
...
  XRT   is   definitely   used   in   lumpectomy   or  
wide  local  based  excision,  but  not  necessarily  so  for  mastectomy)  



Systemic   or   ‘body-­‐wide’   treatment   which   seeks   to   eliminate   undetectable   micro-­‐
metastases=  >  chemotherapy  +/-­‐  endocrine  therapy  +/-­‐  immuotherapy  
 

Locoregional  treatment  

 
 
 

Conventionally   loco-­‐regional   treatment   is   by   surgery   or   radiotherapy   or   a   combination   of  
both
...
   



Since   local   removal   of   the   tumour   (lumpectomy)   with   lymph   nodes   enables   the   patient   to  
retain   her   breast   this   is   known   as   breast   conservation
...
 



After   a   mastectomy   the   decision   whether   or   not   to   prescribe   post-­‐operative   radiotherapy  
depends   on   factors   such   as   tumour   size,   histological   grade,   presence   of   lymphatic   and/or  
vascular  invasion  and  whether  nodes  are  involved  with  the  cancer
...
   



Endocrine   treatment,   the   ‘anti-­‐oestrogen’   tamoxifen   or,   in   pre-­‐menopausal   women,  
oophorectomy  can  be  very  effective  against  oestrogen  receptor  positive  cancers
...
 The  most  common  
are   abnormal   sensations   in   the   axilla   after   surgery   and   redness   and   swelling   of   the   breast  
after  radiotherapy
...
 



Endocrine   therapy   may   cause   symptoms   of   oestrogen   withdrawal   (hot   flushes   and   mood  
swings)  



Chemotherapy   side   effects   include   nausea,   GI   upset,   hairloss,   tiredness,   susceptibility   to  
infections
...
 
 Prognosis  depends  on  the  size,  grade,  type  of  the  cancer  and  number  of  node  metastases  at  
presentation,   the   treatments   given   and,   if   recurrence   of   the   cancer   occurs,   how   the  
recurrence  is  treated
...
 

 
BREAST  PAIN  (MASTALGIA)  


Common  symptom  



Rare  before  menarche  and  after  menopause  (as  often  hormonally  caused)  



Must  distinguish  between  true  mastalgia  versus  referred  pain  versus  MS  pain  (e
...
 pectoralis  
major  pain)  



Only  5%  of  breast  cancer  are  associated  with  mastalgia  



Types  of  mastalgia:  
! Cyclical:  when  the  pain  intensity  is  changing  during  the  menstrual  cycle
...
 This  type  is  less  frequent
...
  Noncyclical   pain   has  
frequently  its  root  cause  outside  the  breast
...
 



After  pregnancy,  breast  pain  can  be  caused  by  breastfeeding
...
g
...
 30%  invasive  cancers    

 

 

 

                                                                         

! Microcalcifications  could  indicate  ductal  carcinoma  in  situ  (DCIS)  


 
 
 

Mammography   just   “detects”   NOT   diagnoses   (diagnosis   requires   full   categorisation  
including  histology)  



Screening   =>   mammography   performed   on   asymptomatic   women   at   regular  intervals   (every  
3  years  between  ages  50  and  70)  with  the  aim  of  detecting  clinically  occult  breast  cancer  at  
an  early  stage  



Symptomatic   patients   =>   mammography   to   demonstrate   if   any   abnormality   and   nature   of  
abnormality  

 
Indications  for  Mammography  


Screening:  detects  most  impalpable  cancers  



all  women  with  a  palpable  mass  over  40y  



to  exclude/confirm  malignancy  &  assess  contralateral  side  

 
When  don’t  we  use  it  
Not  routinely  indicated  


women   <40   y   (screening   or   symptomatic)   =>   US   is   preferred   in   woman   under   40   (due   to  
higher  density  of  breast)  



women  over  40  if  they  have  had  a  mammogram  in  the  past  year  



Consider  it  in  women  under  40  shown  by  US  to  have  a  cancer  

 
Mammography  limitations  


Decreased  sensitivity  in  dense  breasts  



Limited   contrast   inherent   in   technique:   up   to   15%   cancers   are   mammographically   occult  
(hidden)  



Observer  limitations  



Compression  



Irradiation  

 
The  male  breast  


 
 
 

Same  principles  as  for  a  small  female  breast  
Only  if  suspicious  for  carcinoma  



Not  for  gynaecomastia  or  young  men!  

 
What  about  Ultrasound  (US)?  
Indications:  


Mammographic  abnormalities:  differentiation  of  cystic  and  solid  lesions  



Palpable  lesions,  women  <  40y  



Nipple  Discharge  



Breast  Implants  or  augmentation  



Other  e
...
 inflammatory  conditions  (abscesses)  



Evaluation  of  axillae  



Work  up  after  mammography    



Evaluation  of  response  to  chemotherapy  

 
What  about  MRI?  
MRI  advanatages:  


Excellent  intrinsic  tissue  contrast  



Multiplanar  tomographic  capacity  



No  compression  



No  ionising  radiation  



Accuracy  independent  of  breast  density  



However  MRI  is  expensive  and  time  consuming  =>  not  first  line  investigation    

 
MRI  contraindications:  




 
 
 
 

Absolute:   as   for   any   other   MRI   exam   (cardiac   pacemakers,   ferromagnetic   aneurysm   clips,  
cochlear  implants,  renal  impairment  etc
...
    It   is   the   only   population   based   screening   method   shown   to   reduce  
mortality  



In   younger   women   (<40   years)   and   for   evaluation   of   mammographic   abnormalities,   U/S   is  
the  technique  of  choice  



MRI  can  help  –  but  discuss  with  radiologist  first!  

 
 
MENSTRUAL  DISORDERS  
Control  of  Menstrual  Cycle:  Pituitary  and  Ovarian  Events  (Ovarian  cycle)  
Follicular  phase  (approx  day  1-­‐14):  


FSH  stimulates  ovarian  follicle  development  &  granulosa  cells  to  produce  oestrogens  



LH  stimulates  theca  cells  of  follicle  to  produce  testosterone  



Raising  oestrogen  &  inhibin  by  dominant  follicles  inhibit    FSH   production   and   LH   production  
(initially)  



Declining  FSH  levels  cause  follicular  atresia  (breakdown  of  follicles)  of  all  but  the  dominant  
follicle  



Rising  oestrogen  =>  endometrium  proliferation  =>  proliferative  phase  
 

Ovulation  (approx  day  14):  


Occurs  approximately  14  days  before  menstruation  e
...
 approximately  day  14  of  28  day  or  
day  21  of  a  35  day  cycle
...
     



Occurs   due   to   LH   surge   (oestrogen   levels   suddenly   reach   a   threshold   and   cause   +ve  
feedback  of  LH  release,  instead  of  the  usual  –ve  feedback  of  LH  release  =>  LH  surge  occurs)  



Dominant  follicle  matures,  ruptures  and  releases  oocyte  
 

Luteal  phase  (approx  day  14-­‐28):  

 
 
 

Formation  of  corpus  luteum  from  the  remnant  dominant  follicle    



Progesterone  is  produced  by  the  corpus  luteum  =>  causes  secretory  phase  of  endometrium  
(prepares  it  for  implantation)  



LH  maintains  the  corpus  lutem  



Luteolysis   (degeneration   of   corpus   luteum)   occurs   by   14   days   post-­‐ovulation   if   fertilisation  
does   not   occur
...
    Decreasing  
levels  of  LH  result  in  corpus  luteum  degeneration  =>  decreasing  levels  of  progesterone
...
  The   flow   of   menses   normally   serves   as   a   sign   that   a  
woman  has  not  become  pregnant
...
 

Fibrinolysis  inhibits  scar  tissue  formation  

 
Proliferative  phase  


Oestrogen-­‐induced   growth   of   endometrial   glands   and   stroma   =>   proliferation   of  
endometrium  



As   they   mature,   the   ovarian   follicles   (granulosa   cells)   secrete   increasing   amounts   of  
oestradiol   E2
...
   



The   oestrogen   also   stimulates   crypts   in   the   cervix   to   produce   fertile   cervical   mucus,   which  
may  be  noticed  by  women  practicing  fertility  awareness  (Billings  method)  



Oestrogen   E2   is   the   key   hormone   in   the   proliferative   phase   (this   is   why   tamoxifen,   an  
oestrogen  receptor  agonist  in  the  uterus,  can  cause  endometrial  hyperplasia  and  Ca)
...
 



Progesterone-­‐induces  glandular  secretory  activity  



Decidualisation   in   late   secretory   phase   =   essential   for   forming   the   deciduas   (maternal  
placenta)   if   fertilisation   occurs
...
 



Endometrial   apoptosis   and   subsequent   menstruation   if   fertilisation   does   not   occur   (due   to  
degradation  of  corpus  luteum  =>  decreasing  levels  of  progesterone)    
 

Normal  Menstruation  and  Menstrual  Cycle  
Menstual  loss  



 
 
 

Menstrual   loss   usually   lasting   4   to   6   days   (menstrual   loss   is   the   numerator   in   medical  
recording   of   menstrual   cycle   e
...
  4   days   of   menstrual   bleeding   with   a   28   day   cycle   =>   k=  
4/28)  
Menstual  flows  peaks  day  1-­‐2  



<   80   ml   per   menstruation   (e
...
  per   cycle)   –   however   it   is   normally   better   to   go   on   the  
females  opinion  of  wehther  or  not  her  bleeds  are  heavy  or  not
...
    The  
presence  of  clots  is  very  suggestive  of  menorrhagia
...
g
...
g
...
g
...
g
...
g
...
   Common  cause  of  menorrhagia  



Pelvic  inflammatory  disease  (PID):  infection  of  the  female  upper  genital  tract,  including  the  
uterus,   fallopian   tubes   and   ovaries
...
   Common  cause  of  metorrhagia  (IMB)
...
   Excess  columnar  epithelium  can  cause  increased  secretions
...
   Key  symptoms  are  dysmenorrhoea  and  dysparenuia
...
g
...
g
...
g
...
g
...
      Irregular   cycle   (>35  
days   apart   =>   oligomenorrhoea)   with   heavy   menses   =>   oligomenorrhagia
...
    High   oestrogen   to   progesterone   ratio  
causes  overgrowth  of  endometrium  (as  oestrogen  causes  proliferation)
...
       



During  an  anovulatory  cycle,  the  corpus  luteum  fails  to  form,  which  causes   failure  of  normal  
cyclical  progesterone  secretion  



This  results  in  continuous  unopposed  production  of  esotradiol  (E2),  stimulating  overgrowth  
of   the   endometrium
...
   



 The  end  result  is  overproduction  of  uterine  blood  flow  =>  menorrhagia  



The  period  is  delayed    in  such  cases,  and  when  it  occurs  menstruation  can  be  very  heavy  and  
prolonged  (oligomenorrhagia)  



Irregular  cycle  (>35  days  apart)  with  heavy  menses  =>  oligomenorrhagia  



Risk  factors  =  PCOS,  obesity,  perimenopause,  adolescence  

 
Ovulatory  DUB  


10%  of  cases  occur  in  women  who  are  ovulating  



In   ovulatory   DUB,   prolonged   progesterone   secretion   causes   irregular   shedding   of   the  
endometrium  



Ovulatory  DUB  (not  associated  with  anovulation)  is  less  common  than  anovulatory  DUB,  and  
the  bleeding,  though  abnormally  heavy,  is  usually  regular  (menorrhagia)  
 

Investigations  


Full  blood  count:  assess  for  anaemia  (particularly  iron  deficiency  anaemia  IDA)  



Endocrine   screen:   Thyroid   function   tests   (TSH,   fT3,   fT4),   LH/FSH,   oestrogen,   progesterone,  
androgens,  prolactin  



Cervical  smear:  to  assess  for  CIN  (cervical  intraepithelial  neoplasia)  or  cervical  cancer  



HVS  (high  vaginal  swab)  to  assess  for  PID  e
...
 CT/GC  combined  PCR  



Coagulation  screen:  PT,  APTT,  VWF,  assessment  for  other  coagulopathies  



Renal/Liver  function  tests  



Transvaginal  ultrasound  scan:    
! Endometrial  thickness  

 
 
 

! Presence  of  fibroids  and  other  pelvic  masses  –  US  is  gold  standard  for  Dx  fibroids  


Endometrial  sampling  (must  rule  out  endometrial  cancer  and  other  pathology):  
! Pipelle  biopsies  
! Hysteroscopic  directed  
! Dilatation  &  curettage  (D  &  C)  

 
DUB  IS  A  DX  BY  EXCLUSION  
 
Management  of  DUB  (dysfunctional  uterine  bleeding)  
Medical  management  


Progestogens   (drug   of   choice):   controls   the   menstrual   cycle   and   prevents   excessive  
shedding  of  endometrium    



Progestogen-­‐releasing   IUCD:   Mirena   IUS   =>   FIRST   LINE   Tx   for   woman   who   want  
contraception  



Combined   oral   contraceptive   pill   (COCP):   particulary   usefull   if   there   is   dysmenorrhoea   as  
well  (and  pt  wants  contraception)  



If  pt  does  not  want  contraception  =>    
! Transenamic  acid  for  menorrhagia  
! Mefenamic  acid  for  menorrhagia  and  dysmenorrhoea  



Treatments  differ  depending  on  the  patients  and  when  in  the  cycle  bleeding  occurs  

 
Surgical  management  


Endometrial   resection/ablation:   to   destroy   or   remove   the   lining   of   the   uterus   (via  
hysteroscopy)  



Hysterectomy:  removal  of  uterus  

 
Comparison  between  Medical  &  Surgery  Treatments  of  DUB  


 
 
 

Medical  treatments  are  clearly  better:  cheaper,  less  risks/complications,  and  fertility  can  be  
retained  

 
 
Comparison  between  Hysteroscopic  Surgery  (endometrial  ablation)  and  Hysterectomy  


Endometrial  ablation  is  often  the  preferred  method  

 
 
 
Reproductive  microbiology  
Syphilis  laboratory  confirmation  

 
 
 

Causal  organism  is  Treponema  pallidum  (spirochaete  bacterium  which  is  spiral  in  shape)  



Recent  outbreaks  in  UK  cities,  primarily  amongst  men  who  have  sex  with  men  (MSM)  



Diagnosis   is   usually   made   by   serological   tests   e
...
  by   detecting   ABs   in   the   patients   serum
...
 



There  are  two  early  clinical  stages  (primary  and  secondary),  a  latent  stage  (which  can  persist  
for   a   long   time)   and   one   late   clinical   stage   (tertiary   syphilis)
...
 



Primary  stage:  isolated  painless  ulcer  (chancre)
...
     



Secondary   stage:   “copper   penny”   generalised   rash,   Condylomata   latum   (wart   like   genital  
lesions),  painless  lymphadenopathy,  fever  and  weight  loss  



Latent  stage:  often  asymptomatic  ,  can  persist  for  years  and  years,  can  affect  near  enough  
any  organ    



Tertiary   stage:   cardiovascular   syphilis   (e
...
  arotitis,   aortic   dissection),   neurosyphilis   (e
...
 
Argyl-­‐Robertson   pupil,   Charcot   joint,   tabes   dorsalis   of   the   dorsal   columns,   dementia   and  
other  neuropsychiatric  disorders)    

 
Non-­‐specific  serological  tests  


Two  types  of  test  
! VDRL  (Venereal  Diseases  Research  Laboratory)  
! RPR  (Rapid  Plasma  Reagin)  



Non-­‐specific  tests  that  indicate  tissue  inflammation  



May  be  falsely  positive  (e
...
 SLE,  malaria,  pregnancy)  



Useful  for  monitoring  response  to  therapy  



Usually  become  negative  after  successful  treatment  

 
Specific  serological  tests  



TPHA  (T
...
 pallidum  particle  agglutination  assay):  a  test  for  specific  IgG  ABs  

Specific  for  syphilis,  but  remain  positive  for  life  (IgG  stays  positive  for  life  =>  natural  immune  
response  to  generate  immunity)  



Not  useful  for  monitoring  response  to  therapy  (as  TPPA  IgG  remains  positive  for  life)  

 
Other  specific  serological  tests  
IgM  &  IgG  ELISA  (screening  test)  


Combined  IgG  &  IgM  ELISA  used  as  the  “screening”  test  for  syphilis  (on  Tayside  microbiology  
reports  this  is  stated  as  “Total  AB”  e
...
 IgG  +  IgM)  



If  this  is  positive,  further  tests  are  carried  out,  namely:  
! IgM  ELISA  (marker  of  recent,  untreated  acute  infection)  
! TPPA  test  for  specific  IgG  (positive  for  life  in  anyone  who  has  or  has  had  syphilis)  
! VDRL  (marker  of  untreated  active  infection)  

 
Current  practice  in  Tayside  


Combined  IgG  &  IgM  ELISA  screening  test  =>    negative  =>  result  goes  out  as  negative  



Combined  IgG  &  IgM  ELISA  screening  test  =>  positive  =>  do  further  tests:  
! IgM  ELISA  (to  assess  for  recent  acute  infection)  
! TPPA  to  assess  for  IgG  (+ve  lifelong  if  infected)    
! VDRL:   to   assess   for   active   infection   (but   note   that   late   untreated   syphilis  
infection  and  latent  infection  may  have  –ve  VDRL)  

 
Typical  results  in  various  situations  
 

 
 
 

 
 
More  examples  
1
...
   Uninfected  (but  false  +ve  screen)  =>  positive  screen  =>  -­‐ve  IgM,  -­‐ve  TPPA  (IgG),  and  –ve  VDRL  
3
...
   Secondary  syphilis  =>  positive  screen  =>  positive  IgM  (as  still  acute)  =>  double  positive  TPPA  (as  
more  IgG  produced  at  this  stage)  =>  double  positive  VDRL  (as  more  active  infection  =>  more  tissue  
damage)  
5
...
   Recently  treated  =>  positive  screening  test  (IgG  will  remain  for  life)  =>  negative  IgM  =>  +ve  TPPA  
=>  positive  or  negative  VDRL  
 
Important  notes  


 
 
 

IgG  and  TPPA  tests  remain  positive  for  life,  even  after  successful  treatment
...
M  penicillin)  



Quite  complicated  and  does  not  always  behave  according  to  the  rules  above  =>  refer  these  
patients   for   Mx   with   sexual   health   clinic   (they   should   also   receieve   full   sexual   health  
screen)  



It  can  be  difficult  serologically  to  differentiate  properly  treated  syphilis  from  untreated  late  
syphilis  which  is  why  careful  treatment  and  follow  up  of  early  syphilis  is  essential
...
     

 
MICROBIOLOGY  PRACTICAL  
Case  1  
A  28  year  old  man  attends  the  Sexual  Health  clinic  complaining  of  pain  when  he  passes  urine  and  a  
urethral  discharge  (think  either  UTI  or  STD)
...
  You   take   a   urethral   swab   for   microscopy   (done   at   the  
clinic)  and  bacterial  culture  and  a  “first  pass”  urine  for  combined  chlamydia  and  gonococcal  CT  GC  
PCR
...
 You  are  also  provided  with  the  first  pass  urine  PCR  
result
...
    Remember   that   CT   does   not   gram  
stain
...
   
Remember  that  CT  is  much  more  common  than  GC
...
 What  will  
be  discussed  during  that  consultation?  


Contact  tracing  



Safe  sex    



Free    condoms  

 
(f)  The  patient  is  given  an  appointment  to  return  to  the  Sexual  Health  clinic  12  weeks  after  the  date  
of  his  visit  to  Amsterdam
...
    She   had   unprotected   sex   2   weeks   earlier   (don’t   just  
assume   that   it   is   an   STD   because   of   this)   at   a   party   with   a   new   partner,   but   she   is   taking   oral  
contraceptives
...
    On   examination,   the   vulva   is   very   red   and   inflamed   and   there   is   a   thick   white  
discharge
...
 
(a)  

What  is  the  diagnosis?  


Dx=  Vaginal  thrush  (candidiasis):  often  presents  with  itchy  beefy  red  vagina  and  white  curdy  
discharge
...
     
 

(b)  

What  is  the  causal  organism?  


Candidia  sp
...
g
...
  A   high   vaginal   swab   (as   symptomatic   and   we  
suspect  BV/TV)  is  taken  and  submitted  to  the  laboratory
...
 
 (a)  Describe  what  you  see
...
g
...
   He  is  an  asymptomatic  carrier
...
     

 
Case  4  
A  28  year  old  woman  visits  her  GP  complaining  of  the  condition  illustrated  in  this  photograph
...
 The  lesions  start  as  small  blisters,  
i
...
 vesicles  and  then  become  pustular
...
 The  attacks  last  about  two  weeks  and  then  resolve
...
  An   illustration   of   the   condition   is   provided;   and   there  
is  a  photomicrograph  of  the  causal  organism  provided
...
   HSV  is  a  lifelong  infection  
(STD)   and   can   cause   asymptomatic   shedding   of   the   virus   =>   risk   of   sexual   partners   being  
contaminated
...
 


Aciclovir  
! Can  be  used  acutely  (not  particularly  effective  unless  given  at  very  early  stage)  
! Can  also  be  used  prophylactically  to  prevent  outbreaks  (if  occurring  frequently)  

 
Topical  LA  can  also  be  used  for  analgesia
...
 The  lesions  are  
not  particularly  painful  or  tender  unless  he  wears  tight  underpants  and  the  skin  becomes  chafed
...
 An  illustration  of  
the  condition  is  provided
...
   HPV  viral  warts  is  a  clinical  Dx
...
 

 
(d)  Is  the  girl  just  fussy  or  does  she  have  reason  to  worry  about  herself?  


Yes
...
g
...
)  



One  against  oncogenic  strains  +  strains  which  cause  viral  warts  

 
Case  6  
A   30   year   old   man   attends   your   surgery   with   an   ulcerated   lesion   on   his   penis   (picture   provided)
...
  You   can   feels   enlarged   lymph   nodes   in   both   groins
...
 You  refer  the  patient  urgently  to  the  Sexual  Health  clinic
...
   Can  
present   very   similar   to   syphillis   initially   –   use   the   painful   lymphadenopathy   as   a  
distunguisihing  factor!  

 

 

(b)  What  is  the  most  likely  diagnosis  in  this  patient?  

 

Dx=  primary  syphilis  
 

(c)   What   specimen(s)   would   you   send   to   the   microbiology   laboratory   in   order   to   confirm   the  
diagnosis?  


Clotted  blood  sample  for  syphilis  serology  (combined  IgG+IgM  ELISA  screening  test)  



Would  also  be  wise  to  perform  a  full  sexual  health  screen  e
...
 HIV/HepB/HepC  serology  and  
combined  GC/CT  PCR  test  on  first  pass  urine  

 
(d)  Examine  the  first  laboratory  report
...
  Has   this  
patient  been  adequately  treated?  


IgM  =  -­‐ve  



VDRL  =  -­‐ve  



Therefore  treatment  has  been  successful  



Follow  up  at  12  months  (if  HIV  +ve  requires  life  long  follow  up  every  12  months)  

 
(g)  Would  you  suggest  that  this  patient  has  tests  for  any  other  infections,  and  if  so,  which  infections?  


STD  screen:  
! CT/GC  combined  PCR  on  first  pass  urine  
! HIV,  Hep  B  and  syphilis  serology  +/-­‐  Hep  C  

 
 
Reproductive  lecture  notes:  week  3  
DOWNS  SYNDROME  


Three  types:    
! trisomy  21  (non  disjunction)  –  most  common  (95%)  
! partial   trisomy   21   (unbalanced   translocation)   –   4%   (in   prental   Dx,   assess   with  
karyotype  of  parent  has  known  translocation)  
! mosaic  trisomy  21  (some  cells  are  normal,  other  cells  have  trisomy  21)  –  1%  





Affects  1  in  1000  babies  



Congenital  (e
...
 born  with  it)  



 
 
 

Down   syndrome   is   most   commonly   caused   by   trisomy   21   (47,   XX   +21   for   females;   47,   XY,  
+21  for  males)
...
   



Since   the   introduction   of   screening,   pregnancies   with   the   diagnosis   are   often   terminated  
(TOP)
...
 

 
Aetiology  


There  are  three  types  of  Downs  syndrome:  
! Nondisjunction   (trisomy   21):   nondisjunction   occurs   due   to   an   error   in   cell  
division   called   nondisjunction
...
    Prior   to   or   at  
conception,   a   pair   of   21st   chromosomes   in   either   the   sperm   or   the   egg   fails   to  
separate
...
   This  type  of  Down  syndrome,  which  accounts  for  95%  of  cases,  
is  called  trisomy  21
...
    In   translocation,  part   of   chromosome   21   is   duplicated  
(partial   trisomy)   and   breaks   off   during   cell   division   and   attaches   to   another  
chromosome,   typically   chromosome   14
...
   
! Mosaicism:     mosaicism   occurs   when   nondisjunction   of   chromosome   21   takes  
place   in   some,   but   not   all,   of   the   initial   cell   divisions   after   fertilization
...
    Those   cells   with   47   chromosomes  
contain  an  extra  chromosome  21  (trisomy  21)
...
     





 
 
 

Regardless   of   the   type   of   Down   syndrome   a   person   may   have,   all   people   with   Down  
syndrome  have  an  extra,  critical  portion  of  chromosome  21  present  in  all  or  some  of  their  
cells
...
     
The   additional   partial   or   full   copy   of   the   21st   chromosome   which   causes   Down   syndrome  
can   originate   from   either   the   father   or   the   mother
...
 



The   cause   of   nondisjunction   (trisomy   21)   is   currently   unknown,   but   research   has   shown  
that   it   increases   in   frequency   as   a   woman   ages
...
   A  35  year  old  woman  has  about  a  one  in  350  chance  of  conceiving  a  child  with  Down  
syndrome,  and  this  chance  increases  gradually  to  1  in  100  by  age  40
...
   



All  3  types  of  Down  syndrome  are  genetic  conditions  (relating  to  the  genes),  but  only  1%  of  
all   cases   of   Down   syndrome   have   a   hereditary   component   (passed   from   parent   to   child  
through  the  genes)
...
   
However,  in  one  third  of  cases  of  Down  syndrome  resulting  from  translocation  there  is  a  
hereditary   component   -­‐   accounting   for   about   1%   of   all   cases   of   Down   syndrome
...
g
...
   

 
Clinical  features  


What  Does  the  Extra  Chromosomal  material  do?  



Causes   an   excess   amount   of   protein   to   be   present   in   each   cell   =>   disturbs   the   growth   and  
development  of  the  foetus    



Causes  common  characteristics:  
! Eyes:  slanted  eyes  
! Ears:  small,  low  set  ears  
! Face  and  head  shape:  flat  head  
! Height  and  weight:  stunted  growth  e
...
 short  stature  and  low  weight  



Learning  disabilities:  mild  (IQ  50-­‐70)  to  moderate  (IQ  35-­‐50)  learning  disability    



Some  common  health  issues:  
! Congenital  heart  disease  e
...
 VSD  
! Hypothyroidism  
! Poor  fertility  



 
 
 
 
 

Global   developmental   delay:   gross   motor,   fine   motor,   communication   and   social,  
cognitive,  language  

Diagnosis    
Prenatally  (antentally)  


Prenatal  screening  now  routinely  offered  to  women  of  all  ages
...
   If  known  
Robertosnian  translocation  in  F  =>  full  karyotype
...
   
! Prenatal  screens  estimate  the  chance  of  the  fetus  having  Down  syndrome
...
   
! Diagnostic   tests   can   provide   a   definitive   diagnosis   with   almost   100%   accuracy
...
 



The   early   (approx   11-­‐14   weeks)   PAPP   and   bHCG   test,   combined   with   NT   can   give   an  
estimate   of   risk
...
 



The  triple  blood  tests  (or  serum  screening  tests)  measure  quantities  of  various  substances  in  
the  blood  of  the  mother  (hCG,  AFP  and  oestriol  E3)
...
    Together   with   a   woman's  
age,   these   are   used   to   estimate   her   chance   of   having   a   child   with   Down   syndrome
...
g
...
   



The  diagnostic  procedures  available  for  prenatal  diagnosis  of  Down  syndrome  are  chorionic  
villus   sampling   (CVS)   before   15   weeks   and   amniocentesis   after   15   weeks
...
   



Amniocentesis  is  usually  performed  in  the  second  trimester  after  15  weeks  of  gestation;  CVS  
is  performed  in  the  first  trimester  between  9  and  11  weeks
...
     



Because  these  features  may  be  present  in  babies  without  Down  syndrome,  a  chromosomal  
analysis  called  a  karyotype  is  done  to  confirm  the  diagnosis
...
 They  use  
special   tools   to   photograph   the   chromosomes   and   then   group   them   by   size,   number,   and  
shape
...
 



Another  genetic  test  called  FISH  or  QF-­‐PCR  (QF-­‐PCR  often  preferred  over  FISH)  can  apply  
similar  principles  and  confirm  a  diagnosis  in  a  shorter  amount  of  time  =>  used  for  RAPID  
antenatal  diagnosis  

 
 
 
Facts  



People  with  Down’s  syndrome  have  different  skills  and  abilities  just  like  everyone  else
...
   Reading  can  be  one  of  their  strengths
...
 It  is  the  lack  of  work  opportunities  that  is  the  
problem
...
 

People   with   Down’s   syndrome   who   are   adults   should   be   treated   as   such
...
 



Can  have  a  normal  life!  

 
PHYSIOLOGY  OF  PREGNANCY  AND  LACTATION  
Fertilisation  and  implantation  


Egg  released  by  ovaries  =>  captured  by  fimbriae  of  fallopian  tubes  



Fertilised  by  sperm  in  the  ampulla  of  the  fallopian  tubes  



Conceptus   travels   down   the   fallopian   tube   and   the   cells   progressively   divides   and  
differentiates  in  the  process  called  cleavage  =>  results  in  formation  of  morula  (day  4)  



The  morula  becomes  a  blastocyst  as  it  enters  the  uterus  (day  5)  



Implantation   of   the   blastocyst   (trophoblastic   cells   invade   the   endometrium)   in   the  
endometrium  of  the  uterus  occurs  shortly  after  (day  6-­‐9)  



Inner  cell  mass  (embryoblast)  becomes  the  embryo  



Outer  trophoblastic  cells  differentiate  and  become  the  foetal  part  of  the  placenta  

 

 
 
 
 
 

 
 
Timeline  (development  time,  NOT  gestation)  


Day  1:  Fertilization  occurs  in  the  ampulla  of  the  Fallopian  Tube
...
   The  
trophoblast   of   the   blastocyst   invades   the   endometrium   to   accomplish   implantation
...
     



NB:   remember   that   gestation   begins   on   the   first   day   of   the   LMP
...
 

 
Implantation  of  the  Blastocyst  


Blastocyst:    
! Inner  cells  develop  into  embryo
...
   



Advancing  cords  of  trophoblastic  cells  tunnel  deeper  into  endometrium,  carving  out  a  hole  
for   the   blastocyst
...
 



When  implantation  is  finished  the  blastocyst  is  completely  buried  in  the  endometrium    



Blastocyst  becomes  fully  buried  in  uterine  lining  by  day  12  

 
 

 
Placenta  
Placenta  development  




Decidua  =  the  mucous  membrane  of  the  body  of  the  uterus  (outer  layer  of  endometrium)  



 
 
 

Placenta  is  derived  from  both  trophoblast  (derived  from  conceptus)    &  decidual  tissue  from  
endometrium   (mucus   membrane   of   uterus/endometrium   which   is   perfectly   designed   for  
nourishing  the  foetus)  

Decidual  cells  produce  the  nutrients  that  keep  the  foetus  going
...
     



Trophoblast  cells  differentiate  into  multinucleate  cells   (syncytiotrophoblasts)  which  invade  
decidua  and  break  down  capillaries  to  form  cavities  filled  with  maternal  blood  



Early   nutrition   of   the   embryo   =>   occurs   due   to   invasion   of   synctiotrophoblastic   cells   into  
the  decidua  



Developing   embryo   sends   capillaries   into   the   syncytiotrophoblast   projections   to   form  
“placental  chorionic  villi”  



Each  villi  contains  foetal  capillaries  separated  from  maternal  blood  by  a  thin  layer  of  tissue  
=>    no  direct  contact  between  foetal  &  maternal  blood  (AV  shunt)  



This   results   in   two   way   exchange   of   respiratory   gases,   nutrients,   metabolites   etc   between  
mother  and  foetus,  largely  down  diffusion  gradients  



The   placenta   (and   foetal   heart)   is   functional   by   5th   week   of   pregnancy   (gestation   =   5  
weeks)  e
...
 after  only  3  weeks  of  development!    Remember  that  gastrulation  also  occurs  in  
the  third  week  of  development  (e
...
 Progesterone  stimulates  
decidual   cells   to   concentrate   glycogen,   proteins   and   lipids   =>   energy   substrates  
for  placenta  and  foetus
...
     
! Progesterone   is   essential   for   maintaining   the   placenta   and   foetal   development
...
     

 

 
 
Chorion  (chorionic  membrane)  
 
 
 



The  chorion  is  one  of  the  membranes  that  exist  during  pregnancy  between  the  developing  
fetus   and   mother
...
g
...
 



The  chorion  consists  of  two  layers:  an  outer  formed  by  the  trophoblast,  and  an  inner  formed  
by  the  somatic  mesoderm  



The   trophoblast   is   made   up   of   an   internal   layer   (cytotrophoblast)   and   an   external   layer   of  
(syncytiotrophoblast:  this  is  what  invades  the  endometrium)  



The  amnion  is  in  contact  with  the  mesoderm  



The  amnion  and  chorion  become  adjacent  as  the  foetus  is  formed  and  expands  

 
 
Placenta  works  as  a  physiological  arteriovenous  shunt    


 
 
 

As   the   placenta   develops,   it   produces   and   extends   hairlike   projections   (villi)   which   burrow  
into  the  uterine  wall
...
   Developing  embryo  sends  capillaries  into  
the  syncytiotrophoblast  projections  to  form  “placental  villi”  



This  increases  the  contact  area  between  the  uterus  and  placenta  =>  allows  more  nutrients  
(from  the  mother)  and  waste  materials  (from  foetus)  to  be  exchanged  



Blood   vessels   from   embryo   develop   in   the   villi
...
 



Circulation  within  the  intervillous  space  acts  partly  as  an  arteriovenous  shunt
...
    Veins   usually   carry   deoxygenated   blood   (except   adult  
pulmonary  veins),  but  the  single  umbilical  vein  carries  oxygenated  and  nutrient-­‐
rich  blood  from  the  placenta  and  delivers  it  to  the  right  fetal  heart  (via  the  ductus  
venosus  and  IVC),  which  pumps  it  around  the  body  of  the  fetus
...
    Arteries   usually   carry   oxygenated   blood   (except   adult   pulmonary  
artery),  but  the  two  umbilical  arteries  collect  deoxygenated  blood  from  the  body  
of   the   fetus   and   carry   it   to   the   placenta
...
   Umbilical  arteries  arise  from  internal  
iliac  arteries
...
 



The   exchange   takes   place   between   maternal   oxygen-­‐rich   blood   (received   from   maternal  
arteries   e
...
  uterine   arteries)   and   the   umbilical   blood   (umbilical   vein)   =>   AV   shunt   (occurs   in  
intervillous  space)  



Oxygen  diffuses  from  the  maternal  vessels  (uterine  arteries)  into  the  fetal  circulation  system  
(umbilical  vein)  as  PO2  maternal  uterine  artery  >  PO2  fetal  umbilical  vein  



Carbon   dioxide   follows   a   reversed   gradient   from   umbilical   arteries   to   maternal   circulation  
(uterine  veins)  (as  PCO2  foetal  umbilical  arteries  >  PCO2  maternal  uterine  veins)      



Fetal,  oxygen  saturated  blood,  returns  to  the  fetus  via  the  umbilical  vein
...
     



But  how  then  is  sufficient  oxygenation  of  the  fetus  possible?    The  supply  of  the  fetus  with  
oxygen  is  facilitated  by  three  factors:  
! Fetal  HbF  (alpha  2,  gamma  2)  =>  increases  ability  to  carry  O2  (HbF  has  a  greater  
affinity  for  O2  and  a  greater  capacity  for  O2  compared  to  HbA)  e
...
  shift  to  the  
left  of  Hb  dissociation  curve
...
       
! Higher  Hb  concentration  in  fetal  blood    (50%  more  than  in  adults)  
! The  Bohr  effect  (shift  to  right  of  Hb  dissociation  curve)  allows  rapid  release  of  O2  
in   response   to   hypoxia,   hypercapnia,   and   acidosis
...
    Therefore   the   foetus   is   very  
good   at   compensating   during   hypoxia   (due   to   greater   capacity   for   carrying   O2  
and  greater  capacity  to  release  O2  via  the  Bohr  effect)
...
g
...
g
...
  Exchange   increases   during  
pregnancy  up  to  the  35th  week  (3
...
 



Electrolytes  follow  water  (iron  and  calcium  only  go  from  mother  to  child)
...
  Allowing   her   antibodies   to   pass   across   the  
placenta  and  into  the  fetus  is  important  in  providing  protection  for  the  fetus,  and  later  the  
newborn  baby,  against  the  same  infectious  agents
...
   

However,  the  placenta  cannot  prevent  the  transfer  of  alcohol,  other  drugs  and  viruses  to  
the  fetus
...
 



Teratogens   are   substances   or   environmental   agents   which   cause   the   development   of  
abnormal   cell   masses   during   fetal   growth,   resulting   in   physical   defects   in   the   fetus  
(teratogenesis)  



Teratogens  can  cross  the  placental  barrier  and  can  cause  damage  to  the  developing  foetus  



Most  sensitive  time  is  the  first  trimester    



Drugs  (excluding  alcohol)  =>    3%  of  all  congenital    malformations  



Causes  of  teratogenesis  can  broadly  be  classified  as:  
! Teratogens:   toxic   substances   such   as   drugs   and   environmental   toxins   in  
pregnancy
...
 For  example,  lack  of  folic  acid  in  the  nutrition  in  pregnancy  for  
humans  can  result  in  spina  bifida
...
 



Produced  from  approximately  week  5  of  pregnancy  



Effects  on  mother:  
! Its  structure  and  function  is  similar  to  that  of  human  growth  hormone
...
 
! hCS/hPL  has  anti-­‐insulin  properties  =>  decreases  insulin  sensitivity  in  mother  (e
...
g
...
   
Maternal   HT   and   oedema   can   occur
...
g
...
   
The  increase  is  mainly  caused  due  to  an  increase  in  plasma  volume  (50%)  through  increased  
aldosterone
...
   



