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Human M.  Fatemi,  MD,  PhD   Centre  for  Medicine   Brussels,  Belgium   The faculty has provided no information regarding significant relationship with commercial supporters and/or discussion of investigational or non-EMEA/FDA approved (off-label) uses of drugs as of 13 May 2014.

Intrauterine abnormali6es:     Seek  and  treat?   Human  M.  F   atemi  (BEL)

Importance of  oocyte  and  sperm  

Embryo implanta6on  

Human embryo  implanta6on:    a  three-­‐stage  process   Ø Apposi.on   Ø Adhesion   Ø Invasion   – Involving  a  synchronized  crosstalk  between   a  endometrium  and  a  func.onal   blastocyst       Enders  et  al.  1967  

Zondek et  al.  1930  

IVF and  pregnancy   Estrogen  



   U    IVF  pregnancy


embryo  quality    endometrial  recep6vity    1-­‐[(1-­‐U)+U(1-­‐E)n]    

  Rogers  et  al.  1986  

The Uterine  Abnormali6es  in  infer6le  women       Uterine  malforma6ons:     Ø  Myomas     Ø 2.4%  of  subfer.le  women  without  any  other  obvious  cause  of   subfer.lity  (Donnez  2002)   Ø  Endometrial  polyps   Ø   1%  -­‐  41%  of  the  subfer.le  popula.on  (Silberstein  2006)   Ø  Intrauterine  adhesions     Ø  Endometri.s   Ø  Thin  endrometrium   Ø  Endometrial  Hyperplasia   Ø  Cervical  adhesions   Ø  (Sub)septated  uetrus  1%  -­‐  3.6%  of  (Saravelos  2008)   Ø  Endometrial  adhesions  0.3  -­‐  14%  of  subfer.le  women  (Fatemi  2010)  

Uterine/endometrial abnormali6es    

Uterine/Endometrial  abnormali6es:    

To diagnose  intrauterine  pathologies  in   infer6le  women:     •  Transvaginal  ultrasonography   •  Saline  infusion  sonography   •  Hysterosalpingography   •  Hysterosalpingo  foam  sonography  (HyFoSy)   •  Hysteroscopy:  gold-­‐standard  procedure  for   assessment  of  the  uterine  cavity  (BeVocchi  et  al,   2004)  


To resect  or  not  to  resect  a  septum  before  IVF?    

To resect  or  not  to  resect  a  septum   What  about  miscarriage  rate?  

Not a single RCT!

Not a  RCT:  Case  control  study  

Hart et  al,  2001  

Hart et  al,  2001  



Herhaling titel

To treat  or  not  to  treat?  

Fatemi et  al.  2009  

Prevalence of  uterine  abnormali6es     higher  pregnancy  rates  aYer   Ø Observa.onal  studies  suggest   hysteroscopic  removal  of  endometrial  polyps,  submucous   fibroids,  uterine  septum  or  intrauterine  adhesions,  which   are  detectable  in  10-­‐15%  of    women  seeking  treatment  for   subfer.lity.  (Bosteels  et  al.  2013)  

Ø The  presence  of  uterine  pathology  may  nega.vely  affect   the  chance  of  implanta.on  (Cenksoy  et  al.,  2013)       Ø What  about  EMB?  RCTs?  

RCT’s “Randomized,  double-­‐blind,  controlled  trial”  is   considered  as  research  design  par  excellence   and  “Gold  standard”  amongst  research  designs   with  which  results  of  other  studies  are  oYen   compared.  Devia.on  from  this  standard  has  drawbacks  


       Double-­‐blind                            Single-­‐blind   Schulz  and  Grimes.  Lancet  2002  

Prevalence of  uterine  abnormali6es     office  hysteroscopy  prior   Ø 40%  of  pa.ents  undergoing   to  IVF  treatment  do  have  intrauterine  pathological   paVerns.  (Endometri.s,  polyps,  myomas,  adhesions,   septa)    (Hinckley  et  al.  2004)  

Ø Major uterine  cavity  can  be  found  in  10%   to  15%  of  women  seeking  treatment  for  subfer.lity;   they  usually  consist  of  excessive  normal  uterine  .ssue   (Wallach  1972)     Ø Pa.ents  with  a  normal  Us  finding,  only  11%  had  minor   uterine  (Fatemi  et  al.  2010)  

Findings at  office  hysteroscopy.  In  one  case  both  an   endometrial  polyp  and  a  submucous  myoma  were  diagnosed    

Fatemi H  et  al.  Hum.  Reprod.  2010;25:1959-­‐1965  

Cochrane 2013.  

The uterine  abnormali6es:  to  treat  or  not  to   treat?    

Bosteels et  al.  2013  

The uterine  abnormali6es:  to  treat  or  not  to   treat?    

Bosteels et  al.    2013  

Uterine abnormali6es:  to  treat  or  not  to  treat?    

Bosteels et  al  2013  

The Uterine  Abnormali6es:    to  treat  or  not  to  treat?    

Perez Medina et al, 2005

Fatemi and  Popovic  2013  

Hysteroscopy prior  to  IVF?  

Pundir et  al.  2014  

Hysteroscopy prior  to  IVF?  

Pundir et  al.  2014  

Pundir et