Flow  murmurs  are  common  due  to  increased  CO  
 

 
Heart  rate  


Heart  rate  (HR)  increases  up  to  90/min  to  maintain  CO  and  manage  to  pump  all  the  excess  
fluid  

 
 
Blood  pressure  


Blood   pressure   (BP)   drops   during   2nd   trimester:   uteroplacental   circulation   expands  
(resistance  decreases)  &  peripheral  resistance  decreases  



With  twins  BP  drops  more  



Rises  back  up  to  pre-­‐prenancy  BP  in  third  trimester    

 
Haematological  changes  




Erythropoesis  (RBC)  increases  (25%)  =>  red  cell  volume  increase  is  less  than  plasma  volume  
increase  



Thus   Hb   (and   HCT)   is   decreased   by   dilution   (approximately   25%)   =>   this   decreases   blood  
viscosity   and   can   cause   dilutional   anaemia   (as   plasma   volume   increase   >   erythropoiesis  
increase)  



 
 
 

Plasma   volume   increases   (aldosterone   effects)   proportionally   with   cardiac   output   (50%):  
The   plasma   volume   increases   to   provide   for   the   greater   circulatory   needs   of   the   maternal  
organs  and  the  uteroplacental  circulation  

A   pregnant   woman   will   also   become   hypercoagulable   (physiological   change   to   prevent  
haemorrhage   particularly   PPH)   due   to   increased   liver   production   of   coagulation   factors,  
mainly   fibrinogen   and   factor   VIII
...
    This  
hypercoagulable   state   along   with   the   decreased   ambulation   (exercise   involving   legs)  
causes  an  increased  risk  of  both  DVT  and  PE  


Iron   requirements   increases   significantly   (partly   due   to   increased   erythropoisesis)   =>   most  
women  require  iron  supplements    (amount  from  diet  and  iron  stores  is  usually  insufficient)  

 

 
 
 
Respiratory  changes  




Progesterone   has   a   very   interesting   direct   action   on   the   mother's   respiratory   center  
(medulla  oblongata  of  brain  stem)
...
  As   a   result,   the   removal   of   carbon   dioxide   from   the   fetus's  
bloodstream  is  facilitated!    



Progesterone   signals   the   brain   to   lower   CO2   levels   by   increasing   CO2   sensitivity   in  
respiratory  centres  



Progesterone   is   responsible   for   a   decreased   amount   of   carbon   dioxide   in   the   blood   of  
pregnant  women
...
 This  accounts  for  the  feeling  of  shortness  of  
breath,   dyspnea,   or   heightened   awareness   of   the   need   to   breathe   reported   by   many  
pregnant  women
...
   The  growing  uterus  can  therefore  decreases  pO2  slightly  =>  SOB  



In   summary:   The   high   level   of   progesterone   a   hormone   produced   continuously   during  
pregnancy,  causes  the  brain  to  increase  ts  sensitivity  to  CO2  levels  which  results  in  lowering  
of   the   levels   of   carbon   dioxide   in   the   blood
...
 She  may  breathe  deeper  and  faster  also  because  the  enlarging  uterus  limits  how  much  
the   lungs   can   expand   when   she   breathes   in
...
   Virtually  every  pregnant  woman  becomes  somewhat  more  out  of  breath  
when   she   exerts   herself,   especially   toward   the   end   of   pregnancy   (when   uterus   exerts  
pressure  on  diaphragm)
...
 
 

Urinary  system  


During   pregnancy,   maternal   plasma   volume   increases   (due   to   aldosterone   increase)   to   meet  
the   greater   circulatory   needs   of   the   placenta   and   maternal   organs   (e
...
  uterus,   breasts,   skin,  
uteroplacental  circulation)  



Like   the   heart,   the   kidneys   work   harder   throughout   pregnancy
...
 



Glomerulate  filtration  rate  (GFR)  and  renal  plasma  flow  (RPF)  increases    



Increased  re-­‐absorption  of  ions  and  water  due  to:  
! placental  steroids  
! maternal  steroids  and  aldosterone  (aldosterone  is  the  major  stimulus  at  increasing  
the  maternal  plasma  volume)  




The   uterus   presses   on   the   bladder,   reducing   its   size   so   that   it   fills   with   urine   more   quickly  
than   usual
...
g
...
g
...
  It   is   unlikely   you   will   notice   these   signs,   but  
they  should  be  picked  up  during  your  routine  antenatal  appointments
...
g
...
 



Kidney  function  declines  in  pre-­‐eclampsia  
! Renal  blood  flow  and  Glomerular  filtration  rate  decreases
...
g
...
   



Single  most  significant  risk  is  having  had  pre-­‐eclampsia  previously
...
  Severe   cases   should  
be  seen  in  hospital  



What  causes  pre-­‐eclampsia?    
! The  cause  of  pre-­‐eclampsia  is  not  fully  understood
...
 This  is  the  attachment  between  
the   foetus   and   the   uterus
...
   
! Vasoacitve   moleculres   realises   form   placenta   cause   maternal   vasoconstriction  
leading  to  ischaemia  of  organ    
! This   may   also   affect   the   transfer   of   oxygen   and   nutrients   to   the   foetus   =>   can  
cause  IUGR  (assess  with  umbilical  artery  Doppler)  
! Pre-­‐eclampsia   can   also   affect   various   other   parts   of   the   maternal   body
...
    Assess   with  
umbilical  artery  Doppler  scan
...
   Ocurs  due  to  placenta  inflammation
...
   However  may  present  with  pain  and  tense  uterus  without  bleeding
...
g
...
2kg  
! Extra-­‐embryonic  fluid/tissues:  1
...
7kg  
! Fat  accumulation:  1
...
5mg/kg/min  
! Appreciate  that  the  foetus  requires  more  glucose  than  the  mother  in  the  third  
trimester!     Hence   why   human   chorionic   somatomammotropin   (hCS)   /   human  
placental  lactogen  causes  maternal  insulin  resistance  in  last  trimester
...
 last  trimester)  =>  foetal  anabolic  phase  /  maternal  catabolic  phase  (accelerated  
starvation)  


high  metabolic  demands  of  the  fetus  (requires  more  glucose  than  mother)  



accelerated  starvation  of  the  mother  



Maternal  insulin  resistance  =>  more  glucose  available  for  foetus  
! Insulin   resistance   caused   by   HCS   human   chorionic   somatomammotropin   (GH  
like  e
...
 anti-­‐insulinic),  cortisol  and  growth  hormone  

 
 
 



Increased  transport  of  nutrients  through  placental  membrane  



Lipolysis  =>  increase  FAs  for  foetus  

 
 
Special  nutritional  need  in  pregnancy  


Higher  energy  uptake  (eating  for  two)  



High  protein  diet  



Iron  supplements:  300mg  ferrous  sulphate  (increased  erythropoesis)  



B-­‐vitamins  for  erythropoesis    



Folic  acid  (folate)  =>  reduces  risk  of  neural  tube  defects  e
...
 spina  bifida  



Vitamin  D3  and  Ca2+  supplements  



Before  parturition  =>  K  vitamin:  prevention  of  haemorrhagic  disease  of  the  newborn  due  to  
Vit   K   deficiency   =>   prevention   of   foetal   intracranial   bleeding,   (and   other   bleeding   e
...
  GI)  
during  the  labour  



Most  often  prophylaxis  for  haemorrhagic  disease  of  the  newborn  is  Vit  K  IM  injection  after  
parturition  (e
...
 after  birth)  

 
Parturition  (birth  of  baby)  


Toward   the   end   of   pregnancy,   uterus   becomes   progressively   more   excitable   (preparing   for  
birth)  



Estrogen:Progesterone  ratio  increases  =>  increasing  excitability  and  preparing  for  labour:    
! Estrogen   increases   contractility   =>   increases   density   of   oxytocin   receptors   in  
uterus
...
 
! Progesterone  inhibits  contractility  





Fetal  hormones:  oxytocin  and  prostaglandins  control  timing  of  labour  



 
 
 

Oxytocin   (from   maternal   posterior   pituitary   gland):   increases   uterine   contractions   and  
excitability  

Stretch:  

! Mechanical  stretch  of  uterine  muscles  increases  contractility  by  positively  feeding  
back  to  the  hypothalamus  to  increase  oxytocin  release
...
 
However,  they  are  not  usually  felt  until  the  second  trimester  or  third  trimester  of  pregnancy
...
   
Braxton   Hicks   contractions   are   a   tightening   of   the   uterine   muscles   for   one   to   two   minutes  
and  are  thought  to  be  an  aid  to  the  body  in  its  preparation  for  birth
...
     

 
Parturition:  Initiation  of  Labour  


Braxton   Hicks   contractions:   increase   toward   the   end   of   pregnancy   (preparation   for   true  
labour  contractions)  



Eostrogen  from  ovaries  prepares  the  uterus  for  contractions:  
! Induces  oxytocin  receptors  on  uterus  
! Stimulates  PG  release  
! Increases  gap  junction  in  myometrium  



Fetal  hormones  released  :  oxytocin  and  PGs  



Oxytocin  from  foetus  and  mothers  posterior  pituitary  initiates  and  sustains  contractions:  
! stimulate  uterus  to  contract  (“contractions”)  
! stimulate  placenta  to  make  prostaglandins  (PGs)  =>  PGs  stimulate  more  vigorous  
contractions  of  uterus  



Distension/stretch   of   the   cervix   and   uterus   by   foetus   positively   feedback   to   the   placenta  
and  posterior  pituitary  (via  nervous  APs)  =>  even  further  increased  release  of  oxytocin  and  
PGs  =>  more  vigorous  uterine  contractions  



Strong   uterine   contractions   and   pain   from   the   birth   canal   cause   neurogenic   reflexes   from  
spinal  cord  that  induce  intense  abdominal  muscle  contractions        
 

 
 
 

 
 
Labour  (parturition)  


Increasing  uterine  contractions  +  uterine  retraction  (progressive  shortening  of  uterine  fibres  
=>  uterus  becomes  smaller)  result  in  foetus  dropping  lower  in  uterus  



This  results  in  increased  cervical  stretch  



Increased  cervical  stretch  results  in:  
! More   release   of   oxytocin   from   posterior   pituitary   (+ve   feedback)   =>   increased  
uterine   contractions   and   increased   PGs   released   from   uterine   wall,   which   also  
results  in  increased  uterine  contractions  
! Increased  uterine  contractions  (directly)  





PGs  also  cause  cervical  dilation  and  effacement  



 
 
 

Increased  uterine  contractions  continue  to  drop  foetus  lower  into  uterus  =  increase  cervical  
stretch   =>   positive   feedback   continues   =>   magnifying   uterine   contractions   until   baby   is  
foetus  is  born  

NB:  The  “foetus”  is  called  a  baby  after  it  is  born  

 
 
The  Stages  of  Labour  




 
 
 

2nd  stage:  expulsion  of  baby  stage:  passage  of  the  baby  through  birth  canal  (typically  a  few  
min   to   30   min,   however   may   take   up   to   2   hours   in   nuliparous   woman,   and   1   hours   in  
multiparous,   who   have   NOT   had   regional   anaesthesia   e
...
  spinal   or   epidural
...
 



 

1st   stage:   cervical   dilation/effacement   stage   (8-­‐24   hours;   on   average   the   cervic   dilates   at  
1cm   per   hour   and   is   maximally   dilated   10   hours   later   when   it   is   10cm)   +   uterine  
contractions  (increasing  in  frequency  and  duration)  

3rd   stage:   ejection   of   placenta:     Placenta   is   usually   released   just   after   birth
...
   Normally  occurs  within  30  minutes
...
g
...
   Duct  system  =  OO  
=  osterogen  for  growth  of  ducts  and  oxytocin  for  contraction  of  ducts  and  expulsion  of  milk
...
g
...
   Lobules  =  PP  =>  progesterone  for  development  of  lobules  and  prolactin  for  
production  of  milk
...
 Most  species  
will  generate  colostrum  just  prior  to  giving  birth
...
  Colostrum   feeds   the   baby   until   milk   can   be   fully  
produced  in  the  breast  

 
 
 

! 1-­‐7  days  after  birth,  prolactin  induces  high  milk  production
...
    Can   inhibit   PIH  
(prolactin   inhibiting   hormone   e
...
  dopamine)   =>   inhibits   dopamine   release   onto   anterior  
pituitary   =>   increased   prolactin   released   from   anterior   pituitary   =>   stimulates   milk  
production
...
g
...
g
...
 



The   fertilization   age   (also   called   embryonic   age   and   later   fetal   age)   is   the   time   from   the  
fertilization
...
g
...
    This   estimation   assumes   that   conception   occurs   on   day   14   of   a   28   day  
cycle
...
 Basing  GA  on  the  LMP  tends  to  result  in  an  overestimation
...
  Size   can   be   misleading   in   the   presence   of   multiple  
pregnancy,   uterine   fibroids,   or   a   full   bladder   (always   empty   bladder   before  
hand!)
...
    Can   also   measure   the   fundal-­‐symphiseal   height   in   cm   which  
correlates  with  gestation  +/-­‐  2  cm  from  20  weeks  gestation
...
 Most  pregnant  women  have  a  first  trimester  scan  (booking  
scan   at   10   weeks),   followed   by   a   detailed   scan   for   anomalies   in   the   second  
trimester  (approx  20  weeks)
...
g
...
   Very  important  to  
investigate  for  it,  as  pre-­‐eclamsia  may  be  asymptomatic
...
g
...
       



Symphysis   to   fundal   height:   Fundal   height   is   a   measure   of   the   size   of   the   uterus   used   to  
assess  fetal  growth  and  development  during  pregnancy
...
     It  
should  correlate  with  foetal  age  +/-­‐2  cm  from  20  weeks  gestation
...
   For  example  longitudinal  lie  =>  foetal  backbone  (axis)  is  parallel  to  maternal  
backbone   (axis)   =>   results   in   either   cephalic   (head   first)   or   breech   (legs   or   buttocks   first)  
presentation
...
     



Engagement   of   presenting   part:   Engagement   is   when   largest   diameter   of   presenting   part  
reaches  pelvic  inlet  (transvere  diameter  >  AP  diameter  =>  OT  is  the  preffered  presentation  at  
this  stage)  and  can  be  detected  by  vaginal  (pelvic)  exam
...
     



Fetal  heart  auscultation:  sonicaid  (US)  or  pinard  

 
Screening  and  specific  testing  for  fetal  anomaly    


Screening  



Specific  prenatal  (antental)  testing  

 
The  triple  test  (16  weeks)  


Usually  performed  at  16  week  



The  triple  test  measures  the  following  three  levels  in  the  maternal  serum  
! alpha-­‐fetoprotein  (AFP)  –  low  in  Downs  
! human  chorionic  gonadotropin  (hCG)  –  raised  in  Downs    
! unconjugated  estriol  (UE3)  –  low  in  Downs    

 
US  Screening  (18-­‐20  weeks)  


Ultrasound  for  fetal  anomaly  at  18-­‐20  weeks  (mid  pregnancy  scan)  



Assess  growth,  organs,  bones,  etc  



Objectives:  
! Reduction  in  perinatal  mortality  and  morbidity  
! Potential  for  in  utero  treatment  

 
 
 

! Identification  of  conditions  amenable  to  neonatal  surgery  
! Identification  of  malformations  
 
Down  syndrome  


Incidence  dramatically  increases  with  increasing  maternal  age  =>  older  woman  in  high  risk  
group   (however   more   Downs   children   are   born   to   younger   woman,   as   younger   woman   have  
more  children)  



Most   common   cause   is   full   trisomy   21   (due   to   non-­‐disjunction)   =>   complete   extra  
chromosome  21  

 
 
Downs  syndrome  risk  assessment  
First  trimester  (0-­‐13  week’s  gestation)  


At  11-­‐13  weeks:  measure  of  skin  thickness  behind  fetal  neck  using  ultrasound  =>  this  is  the  
nuchal   thickness   (NT)
...
     



At   11-­‐13   weeks:   HCG   (Human   chorionic   gonadotropin)   and   PAPP-­‐A   (Pregnancy-­‐associated  
plasma  protein  A)  



Risk  assessment  in  first  trimester  uses  
! NT  (increased  NT  is  indicator  of  Downs)  
! HCG  (increased  HCG  is  indicator  of  Downs)  

 
 
 

! PAPP-­‐A  (low  PAPP-­‐A  is  indicator  of  Down)  
 
Second  trimester  (13-­‐26  weeks  gestation)  


Maternal  blood  sample  at  15-­‐20  weeks  =>    the  triple  test  



The  triple  test  usually  performed  at  16  weeks  is  an  assay  of:  
! HCG  –  increased  in  Downs  
! AFP  (alpha-­‐fetoprotein)  –  decreased  in  Downs  
! Estriol  E3  –  decreased  in  Downs  

 
For  both  first  and  second  trimester  


Incorporation   of   these   measurements   (NT,   and   triple   test:     HCG,   AFP   and   E3)   and   results  
with  maternal  age  and  gestation  to  give  a  personal  risk  (maternal  age  is  a  big  risk  factor)  



>1:250   =>   high   risk   and   requires   further   diagnostic   investigation   (e
...
  amniocentesis   >15  
weeks   or   CVS   <15   weeks)
...
     

 
Risk  of  Downs  syndrome  according  to  maternal  age  and  serum  levels  


Alpha-­‐fetoprotein   (AFP)   is   made   in   the   part   of   the   womb   called   the   yolk   sac   and   in   the  fetal  
liver,  and  some  amount  of  AFP  gets  into  the  mother's  blood
...
 





 
 
 

Estriol   (E3)   is   a   hormone   produced   by   the   placenta,   using   ingredients   made   by   the   fetal   liver  
and  adrenal  gland
...
 This  test  may  not  
be  included  in  all  screens,  depending  on  the  laboratory
...
 A  specific  smaller  part  of  the  hormone,  called  the  beta  
subunit  beta-­‐hCG  is  increased  in  Down  syndrome  pregnancies
...
 In  the  first  trimester,  low  levels  of  this  protein  are  seen  
in  Down  syndrome  pregnancies
...
 
The   correct   analysis   (comparison   to   “normal   ranges”)   of   the   different   serum   components  
depends   on   knowing   the   gestational   age   precisely
...
 



Once  the  blood  test  results  are  determined,  a  risk  factor  is  calculated  based  on  the  "normal"  
blood  tests  for  the  testing  laboratory
...
"   Test   results   are   sometimes  
reported  to  doctors  as  "Multiples  of  the  Median  (MoM)
...
0   MoM
...
0   MOM
...
0  MoM
...
 



The  final  calculated  risk  from  the  lab  results  based  on  the  fetal  age  is  used  to  modify  the  risk  
already   statistically   calculated   based   on   the   mother's   age
...
g
...
g
...
g
...
 



Good  tissue  viability  



Carries   a   miscarriage   rate   of   1-­‐2%   (higher   than   amnio,   as   performing   on   a   younger   foetus  
and   invading   foetal   placenta)
...
     
 

Amniocentesis  (amnio)  



Procedure   in   which   a   small   sample   of   amniotic   fluid   is   drawn   (urine   and   skin   cells   are  
colleceted)  out  of  the  uterus  through  a  needle  inserted  in  the  abdomen  


 
 
 

Usually  performed  after  15  weeks  

Carries  a  miscarriage  rate  of  1%  (less  than  CVS)  



Poor  tissue  viability    

 

 
 

 
 
 
Downs  syndrome  key  points  
 
 
 



Requires  accurate  pregnancy  dating  =>  essential  to  know  correct  gestation  age  to  calculate  
MoM  blood  values  and  NT  (Nuchal  thickness)  



Triple  blood  test:  hCG,  AFP  and  estriol  are  useful  predictors  of  risk  



High  risk  (>1/250)  =>  diagnostic  tests  indicated  



Increasing  maternal  age  is  also  a  key  risk  factor  (and  taken  into  account  in  risk  calculation)  



Requires  detailed  counselling  



‘Low  risk’  does  not  exclude  Down  syndrome  

 
PRE-­‐TERM  BIRTH  
Pre  term  birth  


Term  (full-­‐term)  =  37-­‐42  weeks  gestation  



Pre-­‐term  =  Delivery  between  24  (24+0)  weeks  and  36+6  (36  weeks  and  6  days):  
! moderate  to  late  preterm  (32  to  <37  weeks)  
! very  preterm  (28  to  <32  weeks)  
! extremely  preterm  (<28  weeks)  



Post  term=  >  42  weeks  



Prevalence  of  pre  term  birth:  Approx  6-­‐7%  



Survival  rates  of  pre  term  birth:    
! 24  weeks  approx  20-­‐30%  
! 27  weeks  80%  
! 32  weeks  >95%  

 
Pre-­‐term  birth:  Aetiology  


Infection:   infections   (e
...
  UTIs,   PIDs,   chorioamnionitis)   play   a   major   role   in   the   genesis   of  
preterm  birth  and  may  account  for  25–40%  of  events
...
  Further   the   decidual   response   may   include   release   of  
matrix-­‐degrading   enzymes   that   weaken   fetal   membranes   leading   to   preterm  

 
 
 

premature   rupture   of   membranes   (ROMs)
...
  Micro-­‐organisms   may   reach   the   decidua   in   a  
number   of   ways,   ascending,   hematogeneous,   iatrogenic   by   a   procedure,   or  
retrograde   through   the   fallopian   tubes
...
     
! Early   rupture   of   membranes   causes   almost   a   third   of   all   premature   births
...
    If   a   mother's   waters   break   before   the   baby   has   reached   full   term,   the  
medical  term  is  preterm  premature  rupture  of  the  membranes  (PPROM)
...
    Give  
prophylactic  ABs  for  PPROM  (e
...
 erythromycin)  
! Therefore  it  is  very  important  to  screen  for  asymptomatic  bacteruria  via  MSSU  
(M  and  C)
...
     


‘Over  distension’  –  stiumates  uterne  contractions:  
! Multiple  pregnancies:  Multiple  pregnancies  (twins,  triplets,  etc
...
 
! Polyhydramnios:  excess  of  amniotic  fluid  in  the  amniotic  sac  (amnion)  
! Macrosomia  –  large  baby  (e
...
 in  poorly  contolled  DM)  
! Placental  abruption:  Abruptio  placentae  is  defined  as  the  premature  separation  
of   the   placenta   from   the   uterus
...
  Vaginal   bleeding   (APH)   usually   follows,  
although   the   presence   of   a   concealed   hemorrhage   in   which   the   blood   pools  
behind   the   placenta   is   possible
...
   Build  up  of  blood  in  the  myometrium  
causes   increased   pressure   =>   stimulates   uterine   contractions
...
  The   myometrium   in   this   area  
becomes   weakened   and   may   rupture   with   increased   intrauterine   pressure   during  
contractions
...
    Placenta   abruption   is   painful   with   a  
tense,  tender  uterus,  +/-­‐  APH
...
   Causes  
uterine  overdistension  =>  initiates  uterine  contractions  and  labour  (see  above)  
! Placenta  previa:  obstetric  complication  in  which  the  placenta  is  inserted  partially  
or  wholly  in  lower  uterine  segment  (low  placenta)
...
  If   the   placenta   does  
overlie  the  lower  segment,  as  is  the  case  with  placenta  praevia,  it  may  shear  off  
and   a   small   section   may   bleed
...
  It   is   a   leading   cause   of  
antepartum   haemorrhage   (vaginal   bleeding   >24   weeks   and   before   birth)
...
    Placenta   previa   is  
painless   (in   comparison   to   placenta   abruption   which   is   painful)
...
       
 


Intercurrent  illness:  
! Pyelonephritis  /  UTI  
! Appendicitis  
! Pneumonia  
! Pre-­‐eclampsia  



Cervical   incompetence:   medical   condition   in   which   a   pregnant   woman's   cervix   begins   to  
dilate   (widen)   and   efface   (thin)   before   her   pregnancy   has   reached   term
...
 
! For   example,   a   woman   who   is   described   as   'gravida   2,   para   2   (sometimes  
abbreviated   to   G2   P2)   has   had   two   pregnancies   and   two   deliveries   after   24  
weeks
...
 
! In  Tayside  we  use  Para  X+Y,  where  X=  the  number  of   deliveries   beyond  24  weeks  
(only   include   after   the   birth);   the   second   is   the   number   of   pregnancies   ending  
before  24  weeks  without  signs  of  life
...
   Remember  that  the  first  figure  includes  deliveries  beyond  24  weeks,  
NOT  necessarily  live  births  
! Example  2:  A  woman  at  8  weeks  into  her  first  pregnancy  =>  Para=0+0  (parity  does  
not   become   1   until   after   birth)
...
   If  this  woman  gave  birth  to  a  baby  after  24  weeks  (alive  or  stillborn)  =>  
Para  1+0
...
 

Small  for  dates  may  be  due  to  

! Small  for  gestational  age  (SGA):    IUGR  or  constitutionally  small  
! Wrong  dates    
! Oligohydraminos:    low  volume  of  liquor  amnii  
! Transverse  lie  


Small  for  gestational  age  (SGA)  can  be  due  to:  
! Intra   uterine   growth   restriction   (IUGR)   which   is   also   called   pathological   SGA:  
pathological   state   where   growth   is   normal   in   the   early   part   of   pregnancy,   but  
slows  in  utero  by  at  least  two  measurements,  normally  ultrasound
...
  They   have   a   wasted   appearance   with  
little  subcutaneous  fat
...
     
! Constitutionally   small   (familial):   basically   a   genetic   trait   of   the   baby
...
  They   are   light-­‐for-­‐dates,   but   otherwise  
healthy
...
 

 
Intra  Uterine  Growth  Restriction  (IUGR)  


Intrauterine  growth  restriction  (IUGR)  refers  to  poor  growth  of  a  baby  while  in  the  mother's  
uterus   during   pregnancy
...
g
...
 



Intrauterine   growth   restriction   can   result   in   baby   being   small   for   Gestational   Age   (SGA),  
which  is  most  commonly  defined  as  a  weight  below  the  10th  percentile  for  the  gestational  
age
...
 

 
Aetiology  


Poor  growth  can  be  caused  by:  
! Maternal  factors  
! Fetal  factors  
! Placental  factors  



Maternal  factors:  
! Poor  nutrition  
! Maternal   disease   e
...
  pre-­‐eclampsia,   hypertension,   gestational   diabetes,   CV  
disease,  respiratory  disease  

 
 
 

! Smoking  
!  Alcohol  
! Drugs  
! Poor  weight  gain  during  pregnancy  
! Age  


Fetal  factors:  
! Vertically  transmitted  infections  e
...
 rubella,  CMV,  toxoplasma  
! Congenital  anomalies  e
...
 absent  kidneys  (renal  agenesis)  
! Chromosomal  abnormalities  e
...
 Down’s  syndrome  



Placental  factors:  
! Often  secondary  to  hypertension  e
...
 preeclampsia  
! Infarcts  
! Placental   insufficiency:   Placental   insufficiency   or   Utero-­‐placental   insufficiency   is  
insufficient  blood  flow  to  the  placenta  during  pregnancy  
! Placenta   abruption:   complication   of   pregnancy,   wherein   the   placental   lining   has  
separated  from  the  uterus  of  the  mother
...
 It  is  less  commonly  known  as  global  growth  restriction,  and  indicates  that  
the   fetus   has   developed   slowly   throughout   the   duration   of   the   pregnancy   and   was   thus  
affected  from  a  very  early  stage
...
  Since   most   neurons   are  
developed  by  the  18th  week  of  gestation,  the  fetus  with  symmetrical  IUGR  is  more  likely  to  
have  permanent  neurological  sequelae
...
  In  
asymmetrical  IUGR,  there  is  restriction  of  weight  followed  by  length
...
 A  lack  of  subcutaneous  fat  leads  to  a  
thin   and   small   body   out   of   proportion   with   the   head
...
  In   these   cases,   the   embryo/fetus   has  
grown   normally   for   the   first   two   trimesters   but   encounters   difficulties   in   the   third,   usually  
secondary  to  pre-­‐eclampsia
...
 This  type  of  IUGR  is  most  commonly  caused  by  extrinsic  factors  that  
affect  the  fetus  at  later  gestational  ages
...
g
...
  This   causes   a   reduction   in   the   fetus’   stores   of  
glycogen  and  lipids
...
6  mmol/L)
...
 



Antenatal  /  in  labour  complications:    
! Risk  of  hypoxia  and  or  death:  If  the  cause  of  IUGR  is  extrinsic  to  the  fetus  (e
...
 
maternal   or   uteroplacental   IUGR),   transfer   of   oxygen   and   nutrients   to   the   fetus   is  
decreased
...
6)  
! Effects  of  asphyxia  e
...
 CP  (cerebal  palsy)  
! Hypothermia  
! Polycythaemia:   polycythemia   can   occur   secondary   to   increased   erythropoietin  
production  caused  by  the  chronic  hypoxemia
...
   Unconjugated  hyperbilirubinaemia  can  cause  kernicterus
...
   It  is  the  opposite  of  polyhydramnios
...
 



Reduced  fetal  movements  

 
Assessing  fetal  wellbeing  in  IUGR  



Cardiotocography  (CTG)  


 
 
 

Assessment  of  growth  

Biophysical  assessment:  BPS  (biophysical  profile  score)  



Doppler  ultrasound  –  umbilical  artery    

 
Assessment  of  growth  


Fetal  growth  charts:  
! head  circumference  
! abdominal  circumference  



Assess  if  symmetrical  (worrying)  or  asymmetrical/head-­‐sparing  (less  worrying)  IUGR  

 
Cardiotocography  


Cardiotocography   (CTG)   is   a   technical   means   of   simultaneously   recording   the   fetal  
heartbeat   and   the   uterine   contractions   during   pregnancy,   typically   in   the   third   trimester
...
 



CTGs   purpose   is   to   monitor   foetal   well-­‐being   &   allow   early   detection   of   foetal   distress
...
g
...
g
...
  This   indicates   good   reflex  
activity   of   the   fetal   circulation
...
 



Decelerations:  A  decrease  in  fetal  heart  rate    
! Early  decelerations:  often  not  worrying
...
 
! Late  decelerations:  Any  deceleration  whose  lowest  point  is  past  the  peak  of  the  
contraction  i
...
 decelerations  with  lag  time
...
   

 
 
 



Loss  of  baseline  variability  (uncomplicated)  is  worrying:  Baseline  fetal  heart  rate  variability  
of  less  than  5  beats  per  minute
...
   In  general,  the  less  variability  present,  the  greater  the  possibility  of  asphyxia  

 
USE  DR  C  BRAVADO  

 
 

 
 
 

   
 

 
 
 

 
 

 
 
 
 
 

Biophysical  assessment  (US)  


Ultrasound  assessment  



Considers:  
! Movement  
! Tone  
! Fetal  breathing  movements  
! Liquor   volume   (amniotic   volume):   low   amniotic   volume   (oligohydraminos)   is   not  
a  good  sign  



Score  out  of  10:  
! 8-­‐10  satisfactory  
! 4-­‐6  repeat  
!  0-­‐2  deliver    

 
Doppler  ultrasound  


Umbilical  arterial  Doppler  scan  



Particulary  usefull  for  assessing  IUGR  



Uses  ultrasound  



Umbilical  arterial  Doppler  assessment  is  a  useful  tool  in  the  evaluation  of  fetal  compromise  
in   high-­‐risk   pregnancies   such   as   those   with   intra-­‐uterine   growth   restriction   (IUGR)   or  
suspected  pre-­‐eclampsia
...
 



Measures  placental  resistance  to  flow  



In  growth-­‐retarded  fetuses  and  fetuses  developing  intra-­‐uterine  distress,  the  umbilical  artery  
(vessel  which  takes  blood  back  to  the  foetus)  blood  velocity  waveform  usually  changes  in  a  
progressive  manner  as  below  
! reduction  in  end  diastolic  flow    
!  absent  end  diastolic  flow  (AEDF)    
! reversal   of   end   diastolic   flow   (REDF)   e
...
  flow   of   blood   travelling   back   to   the  
foetus  

 
 
 

 

 
 
 

 
 
 

 
 
 
Delivery  


Most  infants  with  intrauterine  growth  restriction  are  born  at  term
...
 



Obstetricians   often   induce   labour   in   cases   of   intrauterine   growth   restriction   for   fear   of  
neonatal  morbidity  and  later  stillbirth
...
      For   these   reasons,   expectant   management   with  
maternal  and  fetal  monitoring  is  a  commonly  followed  strategy
...
    Induction   of   labour   to   prevent   the  
uncommon   outcome   of   stillbirth   might   be   the   more   appropriate   strategy   in   some  
settings,  especially  if  intensive  surveillance  is  not  feasible
...
g
...
g
...
   However  cervical  ripening  with  PGs  may  be  used
...
 



It   may   be   due   to   a   variety   of   reasons   such   as   prolapse   or   occlusion   of   the   umbilical   cord,  
placental  infarction  and  maternal  smoking
...
   
! IUGR  can  cause  hypoxia  due  to  placental  dysfunction  +  other  causes  



Intrauterine   hypoxia   can   cause   cellular   damage   that   occurs   within   the   central   nervous  
system  (the  brain  and  spinal  cord)
...
   



Oxygen   deprivation   in   the   fetus   and   neonate   has   been   implicated   as   either   a   primary   or   as   a  
contributing   risk   factor   in   numerous   neurological   and   neuropsychiatric   disorders   such   as  
epilepsy,  ADHD,  eating  disorders  and  cerebral  palsy
...
   



If   small   for   gestational   age   babies   have   been   the   subject   of   intrauterine   growth   restriction  
(IUGR)  the  term  SGA  associated  with  IUGR  is  used
...
g
...
    It   has   a   number   of   purposes,   including   protecting   the   fetus   from   trauma  
and   infection,   allowing   lung   development   and   facilitating   the   development   and   movement  
of  the  limb  and  other  skeletal  parts
...
g
...
 Polyhydramnios  is  therefore  linked  to  fetal  abnormality
...
g
...
  It   occurs   when   abnormal  
amounts  of  fluid  buildup  in  two  or  more  body  areas  of  a  fetus  or  newborn
...
  Various   causes   including   Rhesus  
incompatibility,   heart   problems,   lung   problems,   anaemia   (e
...
  thalassameia),  
infection  (erythrovirus  B19),  and  other  genetic  and  developmental  problems  
! Intrauterine  infections  
! Idiopathic  
 


Clinical  features:  
! Discomfort  
! Large  for  dates  
! Difficult  to  hear  foetus  heart  rate  (due  to  excess  amniotic  fluid  around  baby)  
 



Complications:  
! Premature  labour:  due  to  the  additional  pressure  (distension)  stretching  the  uterus  
=>  stimulates  contractions  
! Membrane  rupture  due  to  increased  pressure  =>  can  also  cause  premature  labour  
! Cord   prolapse:   The   extra   fluid   in   the   uterus   makes   it   difficult   for   the   foetus   to   settle  
its  head  down  into  the  pelvis
...
  If   this   happens,   you   may   need  
an  emergency  caesarean  section
...
    Zygosity   is   the   degree   of  
identity  in  the  genome  of  twins
...
    However   the   resvese   is   not   true,   as  
can  have  dizygotic  twins  with  one  chorion  (chorionic  membrane)  



Dichorionicity   (lambda   sign   on   US)   does   NOT   =>   dizygotic
...
    However,   whether   they   are   monygotic   or   dizygotic,  
dichorionicity  is  reassuring  as  there  are  more  complications  in  monochorinic  prgenancies
...
     

 
Zygosity  


Zygosity  is  the  degree  of  identity  in  the  genome  of  twins
...
 



The  three  most  common  variations  are  all  dizygotic  (fraternal  or  non-­‐identical;  come  from  
seperate  eggs  and  seperate  sperms):  
! Male–female  dizygotic  twins  are  the  most  common  result:  50  percent  of  dizygotic  
twins  are  male-­‐female  and  the  most  common  grouping  of  twins
...
   
Monochorionic:   If   they   share   a   placenta   (monochorionicity),   the   pregnancy   is   at   greater  
risk,   and   you’ll   be   monitored   more   closely,   so   that   any   complications   can   be   prevented   or  

treated   e
...
 polyhydraminos   and   preterm   labour
...
    However   the  
reverse  isn’t  true,  monozygozity  does  NOT  =>  monochrorionic
...
   Can  be  monozygotic  (identical)  or  dizygotic  
(non-­‐identical)
...
 These  are  the  highest  risk  pregnancies  but  they  are  also  very  rare
...
 



Non-­‐identical   twins   (dyzygotic)   come   from   two   eggs   that   are   fertilised   by   two   different  
sperm
...
 They  are  in  separate  sacs
...
  Two   thirds   of   all   twin   pregnancies   are   non-­‐identical
...
 



Identical   twins   (monozygotic)   come   from   a   single   egg   that   is   fertilised   by   a   single   sperm,  
which  then  divides  into  two  identical  embryos
...
 
! If   the   division   into   two   embryos   happens   in   the   first   three   days   after   fertilisation,  
the   twins   will   develop   their   own   placenta   and   membranes
...
g
...
g
...
 
! If  the  division  happens  between  the  fourth  day  and  the  ninth  day,  the  twins  will  
share   a   placenta   and   outer   membrane,   but   each   will   have   their   own   inner  
amniotic   membrane   =>   monochorionic   diamniotic
...
 
! If   division   happens   after   the   ninth   day,   the   twins   will   be   in   a   single   sac   =>  
monochorionic  monoamniotic
...
 
! If   division   happens   after   the   12th   day   after   conception,   the   result   will   be  
conjoined   twins   (identical   monozygotic   twins   joined   in   utero)
...
 





Finding  this  out  early  is  important  because  babies  who  share  a  placenta  have  a  higher  risk  of  
health  problems
...
   

If   your   babies   share   a   placenta   (monochorionic)   it   means   they   are   identical  
('monozygotic')
...
 This  is  because  30%  of  monozygotic  twins  do  not  share  a  
placenta  (monozygotic  and  dichorionic)
...
 But  if  monozygotic  twins  separate  early  enough  (in  the  first  three  
days  after  fertilisation),  the  arrangement  of  sacs  and  placentas  in  utero  is  indistinguishable  
from  dizygotic  twins  

 
 
Complications  




 
 
 

Twin-­‐to-­‐twin  transfusion  syndrome  (TTTS):  Twins  who  share  a  placenta  (monozygotic  and  
monochorionic)   also   share   a   blood   supply
...
  The  
other  twin  will  get  too  little  blood,  and  may  not  grow  very  well  (e
...
 IUGR)
...
 
Twins   sharing   a   placenta   are   usually   scanned   every   two   weeks   from   16   weeks   to   look   for  
early  signs  of  TTTS,  so  treatment  can  be  given  to  correct  the  imbalance
...
 Having  regular  scans  will  help  to  spot  the  
early  signs  and  allow  the  condition  to  be  treated
...
 But  it  is  more  likely  that  
your  twins  will  have  separate  (dichorionic)  rather  than  shared  placentas
...
 



Dichorionic-­‐Diamniotic:   these   twins   have   the   lowest   mortality   risk   at   about   9   percent,  
although  that  is  still  significantly  higher  than  that  of  singletons
...
  Because   of   this,   there   is   an   increased   chance  
that  the  newborns  may  be  miscarried  or  suffer  from  cerebral  palsy  due  to  the  lack  of  oxygen
...
     
 

Chorionicity:  how  can  we  tell  before  birth?  


Ultrasound:  
! Number  of  placental  masses  
! Twin   peak   sign   at   12   weeks:   The   sign   (lambda   sign)   describes   the   triangular  
appearance   to   chorion   insinuating   between   the   layers   of   the   inter   twin  
membrane   and   strongly   suggests   a   dichorionic   (two   chorionic   membranes)   twin  
pregnancy
...
    However   it   does   reassure   us   that   we   have   Dichorionic   pregnancy  
which  has  significantly  less  complications  associated  with  it
...
g
...
g
...
g  placenta  praevia    



Twin  to  twin  transfusion:  Twins  who  share  a  placenta  (monochorionic)  also  share  a  blood  
supply
...
  The   other   twin   will   get   too   little   blood,   and   may   not  
grow   very   well
...
 

 
Management  of  multiple  pregnancy  


More  frequent  antenatal  visits  



Detailed  anomaly  scan  at  18  weeks  



Regular  scans  from  28  weeks  for  growth  



Routine  iron  supplementation  



Warning  to  mother  e
...
 risk  and  signs  of  pre  term  labour  

 
Multiple  pregnancy:  delivery  


Triplets  or  more  =>  Caesarean  section  



Twins:  if  twin  one  is  cephalic  presentation  (head  down)  then  aim  for  vaginal  delivery  



Much  greater  risk  of  Caesarean  section  (approx  50%)  



Epidural  analgesia  

 
DIABETES  IN  PREGNANCY    


Pre-­‐existing  
! T1DM  
! T2DM  

 
 
 



Gestational  DM  (usually  occurs  from  28  weeks)  

 
Gestational  DM  


Gestational   DM:   carbohydrate   intolerance   resulting   in   hyperglycaemia   of   variable   severity  
with  onset  or  first  recognition  during  pregnancy  



Incidence:    
! Increasing  
! 2-­‐18%  
! Ethnic  variation  e
...
 South  Asian,  Middle  Eastern  and  Black  Caribbean  



Risk  factors:  
! Family  history  of  diabetes  
! Previous  big  baby  (macrosomia)  
! Previous  unexplained  still  birth  
! Recurrent  glycosuria  
! Maternal  obesity  
! Previous  gestational  diabetes  

 
GDM  pathophysiology  


Placental  hormones  cause  maternal  insulin  resistance  and  insulin  deficiency  
! Cortisol:  anti-­‐insulinic  
! Progesterone    
! Human   placental   lactogen   (hPL)   which   is   also   known   as   human   chorionic  
somatomammotropin   hCS:   GH   like   effects   e
...
  anti-­‐insulinic   =>   causes   insulin  
resistance   and   high   levels   of   glucose   –   particulary   in   the   third   trimester   (foetus  
anabolic  state  and  maternal  starving  state)  




 
 
 

This   is   primarily   a   response   to   increase   maternal   serum   glucose   so   that   the   foetus   has  
access  to  more  glucose  (in  the  third  trimester)
...
6  (when  constant  maternal  glucose  infusion  is  removed  +  high  foetal  insulin  levels)  

 

 
 
Consequences  


Overgrowth   of   insulin   sensitive   tissues   =>   macrosomia     (large   foetus)   =>   large   for   dates  
uterus  =>  increased  risk  of  preterm  birth  



Hypoxaemic   state   in   utero:   Fetal   hyperinsulinaemia   and   increased   anabolism   leads   to  
decrease  level  of  arterial  O2
...
g
...
6)  



Long   term   metabolic   complications:   Fetal   metabolic   reprogramming   (thrifty   phenotype)    
leading  to  increase  long  term  risk  of  obesity,  insulin  resistance  and  diabetes  

 
Gestational  Diabetes:    Screening  and  Diagnosis  

 
 
 



Women   screened   for   GTT   (glucose   tolerance   test)   based   on   risk   factors   or   random   blood  
glucose  at  booking  and  28  weeks  gestation  (approaching  third  trimester:  the  anabolic  state  
of  foestus  /  starvation  state  of  mother)  



Diagnosis  based  on  GTT  at  28  weeks  



Diagnostic  values  (for  75g  oral  glucose  dose):  
! 0  hour  (fasting)  >  5
...
5   mmol/l   (lower   than   the   usual   definition   of   11   in   non   pregnant  
individuals;   in   non   pregnant   individuals   a   OGTT   between   8   and   11   would   be  
impaired  glucose  tolerance  test  a  form  of  prediabetes)  

 
Diabetes  in  pregnancy:  complications  


All  relate  to  poor  control  



Specific  to  pre-­‐existing  DM:  
! Congenital  anomalies  
! Miscarriage  
! Intra  uterine  death  



Common  to  pre-­‐existing  and  gestational  DM:  
! Macrosomia   (large   for   gestational   age   baby):   due   to   fetal   hyperinsulinaemia  
stimulation  foetal  tissue  growth  =>  can  cause  dystocia  (obstructed  labour)
...
     
! Pre  eclampsia:  unknown  pathophysiology  
! Polyhydramnios  due  to  foetal  polyuria  =>  can  cause  pre-­‐term  labour
...
 At  delivery  
the  baby  should  be  checked  for  congenital  abnormalities  
! Neonatal  hypoglycaemia  (<2
...
 It  is  diagnosed  when  the  shoulders  fail  to  deliver  shortly  after  the  fetal  
head
...
  The   baby   cannot   begin   to   breathe   because   its   chest   is   being  

 
 
 

compressed
...
   One  characteristic  of  a  minority  of  shoulder  dystocia  
deliveries  is  the  turtle  sign,  which  involves  the  appearance  and  retraction  of  the  
fetal   head   (analogous   to   a   turtle   withdrawing   into   its   shell),   and   the  
erythematous  (red),  puffy  face  indicative  of  facial  flushing
...
   Complications  include  Erbs  
palsy  (upper  brachial  plexus  injury),  foetal  hypoxia,  cord  compression,  and  death
...
6)  



Importance  of  glycaemic  control  



Increased  risk  for  the  baby  of  obesity  and  diabetes  in  later  life  



Increased  risk  of  type  2  diabetes  for  the  mother  with  gestational  DM  

 
Prevention  of  hyperglycaemia  


Monitoring  blood  glucose
...
5  –  5
...
8  mmol/l  



Diet  



Weight  control  



Exercise  



Pharmacological  therapy  
 

Pharmacological  therapy  for  gestational  diabetes    


Consider  when:  
! diet  and  exercise  fail  to  maintain  targets  
! macrosomia  on  ultrasound  or  other  complication  such  as  polyhydraminos  


 
 
 

Choice  of  agent:    

! tailored  to  glycaemic  profile  
! individual  woman  
! Oral  medication  or  insulin?  


Potential  advantages  of  oral  anti-­‐diabetic  agents:  
! Avoidance  of  hypoglycaemia  associated  with  insulin  
! Less  weight  gain  
! Less  ‘education’  required  to  ensure  safe  /  effective  administration  
! Avoid   sulphonylureas   (e
...
  glibenclamide,   glicazide,   and   tolbutamide)   as  
potentially  teratogenic  

 
Obstetric  care  of  DM  patients  


Regular  monitoring  for  pre-­‐eclampsia:  BP  measurements  and  urinalysis  for  proteinuria  



Growth:   2-­‐4   weekly   FAC   (fetal   abdominal   circumference)   from   28   weeks   or   diagnosis   =>  
assessing  for  macrosomia    



Assess  for  polyhdraminos  



Fetal  wellbeing:  Research  has  shown  that  umbilical  arterial  Doppler  in  high  risk  pregnancies  
is  more  beneficial  compared  to  CTG  (cardiotocography)  and  BPP  (biophysical  profile)      



Offer  delivery  from  38  weeks  gestation  

 
Timing  of  Delivery  


Offer  delivery  from  38  weeks  gestation  



Case  dependent      

 
Mode  of  Delivery  




‘Diabetes  should  not  in  itself  be  considered  a  contraindication  to  attempting  vaginal  birth’  



 
 
 

‘Pregnant   women   with   diabetes   who   have   ultrasound   diagnosed   macrosomia   should   be  
informed  of  the  risks  of  vaginal  birth  and  Caesarean  section’  

CS   (C-­‐section)   remain   high   even   when   diabetes   well   controlled   and   no   evidence   of  
macrosomia    

 
Future  development  of  Type  2  diabetes  from  GDM  


Risk  up  to  70%  



Main  risk  factors:  
! Obesity  
! Use  of  insulin  during  pregnancy  
! Fasting  glucose  levels  abnormal  during  pregnancy  
! IGT  (impaired  glucose  tolerance)  post  partum  
! Ethnic  groups  e
...
 South  Asian  and  Middle  Eastern  

 
 
Type  1  &  2  Diabetes  in  pregnancy:  Additional  management  points  


Pre  pregnancy  counselling  



Fetal  anomaly  scan  at  18  weeks  



Regular  eye  checks  for  retinopathy  (fundoscopy)  –  pregnancy  can  accelerate  damage    



BP  and  urinalysis  (assess  kidney  function  AND  assess  for  pre-­‐eclampsia)  



Diabetic   foot   exam   and   peripheral   vascular   exam   (as   DM   can   cause   peripheral   vascular  
disease  and  neuropathy)  

 
Key  Points  


Large  for  dates  aetiology:    
! Wrong  dates  
! Multiple  pregnancy  
! Macrosomnia    
! DM  =>  macrosomnia  and  polydraminos    
! Polyhydramnios  
! Fibroids  

 
 
 

! Distended  bladder  
! Hydratiform  mole  in  first  trimester  


Multiple  pregnancy  (particulary  monochorionic)  associated  with  significant  higher  perinatal  
morbidity  and  mortality  and  require  specialist  obstetric  care  (particularly  if  monochorionic)  



Incidence   of   diabetes   (types   2   and   GDM)   in   pregnancy   increasing   as   a   consequence   of  
obesity  epidemic  



Care  of  diabetics  in  pregnancy  is  multidisciplinary  



In   some   women,   gestational   diabetes   will   respond   to   changes   in   diet   and   exercise
...
    Can   cause   foetal   renal   dysfunction   and  
oligohdraminos
...
g
...
g
...
    Function   between   weeks   6-­‐10  
then  regress  
! Metanephric  blastoma:  develops  into  nephron  
! Ureteric   bud:   derived   from   mesonephric   ducts   (Wolffian   duct)
...
 The  failed  induction  will  thereby  cause  the  subsequent  degeneration  
of   the   metanephros   by   apoptosis   and   other   mechanisms
...
  Therefore,   the  
means  by  which  the  fetus  produces  urine  and  transports  it  to  the  bladder  for  excretion  into  
the   amniotic   sac   has   been   severely   compromised   (in   the   cases   of   URA),   or   completely  
eliminated  (in  the  cases  of  BRA)
...
 This  compression  
can  cause  many  physical  deformities  of  the  fetus,  most  common  of  which  is  Potter  facies
...
  It   later   develops   into   a   conduit   for  
urine  drainage  from  the  kidneys  (e
...
 collecting  system),  which,  in  contrast,  originate  from  
the  metanephric  blastema
...
   As  kidneys  ascend  into  abdomen,  they  receive  
their   blood   supply   from   the   aortic   branches   closest   to   them
...
   
Normally   the   more   caudal   blood   vessels   degenerate   as   they   are   no   longer   needed
...
 



The  cloaca  is  the  common  end  of  the  rectal  tube  and  the  urogenital  tract
...
 
! The  spongy  part  of  the  urethra  and  the  urethral  glands    
! The  prostate  



In  females  from  the  definitive  urogenital  sinus  endoderm  arises:  
! Urethra  
! Lower   2/3rds   of   vagina:   In   females,   the   pelvic   part   of   the   UG   sinus   gives   rise   to  
the   sinovaginal   bulbs,   structures   that   will   eventually   form   the   inferior   two  
thirds   of   the   vagina
...
g
...
 



 
 
 

Male  duct  system  =  Mesonephric  duct  (Wolffian  duct)  

The   prostate   forms   from   the   definitive   urogenital   sinus   and   the   efferent   ducts   form   from  
the  mesonephric  tubules
...
 
Testosterone   binds   to   and   activates   androgen   receptor,   affecting   intracellular   signals   and  
modifying  the  expression  of  numerous  genes
...
 



From  the  mesonephric  duct  (Wolffian)  arise:  
!        Epididymis  
!        Deferent  duct  
!        Seminal  vesicle  
!        Ejaculatory  duct    

 
 
Descent  of  the  Testis  


 

 
 
 

The   testes   descend   to   the   scrotum   under   the   control   of   the   gubernaculums   (ligament   like  
structure)  under  the  control  of  testosterone  

 
 
 
Female  Ducts  (Paramesonephric)  


Female  =  Mullerian  ducts  =  Paramesonephric  ducts  



In  the  female,  there  is  an  absence  of  anti-­‐Müllerian  hormone  secretion  by  the  sertoli  cells  =>  
absence  of  Müllerian  apoptosis  



The  Mullerian  duct  (paramesonephric  duct)  persists  and  forms  female  genital  tract  



The  Wolffian  duct  regresses,  due  to  the  absence  of  testosterone    



From  the  paramesonephric  duct  (Müllerian)  arises:  
! Fallopian  tube  
!  Uterus  
!  Upper  1/3  of    vagina    
! NB:  Remember  that  the  lower  2/3rd  of  the  vagina  are  formed  from  the  sinovaginal  
bulbs  (derived  from  definitve  urogenital  sinus)  

 
 
 

 
 
Development  of  Uterus  


The   paramesonephric   ducts   develop   qnd   into   the   fallopian   tubes,   uterus,   cervix   and   upper  
1/3  of  vagina
...
 



Later,  these  genital  swellings  form  the  scrotum  (males)  or  labia  major  (females)  



Controled  by  the  presence  or  absence  of  testsosterone    



Testsosterone  present  =>  male  external  genitalia  



 
 
 

The  external  genital  (like  the  intenal  reproductve  organs)  also  have  an  indifferent  stage  

Testsosterone   absent   or   androgen   insensitivity   sydrome   =>   female   external   genitalia  
develops  

 
Male  genitalia  development  


The  genital  tubercle  becomes  longer  and  out  of  it  forms  the  penis  



The  two  genital  swellings  also  fuse  in  the  middle  and  form  the  scrotum
...
 



From  the  genital  swellings  arise  the  labia  majora  



The  urethral  folds  also  do  not  fuse
...
 

 

 
 
 

 

 
 
Learning  objectives  


Name  the  nephric  systems  involved  in  kidney  development:  
! Metanephric  blastoma  (from  mesoderm)  =>  nephron  
! Ureteric  bud  is  a  protrusion  from  the  mesonephric  duct  =>  collecting  system  
! Metanephros   (develops   into   fully   functioning   kidney)   forms   from   Metanephric  
Blastoma  (nephron)  and  ureteric  bud  (collecting  system)
...
     



Know  that  the  permanent  kidney  is  derived  from  the  metanephros  =  metanephric  blastoma  
+  ureteric  bud  (protrusion  of  Mesonephric/Wolffian  duct)  



Know   the   parts   of   the   kidney   derived   from   the   ureteric   bud   (collecting   duct   system)   and   the  
parts  derived  from  the  metanephros  (filtration  via  nephron)  



Know  the  types  of  anomalies  that  arise  from  failure  of  the  kidneys  to  ascend  
! Pelvic   kidney:   If   a   kidney   does   not   ascend   as   it   should   in   normal   foetal  
development  it  remains  in  the  pelvic  area  and  is  called  a  pelvic  kidney,  
! Horseshoe  kidney:  Horseshoe  kidney  is  a  congenital  disorder  affecting  about  1  in  
500   people
...
 The  fused  part  is  the  isthmus  
of  the  horseshoe  kidney
...
g
...
g
...
   BP  falls  
in   first   and   second   trimester   and   then   rises   back   to   pre   pregnancy   BP   in   third   trimester
...
   

 
Incidence  


Hypertension  (HTN)  in  pregnancy:  10-­‐15%  



PET:  3-­‐5%  
! Severe  PET  5/1000  


 
 
 
 

Eclampsia:  5/10000  

Leading  Causes  of  Child  and  Mother  Deaths:  NOT  TO  BE  MISSED  


Sepsis  



Pre-­‐eclampsia/eclampsia  



Thromboembolism  

 
Pre-­‐eclampsia  
Aetiology  


Placental  pathology:  
! VASOCONSTRICTIVE  MOLECULES  
! It   appears   likely   that   there   are   substances   released   from   the   placenta   that   can  
cause   endothelial   dysfunction   in   the   maternal   blood   vessels   of   susceptible  
women
...
 
! Key  part  of  pathogenesis:    Vasocontrictive  factors  released  which  systemlly  act  on  
maternal  endothelium    
! More  common  in  twins  
! Resolves  after  delivering  placenta  
! Does  not  occur  before  20  weeks  



Prostaglandin   imbalance   -­‐   excess:   aspirin   is   used   to   help   treat   =>   aspirin   (PG   inhibitor)  
decreases  prostaglandins
...
     



Genetic:  If  mother  had  PET  =>  increases  risk  by  20-­‐40%  

 
Pathophysiology  


 
 
 

It  all  has  to  do  with  vasoconstriction  =>  maternal  hypertension  and  decreased  blood  flow  to  
organs,  in  particular  kidneys  and  liver  



Vasoconstrcition  to  systemic  arterioles  =>  HT  



Vasoconstriction  to  kidey  arterioles  =>  kidney  dysfunction  =>  proteinuria  (>300  mg  /24  hours  
–  albuminuria)  



Specific  to  pregnancy  



Placental  cause  



Manifestation  is  variable,  unpredictable,  and  widespread  



Complex   pathophysiology   of   vasoconstriction,   procoagulation   and   IV   thrombosis   all  
resulting  in  tissue  ischaemia
...
g
...
   
Fibrin   forms   crosslinked   networks   in   the   small   blood   vessels
...
   
Additionally,  platelets  are  consumed
...
   
Other  organs  can  be  similarly  affected
...
 
 
 

Placenta  




 
 
 

Placental  abruption  (complication  of  pregnancy,  wherein  the  placental  lining  has  separated  
from   the   uterus   of   the   mother)   =>   severe   uterine   pain,   tense   uterus,   APH   +   contractions  
(due  to  blood  in  myometrium  causing  stretching  of  the  myometrium)  +  premature  delivery  
(due  to  contractons)  


 

↓   blood   flow   to   placenta   and   baby   =>   IUGR   =>   ↓   size   of   baby   (SGA   <10th   centile)   =>  
monitor  with  umbilical  artery  Doppler    

Intra  uterine  death  

Risk  Factors  


Risk  assessment  is  key  



High  and  moderate  risks:  consider  giving  these  patients  aspirin  (prostaglandin  inhibitor)  
 

High  risk  


Previous  HT  or  PET  



Chronic  hypertension  



Chronic  kidney  disease  



Autoimmune  condition:  SLE,  APS  



Type  1/2  diabetes  

 
Moderate  risk  


1st  pregnancy  and  age  >  40  



Pregnancy  interval  >  10  years  



BMI  ≥  35  



Family  history  of  pre-­‐eclampsia  



Multiple  pregnancy  

 
Other  important  risk  factors  


Mother  had  PET  



History  of  hydatidiform  mole  



Triplets:    can  present  with  PET  <  24  weeks  

 
Clinical  Presentation  of  PET  


BP  ≥  140/90  (hypertension)  



Significant  proteinuria:  
! ≥  +1  on  urine  dipstick  

 
 
 

! 30  mg/mmol  (0
...
g
...
    However,   post-­‐partum   pre-­‐
eclampsia  may  occur  up  to  six  weeks  following  delivery  even  if  symptoms  were  not  present  
during  the  pregnancy
...
  Hypertension   can  
sometimes  be  controlled  with  anti-­‐hypertensive  medication,  but  any  effect  this  might  have  
on  the  progress  of  the  underlying  disease  is  unknown
...
 



Interplay  of  three  key  factors  (the  3  Ps):  
! Power:  Uterine  Contractions  (power,  frequency  and  duration)  +  retraction  
! Passage:  Maternal  Pelvis  (shape,  size)  
! Passenger:  Fetus  (shape,  size,  lie,  presentation,  position)  

 
Physiological  considerations  in  labour  


Progesterone  keeps  the  uterus  quiet  e
...
 prevents  early  labour  
! Progesterone   prevents   formation   of   gap   junctions     =>     hinders   contractibility   of  
myocytes  (SMCs  of  myometrium)  =>  decreases  uterine  contractability  



Oestrogen  makes  the  uterus  contract:  
! Eostrogen   simulates   prostaglandin   production   =>   prostaglandins   increase   uterine  
contractions,  increase  sensitivity  to  oxytocin  and  soften  the  cervix  
! Increases  oxytocin  receptors    =>  increases  effects  of  oxytocin  
! Net  effects  =>  Increases  uterine  contractibility  and  promote  cervical  dilation  and  
effacement  


 
 
 

Oxytocin  initiates  and  sustains  contractions:  

! Few  receptors    in  late  pregnancy    
! Peak   level   in   early   labour   (oestrogen   stimulates   expression)   =>   stimulates   uterine  
contractions  
! Enhances  prostaglandin  synthesis  
! Increases  cytosolic  calcium  and  myo-­‐contractibility  
! Can  be  used  to  enhance  labour  or  induce  labour  (e
...
 syntocinon)  
! Positive  feedback  effects  
 
Initiation  of  labour  


Mechanism  uncertain:  foetal  initiation?  



Complex  interaction  between  maternal,  placental  and  fetal  factors:  
! Change   in   the   estrogen:progesterone   ratio   =>   increased   oestrogen:progesterone  
ratio   is   believed   to   play   a   key   role   (oestrogen   prepares   and   stimulates   uterine  
contractions)  
! Fetal   adrenals   and   pituitary   hormones   may   control   the   timing   of   the   onset   of  
labour   =>   directly   affect   placenta   by   decreasing   progesterone   and   increasing  
oestrogen  
! Myometrial   stretch   due   to   foetus   increases   the   excitability   of   myometrial   fibres  
=>   +ve   feedback   loop
...
    Duration   of   latent   phase   is   very   variable:   can   be   a   few   days   or  
much   shorter
...
  Cervix  
softens  &  shortens  (effacement)
...
 
! Active  phase:  cervix  dilates  from  4  cm  to  10  cm  (full  dilatation  is  approximately  
10cm):   in   the   active   first   stage   the   cervix   begins   to   dilate   more   rapidly,   and  
contractions  are  longer,  stronger,  and  closer  together
...
   Presenting  part  descends  more  deeply
...
     
! NB:  The  cervix  dilates  at  an  average  of  approximately  1cm  per  hour
...
 



Second  stage  of  labour:  
! The  second  stage  begins  with  full  dilatation  (approx  10cm)      

 
 
 

! Powerful  sustained  uterine  contractions  +  lots  of  pushing  from  mother  +  uterine  
retraction  =>  delivery  of  baby  
! Approx  1-­‐2  hours  in  multiparous  and  2-­‐3  hours  in  primparous    


Third  stage  of  labour:    
! Expulsion  of  placenta  
! Usually  approx  30  mins  

 
First  stage  of  labour  (cervical  dilation  and  effacement)  


Characteristics:  
! regular   uterine   contractions   which   are   progressively   more   rhythmic   /  stronger   /  
painful  
! Progression  to  complete  cervical  dilatation  (10cm)  
! Presenting  part  (usually  head)  has  descended  into  pelvis  through  the  pelvic  inlet  
(engagement)  –  usually  OT  position    



latent  phase  and  an  active  phase  



latent  phase:      
! mild,  irregular  uterine  contractions  
! cervix  softens,  thins  and  shortens  (effacement)  



Active  phase:    
! cervix  dilates  from  4  cm  to  full  dilation  (10cm)  
! contractions    progressively  more  rhythmic  /  stronger  /  painful  
! descent   of   the   presenting     part   into   the   pelvis   through   the   pelvic   inlet  
(engagement)  
! SO  DESCENT  AND  ENGAGEMENT  OCCUR  IN  FIRST  STAGE  




Monitor  progress  with  Bishops  score:    cervical  effacement,  cervical  dilation,  cervical  
position,  cervical  consistency,  and  foetal  station    
PGs  are  used  in  stage  1  to  help  with  cervical  ripening  (effacement  and  shortening)  
and  are  indicated  with  low  Bishops  score  (e
...
 Bishops  <6)  
 
 
 

Second  stage  of  labour  (birth)  
 
 
 



Begins  with  full  dilation  of  the  cervix,  continues  to  complete  formation  of  the  curved  birth  
canal  and  ends  with  birth  of  the  baby  



Complete    dilatation  (approx  10cm)  =>    delivery  of  the  fetus  can  occur  



Expulsive  stage,  with  stronger  and  more  frequent  contractions  



In  nulliparous  women  (a  woman  who  has  never  completed  a  pregnancy  beyond  24  weeks):    
second  stage  is  considered  prolonged  if  it  exceeds  3  hours  (with  regional  anaesthesia  e
...
 
spinal  or  epidural)  or  2  hours  (without  regional  anaesthesia)    



In   multiparous   women   (pregnancies   of   ≥24   weeks   gestation   ending   in   birth,   which   was  
either   live   or   stillborn),   the   second   stage   should   be   considered   prolonged   if   it   exceeds   2  
hours  (with  regional  anaesthesia)  or  1  hour  (without)
...
 



NB:   epidural   can   slow   down   contractions   and   can   decreases   mothers   awareness   of  
contractions  =>  she  does  not  know  when  to  push  



So  normal  durations  of  second  stage  of  labour  (without  regional  anaesthesia)  


Nulliparous  =>  two  hours  



Multiparous  =>  one  hour  



Consider   stimulating   labour   if   second   stage   is   prolonged   due   to   problems   with   uterine  
contractions  (e
...
 with  syntocinon  -­‐  no  need  for  PGs  as  the  cervix  is  fully  dilated)  



NB:  PGs  are  used  in  stage  1  to  help  with  cervical  ripening  (effacement  and  shortening)  and  
are  indicated  with  low  Bishops  score  (<6)  

 
Third  stage  of  labour  


Begins  with  delivery  of  the  baby  and  ends  with  expulsion  of  the  placenta  &  fetal  membranes  



Expulsion   of   the   placenta   and   foetal   membranes   e
...
  chorion   (membrane   which   is   part   of  
the  placenta)  and  amnion  (membrane  which  surrounds  amniotic  fluid)  



Usually  occurs  within  10  minutes,  however  may  last  30  minutes  



Two  methods  of  managing:  
! Traditional   /   Expectant   management   (active   monitoring)   =>   spontaneous  
delivery  of  the  placenta  and  membranes,  with  no  interference  (takes  longer  and  
may  be  associated  with  heavy  blood  loss  e
...
 postpartum  haemorrhage)  
! Active   management   –   most   commonly   used:   prophylactic   administration   of  
oxytocin  (syntocinon)  and  ergometrine
...
    Combination   of  
syntocinon  (oxytocin)  and  ergometrine  =  syntometrine
...
  Contraction   of   the  
uterus  can  prevent  against  PPH
...
 



Cervical  effacement:  cervical  effacement  refers  to  a  thinning  and  shortening  of  the  cervix
...
   Prior  to  effacement,  the  cervix  is  like  a  long  bottleneck,  
usually  about  four  centimeters  in  length
...
 When  the  cervix  effaces,  the  mucus  plug  is  
loosened   and   passes   out   of   the   vagina
...
 Effacement  (thinning  
and  shortening)  is  accompanied  by  cervical  dilation
...
g
...
  Neither   Braxton   Hicks  
or  true  labour  

 
Braxton-­‐Hicks  contractions  


Braxton  Hicks  contractions  are  sporadic  uterine  contractions  that  sometimes  start  around  six  
weeks   into   a   pregnancy
...
 



Once  or  twice  per  hour,  and  often  just  a  few  times  per  day  



Irregular,  do  not  increase  in  frequency  or  intensity  



Resolve  with  ambulation  (walking  about)  or  a  change  in  activity  



Painless  tightening  of  the  uterus  



Thought  to  prepare  the  uterus  for  true  contractions  

 
True  Labour  Contractions  



Accelerate  to  1  every  2-­‐3  minutes    (e
...
 3  to  5  /10)  


 
 
 

Start  infrequently  1  every  10-­‐15  minutes  (measured  in  ten  minute  intervals  e
...
 1/10  mins)  

Longer  and  more  intense  than  Braxton-­‐Hicks  



Painful  



Progressive  cervical  change  (ripening/softening,  effacement  and  dilation)  



Do  not  resolve  with  change  of  position  
 

Characteristic  of  uterine  contraction  


The  myometrium  is  the  middle  layer  of  the  uterine  wall,  consisting  mainly  of  uterine  smooth  
muscle  cells  (also  called  uterine  myocytes)  



Uterine  muscle:  smooth  muscle  (myocyte)  in  connective  tissue  (collagen  &  elastin)
...
 



Cervical   tissue:   collagen   tissue,   smooth   muscle,   elastin,   held   together   by   connective   tissue  
ground  substance  



Contraction  and  retraction  =>  shortening  of  the  muscle  fibres  =>  propelling    fetus  forward  
down  the  birth  canal  



NB:  retraction  =  contraction  without  regaining  normal  length  =>  musle  fibres  shorter  with  
every   contraction   =>   cause   shortening   of   the   muscle   fibres   and   uterus   becomes  
progressively   smaller
...
g
...
   



Synchronisation  of  contraction  waves  from  both  ostia  (spread  together)  



Uterine  pacemaker  cells  is  same  type  of  muscle  as  rest  of  uterus  (unlike  cardiac  pacemaker)  



Polarity:    
! Upper   segment   contracts   &   retracts   (e
...
  muscle   fibres   shorten   with   each  
contraction   =>   uterus   becomes   smaller)
...
    The   resting   period   is   important   to   allow   the   woman   and   uterus  
muscle   to   rest
...
 

 
Intensity  of  contractions    


magnitude  of  uterine  systole  (contraction)  



maximum  intensity  during  second  stage  (birth  of  baby)  



grades:  mild,  moderate,  strong  (measured  on  palpation  during  contraction)  
 

Frequency  


normal:    up  to  4  every  10  mins  (4  in  10)  during  stage  2  



allows  time  for  resting  tone  



The  resting  period  is  essential  for  “rest”  so  that  the  woman  and  uterus  is  not  overworked
...
g
...
   Therefore  babies  normally  
engage  transversely  (ROT  or  LOT  position)
...
     



Shape  of  passage  changes  as  baby  progresses  downwards  through  the  pelvic  cavity  



At  pelvic  outlet:  AP  diameter  >  transverse  diameter  
! Pelvic  outlet  narrower  =>  baby  internally  rotates  head  through  cavity  &  outlet  
! The   ideal   position   for   the   foetus   to   pass   through   the   pelvic   outlet   is   in   the  
occipito-­‐anterior   (direct   OA,   LOA   or   ROA)   position   e
...
  the   foetus   should  
internally  rotate  from  transverse  (ROT  or  LOT)  to  OA  (direct  OA,  ROA  or  LOA)  as  it  
passes  through  the  pelvic  cavity  
! The  position  of  the  foetus  head  as  it  comes  through  the  pelvic  outlet  is  usually  
left  occiput  anterior  (LOA),  however  occasionally  the  baby  may  be  right  occiput  
anterior  (ROA)  

 

 
 
 

 
 

 
 
 

 
 
 
Types  of  Pelvis  


There  are  four  main  pelvic  types:  

 

 

 

 

 

 

 

! Gynecoid   (“female”)   pelvis:   It   has   an   almost   round   brim   and   will   permit   the  
passage   of   an   average-­‐sized   baby   with   the   least   amount   of   trauma   to   the   mother  
and  baby  in  normal  circumstances
...
 
! Android  (“male”)  pelvis:  It  has  a  heart-­‐shaped  brim  and  is  quite  narrow  in  front
...
 The  pelvic  cavity  and  outlet  is  often  narrow,  straight  and  
long
...
   Women  with  this  shape  pelvis  may  have  
babies  that  lie  with  their  backs  against  their  mothers’  backs  and  may  experience  
longer  labours
...
    Baby   can   get  
caught  if  android  pelvis
...
  The  
outlet  is  large,  although  some  of  the  other  diameters  may  be  reduced
...
 
! Platypelloid   pelvis:   It   has   a   kidney-­‐shaped   brim   and   the   pelvic   cavity   is   usually  
shallow  and  may  be  narrow  in  the  antero-­‐posterior  (front  to  back)  diameter
...
 During  labour  the  baby  may  have  difficulty  entering  the  
pelvis,  but  once  in,  there  should  be  no  further  difficulty
...
    Liquor   is   contained   within   the   amniotic   sac/cavity   (amnion)
...
     It  is  in  close  contact  with  the  amnion
...
   Very  rare!  



Rupture  can  sometimes  initiate  labour  e
...
 preterm  labour  



Important  to  assess  for  meconium  stating  of  the  liquor  which  can  suggest  foetal  distress,  
particularly  with  an  abnormal  CTG  

 
 
Fetal  Position  
Normal  position  


Lie:  
! The   lie   is   the   relationship   between   the   longitudinal   axis   of   fetus   and   the  
longitudinal  axis  of  the  mother  
! Longitudinal  lie  is  the  normal  and  ideal  situation  (with  cephalic  presentation)  
! Longitudinal   lie   =>   axis   of   baby   is   parallel   to   axis   of   mum   =>   either   cephalic   or  
breech  presentation  



Presentation:  
! The   presentation   =   the   leading   part   of   the   fetus   which   occupies   the   lower   pole   of  
the  uterus  
! The  cephalic  presentation  (head  first)  is  the  normal  and  ideal  presentation  
! Can  also  be  breech  



Presenting  part:    
! The   presenting   part   is   the   portion   of   the   foetal   body   that   is   either   foremost  
within  the  birth  canal  or  in  close  proximity  to  it
...
 

 
 
 

! Cephalic   presentation   can   result   in   vertex   (crown   e
...
  top   of   head)   presenting  
part  or  brow  presenting  part    
! Breech  can  result  in  buttock  presenting  part  etc  
! Normal  =  vertex  presenting  part  


Engagement  
! Engagement  =  occurs  when  widest  diameter  of  presenting  part  has  entered  pelvis  
through  pelvic  inlet  
! Corresponds  with  foetal  station  0  
! The  fetus  is  engaged  if  the  widest  leading  part  (typically  the  widest  circumference  
of  the  head)  has  passed  through  the  pelvic  inlet
...
g
...
     
! For  a  cephalic  presentation  the  denominator  is  the  occiput,  and  for  a  breech  the  
denominator  is  the  sacrum
...
 
 



 
 
 

Flexed  head  e
...
 chin  at  chest  is  normal  

 
 

 

 
 
 

 
 
 
Abnormal  presentation  (malpresentation)  and  position  (malposition)  


Lie:  
! Longitudinal  lie  with  breech  
! Oblique  lie  
! Transverse   lie   (labour   will   not   go   ahead   if   transverse)
...
   Can  cause  small  for  dates  on  obs  exam
...
  The   2   parietal   bones   may   also   slip   under   each  
other
...
     



Occiput    =  area  behind  posterior  fontanelle  



Vertex   (crown)   =   area   between   anterior   and   posterior   fontanelle   and   between   parietal  
eminences
...
     



Brow  =  area  between  anterior  fontanelle  and  root  of  face  (can  get  brow  presenting  part  in  
cephalic  presentation)  

   
 

 
 
 

 
 
Mechanism  of  labour  


The  Cardinal  Movements:  change  position  of  foetus  head  in  pelvis  



Described   in   relation   to   a   “normal”   vertex   (crown:     area   between   anterior   and   posterior  
frontanelles)  presentation
...
Engagement   of   the   babies   head   downwards   from   abodmen   into   the   pelvis  
through   the   pelvic   inlet:   occipito-­‐transverse   (ROT   or   LOT)   –   as   the   transverse  
diameter  of  the  pelvic  inlet  >  AP  diamter  
2
...
Flexion  of  head  =>  chin  close  to  chest  
4
...
Crowning  and  extension  (of  head)  resulting  in  delivery  of  the  head  
6
...
Expulsion   (firstly   the   anterior   shoulder   under   the   symphysis   pubis,   followed   by  
the  rest  of  baby)  

 

 
 
 

 
 
 
 
Normal  variations  

 
 
 

Engagement   of   head   in   multigravida   (woman   who   have   been   pregnant   more   than   once):  
only  in  late  labour  does  the  head  suddenly  come  down  then  traverses  quickly  



Moulding:   The   five   separate   bones   (2   frontal,   2   parietal   and   1   occipital)   of   the   fetal   skull   are  
joined  together  by  membranous  sutures,  which  are  quite  flexible  during  the  birth
...
   Movement  in  the  sutures  and  fontanels  allows  
the  skull  bones  to  overlap  each  other  to  some  extent  as  the  head  is  forced  down  the  birth  
canal   by   the   contractions   of   the   uterus
...
   Bones  overlap  during  birthing
...
 Once  born,  come  apart
...
g   crown)   during   labour   and   delivery  
(presenting  part  e
...
 crown)  due  to  pressure  effects
...
   More  likely  to  occur  the  longer  it  takes  to  dilate
...
    Can   cross   sutures
...
     

 

 
 
Descent  of  head  


Abdominal  fifths:  
! Foetal  head  is  divided  into  fifths  in  the  coronal  plane  

 
 
 

! If   you   are   able   to   feel   the   entire   head   in   the   abdomen   it   is   5/5th’s   palpable   =>    
not  engaged  
! When  only  two-­‐fifths  of  the  fetal  head  is  palpable,  the  widest  part  has  descended  
into  the  pelvis  =>  therefore  the  head  is  engaged  (3/5ths   engaged)  =>  corresponds  
to  foetal  0  station    
! If  you  are  not  able  to  feel  the  head  at  all  abdominally  it  is  0/5th’s  palpable  =>  fully  
engaged  


Cervical  assessment  
! Bishops   score   (cervix   score)   can   indicate   behaviour   and   progression   of   cervix
...
 It  has  also  been  
used  to  assess  the  odds  of  spontaneous  preterm  delivery
...
g  vaginal  PGs  
! A   score   of   9   or   more   indicates   that   labour   will   most   likely   commence  
spontaneously
...
     

NB:  Crowning  =  the  appearance  of  a  large  segment  of  the  fetal  scalp  (region  between  the  anterior  
and  posterior  fontanelle)  at  the  vaginal  orifice  in  childbirth
...
     

 
 
 
 
 

 
Partogram  


Partogram   is   a   composite   graphical   record   of   key   data   (maternal   and   fetal)   during   labour  
entered   against   time   on   a   single   sheet   of   paper
...
 



Three  major  components:  progression  of  labour,  maternal  condition  and  medication,  and  
foetal  condition  



Progression  of  labour  
! Contraction  pattern:  frequency,  amplitude  (measured  via  palpation),  duration  
! Cervical  os  dilation    
! Bishops  score  
! Descent  e
...
 foetal  station    



Fetal  condition:  
! Fetal  HR  and  pattern  
! Fetal  monitoring  in  a  graph:  CTG  (Cardiotocography)  
! Character   of   the   amniotic   fluid   (liquor)   and   volume:   should   be   clear   (assess   for  
meconium  staining):    clear  (C)  or  meconium  staining  (M)  
! Presence  of  moulding  
! Presence  of  caput  



Maternal  condition  
! BP  and  pulse  rate  
! Temperature  
! Urine  volume  
! Urine  for  protein,  glucose,  and  acetone  
! Medications  e
...
 oxytocin  (syntocinon)  and  pain  releif  

 

 
 
 

 
 

 
 
 

 
 
Parotgram  is  essential  for  deciding  what  interventions  need  done
...
    It   has   also   been   used   to   assess   the   odds   of  
spontaneous  preterm  delivery  



Components  (4Cs  +  F):  
! Cervix  position  
! Cervix  consistency  (cervical  ripening):  firm,  intermediate  or  soft  
! Cervical  effacement  (thinning  and  shortening  of  cervix):  Effacement  is  a  measure  
of  the  stretch  already  present  in  the  cervix
...
 
! Cervical  dilation:  Dilation  is  a  measure  of  the  diameter  of  the  stretched  cervix
...
 

 
 
 

! Fetal  station:  Fetal  station  describes  the  position  of  the  fetus'  head  in  relation  to  
the   distance   from   the   ischial   spines,   which   can   be   palpated   deep   inside   the  
posterior   vagina   (approximately   8–10   cm)   as   a   bony   protrusion
...
   
Positive  numbers  =>  baby  has  made  more  of  a  descent
...
   For  example,  with  a  positive  foetal  
station   and   enagement,   mid   cavity   forceps   can   be   used
...
     


A  Bishops  score  of  5  or  less  (<6)  suggests  that  labour  is  unlikely  to  start  without  induction  
e
...
  vaginal   PGs
...
   Usueful  for  prolonged  labour
...
g
...
   Often  first  line  for  C-­‐section;  unless  emergency  =>  GA  (as  
spinal  is  trickier  to  perform  and  more  time  consuming)
...
   It  is  also  helpful  just  before  an  episiotomy
...
 Continuous  support  for  women  
during  childbirth  can  reduce  the  incidence  of  operative  vaginal  delivery  (15  trials;  n=13  357;  RR  
0
...
82–0
...
   Use  of  any  upright  
or  lateral  position  in  the  second  stage  of  labour  compared  with  supine  or  lithotomy  positions    
was  associated  with  a  reduction  in  the  number  of  assisted  deliveries  (20  trials;  n=6135;  RR  0
...
69–0
...
   Epidural  analgesia  compared  with  non-­‐epidural  methods  is  associated  with  an  
increased   incidence   of   operative   vaginal   deliveries,   (presumably   due   to   increasing   the   duration   of  
the  second  stage  of  labour)  (17  trials;  n=6162;  OR  1
...
24–1
...
60;  95%  CI  –3
...
3
...
   
The  fetus  must  be  in  a  cephalic  presentation,  and  the  sutures  should  be  palpated  to  
determine  the  position  as  occipitoanterior  or  occipitoposterior
...
   
Vacuum-­‐assisted  delivery  should  not  be  performed  if  the  fetus  has  a  suspected  bone  
mineralization  or  bleeding  disorder,  or  if  cephalopelvic  disproportion  exists    
Although   there   is   little   supportive   evidence,   it   is   recommended   that   vacuum  
deliveries  not  be  routinely  performed  in  pregnancies  at  less  than  34  weeks'  gestation  
because  of  the  potential  increased  risk  of  fetal  intracranial  hemorrhage  
When  the  presenting  part  is  at  the  ischial  spines  the  station  is  0  (synonymous  with  
engagement)
...
  Clinical   evidence   of  
engagement  on  examination  exists  when  the  leading  edge  of  the  fetal  skull  is  at  or  
below  the  ischial  spines  (+0  station)  

 
 

 
 

 
 
 

 
 
 
Blood  loss    
Normal  


Volume  <  500  mls  during  delivery  
 

Abnormal  


Before   delivery   (APH):   any   significant   loss   apart   from   bloody   “show”   (passage   of   a   small  
amount   of   blood   or   blood-­‐tinged   mucus   through   the   vagina   near   the   end   of   pregnancy
...
)  



After  delivery  (post  partum  haemorrhage  PPH)  >  500  mls  

 
Placental  separation  

 
 
 



Separation  takes  place  through  the  spongy  layer  of  decidua  basalis  (mucosa  epithleial  layer  
of  uterus),  as  a  result  of  the  uterine  contractions  being  added  to  the  retraction  (shrinking)  
of  the  uterus  that  occurs  after  the  birth  of  the  child  



Plane   of   separation:   Spongy   layer   of   decidua   basalis   (mucus   membrane   in   the   pregnant  
uterus)  



Mechanics:   Shearing   force   (inelastic   placenta   /   reduced   surface   area   on   the   placental   bed  
due  to  the  sustained  contraction  of  the  uterus  )  



Membrane   separate   by   being   thrown   into   folds   in   the   upper   part   of   the   uterus   and   by   being  
sheared  off  during  expulsion  in  the  lower  part
...
 



Syntometrine  (ergometrine  +  syntocinon)  or  syntocinon  can  be  given  in  the  third  stage  of  
labor   to   prevent   postpartum   hemorrhage   by   causing   smooth   muscle   tissue   in   the   blood  
vessel  walls  to  narrow,  thereby  reducing  blood  flow
...
   Occurs  in  the  6  
weeks  post-­‐natally
...
 
! Oxytocin  contracts  smoothe  muscle  of  breasts  =>  secretion  of  milk  
! Colostrum  (initial  discharge)  rich  in  immunoglobulin,  protective
...
g
...
g
...
    Inject   anaesthetic  
into   the   epidural   space
...
        Due   to   its   hypotensive  
effects,  it  is  the  preffered  analgesia  in  pre-­‐eclampsia
...
    Engaged   when   foetal   head   has   reached   +0  
station
...
     



Signs  of  obstruction  
 

 
 
 

 
 
 

 
 
 

 
 
 

 
 
 
Suspected  Delay  (Stage  1)  


Nulliparous:  <2cm  dilation  in  4  hours  



Parous:  <2cm  dilation  in  4  hours  or  slowing  in  progress  



Use  Bishops  score  



Rememeber  on  average,  females  dilate  at  approx  1cm  per  hour  

 
Suspected  Delay  (Stage  2)  


Nulliparous:    
! No  birth  of  baby  in  2  hours  (no  regional  anaesthesia)  
! No  birth  of  baby  in  3  hours  (with  regional  anaesthesia)  


 
 
 

Parous-­‐  multiparous:  

! No  birth  of  baby  in  1  hour  (no  regional  anaesthesia)  
! No  birth  of  baby  in  2  hours  (with  regional  anaesthesia)  
 
Suspected  Delay  (Stage  3)  


Plancenta  not  expulsed  in  30  mins  

 
 
Causes  of  failure  to  Progress:  the  3  P’s  


Power:  
! Inadequate  contractions:  frequency,  duration  and/or  strength  



Passages:  
! Short  stature  
! Trauma  
! Shape  e
...
 android  pelvis    



Passenger:  
! Big  Baby  (macrosomia)  
! Malposition:   Usually   the   fetal   head   engages   into   the   pelvis   through   the   pelivic  
inlet  in  the  occipito-­‐transverse  position  (e
...
 ROT  or  LOT)  due  to  the  wide  pelvic  
inlet   (transverse   diameter   >   AP   diameter)   and   then   undergoes   a   short   internal  
rotation  to  occipito-­‐anterior  (direct  OA,  LOA  or  ROA)  in  the  mid-­‐cavity  for  exiting  
the  pelvic  outlet  (where  AP  diameter  is  >  than  transverse  diameter)
...
 Anything  but  OA  (direct  OA,  ROA  and  LOA)  is  classed  as  malposition
...
g
...
5cm   and   AP   diameter   11cm   =>   transverse   >   AP   =>  
right/left  occipito-­‐transverse  (ROT  or  LOT)  preferred  for  engagement
...
5cm   =>   AP   >   transverse   =>  
occipito-­‐anterior  (ROA,  LOA  or  direct  OA)  presentation  preferred
...
 

 
 

 
 
 
 
The  Passenger  Attitude  (flexion/extension)  



The  head  should  be  sharply  flexed  so  that  the  chin  is  in  close  contact  with  the  chest    



 
 
 

As  a  general  rule,  the  fetus  forms  a  shaped  mass  roughly  to  the  shape  of  the  uterus  



 

The  fetal  attitude  is  the  posture  of  the  foetus  

The  head  extends  once  the  foetus  has  travelled  through  the  pelvic  outlet  (“crowning”)  

Assessing  Progress:  The  Partogram  


A   graphic   representation   of   the   progress   of   labour,   maternal   well   being,   and   foetal   well  
being  



Commence  as  soon  as  woman  enters  labour  ward  



Three  major  categorises  of  measurement:  
! Maternal  well  being:  HR,  BP,  temp,  medications  etc  
! Foetal   well   being:   HR,   amniotic   fluid   characteristics,   descent,   obstruction   e
...
 
moulding  
! Labour  progression:  cervical  dilation,  effacement,  contractions,  Bishops  score  

 
Identifying  Fetal  Distress  
Intra-­‐partum  Fetal  Assessment  


Doppler  auscultation  of  fetal  heart  (assess  HR  –  should  be  110-­‐160)  
! Stage  1  of  labour:  During  and  after  a  contraction  or  every  15  minutes  
! Stage  2  of  labour:  Every  5-­‐10  minutes  



Cardiotocograph  (CTG)  +/-­‐  STAN  (ST  segment  analysis  on  fetal  ECG)  



Colour  of  amniotic  fluid:  normally  the  amniotic  fluid  is  colourless
...
   Blood  may  also  be  present  in  the  amniotic  fluid  (recorded  
as  B  on  partogram)
...
 This  means  that  
the  baby  has  had  a  bowel  movement  before  or  during  labour,  and  it  is  a  sign  that  the  baby  
possibly   is,   or   has   been,   in   distress,   or   that   the   baby's   gut   is   mature
...
   Amniotic  fluid  is  normally  clear,  often  with  flecks  of  white  vernix
...
 The  midwife  can  tell  from  the  colour  of  
the  waters  whether  the  meconium  is  fresh  or  old
...
  If   the   waters   are   brownish   or   golden,   this   suggests   the   meconium   is  
old,  i
...
 was  passed  some  time  ago
...
 



Epidural  analgesia  



VBAC  (vaginal  birth  after  caesarean)    



PROM  (prelabour  rupture  of  the  membranes)  >24h  



Sepsis  



Induction  and  augmentation  of  labour  

 
Continuous   monitoring   of   fetal   heart   is   essential
...
     
If  foetal  distress  on  CTG  +  meconium  staining  =>  strong  indication  for  C-­‐section
...
  It   is   the   one   of   the   most   common   pathological   cause   of  
late   pregnancy   bleeding   (antepartum   haemorrhage   APH)
...
    If   a   large   amount   of   the   placenta  
separates   from   the   uterus,   the   baby   will   probably   be   in   distress   until   delivery   and  
may   die   in   utero,   thus   resulting   in   a   stillbirth
...
   Bleeding  may  be  absent  per  vagina!    Bleeding  into  the  myoemtrium  can  
cause   early   contractions   and   preterm   labour
...
   May  or  may  not  present  with  foetal  distress  depending  on  the  severity  of  
the  placenta  abruption
...
  These   vessels  
course   within   the   membranes   (unsupported   by   the   umbilical   cord   or   placental  

 
 
 

tissue)  and  are  at  risk  of  rupture  when  the  supporting  membranes  rupture
...
   Charachterised  by  foetal  distress  shortly  after  ROMs
...
  It   is   an   obstetric   emergency   during  
pregnancy  or  labor  that  imminently  endangers  the  life  of  the  fetus
...
 
! Placenta  dysfunction  
! Uterine  Rupture  
! Feto-­‐maternal  Haemorrhage  
! Uterine  Hyperstimulation  
! Regional  Anaesthesia  
! NB:   Vasa   praevia   =   low   set   fetal   blood   vessel   (close   proximity   to   internal   os);  
placenta  praevia  =  low  set  placenta  (e
...
 placenta  attachment  in  close  proximity  
to  internal  os)  
! NB:  Placenta  praevia  does  not  often  cause  foetal  distress  unless  it  transforms  into  
placenta  abruption  


Subacute:  
! Hypoxia  

 
CTG  Assessment  
CTG  Interpretation  


Use  the  pneumonic  “DR  C  BRAVADO”:    
! DR:  Determine  Risk  
! C:  Contractions  
! BRa:  Baseline  Rate  
! V:  Variability  
! A:  Accelerations  
! D:  Decelerations    
! O:  Overall  impression  

 
 
 
 

Define  risk  


You  first  need  to  assess  if  this  pregnancy  is  high  or  low  risk  



This   is   important   as   it   gives   more   context   to   the   CTG   reading   e
...
  If   the   pregnancy   is   high  
risk,  your  threshold  for  intervening  may  be  lowered  



Reasons  a  pregnancy  may  be  considered  high  risk  are  shown  below  
 

Maternal  medical  illness  


Gestational  diabetes  



Hypertension  



Asthma  

 
Obstetric  complications:  


Multiple  gestation  



Post-­‐date  gestation  



Previous  cesarean  section  



Intrauterine  growth  restriction  



Premature  rupture  of  the  membranes  



Congenital  malformations  



Oxytocin  induction/augmentation  of  labor  (avoid  medical  induction  in  foetal  distress)  



Pre-­‐eclampsia  

 
Other  risk  factors  


No  prenatal  care  



Smoking  



Drug  abuse  

 
Contractions  
 
 
 



Record  the  number  of  contractions  present  in  a  10  minute  period  e
...
 3  in  10  



Each   big   square   is   equal   to   1   minute,   so   you   look   how   many   contractions   occurred   in   10  
squares  



Individual  contractions  are  seen  as  peaks  on  the  part  of  the  CTG  monitoring  uterine  activity  



You  should  assess  contractions  for  the  following:  
! Frequency:  How  often  do  they  occur?  E
...
 3  in  10  minutes  
! Duration:    how  long  do  the  contractions  last?  
! Intensity:   how   strong   are   the   contractions?   (assessed   by   magnitude   of  
contraction  on  CTG  and  by  palpation)  

 
 
Baseline  rate  (Bra)  of  foetal  heart  



Look  at  the  CTG  &  assess  what  the  average  heart  rate  has  been  over  the  last  10  minutes  



Ignore  any  Accelerations  or  Decelerations  


 
 
 

The  baseline  rate  is  the  average  heart  rate  of  the  foetus  in  a  10  minute  window  

A  normal  foetal  heart  rate  is  between  110-­‐150  bpm  

 

 
 
 
Foetal  Tachycardia  


Foetal  tachycardia  is  defined  as  a  baseline  heart  rate  greater  than  160  bpm  



Can  indicate  foetal  distress  



It  can  be  caused  by:  
! Foetal  hypoxia  
! Chorioamnionitis:  if  maternal  fever  also  present  
! Hyperthyroidism  
! Foetal  or  Maternal  Anaemia  
! Foetal  tachyarrhythmia  

 
Foetal  Bradycardia  

 
 
 

Foetal  bradycardia  is  defined  as  a  baseline  heart  rate  less  than  120  bpm
...
   



Causes  of  prolonged  severe  bradycardia  are:  
! Prolonged  cord  compression  
! Cord  prolapse  
! Epidural  &  Spinal  Anaesthesia  
! Maternal  seizures  
! Rapid  foetal  descent  
! Placenta  abruption  



If   the   cause   of   severe   prolonged   bradycardia   cannot   be   identified   and   corrected,  
immediate  delivery  is  recommended  

 
Variability  


Baseline  variability  refers  to  the  variation  of  foetal  heart  rate  from  one  beat  to  the  next  



Variability   occurs   as   a   result   of   the   interaction   between   the   nervous   system,  
chemoreceptors,  baroreceptors  &  cardiac  responsiveness
...
 



This   is   because   a   healthy   foetus   will   constantly   be   adapting   it’s   heart   rate   to   respond   to  
changes  in  its  environment  



Normal  variability  is  between  10-­‐25  bpm  (e
...
 large  variability)  



To  calculate  variability  you  look  at  how  much  the  peaks  &  troughs  of  the  heart  rate  deviate  
from  the  baseline  rate  (in  bpm)  



Variability  can  be  categorised  as:    
! Reassuring:    ≥  5  bpm  
! Non-­‐reassuring  :  <  5bpm  for  between  40-­‐90  minutes  
! Abnormal  :  <  5bpm  for  >90  minutes  

 
 
 



Reduced  variability  can  be  caused  by:    
! Foetus  sleeping:  this  should  last  no  longer  than  40  minutes  (most  common  cause)  
! Foetal  acidosis  (due  to  hypoxia):  more  likely  if  late  decelerations  also  present  
! Foetal  tachycardia  
! Drugs  :  opiates,  benzodiazipine’s,  methyldopa,  magnesium  sulphate  
! Prematurity:  variability  is  reduced  at  earlier  gestation  (<28  weeks)  
! Congenital  heart  abnormalities  

 

 

 
 

 
 
Accelerations  

 
 
 

Accelerations  are  an  abrupt  increase  in  baseline  heart  rate  of  >15  bpm  for  >15  seconds  



The  presence  of  accelerations  is  reassuring  



Antenatally  there  should  be  at  least  2  accelerations  every  15  minutes  



Accelerations  occurring  alongside  uterine  contractions  is  a  sign  of  a  healthy  foetus  (uterine  
contractions  cause  decreased  O2  delivery  to  foetus  due  to  pressure  effects  =>  compensatory  
acceleration  of  HR)  



However   the   absence   of   accelerations   with   an   otherwise   normal   CTG   is   of   uncertain  
significance  

 

 
 
 
Decelerations  


Decelerations  are  an  abrupt  decrease  in  baseline  heart  rate  of  >15  bpm  for  >15  seconds  



There  are  a  number  of  different  types  of  decelerations,  each  with  varying  significance  

 
Early  deceleration  




This   is   due   to   increased   foetal   intracranial   pressure   causing   increased   vagal   tone   (Cushing  
reflex)  =>  bradycardia  


 
 
 

Early   decelerations   start   when   uterine   contraction   begins   &   recover   when   uterine  
contraction  stops  

It   therefore   quickly   resolves   once   the   uterine   contraction   ends   &   intracranial   pressure  
reduces  



This  type  of  deceleration  is  therefore  considered  to  be  physiological  &  not  pathological  



Appreciate  belowthat  the  decelleations  are  directly  above  the  uterine  contractions  =>  early  
decelerations    

 
 
Variable  deceleration  


Variable  decelerations  are  seen  as  a  rapid  fall  in  baseline  rate  with  a  variable  recovery  phase  



They  are  variable  in  their  duration  &  may  not  have  any  relationship  to  uterine  contractions  



They   are   most   often   seen   during   labour   &   in   patients   with   reduced   amniotic   fluid   volume  
(oligohydraminos)  



Variable  decelerations  are  usually  caused  by  umbilical  cord  compression  =>  WORRYING  
 

Late  deceleration  


Late  decelerations  begin  at  the  peak  of  uterine  contraction  &  recover  after  the  contraction  
ends
...
25)  it  indicates  significant  foetal  hypoxia  &  the  need  
for   emergency   C-­‐section   or   operative   vaginal   delivery   (hypoxia   causes   acidosis   due   to  
tissue  anaerobic  glycolysis)  



We  use  C-­‐section,  as  medical  induction  of  labour  can  increase  foetal  distress  



Appreciate  below  that  the  decelerations  begin  at  peak  of  uterine  contraction  and  continue  
after  the  uterine  contraction  

 
 
Prolonged  deceleration  


A  deceleration  that  last  more  than  2  minutes  



If  it  lasts  between  2-­‐3  minutes  it  is  classed  as  Non-­‐Reasurring  



If  it  lasts  longer  than  3  minutes  it  is  immediately  classed  as  Abnormal  



Action  must  be  taken  quickly  e
...
 Foetal  blood  sampling  /  emergency  C-­‐section  /  operative  
vaginal  delivery  (if  possible)  
 

Overall  impression  


 
 
 

Once  you  have  assessed  all  aspects  of  the  CTG  you  need  to  give  your  overall  impression  
The  overall  impression  can  be  described  as  either:    

! Reassuring  
! Suspicious  
! Pathological  


The   overall   impression   is   determined   by   how   many   of   the   CTG   features   were   either  
reassuring,  non-­‐reassuring  or  abnormal
...
      Actually   no!     The   variability   is   of   the   baseline,   excluding  
accelerations  and  decelerations
...
     
! Accelerations:  None  
! Decelerations:   Late   deccelerations   (occurring   at   max   of   uterine   contractions   &  
recovering  after  contraction  ends)  
! Overall  impression:     The  presence  of  late  decelerations  is  taken  seriously  &  foetal  
blood   sampling   for   pH   is   indicated
...
g
...
 These  drugs  are  also  useful  for  when  delivery  would  result  in  premature  
birth  as  also  buys  time  for  the  administration  of  betamethasone,  a  glucocorticoid  drug  which  
greatly   accelerates   fetal   lung   maturity   (increases   surfactant   production   which   prevents  
against   RDS),   but   takes   one   to   two   days   to   work
...
g
...
   This  is  because  
palpation   can   cause   local   placental   separation   and   precipitate   massive  
antepartum  hemorrhage  (APH)  



Fetal  blood  sampling  for  blood  gases  



Operative  Delivery:    can  go  straight  to  C-­‐section  if  severe  signs  of  distress    

 
Fetal  Blood  Sampling  


Fetal   scalp   pH   testing   is   a   procedure   performed   when   a   woman   is   in   active   labor   to  
determine  if  the  baby  is  getting  enough  oxygen
...
25  -­‐  7
...
20  -­‐  7
...
20   =>   deliver   with   surgical   methods   e
...
  operative   vaginal  
delivery   with   forceps   or   ventouse   suction   (medical   induction   e
...
  with  
syntocinon  and  PGs  is  contraindicated  in  foetal  distress)  or  C-­‐section  

 
 
 

 
 
Operative  Vaginal  Delivery    


“Standard”  Indications:  
! Delay    (failure  to  progress  during  stage  2;  the  cervic  must  be  fully  dilated  
and   the   foetus   must   be   engaed   before   considering   operational   vaginal  
delivery)  e
...
 due  to  malposition  (e
...
 ROP,  OP  or  LOP)  
! Fetal  distress  

 


“Special”  Indications:  
! Maternal  cardiac  disease  
! Severe  PET  (preeclampsia)  or  eclampsia  
! Intra-­‐partum  haemorrhage  (haemorrhage  during  labour)  
! Umbilical  cord  prolapsed  during  stage  2  




 
 
 

No  indication  is  absolute
...
  They're  
curved   to   fit   around   the   baby's   head
...
  With   a   contraction   and   your   pushing,   an  
obstetrician   gently   pulls   to   help   deliver   your   baby
...
  Some   forceps   are   specifically   designed   to   turn   the   baby   to   the   right   position   to   be  
born,  for  example,  if  your  baby  is  lying  in  an  abnormal  position  (malpositon)  such  as  facing  
upwards  (occipito-­‐posterior  position)  or  to  one  side  (occipito-­‐transverse  position)
...
 
! More   commonly   used   when   babys   head   is   high   in   the   pelvis   (but   must   be  
engaged)  or  when  baby  is  in  malposition  



 
 
 

Use  the  most  appropriate  instrument  for  individual  circumstances
...
     

 
Caesarean  section  (C-­‐section)  


Rate  is  increasing  (NHS  Tayside  27%)  



Main  indications:  
! Previous  CS  (C-­‐section)  
! Fetal  distress  
! Failure  to  progress  in  labour  and  operative  delivery  CI  (e
...
 not  engaged)  
! Breech  presentation  
! Maternal  request  



4  X  greater  maternal  mortality  associated  with  CS  (C-­‐section)  



Morbidity:    
! Sepsis  
! Haemorrhage  
! VTE=  >  LMWH  propylaxis    
! Trauma  
! TTN  (transient  tachypnoea  of  the  newborn)  
! Subfertility  
! Regret  
! Complications  in  future  pregnancy  

 
Conclusions  



Progress   determined   by   3   P’s:   power   of   contractions   (frequency,   duration   and   strength),  
passage,  and  passenger  



Partogram  +  Bishops  score  is  used  to  identify  and  manage  failure  to  progress  



Fetal   distress   is   common   but   recognition   and   appropriate   management  will   reduce   perinatal  
morbidity  


 
 
 

Labour  is  process  leading  to  expulsion  of  fetus  (stage  2)  and  placenta  (stage  3)  

Most  women  will  have  a  spontaneous  vaginal  delivery  (SVD)    

 
 
COMMON  SURGICAL  PROBLEMS  OF  THE  NEONATE  


In  medical  contexts,  newborn  or  neonate  refers  to  an  infant  in  the  first  28  days  after  birth
...
g
...
g
...
  Incarceration   is   the   most   common   cause   of   bowel   obstruction   in  
infants  and  children
...
  In   cases   of   strangulation,  

 
 
 

ischemic  necrosis  develops,  and  intestinal  perforation  may  result,  representing  a  
true  medical  emergency
...
 


DD:   In   boys,   differentiating   between   a   hernia   and   a   hydrocele   is   not   always   easy
...
     Can  get  above  a  hydrocele  but  
cant  get  above  a  hernia
...
 Emesis  caused  by  an  obstruction  
proximal  to  the  ampulla  of  Vater  is  usually  of  gastric  content
...
    In   distal   ileal   obstructions,   vomit   is  
feculent
...
 



Newborns  with  jejunoileal  atresia  or  stenosis  present  with  bilious  vomiting  and  obstructive  
(conjugated   hyperbilirubinaemia)   jaundice;   these   infants   may   not   pass   meconium   in   the  
first  day  of  life
...
   



Abdominal  distention  occurs  more  often  in  patients  with  ileal  atresia
...
     



Patients  (often  infants)  present  acutely  with  midgut  volvulus  (twisting  of  a  loop  of  intestine  
around  its  mesenteric  attachment  site),  manifested  by  bilious  vomiting,  crampy  abdominal  
pain,  abdominal  distention,  and  the  passage  of  blood  and  mucus  in  their  stool
...
     



Malrotation  can  also  be  entirely  asymptomatic
...
   



Meconium  ileus  is  often  the  first  sign  of  cystic  fibrosis
...
 



In   patients   with   meconium   ileus,   symptoms   depend   on   the   level   of   the   obstruction   (which   is  
usually  the  terminal  ileum)  and  may  include  vomiting  (usually  bile-­‐stained),  failure  to  pass  
meconium  in  the  first  48  hours  of  life,  and  possible  abdominal  distension
...
 



Causes  of  delayed  passage  of  meconium  =  CF  and  Hirschprungs  
 

Necrotising  enterocolitis  (NEC)  
 
 
 



Necrotizing   enterocolitis   (NEC)   is   a   medical   condition   primarily   seen   in   premature   infants,    
where  portions  of  the  bowel  undergo  necrosis  (tissue  death)
...
   



 Initial   symptoms   include   feeding   intolerance,   increased   gastric   residuals,   abdominal  
distension   and   bloody   stools
...
   



 Often  occurs  after  RDS      



Breast  feeding  is  the  best  intervention  to  prevent  NEC  



CF  is  among  the  most  common  causes  of  obstruction  in  neonate    



AR  genetic  disorder    



CF  results  in  the  production  of  thick  secretions  



The   meconium   sometimes   becomes   thickened   and   congested   in   the   ileum,   a   condition  
known   as   meconium   ileus
...
    In   cystic  
fibrosis,   the   meconium   can   form   a   bituminous   black-­‐green   mechanical   obstruction   in   a  
segment  of  the  ileum
...
   Thus,  it  allows  oxygenated  blood  from  the  
placenta  to  bypass  the  liver  
! Foramen  ovale:  R  to  L  shunt  (to  bypass  lungs)  from  R  atrium  to  L  atrium    
! Ductus   arteriosus:   R   to   L   shunt   from   pulmonary   trunk   to   proximal   descending  
aorta  


Oxygenated  blood  from  placenta    travels  to  the  foetus  via  the  single  umbilical  vein  



The  oxygenated  blood  bypasses  the  liver  via  the  ductus  venosus  



Arrives  in  right  atrium  via  IVC  



Majority  travels  from  right  atrium  to  left  atrium  via  foramen  ovale  (R  to  L  shunt)
...
     



Blood  which  does  not  travel  through  the  foramen  ovale  travels  from  right  atrium  into  right  
ventricle   and   then   into   the   pulmonary   trunk
...
    Surfactant   deficiency   =>   decreases   lung  
compliance  =>  restrictive  lung  disease  which  makes  it  harder  to  inhale  and  inflate  lungs,  as  
the  alveoli  are  prone  to  collapsing
...
  It   is  
essential   that   fluid   be   breathed   into   the   lungs   in   order   for   them   to   develop   normally
...
    Therefore   amniotic   fluid   prepares   the   lungs,   kidneys   and   GI   tract   for   their  
extra-­‐uterine  job
...
 This  triggers  it  to  take  
the  first  breath,  within  about  10  seconds  after  delivery
...
     

Stimulus  causes  chest  expansion  and  diaphragm  contraction  =>    huge  negative  intrathoracic  
pressure  =>  results  in  large  breaths  



Cries:   baby   breathes   out   against   partially   closed   cords,   generates   PEEP   (positive   end  
expiratory   volume)   =>   Drives   fluid   back   into   interstitium,   which   is   then   absorbed   and  
transported  by  lymphatics  



With  the  first  breaths,  there  is  a  fall  in  pulmonary  vascular  resistance  and  an  increase  in  the  
surface  area  available  for  gas  exchange
...
 Oxygenated  blood  
now   reaches   the   left   atrium   and   ventricle,   and   through   the   descending   aorta   reaches   the  
umbilical  arteries
...
  As   the   pulmonary   circulation   increases   there   is   an  
equivalent   reduction   in   the   placental   blood   flow   which   normally   ceases   completely   after  
about  three  minutes
...
   



Closure   of   formaen   ovale:   The   increase   in   pulmonary   venous   return   results   in   left   atrial  
pressure   being   slightly   higher   than   right   atrial   pressure   (reverse   from   foetal   pressure  
differences  LA  pressure  >>  RA  pressure),  which  closes  the  foramen  ovale
...
     
Within   minutes   or   up   to   a   few   days   after   birth,   the   ductus   arteriosus   closes   due   to   a  
decrease   in   PGs   (due   to   removal   of   placenta,   which   is   a   major   source   of   foetal   PGs;   PG  
inhibitors   can   cause   premature   closure   of   duct;     PG   infusions   can   keep   duct   open   which   is  
important  for  duct  dependent  cyanotic  heart  defects)  and  increased  O2  tension
...
     



The  higher  blood  oxygen  content  of  blood  within  the  aorta,  and  the  removal  of  the  placenta,    
stimulates  the  constriction  and  ultimately  the  closure  of  this  fetal  circulatory  shunt
...
  During   this   transition,   some   types   of   congenital  
heart  disease  that  were  not  symptomatic  in  utero  during  fetal  circulation  will  present  with  
cyanosis  or  respiratory  signs
...
5kPa   (fetal   level)   to   9-­‐13kPa   =>   baby   changes   colour  
from  blue  to  pink  

 
 
 

! Decrease   in   pulmonary   vascular   resistance   +   reduced   flow   back   to   placenta   =>  
increased  pulmonary  blood  flow  =>  pressure  in  left  heart  >  pressure  in  right  heart  


Detachment  from  placenta  and  clamping  of  cord:  
! Transition   from   the   placenta   to   the   lungs   must   take   place   quickly   but   not  
instantly
...
 This  leads  to  a  number  of  changes  which  are  not  completely  
understood
...
  This   differential   in   resistance   results   in   a   high   flow   through   the  
placenta  and  a  low  flow  through  the  pulmonary  circulation
...
 The  output  of  the  heart  does  
not  change  so  the  output  is  reduced  to  the  other  organs,  especially  the  placenta  
as   a   result   of   constriction   within   the   umbilical   arteries   (due   to   increased   PP   of  
O2)
...
  The   two   effects   co-­‐operate   to   redirect   blood   to   the   newborn   infant’s  
lungs  and  away  from  the  placenta  so  that  within  a  few  minutes,  sometimes  in  
less   than   a   minute   in   a   vigorous   baby,   the   pulmonary   circulation   is   fully   opened  
up   and   the   placental   circulation   completely   closed   down
...
      This   facilitates   detachment   of  
the  placenta
...
    However   we   must   balance   the   risk   with  
the  benefits  of  delayed  clamping
...
  In   this  
review,   delayed   clamping,   as   contrasted   to   early   (<   1   minute),   resulted   in   no  
difference   in   risk   of   severe   maternal   postpartum   hemorrhage   or   neonatal  
mortality
...
5   g/dL   with   half   the   risk   of   being   iron   deficient   at   three   and   six  
months,  but  an  increased  risk  of  jaundice  requiring  phototherapy
...
   
Remember  that  prostaglandins  cause  the  ductus  arteriousus  to  remain  open
...
   However,  pathological  processes  such  as  PTE  
can  cause  RA  pressure  >  LA  pressure  which  can  even  result  in  an  embolism  from  a  
DVT   travelling   into   the   systemic   circulation   and   causing   a   stroke   (paradoxical  
embolism)  

 


Ductus  arteriosus  
! Becomes  ligamentum  arteriosus  
! Persistent   ductus   arteriosus   (PDA)   if   persists:   causes   L   to   R   shunt   (Acyanotic)  
which   allows   allows   oxygen-­‐rich   blood   from   the   aorta   to   mix   with   oxygen-­‐poor  
blood   from   the   pulmonary   artery
...
    If   pulmonary   HT  
continues,   the   pressures   in   R   can   become   >   than   L   =>   Eisenmengers   syndrome  
can  occur  (cyanotic  R  to  L  shunt)
...
g
...
6  

 
Nutrition  


Gut  prepared  by  in  utero  swallowing  of  amniotic  fluid  =>  produces  meconium  



Endocrine  factors:  Thyroxine  and  corticosteroids  have  a  role  in  maturing  the  gut  



Feeding:  Introduction  of  milk  causes  increase  in  intestinal  enzymes  



Breast  milk:  Growth  factors  in  breast  milk  regulate  adaptive  changes  



Bacteria:   The   gut   becomes   colonised   with   bacteria   following   delivery   (some   bacteria   are  
important  for  Vit  K  production,  one  factor  for  why  newborns  are  sometimes  deficient  in  Vit  
K)  

 
Breast  Feeding  


Baby   starts   to   suckle   (stimulus)   =>   signals   sent   to   hypothalamus   =>   feedback   loop   causes  
increase  in  supply  



Hormones:  
! Oxytocin  (posterior  pituitary):  smooth  muscle  contraction  =>  milk  ejection  
! Prolactin  (anterior  pituitary)  =>  milk  production  



Composition  changes:  
! Colostrum  (IgA  rich)  
! Foremilk  and  hindmilk  

 

 
 
 

 
 
Benefits  of  breast  feeding  


Passive  immunity:  
! IgA  =>  less  colds,  coughs,  ear  infections  
! Cells  
! Promotes  healthy  colonisation  
! Prevents  against  NEC  



Growth  factors  



Bonding  



Maternal  health  



Financial  

 
 
Haematology  


Fetal  haemoglobin  (HbF=  alpha  2,  gamma  2)  
! Becomes  disadvantageous  
! HbF   has   a   greater   affinity   for   oxygen   (shift   to   left)   due   to   lack   of   fetal  
hemoglobin's  interaction  with  2,3-­‐bisphosphoglycerate  (2,3-­‐BPG)  
! In  adult  HbA,  increase  in  2,3  BPG  shifts  curve  to  right  =>  gives  up  O2  more  readily  
=>  useful  effect  

 
 
 



Haematopoiesis  moves  to  bone  marrow  (which  takes  over  from  Liver)  



Adult  HbA  (alpha  2,  beta  2)  synthesised  more  slowly  than  Fetal  Hb  broken  down  
! Physiological  anaemia  can  occur:  Nadir  (lowest  point)  of  Hb  at  8-­‐10  weeks  
! Physiological   jaundice   can   also   occur   due   to   RBC   breakdown   and   immaturity   of  
liver  

 
 
Liver  


Enzyme  pathways  present  but  immature  



Physiological  Jaundice:  
! Does  NOT  occur  on  first  day  of  life
...
   



Water  loss  up  to  around  10%  of  body  weight  is  important  part  of  adaptation  

 
Adaptation  problems  


Some  important  ones:  not  an  exhaustive  list  
! Persistent  pulmonary  hypertension  of  newborn  or  persistent  fetal  circulation  
! Transient  tachypnoea  of  the  newborn:  associated  with  C-­‐section  
! Hypothermia  
! Hypoglycaemia  (<2
...
     



It   can   be   associated   with   pulmonary   hypertension
...
 



Lung  vascular  resistance  fails  to  fall  =>  pressure  on  right  side  of  heart  remains  >  left  side  of  
heart  



Therefore  R  to  L  cyanotic  shunts  remain:  
! Right  to  left  flow  at  PFO  (patent  foramen  ovale  with  a  R  to  L  shunt)  
! Right  to  left  flow  at  PDA  (patent  ductus  arteriosus  with  a  R  to  L  shunt)  



Cyanotic  heart  problem  due  to  R  to  L  shunt  (pumping  of  deoxygenated  blood  into  systemic  
circulation)  =>  Blue  baby  (cyanosis)  



Causes  pulmonary  hypertension  and  right  heart  strain  (due  to  increased  lung  resistance)  



Large   difference   between   pre   and   post   ductal   oxygen   saturation   e
...
  large   differences  
between  SpO2  of  right  arm  (pre-­‐ductal)  and  left  leg  (postductal)  due  to  the  R  to  L  shunt  PDA
...
g
...
 
! Eisenmengers:    secondary  pulmonary  HT  due  to  long  term  L  to  R  shunt  can  also  
result  in  L  to  R  shunt  
! With  normal  L  pressures  >  R  pressures  =>  L  to  R  shunt  =>  acyantoic  =>  no  notable  
difference  between  pre  and  post  duct  sats  (more  common)  





Surgery  may  be  required  



Note:    If  duct  dependent  cyanotic  heart  disease  we  can  keep  the  duct  open  with  PG  infusion    



 
 
 
 

PDA  can  be  treated  with  NSAIDS  (e
...
 indamethacin  and  aspirin)  which  decrease  PG  activity  
=>  stimulate  closure  of  the  duct  

Aspirin  should  be  avoided  during  the  third  trimester  due  to  possible  bleeding  complications  
and   premature   closure   of   the   ductus   arteriosus,   which   may   lead   to   pulmonary   vasculature  
abnormalities  and  pulmonary  hypertension  in  the  newborn  

Transient  Tachypnoea  of  Newborn  


Lung  fluid  fails  to  clear  completely  



Lungs  remain  waterlogged  and  stiff  



Decreased  gas  exchange  



Increased   work   of   breathing:   Grunting,   tachypnoea,   recession,   nasal   flaring   –   usually  
resolves  within  1-­‐2  days    



Oxygen  requirement  



Need  to  consider  and  exclude:  
! Infection  
! surfactant  deficiency  (infant  respiratory  distress  syndrome)  
! cardiac  disease  
! congenital  anomalies  



Risk  factors:  
! Caesarean  section  (as  vaginal  birth  helps  to  clear  the  fluid  from  the  lungs)  
! Especially  if  not  in  labour  

 
Hypothermia  


Babies  need  help  with  maintaining  temp  
! Dry  –  first  stage  in  neonatal  recussitation  (in  all  circumstances)  
! Hat  
! Clothes  
! Blankets    
! Skin  to  skin  cuddles  
! Incubator  +/-­‐  humidity  



More  at  risk  if  small  or  premature  
! Low  stores  of  brown  fat  (thermogensis  from  fat  is  key  source  of  heat  production  
in  neonates)  

 
 
 

! Little  subcutaneous  fat  (thermogensis  from  fat  is  key  source  of  heat  production  
in  neonates)  
 
Hypoglycaemia  


In  neonate,  hypoglycemia  should  be  diagnosed  if  blood  glucose  is  <2
...
g
...
g
...
g
...
g
...
g
...
 
Immunoglobulin   G   (IgG)   antiplatelet   antibodies   recognize   membrane  
glycoproteins   and   coat   the   platelets,   which   then   are   destroyed   by   the  
reticuloendothelial  system,  predominantly  in  the  spleen
...
 
! As  part  of  DIC  (thrombocytopenia,  low  clotting  factors,  low  fibrin  and  high  FDPs)  
! HELLP:     haemolytic   anaemia,   elevated   liver   enzymes,   low   platelets   –   seen   in  
preeclampsia  



Von   Willebrand’s   Disease   (vWF   deficiency):   low   VWF   and   prolonged   APTT   (as   VwF   binds  
Factor  VIII),  prolonged  bleeding  time  test  (in  contrast  to  Haemohillia)  

 
Consequences  of  failure  of  Platelet  Plug  Formation  


Spontaneous  Bruising,  Purpura  and  Petechia  



Mucosal  Bleeding  
! Conjunctival  
! Epistaxes  
! Gastrointestinal  
! Menorrhagia  –  obviously  not  in  pregnancy!  
! Post  Partum  Haemorrhage  (PPH)  




 
 
 
 

Neonatal   intracranial   haemorrhage:   10%   of   babies   may   have   thrombocytopenia   in  
maternal   ITP:   In   ITP,   antiplatelet   antibodies   (IgG)   may   cross   the   placenta   and   cause  
significant   fetal   thrombocytopenia   which   could   result   in   bleeding   complications   in   the  
neonate  
Retinal  haemorrhages  

Screening  Tests  for  Primary  Haemostasis  


Platelet  count  



vWF  assay  



Bleeding  time:    prolonged  with  primary  haemostasis  problems    



NB:   vWD   can   result   in   prolonged   APTT   (secondary   haemostatic   problem)   as   VWF   is   a   carrier  
protein   for   FVIII   (vWF   protects   the   factor   VIII   from   rapid   breakdown   within   the   blood)
...
 



No  simple  screening  tests  for  other  components  of  primary  haemostasis  

 
Secondary  Haemostasis:  Fibrin  Clot  Formation  


Extrinsic  pathway:    
! Tissue   factor   and   platelets   activate   the   clotting   cascade   to   make   thrombin
...
     
! Factor  VII  important
...
 
!  PT  and  INR  (modified  PT)  is  a  measure  of  the  extrinsic  pathway  function
...
   
! F  VIII  and  F  IX  important  
! APTT  is  a  measure  of  the  intrinsic  pathway  function    




 
 
 

Common  pathway:  F  I,  II,  V  and  X  
See  haematology  notes  

 
 
Failure  of  Fibrin  Clot  Formation:  causes  


Single  clotting  factor  deficiency  
! Usually  hereditary    
! Haemophilia   A:   factor   VIII   deficiency   =>   affects   intrinsic   pathway   =>   prolongs  
APTT
...
g
...
     
! Haemophilia  B:  factor  IX  deficiency  =>  affects  intrinsic  pathway  =>  prolongs  APTT
...
     
! NB:   Haemophilia   does   NOT   usually   manifest   clinically   in   females   (as   X   linked  
disorder  =>  females  have  another  X  chromosome  to  compensate),  however  due  
to  X  linked  inactivation  females  do  often  have  lower  levels  of  clotting  factors  =>  
may   cause   problems   in   pregnancy   e
...
  peri-­‐partum   haemorrhage   (during  
labour)  or  post-­‐partum  haemorrhage  (PPH)  



Multiple  clotting  factor  deficiencies  
! Usually  acquired    

 
 
 

! Disseminated  Intravascular  Coagulation  (DIC)  
! Vit  K  deficiency  (F  2,7,9  and  10)  
! Warfarin  use  (F2,  7,  9  and  10)  
! Liver  disease:    impaired  synethesis  and/or  Vit  K  deficiency  (due  to  impaired  bile  
production)  


Increased  fibrinolysis  
! usually  part  of  complex  coagulopathy  

 
Consequences  of  failure  of  Fibrin  Clot  Formation  (secondary  haemostasis)  


Often  no  characteristic  clinical  syndrome  however  may  present  with  deep  bleeds  



Deep  bleeds:  
! Bleeding  in  to  joints  (haemarthrosis)  
! Soft  tissue  bleeds  e
...
 intramuscular  bleed  or  subcut  bleeds  



May  be  combined  primary/secondary  haemostatic  failure  



Pattern  of  bleeding  depends  on  
! Single/multiple  abnormalities  
! The  clotting  factors  involved  

 
Disseminated  Intravascular  Coagulation  




Wide  spread  inflammation  results  in  innapropriate  activation  of  coagulation  cascade  



DIC   leads   to   the   formation   of   small   blood   clots   inside   the   blood   vessels   throughout   the  
body
...
g
...
   



The  small  clots  also  disrupt  normal  blood  flow  to  organs  by  occulsion  (such  as  the  kidneys),  
causing  ischemia  which  may  malfunction  as  a  result  (end  organ  damage)  


 
 
 

Disseminated   intravascular   coagulation   (DIC)   is   a   pathological   activation   of   coagulation  
(blood  clotting)  mechanisms  that  happens  in  response  to  a  variety  of  diseases
...
g
...
     



Triggers   of   this   process   in   pregnancy   include   endothelial   damage,   the   release   of   placental  
tissue,  amniotic  fluid  (amniotic  fluid  embolism),  incompatible  red  cells  or  bacterial  products  
into  the  maternal  circulation
...
 



DIC   is   essentially   an   abnormal   response   to   tissue   damage   and   represents   a   complex  
interaction  between  the  inflammatory  and  coagulation  pathways
...
g
...
g
...
f
...
g
...
g
...
g
...
  If   it  
happens  before  you  are  due  to  give  birth,  it  might  be  a  sign  of  early  labour
...
   
Can  transform  into  placenta  abruption
...
g
...
 Majority  of  the  time,  bleeding  occurs  after  the  36th  week  



Classification:  Type  I  –  IV:  
! Type   I:   Placenta   in   lower   uterine   segment,   but   the   lower   edge   does   not   reach  
internal  os  
! Type  II:  Lower  edge  of  placenta  reaches  internal  os,  but  does  not  cover  it  
! Type  III:  placenta  covers  internal  os  partially  (placenta  covers  cervix    /  internal  os,  
but  would  not  cover  in  labour  when  dilated)  
! Type   IV:   Placenta   covers   cervix   internal   os   completely   (would   still   cover   in   full  
dilatation)  



Minor  vs
...
    This   is   because   the  
placenta  can  block  the  presenting  part  from  entering  the  internal  os
...
 
May  have  been  a  low-­‐lying  placenta  in  a  previous  US,  or  may  have  been  previously  normal  



Soft  uterus  (usually)  =>  fetus  easy  to  palpate  



High   presenting   part:     head   not   engaged   e
...
  head   not   entered   pelvis   through   pelvic   inlet  
(placenta  is  stopping  head  from  engaging)  



Malpresentation:  Breech  or  transverse  Lie  (as  placenta  is  stopping  head  from  engaging)  
! If  patient  presents  with  high  presenting  part  /  breech  /  transverse  lie  =>  scan,  as  
bleeding  may  not  be  present  in  placenta  praevua  



CTG:     usually   no   fetal   distress   as   blood   loss   is   usually   small   (can   use   to   distinguish   from  
placental  abruption)  

 
Diagnosis  


Ultrasound  Scan,  NOT  clinical  diagnosis  



DO  NOT  PERFORM  DIGITAL  VAGINAL  EXAMINATION  UNTIL  PLACENTAL  PRAEVIA  HAS  BEEN  
EXCLUDED  –  can  provoke  massive  obstetric  haemorrhage  
 

Management    




Admit  to  ward:  IV  access,  blood  tests,  cross  match  



Rescan  after  interval  



Anti-­‐D  if  rhesus  –ve  mother  



 
 
 

DO   NOT   PERFORM   VAGINAL   EXAMINATION   UNTIL   PLACENTA   PRAEVIA   HAS   BEEN  
EXCLUDED:  pelvic  exam  may  cause  massive  bleeding  

Steroids   if   expectant   management   (PP   can   cause   preterm   labour   due   to   preterm   premature  
rupture   of   membranes   =>   preterm   infents   at   risk   of   NRDS   =>   steroids   can   help   mature   lungs  
by  encouraging  surfactant  production)  



Caesarean   section   (if   <2cm   distance   from   internal   os   to   placenta)   at   38   weeks   if   clinically  
stable:  deliver  sooner  if  significant  haemorrhage  

 
Placenta  Accreta  


Abnormally   deep   attachment   (adherence)   of   the   placenta   to   the   myometrium   (middle  
muscular  layer  of  the  uterus)  without  penetrating  it  =>  placenta  grows  completely  through  
endometrium  



Very  significant  complication:  assoc
...
  Placenta   can   implant   over   a   uterine   scar   from   a  
previous  C-­‐section  =>  trophoblast  can  penetrate  through  scarred  decidua  and  myometrium
...
  Majority   will   require  
hysterectomy,  unless  area  of  adherence  is  small  



The   safest   and   most   common   treatment   is   a   planned   elective   caesarean   section   (+/-­‐  
hysterectomy)  if  placenta  accreta  is  diagnosed  before  birth  



The   haemorrhage   is   frequently   accompanied   by   DIC   =>   anticipate   in   women   with   Hx   of   C-­‐
section  
 

Variations  


Placenta   accreata:   The   placenta   attaches   strongly   to   the   myometrium,   but   does   not  
penetrate  it
...
 



Placenta  Increta:  villi  invade  into,  but  not  through,  the  myometrium  



Placenta  Percreta:  villi  invade  through  the  full  thickness  of  myometrium  to  the  serosa;  may  
cause   uterine   rupture
...
    This   variant   can   lead   to   the  
placenta  attaching  to  other  organs  such  as  the  rectum  or  bladder  

 
Placental  abruption  (abruption  placentae)  



Normally  sited  placenta  



Placental  abruption  is  a  serious  condition  where  the  placenta  starts  to  come  away  from  the  
inside   of   the   uterus   wall
...
  If   it  
happens  close  to  your  baby's  due  date,  the  baby  may  be  delivered  early
...
 



Post  partum  Haemorrhage  (PPH)  can  also  occur  from  the  damaged  attachment  site  



Associated   with   DIC:   thromboplastins   released   from   damaged   vessels   =>   widespread  
intravascular   coagulation
...
 
Patients  often  present  with  reduced  fetal  movement  and  abdominal  pain
...
g
...
g
...
     



Large   for   dates   uterus   (uterus   full   of   blood   =>   stretching   of   uterus   =>   increased   uterine  
activity)  



Difficult  to  feel  fetal  parts  



 
 
 

Small  or  large  volume  blood  loss  –  vary  variable  level  of  APH  

May   have   associated   polyhdraminos   –   cause   distension   of   uterus   and   then   when   water  
breaks   we   cget   a   sudden   pressure   change   and   the   placenta   may   rupture   (waters   should  
always  be  brokwn  slowly  in  polyhydraminos)  



CTG:    
! May  be  poor  due  to  foetal  distress  (decreased  blood  supply  to  foetus)  
! Placental   abruption   assoc
...
 with  maternal  morbidity)  



Vaginal  birth  is  usually  preferred  over  caesarean  section  unless  there  is  fetal  distress  (e
...
 
abnormal  CTG  and/or  meconium  staining)  



Caesarean   section   may   be   contraindicated   in   cases   of   disseminated   intravascular  
coagulation
...
  Excessive   bleeding   from   uterus   may  
necessitate  hysterectomy  



Anti-­‐D  if  Rh  –ve  mother  



Steroids  if  expectant  management  

 
Local  causes  of  APH  


 
 
 

Local  causes,  e
...
 vulval  or  cervical  infection,  trauma,  tumours  or  polyp  
Tend  to  be  small  volume  of  blood  loss  



Painless  



Often  a  provoking  factor  e
...
 coitus  (vaginal-­‐penis  penetration)  



Uterus  soft,  non  tender  



Normal  fetal  presentation  



No  fetal  distress  



Normally  sited  placenta  

 
Treatment  


Cervical  causes:  colposcopy  



Infection:  swabs  /  specific  treatment  

 
Compare  and  contrast:  Placenta  Praevia,  placenta  abruption  and  local  pathology  
 

 
 
 
 
 

 
Vasa  Praevia  


Vasa   Praevia   =   fetal   vessels   within   the   membranes   due   to   low   set   foetal   vessels   (e
...
 



Integrity  of  the  myometrial  wall  is  breached  



Incomplete  rupture  =  peritoneum  still  intact  



Complete   rupture   =   contents   of   the   uterus   may   spill   into   the   peritoneal   cavity   /   broad  
ligament  



Life-­‐threatening  for  mother  and  baby  



Usually  occurs  during  labour,  may  occur  late  pregnancy  



1  in  500  risk  if  Hx  C-­‐section  (C-­‐section  weaknes  uterine  wall  due  to  scars)  



1  in  2000  risk  of  losing  baby  



About  40%  of  women  who  have  uterine  rupture  had  prior  surgery  of  their  uterus,  including  
Caesarean   section   (CS)
...
 



Other  risk  factors  for  uterine  rupture  include:  
! More  than  four  pregnancies  

 
 
 

! Trauma  
! Excessive  use  of  oxytocin  
! Shoulder  dystocia  
! Placenta  percreta  
! Some  forceps  deliveries  


The  rupture  may  occur  before  or  during  labour  or  at  the  time  of  delivery
...
g
...
g
...
 She  may  well  not  feel  any  symptoms  but  may  feel  
light  headed
...
 



 A   good   sign   of   significant   hypovolaemia   is   if   the   pulse   rate   is   above   her   systolic   blood  
pressure
...
   



As   more   blood   is   lost   she   will   look   pale   with   cold   clammy   skin   (vasoconstriction   =>  
increased  TPR  =>  increased  MAP  =>  another  compensatory  mechanism)  



Decreased  UO  is  another  compensatory  mechanism    



About   30%   of   circulating   volume   needs   to   be   lost   before   hypotension   sets   in  
(decompensated)    



By  the  time  she  drifts  into  unconsciousness  she  will  have  lost  around  40%  of  her  circulating  
volume
...
   

 

 
 
 
 
 

 
 
Management  of  APH  
History  


Bleeding:   site,   onset,   character   (colour,   clots),   associated   symptoms,   timing,   exacerbating  
and  relieving  factors,  severity  (volume)  



Pain:  distinguishes  between  Placenta  Praevia  (painless)  &  placenta  abruption  (painful)  



Contractions:   placenta   abruption   can   fill   the   uterus   with   blood   (couvelaire   uterus)   =>  
stimulates  contractions
...
     



Fetal  movements:  may  be  reduced  in  abruption  (foetal  distress)  



Provoking  factors:  
! Post-­‐coital?  (after  sex)  =>  suggestive  of  local  pathology  e
...
 cervical  polyp  
! RTA  =>  may  be  suggestive  of  placental  abruption  



Cervical  smear  history:  exclude  cervical  cancer  



Scan  history:  previously  low  placenta?  (Placenta  praevia  has  low  placenta)  



Associated  discharge?  

 
Examination  /  Assessment  



Assess   for   signs   of   hypovolaemia   e
...
  tachycardia,   low   BP,   increased   CRT   (capillary   refill  
time),  decreased  skin  turgor,  dry  mucous  membranes  



Assess  volume  of  APH  



Fundal  height:  large  for  dates  in  Abruption    



Uterine  tenderness:  tender  in  Abruption  



Uterine  activity:  contractions  in  Abruption  (due  to  blood  causing  distension)  



Fetal   lie   and   presentation:   high   presenting   part   in   Placenta   Praevia   +/-­‐   malpresentation   (e
...
 
breech  or  transverse)  


 
 
 

ABCDE  is  the  first  priority:  record  all  vital  signs  

Auscultation  of  Fetal  Heart  and  CTG:  confirm  baby  still  alive  (most  likely  to  be  compromised  
in  Abruption,  Vasa  Praevia  or  Uterine  Rupture)  



Key  point:  foetal  distress  most  likely  in  placenta  abruption,  vasa  praevia  or  uterine  rupture  

 
Initial  Management  


ABCDE  



IV  Access  



Full  Blood  Count  +/-­‐  cross  match  and  group  and  save  



Coagulation  Screen  



Rhesus  status:  
! The   Kleihauer   test,   is   a   blood   test   used   to   measure   the   amount   of   fetal  
hemoglobin   transferred   from   a   fetus   to   a   mother's   bloodstream
...
    It   is   usually  
performed  on  Rhesus-­‐negative  mothers  to  determine  the  required  dose  of  Rh(D)  
immune  globulin  (Rh  Ig)  to  inhibit  formation  of  Rh  antibodies  in  the  mother  and  
prevent  Rh  disease  in  future  Rh-­‐positive  children
...
g
...
 



Placenta   abruption:   C/S   versus   vaginal   (vaginal   usually   preferred   unless   there   is   fetal  
distress)  



Vasa  praevia:  Caesarean  section  (CS)  



Uterine  rupture:  laparotomy  /  CS  



Cervical  causes:  colposcopy  (a  procedure  where  the  surface  of  the  cervix  is  closely  examined  
using  a  magnifying  instrument  called  a  colposcope)  



Infection:  swabs  and  specific  treatment  



PTL   (preterm   labour):   steroids   +/-­‐   tocolysis   (e
...
  terbutaline)
...
 The  therapy  also  buys  time  for  the  administration  
of   betamethasone,   a   glucocorticoid   drug   which   greatly   accelerates   fetal   lung   maturity,   but  
takes  one  to  two  days  to  work
...
   



The   disease   ranges   from   mild   to   severe,   and   typically   occurs   only   in   some   second   or  
subsequent   pregnancies   of   Rh   negative   women   where   the   fetus's   father   is   Rh   positive,  
leading  to  a  Rh+  foetus
...
 
! Haemorrhage  (at  any  time)    
! Invasive  procedures,  e
...
 RTA,  amniocentesis  


 
 
 

Pathophysiology:  

! Fetal  Rh+ve  red  cells  enter  maternal  circulation  (Rh  –ve  mother)  
! Mother  recognises  as  foreign    
! Produces  antibodies  against  Rh  D  –  this  is  IgG  which  can  cross  placenta
...
 


Does   not   usually   affect   initial   pregnancy:   primary   response   is   IgM   antibodies   =>   cannot  
cross  placenta  



Next  pregnancy:  antibody  response  is  amplified,  IgG  antibodies  produced,  cross  placenta  =>  
destroy  rhesus  +ve  red  cells  in  baby  =>  foetal  transfusion  reaction  



Note:    ABO  antibodies  are  nearly  always  IgM  =>  we  do  not  often  see  ABO  mismatch  causing  
problems    



Antibodies  can  cause:  
! Haemolytic   anaemia   and   reticulocytosis:   Profound   anaemia   can   cause   high-­‐
output   heart   failure,   with   pallor,   enlarged   liver   and/or   spleen,   generalized  
swelling,  and  respiratory  distress
...
   
After  delivery  bilirubin  is  no  longer  cleared  (via  the  placenta)  from  the  neonate's  
blood   and   the   symptoms   of   jaundice   (yellowish   skin   and   yellow   discoloration   of  
the  whites  of  the  eyes)  increase  within  24  hours  after  birth
...
   
! Fetal   hydrops   (fluid   builds   up   around   heart,   blood   in   fetal   abdomen):   The  
prenatal   manifestations   are   known   as   hydrops   fetalis   (accumulation   of   fluid,   or  
edema,   in   at   least   two   fetal   compartments)
...
 
! Can  be  fatal  





Routine   prophylaxis:   Rh   disease   is   generally   preventable   by   treating   the   Rh   –ve   mother  
during   pregnancy   with   an   intramuscular   injection   of   anti-­‐RhD   (anti-­‐D)   immunoglobulin  
(Rho(D)  immune  globulin)
...
g
...
     

Measure   quantity   of   rhesus   antibodies,   if   above   a   certain   level   =>   US   scan   &   Doppler   to   find  
out  if  anaemic  =>  refer,  transfuse  baby,  intra-­‐uterine  transfusion  

 
 
Steroids  


Promote  fetal  lung  surfactant  production:  induce  type  II  alveolar  cells  to  produce  surfactant  
=>  decrease  alveolar  surface  tension  =>  increase  pulmonary  compliance  



↓   neonatal   respiratory   distress   syndrome   (RDS)   by   up   to   50%   if   administered   24-­‐48h  
before   delivery     (take   time   to   work),   in   babies   that   need   delivered   early   (e
...
  in  
haemorrhage)  



Administer  up  to  36  weeks
...
 Proven  benefit  up  to  1  
week  



Betamethasone  is  preferred  to  Dexamethasone  



Can  administer  tocolytic  (e
...
 terbutaline)  to  decrease  contraction  and  prolong  preamature  
labour  until  steroids  have  had  effect  (24-­‐48  hours  for  maximal  effect)  

 
Post-­‐partum  Haemorrhage  (PPH)  


Classically  defined  as  vaginal  bleeding  >  500ml  
! Primary    PPH:  within  24h  
! Secondary  PPH:    >24h  to  6/52  



Severity  can  be  categorised  as:  
! Minor  PPH  <500ml  
! Moderate  PPH:  500-­‐1500ml  

 
 
 

! Major  PPH  =  >1500ml  


Up  to  4%  of  all  vaginal  deliveries  =>  common  



In  Scotland  major  obstetric  haemorrhage  (>1500ml)  complicates  3
...
    PPH   more  
common  after  e
...
 forceps  delivery,  C-­‐section
...
  Uterine   atony   is   the   inability   of   the   uterus   to   contract   and   retract  
after  delivery,  which  may  lead  to  continuous  bleeding
...
 If  bleeding  not  stopped  =>  clots  fill  uterus  =>  
distends   even   more   =>   bleeds   further
...
g
...
 

Aetiology  of  secondary  PPH:  
! Infection:   endometritis:   This   occurs   in   1-­‐3%   after   spontaneous   vaginal   delivery
...
 
Risk   factors   are:   Caesarean   section,   prolonged   rupture   of   membranes,   severe  

 
 
 

meconium   staining   in   liquor,   long   labour   with   multiple   examinations,   manual  
removal   of   placenta,   mother's   age   at   extremes   of   the   reproductive   span,   low  
socio-­‐economic   status,   maternal   anaemia,   prolonged   surgery,   internal   fetal  
monitoring  and  general  anaesthetic
...
 
 
PPH:  Prevention  


Identify  antenatal  risk  factors  
! Anaemia:  checked  before  labour  and  treated,  reduces  effects  of  haemorrhage  if  it  
occurs  
! previous  caesarean  section  
! Placenta   praevia   (low   placenta):   Cause   of   APH   and   risk   factor   for   PPH
...
     
! Placenta   accreta   (attaches   strongly   to   myometrium   but   does   not   penetrate   it):  
Cause  of  APH  and  risk  factor  for  PPH
...
     
! Placenta  increta  (penetrates  myometrium):  Cause  of  APH  and  risk  factor  for  PPH
...
     
! Placenta  perceta  (penetrates  entire  myometrium)  :  Cause  of  APH  and  risk  factor  
for  PPH
...
     
! Previous  PPH  or  retained  placenta  
! Multiple  pregnancy  

 


Identify  intrapartum  risk  factors  
! prolonged  labour  
! operative  vaginal  delivery  /  caesarean  section  
! retained  placenta  

 


Active  management  of  third  stage  (delivery  of  placenta)  
! Use   of   oxytocic   drug   (stimulates   uterus)   e
...
  sytocinon   or   syntometrine  
(syntocin/oxytocin  &  ergometrine)  
! Clamping  &  cutting  umbilical  cord:  between  1  and  3  minutes  

 
 
 

! Controlled  cord  traction  to  deliver  placenta  
 
NICE  guidelines  

 
 
Identifying  aetiology  




Usually  this  requires  transfer  to  theatre  for  an   examination  under  anaesthesia  and  possible  
laparotomy  to  arrest  the  bleeding
...
   

Inverted  uterus  =  rare  obstetric  emergency  

 
 
 
Immediate  management  of  PPH  


ABCDE  



Stimulate  uterine  contractions  
! Uterine   massage   to   treat   atonic   uterus:   Uterine   massage   is   done   by   making  
gentle   squeezing   movements   repetitively   with   one   hand   on   the   woman’s   lower  
abdomen   in   order   to   stimulate   the   uterus
...
   Treats  atonic  uterus,  and  it  is  1st  assumed  
that  this  is  cause,  as  it  is  the  most  likely
...
g
...
g
...
g
...
g
...
g
...
     

Review  whether  drug  therapy  necessary  

1st  trimester  


Risk  of  early  miscarriage  



Organogenesis  



Period  of  greatest  teratogenic  risk:  4th  -­‐11th  week  (embryogenesis)  



Avoid  drugs  if  at  all  possible  unless  maternal  benefit  outweighs  risk  to  foetus  

 

 
 
Teratogenic  drugs  


ACE   inhibitors/ARB   e
...
  lisonopril/rapimril   (ACE-­‐I)   or   losartan/valsartan   (ARBs):     can   cause  
renal  dysfunction  and  oligohydraminos  



Androgens  

 

 

 



Antiepileptics    

 

 



Cytotoxics  

 

 

   



Lithium    

 

 

   



Methotrexate    

 

   



Warfarin  

 

   

 

 

 
2nd  +  3rd  trimesters  


Growth  of  foetus  (end  of  embryogenesis)  



Functional  development  
! Intellectual  impairment  
! Behavioural  abnormalities  


 
 
 

Toxic  effects  on  foetal  tissue  

 

   

 
Around  term  


Adverse  effects  of  drugs  on  labour  
! Progress  of  labour  
! Adaptation  of  foetal  circulation:  Premature  closure  of  ductus  arteriosus  e
...
 due  
to  NSAIDs  (cause  decreased  PGs)  
! Suppression  of  foetal  systems:  Opiates  =>  can  cause  respiratory  depression  
! Bleeding:  Warfarin  (avoid  all  together  in  pregnancy  =>  use  heparin  instead)  



Adverse  effects  of  drugs  on  baby  after  delivery  
! Withdrawal  syndrome:  opiates,  SSRIs  
! Sedation  

 
Delayed  effects  


Diethylstilbestrol  (oestrogen)  
! Previously  used  to  prevent  recurrent  miscarriage  in  pregnant  women  
! Vaginal  adenocarcinoma  in  girls  aged  15-­‐20  years  whose  mothers  were  exposed  
to  diethylstilbestrol  

 
Chronic  conditions  and  pregnancy  


Need  to  discuss  risk/benefit  balance  with  patient:  Ideally  pre-­‐conception  



Compliance  with  medication  may  be  poor  



Many  women  avoid  taking  their  asthma  inhalers  in  pregnancy  



Up  to  20%  of  women  discontinue  antiepileptic  medication  in  pregnancy  

 
Epilepsy  



 
 
 

Incidence   of   congenital   malformations   higher   in   untreated   women   with   epilepsy   than  
women  without  epilepsy  
Increased  seizures  in  10%  of  women  

! Non-­‐compliance  
! Changes   in   plasma   concentrations   of   drugs   e
...
  due   to   persistent   vomiting   and  
increased  renal  clearance  


Frequent   seizures   during   pregnancy   are   associated   with   lower   verbal   IQ   in   child,   hypoxia,  
bradycardia,  antenatal  death,  maternal  death  



Antiepileptics  increase  risk  of  congenital  malformations  
! 20-­‐30%  risk  if  on  4  drugs  
! Monotherapy  preferred  



Avoid  valproate  and  phenytoin  



Folic  acid  5mg  daily  



96%   of   babies   born   to   women   taking   antiepileptics   will   not   have   major   congenital  
malformations  



Benefits  of  treatment  outweigh  risks  in  most  cases  

 
Diabetes  


Insulin  thought  to  be  safe  



Requirements  change  during  pregnancy  



Poor  control  increases  risk  of  congenital  malformations  and  intra-­‐uterine  death  



Sulfonylureas  (e
...
 glicazide,  glibenclamide  and  tolbutamide)  not  safe  =>  convert  to  insulin  

 
Hypertension  


BP  falls  during  1st  and  2nd  trimester,  then  rise  back  up  to  normal  in  third  trimester    



If  need  to  treat,  use  one  of  (LMN):  
! Labetalol  (alpha  and  beta  blocker)  
! Methyldopa  
! Nifedipine    



 
 
 

Avoid  ACE  inhibitors  /  ARB  (teratogenic)  
Beta  blockers  may  inhibit  foetal  growth  in  late  pregnancy  

 
Common  acute  problems  


Nausea  and  vomiting:  Cyclizine    



UTI:  Amoxicillin  or  cefalexin  



Pain:  Paracetamol  



Heartburn:  Antacids  

 
Prevention  of  venous  thromboembolism  in  pregnancy  


Pregnancy   has   10-­‐fold   increased   risk   of   VTE   (versus   non-­‐pregnant)   as   pregnancy   induces   a  
hypercoagulabale  state  (physiological  mechanism  to  prevent  postpartum  haemorrhage  PPH)  



Highest  risk  of  VTE  is  in  the  6  week  postpartum  period  



VTE  is  leading  cause  of  maternal  death  in  pregnancy  



Thromboprophylaxis  reduces  the  risk  



All  pregnant  women  should  be  assessed  for  risk  of  VTE  



Regardless   of   risk,   all   women   who   are   pregnant,   in   labour   or   in   the   puerperium   should   be  
encouraged  to  mobilise  and  be  adequately  hydrated  



Those  with  significant  risk  factors  should  receive  thromboprophylaxis  with  LMWH  ➢   at  
delivery  and  up  to  7  days  post-­‐partum  (as  this  is  the  highest  risk  period)  
! 2  or  more  risk  factors  e
...
 obesity,  age>35yrs,  smoking,  para  >3,  previous  DVT,  
Caesarean  delivery  (CS)  
! any  pt  with  previous  unprovoked  DVT/PE  
 

LOW  THRESHOLD  FOR  INTERVENTION    
 
Treatment  of  venous  thromboembolism  in  pregnancy  



Avoid  warfarin  in  early  pregnancy,  as  warfarin  is  teratogenic  


 
 
 

Treat  suspected  or  established  DVT  or  PE  with  therapeutic  dose  LMWH  

Avoid   warfarin   in   late   pregnancy,   as   risk   of   haemorrhage   during   delivery   (peri-­‐partum  
haemorrhage)  



AVOID  WARFARIN  FULL  STOP  



LMWH  is  the  anti-­‐coagulant  of  choice  in  pregnancy    

 
Breastfeeding  


Most  drugs  enter  breast  milk,  especially  
! Small  molecules  
! Fat  soluble  (lipophilic)  drugs  



Few  enter  in  sufficient  quantities  to  cause  a  problem  



Immature  metabolism  –  drugs  may  accumulate  



Some  drugs  are  actively  concentrated  in  breast  milk  



POP   is   the   OCP   of   choice   when   breast   feeding   –   the   progesterone   is   good   for   the   milk  
production  too!  



Paroexetine  is  the  SSRI  of  choice  when  breast  feeding    

 
 
Summary  


All  women  of  childbearing  age  are  potentially  pregnant  
! Check  before  you  prescribe  
! BNF  or  UK  Teratology  Information  Service  



Pre-­‐conception  counselling  



Balance  risk  vs  benefits  



Treat  if  necessary  
! Safest  drug,  lowest  effective  dose,  shortest  possible  time  

 
Quiz  
Question  1
...
 Also  avoid  in  children  up  to  age  12  years
...
     


Which  ‘drug’  taken  in  excess  in  early  pregnancy  could  have  caused  this  facial  appearance?  

 

 
 


Answer=  Alcohol  =>  Fetal  alcohol  syndrome  

 
Question  3  
 
 
 



Which  antiepileptic  drug  is  particularly  associated  with  the  following  congenital  anomaly?  

 

 
 


Answer=  Phenytoin  (more  likely)  or  carbamazepine=>  cleft  lip  and  palate  

 
Question  4      


Which  antiepileptic  drug  is  particularly  associated  with  the  following  defects?  

 
 
 
 
 



Answer:  Valproate  =>  neural  tube  defects  e
...
 spina  bifida  and  anencephaly  

 
 
PHYSIOTHERAPY  MANAGEMENT  OF  GYNAECOLOGICAL  CONDITIONS  
Pelvic  Floor  Dysfunction  


The   pelvic   floor   is   related   to   more   than   one   system
...
  The   function   of   the  
pelvic  floor  is  to  support  the  pelvic  organs
...
  Practical   inconveniences   include   frequent   change   of  
clothing  and  bed  linen  and  bathing  more  often  



Interference   with   sexual   activities   and   night-­‐time   incontinence   are   associated   with   greater  
reported  impact  on  quality  of  life
...
 



Prevalence:  in  middle  age  and  older  adults  in  range  of  30-­‐60%  of  population
...
  It   is   present   in   all   age   groups   and  
both  genders  increasing  in  prevalence  with  age  from  1
...
   



Many  women  post-­‐natally  can  have  bowel  disorders
...
6–9
...
   



NB:   episotomy=   planned,   surgical   incision   on   the   perineum   and   the   posterior   vaginal   wall  
during  second  stage  of  labor  (helps  with  delivery  of  the  baby)  

 
Vagina  symptoms  


Pelvic   organ   prolapse:   Loss   of   support   (from   PFMs)   for   uterus,   bladder,   colon   or   rectum  
leading  to  prolapse  of  one  or  more  of  these  organs  into  the  vagina
...
   
Key  diagnostic  test  for  urinary  incontinence
...
g
...
 They  relax  at  the  same  time  as  the  bladder  contracts  (tightens)  in  order  to  let  the  
urine  out
...
g
...
g
...
g
...
 



Thrush:   caused   by   Candida   albicans
...
 Always  consider  other  causes  of  breast  pain
...
 



Worsens  at  the  start  of  feeding  



Breasts  may  also  be  engorged  



Redness,  blisters,  bleeding  and  scabs  



Baby  may  vomit  blood  

 
Treatment/Management:  



Discuss/demonstrate  the  principles  of  good  positioning  and  attachment  



Hand  expressing  where  appropriate  e
...
 express  some  milk  to  soften  the  areola  to  lubricate  
the  nipple  before  breast  feeding  


 
 
 

Observe  and  assess  a  breastfeed  

Creams,  sprays  and  heat  treatments  are  generally  of  little  value    



Nipple  shields  can  be  used  as  a  last  line  of  management  to  prevent  the  mother  from  giving  
up
...
  Always  
consider  other  causes  of  breast  pain
...
 



Can  be  passed  between  mother  and  baby
...
 



Swab  for  candida  albicans  



Essential   to   continue   feeding   directly   from   breast   to   prevent   engorgement/reduced   milk  
supply/mastitis  
 

Clinical  features  


Itching  or  burning  of  the  skin  over  the  nipples  /areola  



Soreness  of  the  skin  to  start  with  



Severe   pain   when   the   baby   initially   latches   on   to   the   breast   which   becomes   progressively  
worse  with  each  re-­‐latch  



Bilateral  



NB:  no  white  rash  or  discharge  as  seen  in  oral  and  vaginal  thrush  

 
Management:  



Observe  breastfeed  



Dummies,  teats  boiled  20minutes  daily  



Bras,  towels  washed  in  hot  wash  


 
 
 

Observe  breast  

Essential  to  continue  feeding  directly  from  breast  to  prevent  engorgement,  reduced  milk  
supply  and  mastitis  



Antifungal  Tx    
! Miconazole  cream  (superficial  infection)  for  mum  
! Oral  fluconazole  (for  deep  infection)  for  mum  
! Nystatin  or  miconazole  for  infant  



If   symptoms   have   not   improved   at   all   after   a   10   day   course   combined   with   topical  
treatment,   re-­‐consideration   should   be   given   to   whether   the   diagnosis   was   correct   rather  
than  continuing  to  treat  the  mother  and  child  

 
Engorgement  


Breast  engorgement  occurs  in  the  mammary  glands  due  to   expansion  and  pressure  exerted  
by  the  synthesis  and  storage  of  breast  milk
...
 



While   it   is   normal   for   the   breasts   to   enlarge,   one   study   found   that   the   more   minutes   the  
newborn  spent  nursing  during  the  first  48  hours  the  less  painful  breast  engorgement  was    



When   breastfeeding   is   unrestricted,   mothers   are   less   likely   to   be   painfully   engorged
...
 



The  breast(s)  may  be  red  



The  mother  may  be  feverish
...
 



Ensure   good   attachment   and   complete   emptying   of   at   least   one   breast   per   feed   with   the  
second  side  also  softened  by  the  baby  feeding  or  by  expressing  fore  milk
...
g
...
 



Antibiotics  are  unhelpful  and  may  lead  to  Candida  infections
...
 
 

Mastitis  


Inflammation  of  breast  tissue  



May  be  caused  by  a  plugged  duct  (duct  ectasia)  and/or  an  infection  



A  plugged  duct:  
! Comes  on  gradually  
! May  shift  location  
! The  mother  feels  little  or  no  warmth  in  the  area  
! The  pain  is  mild  and  localised  
! The  mother  feels  generally  well  
! Temperature  is  lower  than  38
...
4  degrees  Celcius
...
g
...
aureus  
! Erythromicin  (if  penicillin  allergy)  


 
 
 

Abscess:  

 

! ABS  e
...
 flucloxacillin  
! Aspiration)  of  abscess  if  no  response  to  ABs
...
g
...
 

 
 
 
THE  HEALTHY  TERM  INFANT  


Term  =  37  to  42  weeks  gestation  



Preterm  =  <  37  weeks  gestation  
! Very  preterm  <  32  weeks  
! Extremeley  preterm  <28  weeks  
! Fetal  loss  <  23  weeks  



 
 
 

Post-­‐term  =  >  than  42  weeks  gestation  
Epidemiology  is  not  a  strict  cut-­‐off,  but  a  spectrum  e
...
 can  get  problems  of  “prematurity”  
at  37  weeks  gestation  

 
 
Birth  weight  of  term  baby  


Birth  weight  is  often  talked  about  



Corrlated  with  prognosis    



3
...
5kg  is  low  
! Less  than  1
...
    Adults  
would  probably  die  if  subjected  to  this  level  of  hypoxia  =>  foetal  adaptations  are  important  



Foetal   adaptions   include   metabolic   and   haematological   adaptions   e
...
  HbF   (left   shift)   and  
increased  Hb  concentration  



Fetal   Hb   (alpha   2,   gamma   2)   increases   oxygen   binding   capacity,   due   to   shift   of   the  
haemoglobin   dissociation   curve   to   the   left   =>   resulting   in   enhanced   oxygen   affinity   in   the  
blood
...
g
...
   Various  hormonal  and  environmental  stimuli  make  the  baby  
take  at  least  a  breath  if  not  a  cry  which  inflates  the  lungs  



Alveolar  expansion:  Move  from  relying  on  the  placenta  for  oxygen  to  relying  on  the  lungs  



Decreased  pulmonary  arterial  pressure  



Change  from  fetal  to  newborn  circulation  (pressure  in  left  heart  becomes  greater  than  right  
heart;  ducts  close)  



Increased  PaO2  



Apgar   score:   Apgar   score   describes   how   well   the   baby   is   adapting   to   extra-­‐uterine   life
...
     



Simple  things  like  drying  the  baby,  keeping  next  to  mum’s  skin,  putting  a  hat  on,  if  necessary  
using  more  advanced  measures  like  transwarmers  or  incubators  



DRYING  BABY  IS  FIRST  STAGE  OF  NEONATAL  RECUSSITATION  GUIDELINES    

 
Feeding  


Well  grown  term  infants  have  little  calorific  intake  in  the  first  24  hours  



Dramatic   change   from   continuous   glucose   infusion   (via   placenta)   to   intermittent   bolus  
enteral  feeds  



Blood   sugar   of   2-­‐2
...
6  



Gluconeogenesis  is  the  most  important  mechanism  here  



Brain  can  also  survive  on  other  fuels  such  as  ketones  (different  if  sick  of  pre-­‐term)  



Skin  to  skin  contact  important  for  establishing  breast  feeding  

 
Attachment  
 
 
 



To  parents  their  baby  is  always  beautiful  



Babies  often  very  alert  immediately  after  delivery  



Hormonal  and  emotional  response  to  infant  



Feeding  and  warming  are  very  important  to  attachment  



Poor  attachment  in  early  life  dramatically  changes  relationship  further  down  the  line  



Post-­‐natal   depression   is   much   higher   in   mothers   whose   children   have   been   admitted   to  
NICU  

 
Haemorrhagic  disease  of  the  newborn  (HDN)  


Haemorrhagic   disease   of   the   newborn   is   an   uncommon   UK   problem   now   (more   in   other  
parts  of  the  world)  



Vit  K  is  essential  for  the  production  of  F2,7,9  and  10  in  the  liver
...
 They  have  low  vitamin  K  
stores  at  birth,  vitamin  K  passes  the  placenta  poorly,  the  levels  of  vitamin  K  in  breast  milk  are  
low   and   the   gut   flora   has   not   yet   been   developed   (vitamin   K   is   normally   produced   by  
bacteria  in  the  intestines)
...
g
...
g
...
g
...
  If   you   know   there’s   a   maternal   history   of   these   diseases   or   drug   abuse,   consider  
screening  the  baby,  as  may  be  able  to  treat
...
g
...
   GBS  is  a  major  cause  of  sepsis  and  meningitis  in  neonates  



Hepatitis  B:  vaccination  and  immunoglobulin  to  at  risk  neonates  



Hepatitis  C:  no  vaccination    



HIV:  can  offer  mum  HAART  (irrelevant  of  CD4)  to  decrease  viral  load  and  reduce  chance  of  
transmission
...
   Breast  feedng  CI  even  on  
HAART
...
g
...
 



Moulding:   head   contours   to   shape   of   the   pelvis
...
   More  likely  to  occur  in  prolonged  stage  1  of  
labour
...
     



Cephalohaematoma:  subperosteal  bleed,  cant  cross  sutures
...
g
...
g
...
   



Ophthalmoscopy  for  diminished  red  reflex  (loss  of  red  reflex  may  be  a  sign  of  cataracts  and  
retinoblastoma)  



Aggressive  early  management  improves  visual  outcomes  



Conjunctivitis  

 
Ears  


Position  



External  auditory  canal  -­‐  patent  



Family  history  of  hearing  loss  



Tags/pits  
 

Mouth  


 
 
 

Shape  



Philtrum:   vertical   groove   in   the   middle   area   of   the   upper   lip,   common   to   many   mammals,  
extending  from  the  nose  to  the  upper  lip
...
   Feel  with  little  finger
...
 Unusual  
for  a  routine  newborn  midwife  exam  to  pick  this  up,  but  still  look  for  it  just  in  case  

 
Cardiovascular  

 
 
 

Inspection,  palpation,  percussion  and  auscultation    



Colour:   Colour   is   important   but   we   are   bad   at   picking   up   cyanosis     =>   so   routine   sats  
monitoring  has  become  part  of  newborn  care  in  some  areas  



Saturation:  SaO2  or  SpO2  (preductal  and  postductal)  



Pulses:  femoral    
! Reduced/absent   femoral   pulses   is   a   sign   of   coarctation   of   the   aorta   and   aortic  
stenosis
...
     Although  radiofemoral  delay  unlikely  to  be  
detected  in  neonates  due  to  the  short  distance!  



Apex  



Heaves  and  thrills  



Heart  sounds  



Hepatomegaly  –  early  sign  of  HF  

 
Abdominal  


Inspection,  palpation,  percussion  and  auscultation    



Moves  with  respiration  



Distension  



Bile  stained  vomiting  



Passage  of  meconium:  Lack  of  meconium  passage  is  associated  with  CF  or  obstruction  



Anus:  Look  for  patency  of  anal  passage  (may  be  anal  atresia  or  abnormal  position)
...
   Barlow  and  Ortolani  manoeuvres  try  to  dislocate  and  relocate  the  hips
...
   US  all  babies  with  
risk  factors
...
     



Ensure  baby  is  in  proportion  e
...
 no  skeletal  dysplasia  

 
Neurological  


Posture  



Tone  



Movement  



Reflexes  



Primitive   reflexes   (e
...
  grasp,   moro)
...
   



Every  baby  in  the  UK  gets  this  on  day  5  

 

 
 
Health  promotion  




Weaning  from  6  months  


 
 
 

Breast  feeding  exclusively  to  6  months  (when  weaning  should  begin)  and  recommended  to  
at  least  2  years  (unexclusively)  

No  cows  milk  before  12  months  



Smoking  cessation  



Alcohol  limitation  to  recommended  limit  



Drug  use  



Diet:  balanced  



Now   good   evidence   that   health   as   babies   and   toddlers   strongly   impacts   on   adult   health:  
particularly  diabetes,  cardiovascular  disease,  some  data  on  cancers  now  



If   there’s   an   opportunity   to   try   to   raise   issues   of   lifestyle   change,   give   it   a   go:   however   some  
will  continue  drinking,  smoking  etc  



Most  parents  highly  motivated  to  change  for  their  children  

 
 
THE  SICK  TERM  INFANT  
Causes  of  sick  term  infant  


Asphyxia  



Cardiac  



Metabolic  



Infection  



Congenital  anomalies  



Respiratory    

 
Perinatal  asphyxia  




Hypoxic  damage  can  occur  to  most  of  the  infant's  organs  (heart,  lungs,  liver,  gut,  kidneys),  
but  brain  damage  is  of  most  concern  and  perhaps  the  least  likely  to  quickly  or  completely  
heal
...
   

In   the   more   pronounced   cases,   an   infant   will   survive,   but   with   damage   to   the   brain  
manifested   as   either   mental,   such   as   developmental   delay   or   intellectual   disability,   or  
physical,  such  as  spasticity  (cerebral  palsy)
...
g
...
   
! Can   also   occur   due   to   inadequate   circulation   or   perfusion,   impaired   respiratory  
effort,  or  inadequate  ventilation
...
   



Clinical  features  
! Poor  apgar  scores  
! Multi  organ  damage  due  to  tissue  hypoxia  
! Resuscitation  required  
! Seizures/neurological  abnormalities  
! Renal  failure  
! Liver  dysfunction  

 
Infection  


Septicaemia:    E-­‐coli,  Strep  agalactiae  (GBS)  and  Listeria  monocytogenes  are  the  commonest  
pathogens  in  the  neotal  period
...
 Coli  –  gram  –ve  coliform    



Listeria    myogenes  –  gram  +ve  aerobic  bacilli  



Staphloccus  aureus  –  gram  +ve,  coagulase  +,  aerobic  cooci  



Often  Tx  with  Benpen  and  Gent  –  also  used  prophylactically    

 
Cardiac  


Congenital  heart  disease  
! Tetralogy   of   Fallots:   pulmonary   stenosis,   right   ventricular   hypertrophy,  
ventricular  septal  defect  and  overriding  aorta
...
   R  to  L  shunt  occurs  as  pressure  in  right  ventricle  
is  higher  than  left
...
   When  a  patient  has  a  coarctation,  the  left  ventricle  has  to  work  harder
...
  If   the   narrowing   is   severe   enough,   the   left  
ventricle  may  not  be  strong  enough  to  push  blood  through  the  coarctation,  thus  
resulting  in  lack  of  blood  to  the  lower  half  of  the  body
...
   Radio-­‐femoral  delay  of  pulses  is  characteristic  of  co-­‐
arctation  of  the  aorta
...
    Many   causes   e
...
  anaemia,   heart  
failure,  haemolytic  disease  of  the  newborn  etc  


Failure  to  adapt  to  postnatal  life  
! PPHN  (persistent  pulmonary  hypertension  of  the  newborn):  The  baby's  lungs  are  
not  used  during  pregnancy
...
 This  means  most  of  the  baby's  blood  does  not  need  to  
pass  by  the  lungs
...
 The  
blood   flow   should   switch   so   that   it   will   pass   by   the   lungs
...
 The  blood  does  not  flow  to  the  lungs  as  it  should
...
   PPHN  
can  be  caused  by  a  variety  of  factors
...
   Therefore   measurement  
of   pre-­‐duct   sats   and   post   duct   sats   is   useful   in   the   Dx   (R   to   L   shunt   =>   cyanotic  
shunt  =>  difference  between  pre-­‐duct  an  post  duct)
...
     

 
Note:    If  duct  dependent  cyanotic  heart  defect  =>  give  PG  infusion  to  keep  the  ductus  arteriosus  
open
...
5mmol/l)  
! related  to  Low  Birth  Weight  (low  glycogen  stores)  
! related  to  large  birth  weight  (macrosomia)  with  maternal  diabetes  
! side  effect  of  poor  feeding  
! evidence  of  more  complex  metabolic  disorder  



Acidosis  (pH  <7
...
     
! Most  common  cause  of  respiratory  distress  in  term  neonates  
! It  consists  of  a  period  of  rapid  breathing  >60  breaths  per  minute  (higher  than  the  
normal  range  of  40-­‐60  times  per  minute  in  the  neonate)
...
   
! Usually,   this   condition   resolves   over   24–48   hours
...
  The   chest   X-­‐Ray   shows  
hyperinflation  of  the  lungs  (due  to  excess  fluid)  including  prominent  pulmonary  
vascular  markings,  flattening  of  the  diaphragm,  and  fluid  in  the  horizontal  fissure  
of  the  right  lung
...
 
!  On   CXR   we   see   decreased   lung   volumes   (alveolar   collapse)   and   ground   glass  
appearance    
!  Most   cases   of   infant   respiratory   distress   syndrome   can   be   ameliorated   or  
prevented   if   mothers   who   are   about   to   deliver   prematurely   can   be   given  
glucocorticoids,  one  group  of  hormones
...
g
...
 

 
 
 

! Spina  bifida:  developmental  congenital  disorder  caused  by  the  incomplete  closing  
of  the  embryonic  neural  tube
...
 If  the  opening  is  large  enough,  this  
allows  a  portion  of  the  spinal  cord  to  protrude  through  the  opening  in  the  bones
...
     


Renal  
! Potters   syndrome:   atypical   physical   appearance   of   a   fetus   or   neonate   due   to  
oligohydramnios  experienced  in  the  uterus
...
    Oligohydramnios   is   the   causative  
agent   of   Potter   sequence,   but   there   are   many   things   that   can   lead   to  
oligohydramnios
...
 



Muscular  
! Myotonic  dystrophy:  chronic,  slowly  progressing,  highly  variable,  inherited  
(genetic)  multisystemic  disease
...
 Two  types  of  myotonic  dystrophy  exist
...
 
 

Assessment  


History  
! Maternal  
! Infant  



General  examination  and  APGAR  
! APGAR:  appearance  (colour),  pulse  (HR),  grimace  (reflexes),  activity  (muscle  
tone),  respiratory  effort  
! Perform  APGAR  at  1  and  5  minutes  +/-­‐  10  minutes  
! Level  of  arousal  



Vital  signs:  record  on  NEWS  chart  (neonatal  observing  chart)  =>  helps  focus  on  those  who  
need  monitoring  



Respiratory  
! Rate  (normally  40-­‐60  in  the  neonate)  

 
 
 

! Effort  e
...
 sterna  recession,  intercostals  recession,  nasal  flare,  grunting,  stridor,  
use  of  accessory  muscles  


CVS  
! HR  (normally  120-­‐150  in  neonate)  
! CRT:  capillary  refill  time  (normally  less  than  2  seconds  in  neonate)  
! BP  (significantly  lower  compared  to  adults)  



Abdomen  
! Urine  
! Stool/meconium  
! Bile  
! Distension  



Neurological  
! Tone  
! Seizures  
! Cry  
! Posture  

 
Apgar  score  


Appearance  (colour):  0-­‐2  



Pulse  (heart  rate):  0-­‐2      



Grimace  (reflex  activity):  0-­‐2  



Activity  (muscle  tone):  0-­‐2  



Respiratory  effort:  0-­‐2  



Total  score  is  out  of  10  



Scores  7  and  above  are  generally  normal,  4  to  6  fairly  low,  and  3  and  below  are  generally  
regarded  as  critically  low
...
g
...
g
...
9%  saline  



Investigations  to  find  cause  



Further  support  and  treatment  
! Ventilation  
! Drugs  
! Surgery  



Care  of  the  family  

 
THE  PRETERM  INFANT  
Terminology  


Term:  a  birth  between  37  weeks  and  42  weeks  of  gestation  



Preterm:  a  birth  that  occurs  after  22  weeks  but  before  37  completed  weeks  of  gestation    
! Very  preterm  =  28-­‐32  weeks  
! Extremely  preterm  =  23  to  28  weeks  
! Fetal  loss  =  <  23  weeks  



 
 
 

Post  terms:  a  birth  that  occurs  after  42  completed  weeks  of  gestation  

 
 
Infants  according  to  their  weight  


Small  for  Gestational  Age  (SGA):  <10th  centile  in  weight  expected  for  gestation  



Appropriate  for    gestational  age  (AGA)  :  10th-­‐90thcentile  in  weight  expected  for  gestation  



Large  for  Gestational  Age  (LGA):  >90th  centile  in  weight  expected  for  gestation  

 
Low  birth  weight  


In  developed  countries,  the  average  birth  weight  of  a  full-­‐term  newborn  is  approximately  3
...
5kg)  or  less  



Very  low  birth  weight  (VLBW):  birth  weight  1500g  (1
...
g
...
g
...
g
...
g
...
4%  before  28  weeks  



0
...
9%  at  32–36  weeks  



93
...
 “Resuscitation”  


Most   very   preterm   babies   need   help   with   transition   to   air   breathing   =>   assistance   not  
resuscitation  



Careful  assessment  and  gentle  support  



Though  these  babies  may  well  require  a  similar  general  approach  to  that  we  have  developed  
for  asphyxiated  term  babies  they  need  these  interventions  for  slightly  different  reasons
...
  Generally   speaking   they   will   be   born  
in   good   condition
...
   

 
Cord  clamping  




Because   these   babies   are   generally   in   reasonable   condition   at   delivery   you   will   almost  
always  be  able  to  pause  for  a  minute  to  allow  placental  transfusion  to  take  place,    provided  
you    can  keep  the  baby  warm  during  the  process
...
 

Keep  warm  


Keeping  these  very  small  babies  warm  is  best  achieved  by  placing  them  immediately,  while  
still  wet,    in  a  suitable  plastic  bag  and  later  under  a  radiant  heater
...
  If   you   overinflate  
(e
...
  This   damage   will   set   in  
motion   an   inflammatory   cascade   which   will   predispose   to   bronchopulmonary   dysplasia  
(chronic  lung  disease  of  newborn)  
 

Summary  of  management  of  preterm  infant  at  birth  


Allow  at  least  one  minute  for  placental  transfusion  (e
...
 allow  at  least  one  minute  before  
cord  clamping  and  cutting)  



Keep   the   baby   warm   –   straight   into   incubator   (different   to   term   neonatal   recussitation  
protocol  where  we  dry  babies  initially)  



Assess  the  situation:  APGAR  



Airway  



Breathing:  Inflation  breaths  (be  careful  of  baro  trauma)  



Chest  compressions  (only  if  brachial  pusle<60bpm)  

 
Common  concerns  in  preterm  infant  


Temperature  control:  due  to  low  fatty  tisse  



Feeding/nutrition  



Sepsis    



System  immaturity  /  dysfunction    
! Respiratory  distress  syndrome  (RDS)  

 
 
 

! Patent  ductus  arteriosus  (PDA)  
! Intraventricular  haemorrhage  (IVH)  
! Nectrotising  enterocolitis  (NEC)  


Others:  
! Metabolic  e
...
 hypoglycaemia  and  hyponatremia    
! ROP  (retinopathy  of  prematurity)  

 
Hypothermia  


Low  admission  temperature  is  an  independent  risk  factor  for  neonatal  death  



Increases  severity  of  all  preterm  morbidities  



In  the  newborn  is  due  more  to  lack  of  knowledge  than  lack  of  equipment  



Why  is  thermal  regulation  ineffective  ?  
! Low  BMR  
! Minimal  muscular  activity  
! Subcutaneous  fat  insulation  is  negligible  
! High  ratio  of  surface  area  to  body  mass  



Methods  for  keeping  warm:  
! Skin  to  skin  contact  
! Clothing  and  hats  
! Wraps  or  bags  
! Prewarmed  incubator  
! Tranwarmer  mattress  

 
Growth  and  Nutrition  



Limited  nutrient  reserves  


 
 
 

Increased  risk  of  potential  nutritional  compromise  

Immature  metabolic  pathways  



Increased  nutrient  demands  



Medical   /   surgical   conditions   commonly   associated   with   prematurity   have   the   potential   to  
alter  nutrients  requirement  and  complicate  adequate  nutrient  delivery  



Plot  growth  charts  with  gestational  correction:  
! Head  circumference  
! Height    
! Weight  

 
Plotting  preterm  infants  

 
 
 
Mortality  in  neonates  


Approximately  5  million  neonatal  deaths  a  year    



98%  occurring  in  developing  countries  



Major  causes  
! Infection  (32%)  

 
 
 

! Prematurity  (29%)  
! Birth  asphyxia  (24%)  


Infections:  septicaemia,  meningitis,  respiratory  infections,  diarrhoea,  and  neonatal  tetanus  

 
Neonatal  sepsis  


Early  onset  (EOS):  mainly  due  to  bacteria  acquired  before  and  during  delivery  e
...
 GBS  from  
mothers  vagina,  E-­‐coli,  and  Listeria  monocytogenes    



Late  onset  (LOS)  
! acquired  after  delivery    
! Nosocomial  or  community  sources  e
...
 Staph  
 

Clinical  features  of  neonatal  sepsis  


Remember   that   the   very   young   and   very   old   can   have   atypical   presentations   e
...
  may  
present  with  low  temperature  during  infection  



Look  for  focal  signs  of  infection  e
...
 respiratory,  GI,  skin,  CNS,  ear,  pharynx  



Measure  all  vital  signs  



Signs  of  neonatal  sepsis  include:  
! Increases  respiratory  rate  >60  breaths  per  minute  
! Tachycardia  >150  bpm  
! High  or  low  temperature  
! Decreased  consciousness  
! Reduced  movements  
! Not  able  to  feed  
! Convulsions  
! Crepitations  (lung  infection)  
! Bulging  frontanelle  (CNS  infection)  

 
MOST  VERY  NON  SPECIFIC    
 
 
 

 
Organisms  causing  Neonatal  Sepsis  


Gram  negative  organisms  (gut  pathogens):  
! Klebsiella  
! Escherichia  coli  
! Pseudomonas  
! Salmonella  



Gram  positive  organisms:  
! Group  B  streptococcus  (GBS)  e
...
 Strep  agalactiae  (beta/complete  haemolysis)  
! Listeria  monocytogenes  
! Staphylococcus  aureus  (coagulase  +ve)  
! Coagulase  negative  staphylococci  (CONS)  e
...
 Staph  epidermidis  
! Streptococcus  pneumonia  (alpha/partial  haemolysis)  
! Streptococcus  pyogenes  GAS  (beta/complete  haemolysis)  

 
Management  


Prevention  



Hand  washing  



Super  vigilant  and  infection  screening  and  risk  assessment    



Sensible  use  of  antibiotics  (ABx)  



Optimum  supportive  measures  



NB:  Incubators  increases  infection  

 
Respiratory  complications  of  prematurity    



 
 
 

Respiratory  distress  syndrome  (RDS)      
Apnoea   of   prematurity:   cessation   of   breathing   by   a   premature   infant   that   lasts   for   more  
than   15   seconds   and/or   is   accompanied   by   hypoxia   or   bradycardia
...
  A   secondary   stimulus   is   hypoxia
...
   


Bronchopulmonary  dysplasia  (chronic  lung  disease  of  prematurity):   most   commonly   occurs  
in  premature  infants  who  have  needed  mechanical  ventilation  and  oxygen  therapy  for  infant  
respiratory  distress  syndrome
...
     

 
Respiratory  distress  syndrome  (Hyaline  Membrane  Disease)  


Primary  pathology  
! Surfactant   deficiency   =>   increased   alveolar   surface   tension   and   alveolar  
collapse    =>  decreased  pulmonary  compliance  (restrictive  lung  disease)  
! Structural  immaturity  



Secondary  pathology    
! Alveolar  damage  
! Formation  of  exudate  from  leaky  capillaries  
! Inflammation  
! Repair  



Common:  75%  of  infants  born  before  29  week,  10%  in  infants  born  after  32  weeks  
 

Clinical  features  of  RDS  


Respiratory  distress  
! Tachypnoea  
! Grunting  
! Intercostal  recessions  
! Nasal  flaring  
! Hypoxia  and  Cyanosis  




Ground  glass  appearance  of  lungs  on  CXR  


 
 
 

Worsen  over  minutes  to  hours  

Natural  history:  Gradual  worsening  to  a  nadir  (peak)  at  2-­‐4  days  then  gradual  improvement  



NB  natural  history  is  modified  with  active  treatment  

 
Management  of  RDS  


Maternal   steroid:   can   give   tocolytic   (e
...
  terbutaline)   to   prolong   labour   until   steroids   have  
an  effect  (approx  48  hours)  



Surfactant  (curosurf)  



Ventilation  



Invasive  /  non  invasive  ventilation  

 
 
Cardiovascular  concerns  in  preterm  infants  


Patent  ductus  arteriosus    



Systemic  hypotension  

 
Patent  Ductus  Arteriosus  



Duct  does  not  respond  to  “close”  signals  e
...
 decrease  of  PGs  and  increase  in  PO2  



Leads  to  symptoms  of  congestive  heart  failure  =>  L  to  R  shunt  results  in  fluid  overload  for  
heart  and  lungs  which  can  cause  RHF  and  hydrops  fetalis  if  severe  



Machinery  murmur  –  heard  loustes  at  upper  left  sternal  border,  may  radiate  to  back  


 
 
 

Premature  infants  at  risk  

Oxygen  requirements  are  high  due  to  hypoxia  –  as  a  result  of  HF  



Exacerbates  RDS    



RDS  is  also  a  risk  factor:  as  hypoxia  prevents  closure  of  the  duct  



RDS  is  a  major  risk  factor  for  many  of  the  common  preterm  complications  e
...
 PDA,  NEC  
and  IVH  

 
 
Intraventricular  Haemorrhage  


Form  of  intracranial  haemorrhage  that  occurs  in  preterm  infants,  which  begins  with  bleeding  
into  the  subependymal  germinal  matrix
...
 



Wide  spectrum  of  clinical  manifestations:  
! Clinically  silent  (25-­‐50%)
...
6)  and  hyponatraemia  
! Late  :  osteopenia  of  prematurity  

 
Complications  of  prematurity  

 
 
 

Higher  mortality    



Morbidity  



Neurodevelopmental  outcome    
! Motor  deficits  including  mild  fine  or  gross  motor  delay,  and  cerebral  palsy  
! Sensory  impairment  including  vision  and  hearing  losses  
! Behavioral  and  psychological  problem  



Chronic   health   issues:   have   higher   rates   of   chronic   medical   conditions   compared   with  
children  who  were  born  full  term  



Growth  issues:  more  likely  to  exhibit  poor  growth  compared  to  those  born  full-­‐term    



Effect  on  adult  health  

 
Risk  factors  for  preterm  birth  


Carrying  more  than  one  baby  (twins,  triplets,  or  more)
...
   



Certain   infections   during   pregnancy   =>   can   cause   inflammation   of   membranes   and  
premature  rupture  (common  cause)
...
 



Cigarette  smoking,  alcohol  use,  or  illicit  drug  use  during  pregnancy  

 
Preventing  preterm  birth  


Lowering  the  risk  of  having  a  premature  baby  



Even   if   a   woman   does   everything   "right"   during   pregnancy,   she   still   can   have   a   premature  
baby  



Tocolytics  (e
...
 terbutaline  or  salbutamol)  may  be  used  to  delay  labour  in  order  for  maternal  
steroids  to  have  effect    

 
Summary  


 
 
 

Survival  rates  for  extremely  preterm  infants  have  improved  



Antenatal   steroids   and   surfactant   replacement   has   contributed   to   improved   preterm   care
...
     



Impairments   may   have   an   adverse   effect   on   family   life,   impact   on   social,   education,   and  
health  service  resources
...
 



Also  used  to  monitor  progression  of  labour  



It  has  also  been  used  to  assess  the  odds  of  spontaneous  preterm  delivery
...
 
The   duration   of   labor   is   inversely   correlated   with   the   Bishop   score;   a   score   that   exceeds   8  
describes  the  patient  most  likely  to  achieve  a  successful  vaginal  birth
...
g
...
 

 
 
 
Methods  of  IOL  


Prostaglandins:   PGE2   Dinoprostone   or   misoprostol:   used   for   cervical   ripening   (paritculary   if  
low   Bishops   score   <6)   and   stimulation   of   uterine   contractions
...
     



Syntocinon   (oxytocin)   IVI   (intravenous   infusion):   stimulates   uterine   contractions
...
   If  the  woman  has  fully  dilated  but  
uterine  contractions  are  insufficient  then  can  use  sytocinon
...
     



Mechanical    

 

! Membrane   sweep:   the   practitioner   moves   her   finger   around   the   cervix   to  
stimulate  and/or  separate  the  membranes  around  the  baby  from  the  cervix
...
 
! Extra-­‐amniotic  saline  infusion:  Foley  Balloon  Catheter  is  inserted  into  the  cervix  
and  the  distal  portion  expanded  to  dilate  it  and  to  release  prostaglandins
...
  The   membranes  
may  be  ruptured  using  a  specialized  tool,  such  as  an  amnihook  or  amnicot,  or  they  may  be  
ruptured  by  the  proceduralist's  finger
...
   
Terbutaline   (beta   2   agonist:   SABA)   is   an   example   of   a   tocolytic   agent
...
     

 

 
 

 
 
 

 
 
 
Reproductive  lecture  notes:  week  5  
URINARY  INCONTINENCE  (UI)  AND  PELVIC  ORGAN  PROLPASE  (POP)  
Pelvic  anatomy  
 

 
 
 
 

 

 

 
 
Aetiology  of  UI  and  POP  
 
 
 



Many  causes  and  risk  factors:  
! Aging  
! Childbirth  
! Neurological  –  ALWAYS  CONSIDER  NEURO  CAUSES  
! Muscular  
! Medications  
! Co-­‐morbidities  
! Infections  
! Debility  
! Many  more  

 
 
Urinary  Incontinence  (UI)  


UI   =   involuntary   loss   of   urine   which   can   be   objectively   demonstrated   and   is   a   social   or  
hygienic  problem  



Types:  
! Stress  urinary  incontinence  (SUI):  leakage  of  urine  during  raised  intra-­‐abdominal  
pressure  e
...
 coughing,  sneezing,  laughing  or  lifting  heavy  objects  
! Overactive  bladder  (OAB),  also  called  urge  incontinency:  leakage  associated  with  
urgency,  usually  with  overactive  detrusor  activity
...
    Also   perform  
MSK  exam  (particulary  back)  to  assess  for  any  spinal  lesions
...
g
...
g
...
g
...
g
...
   Remember  the  detrusor  muscle  receives  parasympathetic  stimulation  (S2-­‐S4)  from  
the  sacral  plexus
...
     



Remember  that  anti-­‐muscarinic  drugs  can  cause  urinary  retention    

 
Surgical  (rarely  used)  


Botox  injections  



Sacral  nerve  modulation  



Augmentation  cystoplasty  



Bladder  overdistension  

 
Investigation  of  urinary  incontinence    


History:    
! Onset  and  timing  and  duration  
! Character:   frequency,   urgency   (strong   urge   preceding   urination?),   stress   (e
...
 
associated  with  coughing  or  sneezing?)  
! Radiation:  bowel  problems?  

 
 
 

! associated  symptoms  (e
...
 dysuria,  pelvic/abdominal  pain,  haematuria,  back  pain,  
neurological   deficits   such   as   sciatica,   back   pain,   bladder/bowel   dysfunction,   and  
perineal  anaesthesia)  
! Precipitating  factors  e
...
 lose  urine  when  coughing  sneezing  or  laughing?    
! Relieving  factors  
! Severity:  volume  of  leakage,  effects  on  QOL  


Examination:  important  to  perform  neurological  examination,  as  the  incontinence  may  have  
a  neurological  cause  e
...
 spinal  cord  conpression  



Investigations:  
! Urodynamics  (gold  standard)  
! Urinalysis:  assess  for  UTI  or  kidney  abnormality    
! Blood  for  renal  function  if  suspect  renal  impairment  
! Bladder  Chart  (records  voided  volumes,  frequencies  and  UI  episodes)  
! Pad  test  (quantifies  urine  leakage  over  specified  time)  
! Others:  electromyography,  imaging  renal  tract,  cystourethroscopy  

 
Urodynamics  




Includes  uroflowmetry  and  cystometry  



Uroflowmetry:  Flow  rate  enables  you  to  measure  peak  flow,  mean  flow  and  voided  volume  
(minimum  of  200mls  void  is  required)  



 
 
 

Useful   to   differentiate   between   stress   urinary   incontinence   and   overactive   bladder   in  
patients  in  whom  surgery  considered  

Cystometry   is   a   method   by   which   the   pressure/volume   relationship   of   the   bladder   is  
measured  during  filling,  provocation  and  during  voiding  

 
 

 
 
 

 
 
 

 
 

 
 
 
 
 

 
 
Pelvic  organ  prolapse  




Common  (up  to  50%  of  parous  woman,  10-­‐20%  symptomatic)  



Lifetime  risk  of  surgery:  11%  



20%  of  patients  on  gynaecology  waiting  lists  



Increasing  incidence:  women’s  life  expectancy  is  increasing  and  increased  expectations  for  
quality  of  life  



Occurring   in   women   of   all   ages,   it   is   more   common   as   women   age,   particularly   in   those   who  
have  delivered  large  babies  or  had  exceedingly  long  pushing  phases  of  labor
...
   

Minor   prolapse   can   be   treated   with   exercises   to   strengthen   the   pelvic   floor   muscles;   more  
serious  prolapses  require  pessary  use  or  reconstructive  surgical  treatment  (e
...
 anterior  or  
posterior  repair)
...
   



The   rectum   or   urinary   bladder   may   also   prolapse   as   a   result   of   changes   in   the   integrity   of  
connective   tissue   in   the   posterior   or   anterior   vaginal   walls,   respectively
...
 



Prolapse  is  almost  never  painful,  but  the  change  in  position  of  organs  may  cause  urinary  or  
bowel  symptoms
...
   Rectum  bulging  into  vagina
...
     



Enterocele   (pouch   of   Douglas   containing   small   bowel):   remember   the   pouch   of   Douglas   is  
also   called   the   rectouterine   pouch,   which   is   an  extension   of   the   peritoneal   cavity   between  
the  rectum  and  the  posterior  wall  of  the  uterus
...
     



Vaginal  vault:  occurs  when  the  upper  portion  of  the  vagina  loses  its  normal  shape  and  sags  
or  bulges  down  into  the  vaginal  canal  



Uterus  prolapse  



 
 
 

Cytocele   (bladder):   due   to   weakness   in   anterior   vaginal   wall
...
   
Anterior  repair
...
   Urethrocoele  is  the  bulging  of  
the  urethra  into  the  lower  one  third  of  the  anterior  vaginal  wall
...
     

Cervical  prolapse  

 
 
Classification  of  pelvic  organ  prolapse  


1st  degree  (in  vagina)  



2nd  degree  (at  vaginal  interiotus)  



3rd  degree  (outside  vagina)    



Procidentia  (entirely  outside  vagina)  

 
Symptoms  of  pelvic  organ  prolapse  


Any  prolapse:  
! asymptomatic  
! worry  
! coital  difficulties  (sexual  intercourse  difficulties)  

 
 
 



Cystourethrocele  (bladder/urethra  prolapsed  through  anterior  vaginal  wall):  
! stress  urinary  incontinence  
! urinary  retention  
! recurrent  UTI  



Uterine/vault  prolapse  
! backache  
! ulceration  if  procidentia  (completely  out  of  vagina)  



Rectocele  (rectum  prolapsed  through  posterior  wall):  
! constipation  
! dyschezia  (difficulty  defecating)  

 
Assessment  of  Prolapse  Organ  Prolapse  
History  


Age  and  Parity  



PC:  urinary  symptoms,  bowel  symptoms,  sexual  symptoms,  other  symptoms  



PMH:  including  past  Obs  and  Gynae  history  and  past  surgical  history  



FH  



DH  



Allergies  



SH  and  occupational  history  



Concerns  and  expectations  

 
Examination  



BP  



Urinalysis  


 
 
 

Weight,  height  and  BMI  

Abdominal  Examination  



Pelvic  Examination:  
! Urinary  incontinence  and  evidence  of  pelvic  prolapse  on  coughing  
! Uterine  size  and  position  
! Adnexal   mass:   lump   in   tissue   of   the   adnexa   of   uterus,   usually   in   the   ovary   or  
fallopian  tube
...
g
...
  It   is   designed   to   support  
areas  of  pelvic  organ  prolapse
...
   

 
 
 
THE  MENOPAUSE  AND  HRT  


Menopause  is  the  cessation  of  a  woman's  reproductive  ability,  the  opposite  of  menarche
...
g
...
    The  
perimenopause  describes  a  six  to  ten  year  phase  ending  12  months  after  the  last  menstrual  
period  e
...
 ending  at  the  menopause  



Premateur  menopause  =  <  40  years  



Early  menopause  <  45  years  



Contaception  during  menopause:  
! If  <  50  =>  contraception  for  2  years  after  LMP  
! If  >  50  =>  contraception  for  1  year  after  LMP  

 
Reminder  of  normal  menstrual  cycle  


 
 
 

Follicular  phase  (begins  on  first  day  of  menstruation  and  lasts  approximately  14  days  in  a  28  
day  cycle):    

! Follicle-­‐stimulating  hormone  (FSH)  is  released  from  anterior  pituitary  in  response  
to   GnRH   stimulation
...
   
! FSH   stimulates   granulosa   cells   (cellular   layer   which   surrounds   follicles   in   the  
ovaries)   to   convert   androgens   (coming   from   the   thecal   cells)   to   estradiol   (E2)   by  
aromatase  during  the  follicular  phase  of  the  menstrual  cycle  
! With   the   rise   in   oestrogens   E2   (from   granulosa   cells),   LH   receptors   are   also  
expressed   on   the   maturing   follicle,   which   causes   it   to   produce   more   estradiol  
(and  prepares  follicles  for  LH  surge)  
! LH   supports   theca   cells   in   the   ovaries   that   provide   androgens   and   hormonal  
precursors  for  estradiol  production
...
  This   "LH   surge"  
triggers  ovulation,  thereby  not  only  releasing  the  egg  from  the  follicle,  but  also  
initiating  the  conversion  of  the  residual  follicle  into  the  corpus  luteum  that,  in  
turn,   produces   progesterone   to   prepare   the   endometrium   for   a   possible  
implantation    



Luteal  phase  (approximately  day  14-­‐28  of  28  day  cycle):  
! After   ovulation   (triggered   by   LH   surge)   the   granulosa   cells   turn   into   granulosa  
lutein  cells  (corpus  luteum)  that  produce  progesterone
...
 
! If   fertilisation/implanatation   does   not   occur   then   rising   levels   of   progesterone  
released   from   the   corpus   luteum   will   –vely   feedback   to   the   hypothalamus   and  
pituitary  =>  will  cause  a  decrease  in  LH  which  will  cause  regression  (degeneration)  
of  the  corpus  luteum
...
   



Ovaries   produce   oestrogen   (mostly   eostradiol   E2),   progesterone   and   testosterone  
(androgens  also  produced  in  adrenals)
...
g
...
   
Estriol  is  only  produced  in  significant  amounts  during  pregnancy  as  it  is  made  by  
the  placenta
...
g
...
   



Hormone  levels  fluctuate  and  become  unpredictable  

 

 
 
Effects  of  the  menopause  


Effects  of  menopause  can  be  classified  as:  
! Acute  symptoms  
! Medium  term  effects  
! Long  term  consequences  

 
 
Acute  symptoms  
!

Vasomotor  (effects  majority  of  woman)  
! Hot  flushes  
! Nights  sweats  

!

General    
! Headache  
! Fatigue  

 
 
 

! Insomnia  
! Arthralgia    
! Dizziness    
! Many  other  non  specific  features  
!

Psychological  
! Poor  memory  
! Loss  concentration  
! Irritability  
! Low  mood  
! Anxiety  
! Reduced  libido  

 
Medium  term  effects  
!

Vaginal  
! Dryness/itch/burning:    atrophic  vaginitis    
! Dyspareunia  (pain  during  sex)  due  to  vaginal  dryness  
! Sexual  dysfunction  
! Prolapse    
! Atrophy  which  may  cause  vaginal  bleeding  

!

General    
! Dry  skin  
! Hair  thinning  

!

Urinary  tract  
! Urinary  frequency/nocturia    
! Urgency  
! Stress/urge  incontinence  
! Recurrent  UTI  

 
 
 

 
Many  of  these  effects  primarily  occur  due  to  oestrogen  depletion  in  skin  in  urogenital  tissues
...
 Oestrogen  reduces  LDL,  increases  HDL,  
reduces  cholesterol  deposition  and  fat  distribution  =>  “normal”  levels  of  oestrogen  are  CV  
and  cerebrovascular  protective
...
     

!

Osteoporosis   (decreased   BMD   <   -­‐2
...
    Occurs   due   to   loss   of   protective  
effect   from   oestrogen   in   premenopausal   state   (oestrogen   protects   bones)
...
 Hip  fracture  30%  mortality  rate
...
   High  burden  to  society
...
     

 
Management  of  the  menopause  


To   minimise   symptoms   and   reduce   risk   long   term   consequences   (e
...
  CV   disease   and  
osteoporosis)  



Lifestyle  measures:  healthy  diet,  regular  exercise,  stop  smoking    



HRT   if   young   onset   or   decreased   QoL   (e
...
  due   to   symptoms)
...
    This   is   in   contrast   to   COCP,   which   increases   the   levels   of  
hormones  in  the  body
...
g
...
g
...
    This   is   because   progesterone   is   essential   for   maintaining   endometrial  
protection
...
     
Subtotal  hysterectomy  =>  may  also  need  progestogens  (some  endometrium  may  remain)    

!

If  woman  have  uterus  =>  must  use  combined  oestrogen  and  progestogen  HRT  

!

NB:   The   Mirena   is   now   licensed   for   use   with   Oestrogen   only   HRT   for   4   years
...
    In   women  
with   an   intact   uterus,   oestrogen   HRT   stimulates   the   growth   of   the   womb   lining  
(endometrium),   which   can   lead   to   endometrial   cancer   if   the   growth   is   unopposed
...
   In  this  case  you  are  technically   giving   them   combined   HRT,  except  the  mirena  is  
better  because  the  progesterone  is  less  systemically  absorbed  so  that's  why  you  can  give  it  
to   people   who   have   a   uterus,   because   the   mirena   is   protecting   their   uterus   without   needing  
to   give   them   a   progesterone   pill
...
    Also   usefull   if   woman   wants   a   form   of   contraception   (as  
they   may   still   be   fertile   during   the   peri-­‐menopause)
...
     
 

 
 
Sequential  Combined  HRT  
!
!

Oestrogen  for  28  days  –  continuous  oestrogen    

!

Progesterone  for  10-­‐14  days  =>  then  a  14-­‐18  day  progesterone  free  period    

!

Mimics   normal   menstrual   cycle,   oestrogenic   proliferation   of   endometrium   (in   the   follicular  
phase   /   proliferative   phase)   followed   by   shedding   in   2nd   half   cycle   (luteal   phase   =>   corpus  
luteum  regression  causes  falling  levels  of  progesterone  =>  shedding  of  the  endometrium)  

!

For  use  in  peri-­‐menopausal  women  with  uterus  (as  simulates  normal  cycle)  

!
 
 
 

Sequential  oestrogen  and  progestogen    

Progestogen  protects  the  endometrium  and  leads  to  a  regular  bleed    

!

Single  named  product  available  as  patch/tablet  or  combine  two  different  preparations  

 
Continuous  Combined  HRT  
!

Continuous  Combined  HRT  (CCT:  continuous  combined  therapy)  

!

Oestrogen  combined  with  progestogen  for  28  days  =>  inhibits  monthly  bleeds  

!

This  should  not  be  started  until  1  year  after  the  LMP  (menopause)  or  aged  54  

!

Single  named  products  available  as  tablets/patches    

!

No  monthly  bleed  (after  1st  6  months)  

 
When  to  start/switch?  
!

Sequential  combined  HRT  (14-­‐18  day  progesterone  free  period)  
! Started   when   required   in   perimenopausal   women   (may   still   have   periods)   –   as  
simulates  natural  cycle    
! Prolonged   use   can   increase   the   risk   of   endometrial   cancer   (due   to   oestrogen  
induced  hyperproliferation)  =>  max  duration  5  years  

!

Continuous  combined  HRT  (no  progesterone  free  period)  
! This  should  not  be  started  until  1  year  after  the  LMP  (menopause)  or  aged  54  
! Should  also  be  used  after  2  years  of  sequential  therapy  if  under  the  age  of  54    
 

Key  points  


Over  54  or  LMP>  1yr  (menopause)  =>  start  CC  HRT  (continuous  combined  HRT)  –  in  woman  
with  uterus    



Under   54   and/or   peri-­‐menopause   =>   Sequential   HRT   (progesterone   free   period)   for   2   yrs  
then  switch  to  CC  (continuous  combined)  HRT  –  in  woman  with  uterus  

 
Tibolone  (Livial®)  
!
!

 
 
 

Alternative  to  CC  HRT  (postmenopausal  women)  
Synthetic   steroid   →   weak   oestrogenic,   progestogenic   and   androgenic   properties   (non-­‐
selective)  

!

Licensed  for  vasomotor,  psychological  and  libido  problems  

!

Conserves  bone  mass  and  reduces  risk  fractures  (not  hip)  

!

The  risk:  benefit  ratio  similar  to  HRT  in  women  under  60,  but  over  60  increased  risk  of  stroke  

!

Slightly  increased  risk  for  endometrial  cancer  (due  to  oestrogen  component)  

!

Less  risk  of  breast  cancer:  similar  risk  to  E2  only  HRT  (less  than  combined  HRT)    

 
Testosterone  
!

Testosterone   levels   may   drop   by   up   to   50%   after   menopause   or   BSO   (Bilateral   salpingo-­‐
oophorectomy)
...
g
...
g
...
     
 
 

Benefits  of  HRT  
Menopausal  Symptoms:  
!

HRT   shown   to   effectively   relieve   vasomotor   symptoms   e
...
  relieve   hot   flushes   and   night  
sweats  (one  of  the  main  reasons  woman  start  HRT)  

!

In  most  cases,  <5  years  therapy  is  sufficient  

!

Symptoms  may  recur  for  a  short  time  after  stopping  it    
 

Colorectal  cancer:  
!

HRT  reduces  the  risk  of  colorectal  cancer  

!

This  is  likely  to  be  the  anti-­‐oxidant  effect  of  oestrogen    
 

Osteoporosis:  
 
 
 

!

Used  in  prevention  and  treatment    

!

Reduced  risk  of  osteoporotic  fractures  with  HRT  in  RCTs  

!

Not  1st  line  in  older  women  as  Tx  osteoporosis  as  less  risky  alternatives  e
...
 bisphosphonates  
e
...
 pamidronate  

 
Osteoporosis:  risk  factors  
Minor  
!

Cigarette  smoking  

!

Sedentary  lifestyle  

!

Low  Calcium  intake  –  must  ask  about  calcium  intake    
 

Moderate  
!

FH  of  osteoporosis  

!

Underweight  

!

High  alcohol  consumption    
 

Major  
!

Early  menopause  

!

Prolonged  steroid  therapy  –  must  take  life  long  steroid  history  

!

Prolonged  amenorrhoea  

 
HRT  is  a  very  good  option  in  younger  perimenopausal  women  if  other  risk  factors  present
...
 
 
Major   secondary   causes   of   osteoporosis   =   GI   malabsorption   (coeliac   and   crohns),   iatrogenic  
(steroids),  endocrine  (Cushings,  DM,  thyroid),  etc
...
g
...
   
Progesterones  have  the  dominant  effect  in  HRT  as  the  levels  of  progesterone  are  high  in  HRT  
(similar  to  levels  in  OCP)
...
   
ER  +ve  and    PgR  +ve  breast  cancers  can  be  stimulated  by  combined  HRT
...
  Combined  
significantly  higher  than  oestrogen  only
...
 

!

Higher   with   combined   HRT   than   oestrogen-­‐only   (although   oestrogen   is   major   risk   factor,  
progesterones  may  contribute)  

!

More  common  in  the  first  year  of  use  

!

Risk  may  be  lowered  by  transdermal  route/changing  progestogen    

 
Stroke  and  CV  disease:  
!

In  RCT’s  HRT  increased  the  risk  of  stroke  (mostly  ischaemic)  compared  with  placebo  

!

Older  women  have  a  greater  absolute  risk  of  stroke  

!

Risk  may  depend  on  oestrogen  dose  

!

No  significant  difference  between  E2  only/combined  preparations    

!

HRT  may  raise  BP  

 
Therfore   it   is   important   to   also   perform   a   CV   assessment   at   initial   HRT   consultation   (similar  
consultation   initating   COCP):     migraine   with   aura,   previous   cerebrovascular   accident   or   CV  
accident,   CV   risk   factors,   personal   or   family   history   of   DVTs,   personal   or   family   history   of   O&G  
cancers,  smoking  status,  BMI,  BP  
 
HRT  Uncertainties:  CVD  
!

Initially  thought  to  be  beneficial  

!

Re-­‐analysis   WHI   study   suggests   a   cardio-­‐protective   effect   if   HRT   taken   in   the   early  
menopausal  years  

!

Increased  risk  of  CVD  in  women  who  started  combined  HRT  more  than  10  years  after  the  
menopause  

!

No  increased  risk  of  CVD  has  been  identified  to  date  with  oestrogen-­‐only  HRT  

!

Oestrogen  can  raise  BP  =>  may  act  as  a  CV  risk  factor  

!

Increased  absolute  excess  risk  the  longer  after  menopause  it  is  started
...
 
! Premature  menopause  (<45  years)  



Starting  HRT  in  women  over  the  age  of  60  years  is  generally  not  recommended
...
 



Current  indications  for  the  use  of  HRT  are:  
! For   the   treatment   of   menopausal/perimenopausal   symptoms   where   the  
risk:benefit  ratio  is  favourable,  in  fully  informed  women
...
 

 
HRT  contraindications  
HRT  may  not  be  suitable  if  you  are  pregnant  or  have:  



a  history  of  heart  disease  or  stroke  



untreated   high   blood   pressure   (your   blood   pressure   will   need   to   be   controlled   before   you  
can  start  HRT),  high  BMI,  smoker  or  have  other  DVT  risk  factors  



 
 
 

a  history  of  blood  clots,  DVTS  or  PTEs  



 

a  history  of  breast  cancer,  ovarian  cancer  or  endometrial  cancer  

liver  disease  

VERY  SIMILAR  TO  COCP!  
 
HRT:  In  summary  
!

Serum   FSH   level   >   30   IU/l   on   2   separate   occasions   +   low   oestrogen   =>   ovarian   failure   =>  
often   menopause   (primary   ovarian   failure)   in   woman   of   middle   ages   (in   younger   woman  
<45  must  rule  out  secondary  causes)  

!

Offer   HRT   to   if   very   symptomatic   =>   Lowest   possible   dose   to   control   symptoms   for   the  
shortest  possible  time  

!

Offer  HRT  if  early  (<45)  or  premature  (<40)  menopause    

 
Non-­‐oestrogen  based  therapy  
!

Clonidine:   no   firm   evidence   in   clinical   trials   but   some   women   get   benefit   for   ‘hot   flushes’
...
  Antidepressants   may   also   act   on  
thermogenic  centres  of  brain  therefore  may  provide  some  relief  from  hot  flushes  although  
unproven  in  trials
...
g
...
g
...
     



While   we   can   not   endorse   their   efficacy   or   safety,   we   should   be   able   to   provide   unbiased  
information   to   aid   choice
...
g
...
g
...
    Herbal   methods  
often   marketed   as   ‘food   supplements’   so   not   subject   to   same   regulations   as   conventional  
drugs  therefore  should  be  used  with  caution
...
g  hot  flushes,  night  sweats,  irritability)  
! Longer   term:   bone   loss,   CVS   and   stroke   risk,   cognitive   decline/dementia,  
reduced  fertility  and  infertility  (due  to  anovulation),  ↓  life  expectancy  

 
Premature  ovarian  failure  causes  
Primary  causes  
! Idiopathic  
 
 
 

! Chromosomal  e
...
 Turners  45X,  Down  syndrome,  Fragile  X  
! AI:  Hypothyroidism,  Addisons,  DM,  SLE,  RA  
! Enzyme  deficiencies:  Galactossaemia  
 
Secondary  causes  


Chemotherapy/radiotherapy  



Surgery:  bilateral  oophrectomy,  hysterectomy  



Infection:  TB,  mumps  

 
POF:  Treatment  
!

Hormone   replacement   (HRT)   required   to   keep   tissues   healthy   and   reduce   long   term  
complications  

!

HRT  (higher  doses)  or  COCP  (optional  pill  free  week)  to  age  52  

!

Sequential  combined  HRT  as  simulates  natural  cycle    

!

Testosterone  as  patch  or  implant  

!

Additional  vaginal  oestrogen  may  be  needed  

!

Risks   at   this   age   are   due   to   non-­‐use   of   HRT   (e
...
  early   CV   disease   and   bone   disease)   rather  
than  use    (on  HRT  same  risk  as  age-­‐equivalent  population  for  breast  cancer,  VTE  etc;  this  is  
because  we  are  just  “normalising”  hormone  levels)  =>  patients  with  POF  should  definitely  
be  on  HRT  

!

No  studies  have  clearly  shown  best  replacement  hormones  (HRT  vs  OCP)  

 
 
PATHOLOGY  OF  THE  OVARY  AND  FALLOPIAN  TUBE  
Anatomy  reminder  

 
 
 

 
 
Physiological  Ovarian  Cysts  
1
...
g
...
 Corpus  Luteum    Cyst  


>3cm  diameter  



Derived  from  post-­‐ovulatory  follicle    



May  rupture    =>  haemoperitoneum  

 
Ovarian  Tumours  

 
 
 

Functional  tumours  usually  present  when  small  i
...
 secreting  oestrogen  or  androgens  



Extremely  large  tumours  may  be  benign  



Non-­‐functioning  tumours  present  late  due  to  inaccessible  location  of  ovaries  



Malignant   ovarian   tumours,   mainly   epithelial   (adenocarcinoma),   generally   have   a   poor  
prognosis
...
   



Can  be  benign,  borderline  or  malignant  



Malignant  tumors  of  this  type  are  also  called  ovarian  adenocarcinoma
...
       



No  solid  areas  



Can  weigh  several  kg  and  cause  abdominal  distension
...
 



Pathology:   papillary   pattern   (pappilary   cores)   covered   by   serous   type   epithelium   similar   to  
the  Fallopian  tube
...
e
...
 



The   COCP   is   also   protective   for   ovarian   cancer   and   endometrial   cancer;   however   is   a   risk  
factor  for  breast  and  cervical  cancer  



Aetiology  
! Repeated  ovarian  surface  trauma  due  to  ovulation  is  the  probable  aetiological  
factor  
! Therefore  pregnancy  (multigravida)  and  oral  contraception  decrease  the  risk  (as  
generate  an  anovulatory  state)  

 
 
 

 
Ovarian  adenocarcinoma  


Surface  epithelial-­‐stromal  tumour,  also  known  as  ovarian  glandular  epithelial  carcinoma  or  
ovarian  adenocarcinoma  



Most  common  type  of  ovarian  cancer  



It   includes   serous   adenocarcinoma,   endometrioid   adenocarcinoma   and   mucinous  
cystadenocarcinoma
...
 
 

Features  of  epithelial  ovarian  cancer  


Presents  late,  vague  symptoms:  
! Dyspepsia  like  picture    
! Abdominal  pain  and  swelling  and  bloating  
! Early  satiety    
! Ascites    

 

! Pressure  effects  on  other  organs  e
...
 urinary  symptoms  


Spreads  throughout  peritoneal  cavity  



Poor  prognosis:    5  year  survival    43%    



6th  commonest  female  malignancy    



Kills  more  women  each  year  than  all  other  gynaecological  cancers  combined    

 
Mucinous  Adenocarcinoma  



Multiloculated  cysts,  solid  areas,  necrosis,  haemorrhage
...
 



Invasive  



pseudomyxoma  peritonei  –  as  mucus  filled  tumour    

 
 
Serous  Adenocarcinoma  


Cancer  of  fallopian  tube  type  epithelium  



Often  bilateral  



Solid/cystic  tumour  with  necrosis  



Papillary  projections  from  outer  surface  of  capsule
...
 



Sex  cord-­‐stromal  tumours  retain  bisexual  potential
...
    Most   cases   of   endometrial   hyperplasia   result   from   high  
levels   of   estrogens,   combined   with   insufficient   levels   of   the   progesterone-­‐like   hormones  
which  ordinarily  counteract  estrogen's  proliferative  effects  on  this  tissue
...
 

! If   the   patient   is   postmenopausal,   she   usually   presents   with   abnormal   uterine  
bleeding  (due  to  uterine  endometrial  hyperplasia)  e
...
 PMB  
!  If  the  patient  is  of  reproductive  age,  she  would  present  with  menometrorrhagia  
(prolonged   or   excessive   uterine   bleeding   occurs   at   usual   time   of   menstrual  
periods  and  IMB)
...
 


Behaviour  difficult  to  predict
...
 



However,  thecomas  often  secretes  oestrogen    =>  can  cause  endometrial  hyperplasia  =>  can  
cause  abnormal  uterine  bleeding    
! Pre-­‐menopause:  IMB  (inter-­‐menstrual  bleeding)  or  menometorrhagia  
! Post  menopause:  PMB  (post  menopausal  bleeding)  



Yellow  colour,  due  to  lipid  in  cells
...
    A   rare   type   of   thecoma,   called   a   Sertoli-­‐
Leydig   tumor,   produces   testosterone,   so   women   with   this   type   of   thecoma   may   develop  
masculine  characteristics  such  as  a  deepening  voice  and  excess  facial  hair  e
...
 virilisation
...
 



Sertoli-­‐Leydig   cell   tumours   often   secrete   androgens,   which   can   cause   virilisation  
(masculinisation):  
! Voice  deepening  
! Clitomegaly  
! Excessive  hair  growth  (hirsutism)  



Acne  can  also  occur  due  to  increased  testosterone  levels  



Masculinization   (virilisation)   is   preceded   by   anovulation,   oligomenorrhoea,   amenorrhoea  
and   defeminization
...
 



Serum  testosterone  level  is  high
...
    Most   common   germ   cell   tumour
...
 



Choriocarcinoma   (produces   HCG):   Extra-­‐embryonic   germ   cell   malignant   tumour   producing  
tumours  of  placental  tissues
...
     



Endodermal   sinus   tumor   (EST),   also   known   as   yolk   sac   tumor   (produces   AFP):   Extra-­‐
embryonic   germ   cell   malignant   tumour   producing   tumours   of   placental   tissues
...
     



Dysgerminoma:  undifferentiated  germ  cell  tumour  (malignant)  

 
Benign  cystic  teratoma    (Dermoid  cyst)  



Does  not  produce  hormones  


 
 
 

Benign  

Common,  up  to  20%  of  all  ovarian  tumours
...
 



Can  also  produce  thyroxine  from  ectopic  thyroid  tissue  

 
Metastatic  Tumours  


7%  of  lesions  presenting  as  ovarian  tumours  are  metastatic
...
 



Krukenberg   tumour:     solid,   fibrotic,   metastatic   tumour   with   signet-­‐ring   cells,   often   from  
stomach
...
   In  contrast,  salpingitis  only  refers  to  infection  and  inflammation  in  the  fallopian  
tubes
...
 



Anyythich   which   can   obstruct   the   path   of   the   fertilised   egg   from   tube   to   uterus   is   a   risk  
factor  for  ectopic  pregnancy    



Risk  factors:    
! PID  and  Tubal  obstruction  
! I
...
C
...
 (intrauterine  copper  device)  and  Mirena  (Levonrgestrel-­‐IUS)  

 
Fallopian  Tube  Tumours:  Adenocarcinoma  


 
 
 

Serous  adenocarcinoma  –  commonest    
Rare  



Presents  late  



Poor  prognosis  

 
 
PELVIC  MASSES  
Anatomy  

 
 
 
Pelvic  mass:  non  gynaecological  causes  


Bowel  
! Constipation!  
! Caecal  carcinoma  
! Appendix  abscess  
! Diverticular  abscess  (partciulary  in  LIF)  

 
 
 



Bladder/Urological
...
g
...
 

 
Pelvic  mass:  Gynaecological  causes  


Uterine  
! body  
! cervix  



Tubal  &  para-­‐tubal  



Ovarian  e
...
    Can  
become  very  large
...
    It   is   effectively   endometriosis   of   the   myometrium
...
 



Usually  few  cm,  but  may  be  much  bigger  &  multiple  



Therefore  common  cause  of  pelvic  mass  



Presentation:  
! May  be  asymptomatic/incidental  finding  
! Menhorrhagia  (heavy  menstruation  loss  >70ml)  
! Pelvic  mass  or  “bulky  uterus”  
! Pain/tenderness  
! Red  degeneration:  A  rare  complication  of  a  fibroid  during  pregnancy  is  a  problem  
known   medically   as   red   degeneration
...
 This  usually  happens  in  the  middle  
trimester   (three   months)   of   pregnancy   and   is   thought   to   result   from   the  
leiomyoma  (fibroid  tumour)  growing  rapidly  and  outgrowing  its  blood  supply
...
   Can  also  occur  in  menopause
...
g
...
 
! MRI  for  more  precise  localisation    



 
 
 

Management:  

! Expectant  if  asymptomatic  (after  menopause  fibroids  shrink  and  it  is  unusual  for  
fibroids  to  cause  problems
...
  In   contrast   to   a   hysterectomy   the  
uterus  remains  preserved  and  the  woman  retains  her  reproductive  potential
...
 
! Hysteroscopic  Resection
...
 



Occasionally  asymptomatic  until  large  chocolate  cyst,  which  may  rupture
...
g
...
g
...
g   Krukenberg   tumor:   signet   cells)   and   GI  
primaries
...
 
! Bloating    
! ‘Pressure’  symptoms  (especially  bladder  e
...
 incontinence)  
! Change  of  bowel  habit  
! SOB/  Pleural  effusion  
! Leg  oedema    or  DVT  
! Even  generalised  oedema  if  low  albumin
...
B  There  may  not  be  a  pelvic  mass
...
B:  OCP  is  protective  



This   is   in   contrast   to   cervical   cancer:   where   younger   age,   multiparity   and   OCP   are   risk  
factors  



The   menstrual   cycle   causes   damage   to   ovarian  cells   over   a   long   period   of   times   =>   therefore  
suppression   of   menstrual   cycle   (e
...
  multiparity   and   OCP)   decreases   the   risk   of   ovarian  
cancer  
 

Investigation  of  suspected  ovarian  CA  


Triple  assessment    



History  &  examination  



Tumour  markers  
! CA   125   (cancer   antigen   125):   particularly   a   sign   of   ovarian   serous  
adenocarcinoma  (most  common  ovarian  cancer)  
! Carcino-­‐embryonic  antigen  CEA  



Imaging  
! USS  better  for  imaging  nature  of  cyst  
! CT   better   for   assessing   disease   outwith   ovary   especially   omental   disease,  
peritoneal  disease  and  lymph  nodes
...
 



Normal  level  does  not  exclude  cancer  



Moderate  elevation  seen  in  numerous  situations  e
...
 
! Endometriosis  
! Peritonitis/infection  
! pregnancy  
! Pancreatitis  
! Ascites  from  any  cause
...
g
...
 



CEA  is  classically  associated  with  cololrectalCa  

 
Diagnosis  of  ovarian  cancer:  suspicious  USS  findings  


Complex  mass  with  solid  &  cystic  area  



Multi-­‐loculated  



Thick  septations  



Associated  ascites  



Bilateral  disease  



Any  ovarian  cyst/mass  in  older  woman  is  red  flag  and  should  be  removed    

 
Diagnosis  of  ovarian  cancer  ‘Risk  of  Malignancy’  index  


 RMI  (risk  of  malignancy  index)  combines  three  pre-­‐surgical  features:    
! Serum  CA125  
! Menopausal  status  (M)  
! Ultrasound  score  (U)  



The   RMI   is   a   product   of   the   ultrasound   scan   score,   the   menopausal   status   and   the   serum  
CA125  level  (IU/ml)
...
 
 

Treatment  of  ovarian  cyst/mass  


Removal  or  drainage  if  likely  benign  



Malignant:   removal   of   ovaries   (oophorectomy)   and   uterus   (hysterectomy)   withwith  
removal/biopsy  of  omentum,  ‘debulking’  of  tumour  and  complete  examination/inspection  of  
all  peritoneal  surfaces  (laproscopically)  
! Total  abdominal  hysterectomy  (TAH)  with  bilateral  salingo-­‐oophorectomy  and  
omenal  debulking    



Chemotherapy  may  be  given  pre-­‐surgery  or  after  surgery  e
...
 platinum  based  



Cure  unlikely  unless  confined  to  ovary  at  presentation
...
g
...
 


 
 
 

Speed  of  onset/duration  of  all  symptoms  

Family  history  



Previous  gynaecological  and  surgical  history
...
 

 
 
 
 

Describe  the  mass  


Three   C’s,   three   S’and   three   T’s:   colour,   contour,   consistency,   shape,   size,   site,   tethered,  
texture,  tempetrature  
! Location  
! Size:  cms  or  ‘weeks  gestation’    
! Consistency  e
...
 soft,  firm,  hard,  fluid  filled  
! Surface:  Smooth,  irregular,  speculated,  craggy  
! Tenderness  
! Mobility:  tethered,  mobile  

 
 
THE  PATHOLOGY  OF  THE  UTERUS  AND  ENDOMETRIOSIS  
Endometrium:  Normal  endometrial  cycle  
1
...
    As   they   mature,   the   ovarian   follicles   secrete   increasing   amounts   of  
estradiol   E2
...
  The   estrogen   also  
stimulates   crypts   in   the   cervix   to   produce  fertile   cervical   mucus,   which   may   be   noticed   by  
women  practicing  fertility  awareness  (Billings  method)  

 
2
...
  During   the   secretory   phase,   the   corpus   luteum   produces  
progesterone,   which   plays   a   vital   role   in   making   the   endometrium   receptive   to  
implantation  of  the  blastocyst  and  supportive  of  the  early  pregnancy,  by  increasing  blood  
flow   and   uterine   secretions   and   reducing   the   contractility   of   the   smooth   muscle   in   the  
uterus
...
 Menstrual  phase  


Loss   of   functional   layer   as   hormone   levels   decrease   (particularly   progesterone):   corpus  
luteum   releases   progesterone   which   –vely   feedsback   to   the   hypothalamus   resulting   in  
decreasing  levels  of  LH  =>  regression  of  corpus  luteum  (if  implantation  does  not  occur)  =>  
decreasing   levels   of   progesterone   and   oestrogen   =>   shedding   of   the   endometrium
...
 The  decidua  becomes  part  
of   the   placenta;   it   provides   support   and   protection   for   the   gestation
...
   The  corpus  luteum  is  
maintained  by  hCG  released  from  the  trophoblasts  of  the  placenta
...
OCP/Hormone  therapy:    


Appearances   depend   on   type   and   dose   of   hormone   e
...
  HRT   has   much   lower   levels   of  
oestrogen  compared  to  OCP  (but  similar  progesterones)  



Oral   contraceptives   "fool"   the   pituitary   gland   so   that   it   produces   less   follicle   stimulating  
hormone  and  luteinizing  hormone
...
 



The   primary   contraceptive   mechanism   of   the   combination   OCP   is   to   prevent   ovulation   by  
inhibiting   gonadotropin   secretion   at   both   the   level   of   the   pituitary   gland   and   the  
hypothalamus
...
 
The   progestin   component   of   the   OCP   suppresses   luteinizing   hormone   (LH)   secretion   and  
thus  reliably  prevents  the  LH  surge  which  triggers  ovulation  



Oral  contraceptives  have  two  other  main  effects:  
! They  thin  the  inner  lining  of  the  uterus  (called  the  endometrium),  depleting  it  of  
glycogen   (ie,   a   type   of   sugar),   and   decreasing   its   thickness
...
   In  a  normally  menstruating  woman  
who   is   not   taking   contraceptive   hormones,   progesterone   is   only   present   in  
appreciable   quantities   during   the   luteal   phase   (uterine   secretory   phase)   of   the  
menstrual  cycle,  after  the  development  of  the  endometrium  (uterine  proliferative  
phase)
...
   
The   result   is   a   thin   (as   oestrogen   is   not   properly   doing   its   job   in   repro   tract),  
decidualized   endometrium   with   atrophied   glands   that   is   not   receptive   to  
embryo  implantation
...
 I
...
C
...
g
...
 Pregnancy        


Hypersecretory  pattern  as  corpus  luteum  does  not  regress  



‘Arias-­‐Stella’  reaction  (chorionic  tissue)  



If  a  blastocyst  implants,  then  the  thick  secretory  endometrial  lining  remains  as  decidua
...
 

 
4
...
       


 

Drop  in  hormone  levels  (drop  in  oestrogen  and  progestogens  =>  increased  LH  and  FSH)  

Cystic  change  

Endometritis:  Inflammation  of  endometrium  
1
...
U
...
D
...
 Chronic  


May  follow  acute  or  be  chronic  from  start  



Associated  with  pelvic  inflammatory  disease  and  I
...
C
...
 



Lymphocytes  and  plasma  cells  present  

 
 
3
...
g
...
g
...
g
...
g
...
   
Even   though   it   is   an   oestrogen   receptor   antagonist   in   breast   tissue   (and   used   to   target   ER  
+ve   breast   cancers)   it   acts   as   partial   agonist   on   the   endometrium   and   has   been   linked   to  
endometrial  cancer  in  some  women
...
 



Risk  of  adenocarcinoma  increases  with  the  degree  of  atypia
...
 



Hysterectomy  usually  indicated
...
g
...
  The   high   levels   of   progesterone   produced   during  
pregnancy  has  a  protective  effect  against  endometrial  cancer
...
g
...
g
...
g  oestrogen  only  HRT  or  tamoxifen  
! Some  types  are  not  oestrogen-­‐related  e
...
 DM  
! Pelvic  irradiation  implicated  occasionally  

 
Pathology  of  Endometrial  Adenocarcinoma  


Diffuse  endometrial  thickening  or  polypoid  mass
...
 



Grades  1  (low),  2  (intermediate)  and  3  (high)  



Most  are  Grade  1  (well  differentiated)  

 
Diagnosis  




 
 
 

Transvaginal   ultrasound   to   examine   the   endometrial   thickness   in   women   with  
postmenopausal   bleeding   is   increasingly   being   used   to   aid   in   the   diagnosis   of   endometrial  
cancer  
In   the   United   Kingdom,   both  transvaginal   ultrasound   and   an   endometrial  biopsy   are  used  
for  diagnosing  endometrial  cancer
...
  Ultrasound   findings   alone   are   not   conclusive   in   cases   of  
endometrial  cancer,  so  another  screening  method  (for  example  endometrial  biopsy)  must  be  
used  in  conjunction
...
 Endometrial  biopsy  is  the  less  invasive  option,  but  it  may  not  give  
conclusive   results   every   time
...
  CT   scans   are   used   for   preoperative   imaging   of  
tumors  that  appear  advanced  on  physical  exam  or  have  a  high-­‐risk  subtype  (at  high  risk  of  
metastasis)
...
 These  include  a  
chest   x-­‐ray,   liver   function   tests,   kidney   function   tests,   and   a   test   for   levels   of   CA-­‐125,   a  
tumor  marker  that  can  be  elevated  in  endometrial  cancer
...
 



Distant  spread  (liver,  lung)  occurs  late
...
 

 
Treatment  



Radiation   therapy,   hormonal   therapy,   and   chemotherapy   are   additional   treatments   (called  
adjuvant  therapy)
...
 



Most  women  with  endometrial  cancer,  except  those  with  stage  IV  disease,  are  treated  with  
hysterectomy
...
  Hysterectomy   is  
traditionally   performed   through   an   incision   in   the   abdomen   (laparotomy),   however,  
endoscopic  surgery  (laparoscopy)  with  vaginal  hysterectomy  is  also  being  used
...
 This  may  be  necessary  because  endometrial  cancer  often  spreads  
to  the  ovaries  first
...
   

The   lymph   nodes   in   the   pelvic   region   may   also   be   biopsied   or   removed   to   check   for  
metastasis
...
 



Malignant  glands  and  stroma  =>  carcinosarcoma  



Elderly  women  



Poor  prognosis  (~  six  months)  



Rapidly  growing,  bulky  necrotic  mass    



Heterologous  elements:  
! malignant  cartilage  
! skeletal  muscle  

 
Tumours  of  the  myometrium  
Leiomyoma  (fibroids)  


A  leiomyoma  is  a  benign  smooth  muscle  neoplasm  



Arise  from  smooth  muscle  of  uterine  wall  (myometrium)  



Very  common  (fibroids)  
! 20%  of  women  over  35  years  
! 40%  of  women  over  50  years  (more  common  in  older  woman)  


 
 
 

Usually  multiple  and  can  be  very  large  =>  bulky  uterus,  large  for  dates  in  pregnancy    



May  transform  into  leiomyosarcoma  (malignant)  



Occur  in  three  main  sites:  
! Submucosal:  A  submucosal  fibroid  lies  just  under  endometrium  
! Intramural:  An  intramural  fibroid  that  lies  completely  within  the  myometrium  of  
the  uterus    
! Subserosal:  serosal  or  subserosal  fibroid  lies  on  the  outer  part  of  the  uterus,  just  
under  the  covering  of  the  outside  of  the  uterus,  which  is  called  the  serosa
...
 
! Histopathology:  Interweaving  smooth  muscle  bundles  in  benign  leiomyoma  

 

 
 
 

 
 
 
 
Leiomyosarcoma  (cancerous  fibroid)  


Malignant  smooth  muscle  tumour  



Older  women  



Rare  compared  with  leiomyoma  



Poor  prognosis      



Mostly  solitary,  some  arise  from  benign  leiomyoma
...
e
...
 



Endometrial  cells  in  areas  outside  the  uterus  are  also  influenced  by  hormonal  changes  and  
respond  in  a  way  that  is  similar  to  the  cells  found  inside  the  uterus
...
   



The   pain   often   is   worse   with   the   menstrual   cycle   and   is   the   most   common   cause   of  
secondary  dysmenorrhea
...
g
...
  As   endometriosis   can   lead   to   anatomical   distortions   and  
adhesions   (the   fibrous   bands   that   form   between   tissues   and   organs   following  
recovery  from  an  injury)
...
 
! Pelvic   pain:   A   major   symptom   of   endometriosis   is   recurring   pelvic   pain:  
dysmenorrhoea  (painful  menstruations),    dyspareunia  (pain  during  sex),  dysuria  
(painful  micturition),  chronic  pelvic  pain  
! Catamenial   pneumothorax   is   a   condition   of   collapsed   lung   (pneumothorax)  
occurring   in   conjunction   with   menstrual   periods   (catamenial   refers   to  
menstruation),   believed   to   be   caused   primarily   by   endometriosis   of   the   pleura  
(the  membrane  surrounding  the  lung)  

 
Endometriosis:  occurs  anywhere  in  genital  tract  


Ovary:  Endometrioma  (‘chocolate  cysts’)  –  commonest  site    



Fallopian  tube  



Pouch  of  Douglas  /  rectouterine  pouch  (pelvic  peritoneum)  –  can  cause  dyparenuia    



Wall  of  intestine,  appendix  



Ureters,  bladder  



Surgical  scars  e
...
 Caesarean  section  



NB:   Adenomyosis   is   endometrial   glands   &   stroma   within   the   myometrium   of   the   uterus
...
     Can  cause  a  boggy  uterus
...
 
However,  smaller  endometriosis  implants  cannot  be  visualized  with  ultrasound  technique
...
  These   tumours   are   not   common,   and   they   appear   when   cells   in   the   uterus  
(trophoblast   cells   of   the   conceptus   placenta)   start   to   proliferate   uncontrollably
...
   The  trophoblasts  are  derived  from  the  
blastocyst
...
 



Partial   and   complete   hydatidiform   moles   will   not   produce   a   live   baby   (they   are   'non-­‐
viable'  pregnancies)  



 A  pregnancy  that  results  in  a  hydatidiform  mole  is  called  a  molar  pregnancy
...
  It   is  
usually  due  to  two  sperm  fertilising  one  normal  ovum  (which  should  not  usually  happen)
...
  The   growth   of   the   trophoblastic   tissue   overtakes   the   growth   of   any  
fetal   tissue   and   the   fetus   does   not   develop   normally   (unviable   foetus;   however   unlike  
complete   Hydratiform   mole   the   foetus   does   initially   develop   (abnormally)   because   both  
maternal   and   paternal   DNA   are   present)
...
       



 

Complete  Hydratiform  mole:  Sometimes,  during  conception,  a  sperm  (23,X  or  23,Y)  fertilises  
an  'empty'  egg  (ovum)
...
 
Under   normal   circumstances,   the   fertilised   empty   ovum   would   die   and   not   implant   in   the  
uterus
...
  Complete  
Hydratiform  mole  is  caused  by  a  single  sperm  combining  with  an  egg  which  has  lost  its  DNA  
(the  sperm  then  reduplicates  forming  a  "complete"  46  chromosome  set)
...
    The  
combination   46,YY   (diploid)   is   not   observed   (as   X   is   essential   to   even   initiate  
embryogenesis)
...
 This  is  a  complete  hydatidiform  mole
...
g
...
     

A   hydatidiform   mole   conception   may   be   categorized   in   medical   terms   as   one   type   of   non-­‐
induced   (natural)   "missed   abortion",   referred   to   colloquially   as   a   "missed   miscarriage",  
because   the   pregnancy   has   become   non-­‐viable   (miscarried)   but   was   not   immediately  
expelled  (therefore  was  "missed")
...
 



Ovarian  cancer  is  the  6th  most  frequency  diagnosed  cancer  in  women  in  Scotland  in  2011
...
  In   women   in   scotland   with   no   FH   the   life   time   risk   of  
developing   ov   cancer   is   1in   55
...
   It  is  not  a  “silent  killer”
...
 
CA125   blood   serum   level   should   be   measured   and   urgent   pelvic   ultrasound   carried   out
...
   Cheap  and  effective  screening  test
...
 
 
Risk  of  malignancy  index  (RMI)  


So,   once   the   diagnosis   is   suspected,   how   do   we   go   on   to   make   the   diagnosis?     Of   course  
CA125   can   be   raised   in   other   benign   conditions   such   as   endometriosis   and   patient   with  
ovarian  cancer  can  have  a  normal  CA125
...
   



Pathology  is  the  “gold  standard”:  usually  from  a  CT  guided  biopsy  of  an  omental  deposit  or  
following  laparoscopy  guided  biopsy  of  an  abnormal  ovary  



Calculate  the  RMI  based  on:  
! US   features:   high   risk   feature   include   multinodular   cyst,   solid   areas,   bilateral  
lesions,  ascites,  intra-­‐abdominal  masses  
! Menopausal  state:  post  menopausal  has  higher  risk  =>  higher  score  
! CA125  levels  



RMI=  US  score  *  menopause  score  *  CA125  levels  
 



Patients  with  an  RMI  >200  should  be  referred  to  a  gynaecology-­‐oncology  multidisciplinary  
team
...
 



CT  scan  is  performed  before  surgery    



NO  TISSUE  BIOPSY  REQUIRED  FOR  Dx  

 
 
Ovarian  Cancer:  Pathology  
 
 
 



Pathology  is  the  “gold  standard”  for  diagnosis  and  “typing”
...
g
...
transcoelomic  spread/  peritoneal  seeding  within  pelvis  →  abdominal  cavity  
2
...
incidence  of  brain  metastases  in  ovarian  cancer  <2%  
 
Ovarian  Cancer:  Treatment  


Surgery:  
! Bilateral   salpingo-­‐oophorectomy   (BSO):   removal   of   both   ovaries   and   both  
fallopian  tubes  
! Total  abdominal  hysterectomy  TAH    
! Omentectomy:  part  or  all  of  the  abdominal  lining  is  removed
...
  It   is   used   only   in   specific   malignancies,   as   generally  
partial  removal  of  a  tumor  is  not  considered  a  worthwhile  intervention
...
   


Surgery   and   chemotherapy:   hope   for   cure
...
   



Chemotherapy:  chemo  alone  can  be  used  in  incurable  relapsing/remitting  chronic  disease  to  
prolong  life  



Hormone  therapy  

 
Ovarian  Cancer:  Hormone  Manipulation  


Tamoxifen   (oestrogen   modulator):   10%   ovarian   cancers   respond   to   tamoxifen   with   about  
30%   achieving   disease   stabilisation
...
   However,  remember  that  it  is  a  risk  factor  for  endometrial  cancer
...
 

 
BRCA  Ovarian  cancer  


Caused   by   the   BRCA   mutations:   causes   high   risk   of   breast   and   ovarian   cancer   (+   prostate  
cancer  in  men)  



Often  a  significant  FH  of  BRCA  related  cancers  (but  not  necessarily  so)  



Younger  age  at  presentation  



Most  BRCA  ovarian  cancers  are  papillary  serous  subtypes  



Do  not  present  typically:  
! High   incidence   of   visceral   disease   at   presentation   and   relapse   including   brain  
metastases  
! Good  responses  to  numerous  courses  of    platinum  based  chemotherapy  
! long  remissions  
! unusual  patterns  of  relapse  
! Improved  overall  survival  stage  for  stage  




 
 
 

Increasing   numbers   of   referrals   for   BRCA   testing   based   on   characteristics   of   a   patients  
cancer  rather  than  FH  (e
...
 young  age,  papillary  serous  type,  early  spread  to  brain)  
Different  management  of  this  “different”  disease  

 
The  role  of  prophylactic  salpingo-­‐oophorectomy  


Women  with  a  family  history  that  appears  to  place  them  at  high  risk  of  developing  ovarian  
cancer  should  be  offered  referral  to  a  Clinical  Genetics  Service  for  assessment,  confirmation  
of  family  history  and  consideration  of  genetic  testing  of  an  affected  family  member
...
g
...
    Women   with   ovarian   cancer   who   have   a   family   history   of   breast   or  
ovarian  cancer  should  have  a  genetic  risk  assessment
...
 



Prophylactic  salpingo-­‐oophorectomy:    “Women  with  genetic  mutations  of  BRCA1  or  BRCA2  
genes   should   be   offered   prophylactic   oophorectomy   and   removal   of   fallopian   tubes   at   a  
relevant  time  of  their  life
...
    Hormone   replacement   can   be   used   after   oophorectomy   until   the  
time   of   natural   menopause   without   losing   the   benefits   of   breast   cancer   risk   reduction
...
”  

 
Screening    


A  large  US  study  showed  there  is  no  benefit  in  screening
...
 

 
BEAT  ovarian  cancer  


B  for  bloating  that  is  persistent  and  doesn't  come  and  go    



E  for  eating  less  and  feeling  fuller    



A  for  abdominal  pain    



T  for  telling  your  GP  
 

Summary  

 
 
 



Ovarian  cancer  is  not  an  asymptomatic  condition
...
   All  studies  
identify   abdominal   distension/bloating   as   the   most   important   symptom   together   with  
early   satiety   and   abdominal/pelvic   pain
...
    This   is   likely   because   the   clinical  
features  is  very  similar  to  the  presentation  of  dyspepsia,  a  very  common  GI  condition
...
   

 
 
Why  is  cytoreduction  (surgical  debulking)  essential?  
•  Immediate  reduction  of  tumour  mass  (improvement  of  bowel  function,  diet)  
•  Chemotherapy  is  more  effective  if  tumour  volume  is  small  (perfusion)
...
 



However  it  can  be  used  as  a  palliative  treatment  for  metastatic  bone  or  brain  lesions  or  of  
localized  recurrence  to  alleviate  the  pain
...
 in  3  years)  

 
 
Colposcopy  


Magnified  inspection  of  cervix  



Use  of  stains  to  identify  abnormality  =>  cant  take  biopsy  or  remove  (LLETZ)  



Colposcopist  -­‐  assessment  of  abnormality  



Options  (usually  outpatient):  
! Biopsy  and  follow  up  
! Biopsy  and  treat  with  cold  coagulation  
! LLETZ  

 
Following  assessment  


Biopsy  gives  histology  results:  
! CIN1  =>  follow  up  in  6  months  (cervical  smear)  
! CIN  2  =>  treat  e
...
 cold  coagulation  or  LLETZ  
! CIN  3    =>  treat  e
...
 cold  coagulation  or  LLETZ  
! cGIN  (cervical  glandular  interepithelial  neoplasia)  

 
 
 

! Cancer  =>  treat  e
...
 cold  coagulation  or  LLETZ  +/-­‐  chemo  and/or  radio  


Treatment:  
! Cold  Coagulation  (destructive):  Hot  probe  which  causes  cells  to  burst  
! LLETZ  (Excisional):  Electosurgical  wire  (cautery)  can  cut  through  tissue  (loop)  

 
 
Following  treatment:  Follow  up  


To  identify  treatment  failures  



To  identify  patients  with  recurrence  early  



While  not  causing  significant  anxiety  to  those  who  are  not  at  risk  



Test  of  Cure:  
! Combined  smear  and  HPV  test:    assessing  for  CIN  (smear)  and  HPV  
! Double  negative:  3  yearly  repeat  smear  
! If  positive  need  further  colposcopic  assessment  

 
 
Reassure  patients  with  knowledge  and  be  empathetic  


Knowledge  of  procedure  



Knowledge  of  relevance  of  HPV  



Knowledge  of  follow  up  



Knowledge  of  vaccination  programme  for  the  future  



Patient  leaflets  and  website  links  

 

Counselling  for  an  Abnormal  Cervical  Smear  
 
The  following  points  should  be  covered  when  counselling  patients  about  a  dyskaryotic  smear:  


 
 
 

The  smear  does  not  indicate  cancer  
Abnormal  cells  have  been  identified
...
     



Further  investigation  and  treatment  is  required  with  the  aim  of  preventing  the  development  
of  cancer  in  the  future  



Investigation  includes  colposcopy  and  a  description  of  what  this  involves  



Biopsies  will  be  taken  



Treatment  will  be  carried  out  by  ‘coagulating’  the  cervix,  destroying  the  abnormal  cells/area  
either  by  laser  or  surgery  (large  loop  excision  of  transformation  zone  LLET2)
...
   Sometimes  the  treatment  
will  be  undertaken  when  the  results  of  the  biopsy  are  known
...
 



Test  of  cure  at  6  months:    If  you  have  had  treatment  for  cervical  abnormalities  called  CIN  
(cervical  intraepithelial  neoplasia),  you  will  be  screened  again  six  months  afterwards
...
 



Follow-­‐up  in  the  form  of  regular  smears  will  be  required  e,g,  every  3  years  (20-­‐60  year  olds  

 
 
 
Endometrial  and  ovarian  disorders  
Endometriosis  




 The  uterine  cavity  is  lined  with  endometrial  cells,  which  are  under  the  influence  of  female  
hormones  =>  cyclical  symptoms    



Endometrial  cells  in  areas  outside  the  uterus  are  also  influenced  by  hormonal  changes  and  
respond  in  a  way  that  is  similar  to  the  cells  found  inside  the  uterus
...
   



The   pain   often   is   worse   with   the   menstrual   cycle   and   is   the   most   common   cause   of  
secondary  dysmenorrhea
...
g
...
 When  blood  touches  these  other  organs,  especially  inside  the  abdomen,  it  can  cause  

inflammation  and  irritation,  creating  pain
...
   This  scar  tissue  can  also  contribute  to  
sub-­‐fertility  


Linked  with  retrograde  mensruation    



Defnitive  Dx  =  laporoscopy    

 
Clinical  features  


Pain:  a  major  symptom  of  endometriosis  is  recurring  pelvic  pain  
! Dysmenorrhea  (secondary):  painfull  periods    
! Dyspareunia:  painful  sex  (coitus)  –  often  deep    
! Dysuria:  painful  voiding  



Infertility  



As   endometriosis   can   lead   to   anatomical   distortions   and   adhesions   (the   fibrous  
bands  that  form  between  tissues  and  organs  following  recovery  from  an  injury),  
the   causality   may   be   easy   to   understand;   however,   the   link   between   infertility  
and   endometriosis   remains   enigmatic   when   the   extent   of   endometriosis   is  
limited
...
 




Many  women  with  infertility  may  have  endometriosis
...
   Occurs  during  the  
normal   menstrual   cycle   because   the   endometriosis   responds   to   hormones   just   like   the  
endometrium
...
   

 
Endometriosis  of  ovary  



 
 
 

An   endometrioma,   endometrial   cyst,   or   chocolate   cyst   of   ovary   is   a   condition   related   to  
endometriosis  =>  endometriosis  of  the  ovary  
Endometriomas   usually   cause   the   symptoms   associated   with   endometriosis,   including  
dysmenorrhoea,  dyspareunia,  pelvic  pain
...
   



There  may  also  be  an  adnexal  mass  (RIF  or  LIF)  



Ultrasound  scan  can  be  helpful  in  diagnosis,  and  CA125  may  be  slightly  elevated
...
  On   pelvic  
examination  she  has  a  10  cm  fixed  smooth  pelvic  mass  in  her  left  adnexal  region
...
 



Dx=   Endometrioma   (endometriosis   of   the   ovary,   endometrial   cyst,   or   chocolate   cyst)
...
   Due  to  the  adnexal  
mass  =>  suggestive  of  endometrioma
...
  The   malignant   version   of   a  
fibroid  is  extremely  uncommon  and  termed  a  leiomyosarcoma
...
   



Ostrogen  driven  so  regress  post  menopause    



While   most   fibroids   are   asymptomatic,   they   can   grow   and   cause   heavy   menstruation  
(menorrhagia),   painful   menstruation   (dysmenorrhoea),   painful   sexual   intercourse,   and  
urinary  frequency  and  urgency
...
 Symptoms  depend  on  the  
location  of  the  lesion  and  its  size
...
g
...
 A  35  year  old  woman  complains  of  dysmenorrhoea  and  dyspareunia
...
 A  serum  CA125  is  mildly  elevated
...
  Ultrasound   scan   can   be   helpful   in   diagnosis,   and  
CA125  may  be  slightly  elevated
...
 A  68  year  old  present  with  vaginal  bleeding  15  years  after  she  had  her  last  period  e
...
 PMB
...
     


Dx  =  Endometrial  adenoCa  usually  presents  as  post-­‐menopausal  bleeding
...
     Therefore  the  patients  age  is  key  for  the  formation  of  
the  DD  and  a  woman  of  68  years  presenting  with  postmenopausal  bleeding  =>  endometrial  
cancer  is  right  at  the  top  of  the  DD
...
 
 

Example  3  
3
...
  On  
examination   she   has   a   fixed   irregular   pelvic   mass,   measuring   8cm
...
   
 


Dx   =   Ovarian   cancer   commonly   presents   non-­‐specific   symptoms,   such   as   anorexia,   weight  
loss  and  constipation
...
   



Commonest  cause  is  (pappilary)  serous  cytadenocarcinoma  

 
 
INFERTILITY,  INFERTILITY  SCREEN  AND  LABORATORY  INVESTIGATION  OF  AMENORRHEA  
 
 
 
 

DEFINITIONS  
Primary   amenorrhea:   Failure   to   establish   spontaneous   periodic   menstruation   by   the  age   of   16   years  
regardless   of   whether   secondary   sex   characteristics   have   developed   (e
...
  Turners   sundrom   45   X)
...
g
...
     
Secondary  amenorrhea:  Absence  of  periodic  menstruation  for  at  least  6  months  in  women  who  have  
previously  experienced  menses
...
g  
pre-­‐ovarian  causes  (hypothalamus  and  pituitary),  pelvic  causes,  post-­‐ovarian  (obstructive)  



Use  endocrinology  block  lectures  

 
ESTROGENS  AND  OVARIAN  FUNCTION  


The   normal   human   ovary   produces   all   3   classes   of   sex   steroids,   estrogens,   progestins   and  
androgens;  however,  estradiol  (E2)  and  progesterone  are  its  primary  secretory  products
...
 
Granulosa   cells:   conversion   of   androgens   to   estrogens   (mainly   estradiol   E2)   by  
aromatisation,  regulated  by  FSH
...
 

Effect  on  pituitary:  


 
 
 

Slowly  rising  or  sustained  high  levels  of  estrogen  together  with  progesterone  inhibit  pituitary  
gonadotrophin  (LH  and  FSH)  secretion  by  NEGATIVE  FEEDBACK
...
 

 
PROGESTERONE  
In  nonpregnant  women,  progesterone  is  secreted  mainly  by  the  corpus  luteum  under  the  influence  
of  LH,  during  the  luteal  phase  of  the  menstrual  cycle
...
 
As   estrogen   concentrations   rise,   FSH   secretion   declines   until   regulatory   mechanism   take   a  
drastic   change   and   high   levels   of   estrogens   E2   trigger   a   positive   feedback   mechanism,  
causing  an  explosive  release  of  LH  (mid-­‐cycle  LH-­‐surge)  and  to  a  lesser  extent  FSH
...
 Inhibin  (also  produced  by  ovaries)  also  inhibits  FSH  secretion
...
Anatomical  defects  e
...
 fibroids,  endometriosis,  fibrosis  
 

 
 
 
 

B
...
g  radiation,  chemo,  mumps,  AI  

C
...
Hypothalamic   deficiency   of   GnRH   (hypogonadotrophic   hypogonadism):   ↓   LH   and  
FSH  =>  ↓  Estradiol  E2)  
• Organic  causes:  tumors,  infection  and  other  disorders  
• Functional   disorders:   Stress,   weight   loss/diet   (anorexia   nervosa),  
exercise,   malnutrition,   chronic   debilitating   diseases   (eg   end-­‐stage  
kidney  disease,  AIDS)
...
Pituitary:  
• Deficiency   of   LH/FSH   e
...
  Sheehans   syndrome   or   adenoma  
(hypogonadotrophic   hypogonadism):   ↓   LH   and   FSH   =>   ↓   Estradiol  
E2)  
• Inappropriate   seceretion   of   prolactin:   Drugs   (e
...
  anti-­‐psychotics  
and   other   dopamine   blockers,   metoclopramide   and   domperidone),  
hypothyroidism,   prolactinoma
...
Chronic  anovulation  with  estrogen  present:  
1
...
Adrenal  disease  
• Cushing  syndrome  
• Adult-­‐onset  adrenal  hyperplasia  
3
...
Ovarian  tumors  
 
Note:   classicaly   hyperthyroidism   is   associated   with   amenorrhoea   and   hypothyroidism   is   associated  
with  menorrhagia    
A  good  way  to  consier  the  causes  of  infertility  is:    pre-­‐ovarian,  gynae  causes,  and  post  ovarian  
 
PRIMARY  OVARIAN  FAILURE  (HYPERGONADOTROPHIC  HYPOGONADISM)  
 
Primary  defect  in  the  ovaries  (absent/destruction):  




↓  Estradiol-­‐production  (hypogonadism)  
↓  Negative  feedback  =>  ↑  LH  and  FSH  (hypergonadotrophic)  
No   withdrawal   bleeding   following   progesterone   challenge   (as   not   enough   oestrogen  
present  to  cause  proliferation  of  the  endometrium)  

 
Causes  

 
 
 

Primary  amenorrhea  



! Androgen  insensitivity  syndrome  –  chrosomally  male!  
! 45  X:  Turner  syndrome  
Secondary  amenorrhea  
! Premature  ovarian  failure  (before  age  of  40):  often  idiopathic,  many  contributing  
factors  e
...
 radio  and  chemo  and  AI  
 
 

SECONDARY  OVARIAN  FAILURE  (HYPOGONADOTROPHIC  HYPOGONADISM)  
 
Ovarian   failure   is   secondary   to   organic   or   functional   disorders   of   the   CNS-­‐hypothalamic-­‐pituitary  
axis:  




↓   GnRH   (hypothalamic   disorder   e
...
  anorexia,   severe   illness)   or   ↓   (or   inappropriately  
normal)  LH  and  FSH  (pituitary  disorder)  =>    hypogonadotrophic  
↓  Estradiol  (hypogonadism)  
No  withdrawal  bleeding  following  progesterone  challenge  (due  to  low  oestrogen  and  
minimal/absent  proliferation  of  endometrium)  

   
Several  disorders  of  the  pituitary  can  lead  to  hypogonadism:  



 

Space-­‐occupying   lesions   that   directly   inhibit   gonadotropin   secretion   by   destruction   of   the  
producing  cells  or  by  blocking  delivery  or  secretion  of  GnRH  
Necrosis  of  the  pituitary  (following  postpartum  hemorrhage:  Sheehan  syndrome)  
Inappropriate   secretion   of   prolactin   (including   drugs,   other   diseases   eg   hypothyroidism,  
prolactinoma)  =>    ↓  secretion  of  LH  and  FSH
...
g
...
5)
...
 
Obesity   and   ↑   androgens   →   ↑   peripheral   aromatisation   and   ↑   acyclic   estrogen   production  
→  anovulation/amenorrhea
...
5)  
Normal  estrogen  and  withdrawal  bleeding  following  progesterone  challenge  
↑  testosterone  and  androstenedione  
↓  SHBG  (↓  synthesis  due  to  ↑  androgens)  
Insulin  resistance  and  IGTT  
 
 

LABORATORY  TESTS  AVAILABLE  FOR  EVALUATION  OF  PATIENTS  WITH  AMENORRHEA  
 
A
...
 


Any  woman  of  reproductive  age  with  amenorrhea  is  assumed  to  be  pregnant  until  proved  
otherwise
...
     

 
B
...
g
...
g
...
 Thyroid  function  tests:  

 
 
 





TSH  and  free  T4/T3  
Primary  hyperthyroidism:  ↓  TSH,  ↑  free  T4  –  associated  with  amenorroheea  
Primary  hypothyroidism:    ↑  TSH,  ↓  free  T4  –  associated  with  menorrhagia    

 
D
...
 Progesterone  challenge  test  (to  assess  for  oestrogen  status)  






Determination  of  relative  estrogen  status  (not  commonly  used  due  to  eoestrogen  assays)  
Give  additional  information  regarding  the  outflow  tract
...
   If  withdrawal  bleeding  occurs  5-­‐7  days  
later   then   the   endometrium   must   have   been   previously   exposed   to   adequate   levels   of  
oestrogen,   and   the   endometrium   is   able   to   proliferate   in   response   to   oestrogen   +  
progesterone
...
25   mg/day   for   21   days)   followed   by   another  
progesterone  challenge:    
! If   bleeding:   normal   outflow   tract,   but  estrogen   deficiency   corrected   by   administered  
estrogen:   primary   or   secondary   gonadal   failure
...
  This   may   be   due   to   ovarian   failure,   indicated   by   raised  
FSH,  or  hypothalamic-­‐pituitary  failure
...
g
...
 
Clinical   examination   found   a   euthyroid   woman   with   some   findings   suggestive   of   low   estrogen  
production
...
3   U/l               (1
...
5)   =>   innapropriately   normal   (E2   is   low   so   we   would  
expect  FSH  and  LH  to  be  raised)  
LH                          3
...
5-­‐9
...
 
Lab  results:  
B-­‐HCG          Negative  
Prolactin      7
...
6  U/l          (0
...
0)  
Bleeding  following  progesterone  challenge  
FSH                  2
...
0-­‐6
...
0  U/l            (1
...
0)  
Testosterone          2
...
6-­‐2
...
0  nmol/l  (15-­‐90)  
 


Dx=  PCOS  
! LH/FSH  ratio  is  high  
! Hirsutism  and  amenorrhoea  and  obesity  are  key  clinical  features  
! Bleeding  occurs  on  progesterone  challenge  test  

 
 

Small Group Work: Intrapartum Care
You will be working in a small group to examine this clinical case and to go over your
answers
...

Scenario
Julie Evans, a primigravida (first pregnancy), is admitted in spontaneous labour at 41
weeks gestation
...
On admission, she is
experiencing uterine activity with mild to moderate uterine contractions occurring
every 5 minutes
...
The fetal heart rate is regular and within normal limits
...
The vertex is found to be 2 cms above the ischial spines (-2 foetal
station) and the pelvis is clinically adequate
...
She is accompanied by her husband
...
Most of the discussion concentrated upon Julie’s choice of pain relief
during labour
...
However, Julie also indicated that she
would consider Epidural Analgesia as a ‘last option’
...

Questions
 
 
 

A  

Pain  relief  in  labour  

Following discussion, Julie opts for intramuscular injection of Diamorphine, 10 mgs
...
 Strong  in  nature
...
 
Inhibit  GABA  inhibitory  interneurons  to  reduce  descending  pain  pathway  
signals  →  increased  tolerance  for pain
...
 

3

Are there any effects on the fetus from Diamorphine?

Fetal  respiratory  depression
...
Following discussion,
Julie requests an Epidural to be sited and the obstetric anaesthetist is called
...


4

What is an Epidural and how does it relieve pain?

Epidural  anaesthesia  is  inserted  to  the  epidural  spaces  between  L3  and  L4
...
 
Monitor  BP  (can  cause  hypotension)
...
 
 Catheter
...
 Helps  with  
managing  exhaustion  and  distress
...
 This  also  avoids  the  
risks associated  with  GA  and  there  is  less  nausea  associated
...
       Can  cause  
fetal  bradycardia  
Loss  of  Bladder  Control  (unable  to  tell  it  is  full)  
Itchy  Skin,  Sickness,  Backache
...
 Nerve  damage
...
   

Progress of labour
To assess the progress of labour, a number of observations/assessments are made with
regard to the mother and fetus
...

8

What observations/assessments are made to assess the progress of labour?
•  

Fetal  Heart  and  CTG  

•  

Amniotic  Fluid  

•  
Bishops  score:    Cervical  Dilatation,  cervical  effacement,  cervical  consistency,  cervical  
position  and  foetal  station  
•  

Contractions:  length,  frequency,  strength  (intrauterine)  

•  

Obstruction  -­‐  Moulding    

•  

Maternal  Observations  

 
 
 
 

9

Using the partogram, discuss the various observations/assessments recorded
...
   If  meconium  present  =>  label  M
...
 
Positive  caput  and  moulding  
Dilated  7cm    
1/5  palpable    
Frequent  but  weak  contractions  
ROP  
Dimorphine  and  epidural  
BP  fine  
Urinalysis  fine  

 

 
 
 

10

From the partogram, it can be seen that by 1800 hours Julie is not progressing in
labour
...


The three P’s: Power, passage and passenger
Pow er is the problem s – as w eak contractions
...


If the cervix was poorly

dilated and unfavourable could sue vaginal PGs
...

2 nd stage C - section is very dangerous
...
 
individually
...


Gravidity  and  Parity  




Gravida   (Grava   or   G)   is   the   number   of   times   a   woman   has   been   pregnant
...
 



Parity   (Para   or   P)   is   the   number   of   completed   pregnancies   beyond   24   weeks   gestation,  
whether  viable  or  stillborn
...
 



For  example  a  woman  who  has  been  pregnant  3  times  (where  one  pregnancy  was  a  set  of  
triplets)  has  one  term  delivery,  one  preterm  delivery  (of  her  triplets),  and  one  termination  at  
16  weeks  would  be  described  as:    G3,  P2  



For  example,  a  woman  who  is  described  as  'gravida  2,  para  2  (sometimes  abbreviated  to  G2  
P2)   has   had   two   pregnancies   and   two   deliveries   after   24   weeks,   and   a   woman   who   is  
described  as  'gravida  2,  para  0'  (G2  P0)  has  had  two  pregnancies,  neither  of  which  survived  
to  a  gestational  age  of  24  weeks
...
 



 
 
 

In  an  obstetrical  history  the  gravida  (G)  and  para  (P)  status  of  a  woman  is  often  written  in  
abbreviated  form
...
   In  a  survey,  only  20%  of  British  midwives  and  obstetricians  recognised  a  twin  

delivery  as  a  single  parous  event  -­‐  G1  P1  rather  than  G1  P2,  revealing  the  potential  lack  of  
standardisation  in  our  documentation
...
  A   woman   does  
not  become  primiparous  until  she  has  delivered  her  baby/stillborn
...
 



A  primagravida  is  in  her  first  pregnancy  



A  multigravida  has  been  pregnant  more  than  once
...
 

 
Relationship  of  gravidity  and  parity  to  risk  in  pregnancy  


Obstetric   histories   should   always   record   parity,   gravidity   and   outcomes   of   all   previous  
pregnancies,    as:  
! Outcomes   of   previous   pregnancies   give   some   indication   of   the   likely   outcome  
and  degree  of  risk  with  the  current  pregnancy
...
 




Normal   labour   in   a   primagravida   is   significantly   different   to   normal   labour   in   multiparous  
women,   as   physiologically   the   uterus   is   a   less   efficient   organ,   contractions   may   be   poorly  
coordinated   or   hypotonic
...
    Therefore,  
progress   is   expected   to   be   slower   but   delay   longer   than   expected   should   prompt  
augmentation  in  managed  labour
...
 After  6  cm  dilation,  

partogram  curves  for  lower  parity  multips  and  grand  multips  are  indistinguishable
...
[5]  
 
Risks  associated  with  nulliparity/primagravidae  


Higher  risk  of  developing  pre-­‐eclampsia    



Delayed  first  stage  of  labour,  though  this  could  be  considered  normal  in  a  primagravida
...
 
• HPV   is   a   DNA   virus   which   infects   immature/metaplastic   squamous   epithelium   as   found   at  
the  cervical  transformation  zone
...
 The  virus  therefore  
alters  the  host  cell's  signaling  to  stimulate  proliferation
...
 
• High  risk  HPV  –  16  and  18,  increased  risk  of  in-­‐situ  neoplasia  (CIN)  and  invasive  malignancy  
 
 
 












(cervical  carcinoma)
...
 
Cervical   intraepithelial   neoplasia   (CIN)   is   dysplasia   (altered   growth   and   maturation)   of   the  
cervical  stratified  squamous  epithelium
...
 
CIN   2   and   3   =   high   grade,   pre-­‐cursor   lesions   to   invasive   carcinoma
...
 
The   cervical   screening   programme   aims   to   detect   CIN   using   cytology   (cervical   smear)   and  
enables  early  treatment  of  CIN  to  prevent  progression  to  carcinoma
...
 
Low  grade  dyskaryosis  correlates  with  CIN  1  (low  grade)  
Moderate  dyskaryosis  correlates  with  CIN  2  (high  grade)  
Severe  dyskaryosis  correlates  with  CIN  3  (high  grade)  
The   HPV   vaccine   aims   to   prevent   HPV   infection   and   we   hope   that   over   coming   years   we   will  
see  a  further  decrease  in  CIN  and  cervical  carcinoma
...
 
•  Oestrogen  causes  proliferation  of  the  endometrium
...
 
•  Obesity  is  a  risk  factor
...
 
•  Tamoxifen  increases  the  risk  of  endometrial  cancer
...
 
•  Diagnosis  is  usually  made  on  pipelle  endometrial  biopsy  or  hysteroscopy  and  
endometrial  curettings  (D&C)  
•  Most  endometrial  carcinoma  is  adenocarcinoma
...
 These  are  graded  1-­‐3  based  on  
percentage  of  solid  growth  and  nuclear  atypia
...
 These  are  all  by  
definition  high  grade  (grade  3)  and  show  more  aggressive  behaviour
...
 
•  High  grade  (grade  3)  carcinomas  are  more  likely  to  show  advanced  local  invasion  and  
metastases
...
 
 
 
 

•   Tumour   stage   (TNM   system)   is   based   on   depth   of   myometrial   invasion   and   involvement   of  
cervix,  vagina,  parametrial  tissue  and  adnexae
...
 Other  uterine  
tumours  to  be  aware  of:  
 
Fibroids  
•  Leiomyoma  –  benign  smooth  muscle  tumour  of  myometrium  (fibroids)
...
 
 
 
Ovarian  tumours  
 
Tumour  Origin    

Name  

Behaviour  

Description  

Epithelial  (60-­‐70%)    

Serous  cystadenoma  

Benign  

Cystic  tumour  lined  by  benign  (single  
layer)  serous  epithelium
...
 Most  common  ovarian  tumour      

 

Mucinous  cystadenoma    

Benign    

Cystic  tumour  lined  by  benign  (single  
layer)  of  mucinous  epithelium
...
 

 

Borderline   tumour   (serous  
or  mucinous)  

 

Some  cystic  tumours  can  show  
borderline  change
...
 Rarely  can  metastasise
...
   
Ca125  
Peritoneal  
metastases  common
...
 
Peritoneal  involvement  results  in  
mucinous  ascites  (Pseudomyxoma  peritonei)  

Germ  Cell  

Mature  teratoma  (dermoid  
cyst)  

Benign    

Usually  a  mixture  of  differentiated  
tissue  types  e
...
 skin,  hair,  cartilage,  
teeth,  fat  and  thyroid
...
 

Metastases  

Metastases  
(type   Malignant  
depends  on  
primary  tumour)  

 Often  bilateral
...
 
 
A   Krukenberg   tumor   refers   to   a   malignancy   in   the  
ovary   that   metastasized   from   a   primary   site,  
classically   the   gastrointestinal   tract,   although   it   can  
arise   in   other   tissues   such   as   the   breast
...
 
•  Recent  research  suggests  that  ovarian  epithelial  carcinomas  actually  arise  from  the  
 
 
 

epithelium  lining  the  fimbrial  end  of  the  fallopian  tube  not  the  ovarian  surface  epithelium
...
 It  is  usually  not  diagnosed  until  an  advanced  
stage  (stage  3  or  4)
...
 
•  The  tumour  marker  Ca125  is  usually  elevated
...
 
•  5  year  survival  rates;  stage  1,  76%,  stage  2,  56%  ,  stage  3,  25%  and  stage  4  <10%
...
 The  tumour  is  high  grade  
(high  rate  of  proliferation)  and  therefore  tends  to  be  chemo-­‐sensitive
...
 Women  under  60  at  
diagnosis  are  often  tested  for  BRCA  mutations  as  this  can  have  an  effect  on  novel  treatments  
(PARP  inhibitors)  and  has  consequences  for  female  relatives
...
  This   is   when   the   baby's   head   is   even   with   the  
ischial   spines
...
 
• Key  points  
! -­‐3  =>  3/5th  palpable  =>  2/5th  engaged  
! -­‐2  =>  2/5th  palpapble  =>  3/5th  engaged    
! -­‐1  =>  1/5th  palpable  =>  4/5th  engaged    
! 0  =>  0/5th  palpable  =>  5/5th  engaged  or  fully  engaged    
! +1:    nearly  there  
! +2:    starting  to  crown  (extend  neck)  
 

 
 
Questions  
 
 
 

 

 
Scenario  1  
 
A   32   year   old   woman   attends   for   her   routine   smear   test
...
 At  colposcopy  the  
gynaecologist  sees  an  abnormal  acetowhite  area  on  the  cervix  and  decides  to  take  a  punch  biopsy
...
 
 
• What  is  the  aetiology  of  this  patient's  disease?  HPV  16  and  18  
 
• What  is  the  relevant  pathology  in  this  case?  CIN  III  (high  grade  severe  dyskaryosis)  
 
• What  further  treatment  or  management  does  this  patient  need  and  why?  Cold  coagulation  
or  LLETZ  electrowire  technique  (as  significant  risk  of  preogressing  to  cervical  squamous  cell  
carcinoma)  
 
• Combined  test  of  cure  (smear  +  HPV  test)  in  6  months  
 
• How   do   you   think   the   HPV   vaccination   programme   will   affect   this   disease   over   coming  
years?    Incidence  will  decrease  
 
 
Scenario  2  
 
A  59  year  old  obese  lady  is  referred  to  the  gynaecology  clinic  with  persistent,  heavy  postmenopausal  
bleeding
...
 
Ultrasound   scan   shows   an   abnormally   thickened   endometrium
...
 
 
• What  is  the  likely  diagnosis?  Endometrial  cancer  (adenoCa)  
 
• What  are  the  risk  factors?  High  levels  of  endogenous  or  exogenous  oestrogens  (unopposed),  
DM,  obesity,  PCOS  
 
• What  is  the  relevant  pathology?  Adenocarcnioma  in  majority  of  cases  
 
• What  is  the  prognosis  for  this  patient?    Nornally  very  good
...
  Her   Ca125   is   elevated   at   331
...
 The  patient  
 
 
 

also  has  a  family  history  of  breast  cancer
...
 Why?  Risk  of  BRCA1/2  mutation  

 
 
 
Para  note  
 
• Some  teminology  uses:  Para  =  X  +Y  (e
...
 two  numbers  assigned  to  Para)  
• X  =  number  of  pregnancies  exceeding  24  weeks  gestation  (with  a  delivery  of  live  or  stillborn  
baby)  
• Y  =  number  of  pregnancies  ending  before  24  weeks  gestation    
 
 
Example  1  


A  woman  at  8  weeks  into  her  first  pregnancy  =  para  0+0  



Parity  does  not  become  1  until  after  delivery  



Para  1+0  =  single  pregnancy  with  delivery  of  baby(s)  born  after  24  weeks  gestation  (alive  or  
still  born)  



Para  0+1  =  single  pregnancy  with  loss  of  baby(s)  before  24  weeks  

 
Example  2  



 
 
 

 
 
 

A   woman   who   has   had   a   previously   still   birth   at   32   weeks   and   a   previous   live   birth   at   40  
weeks  =  para  2+0  
Remember  that  the  first  figure  =  deliveries  beyond  24  weeks  (live  or  stillborn)  


Title: Obstetrics and Gynaecology lecture notes
Description: A very comprehensive and detailed set of notes covering all aspects of Obstetrics and Gynaecology. Complete with a nice set of diagrams to aid learning. Useful for medical students.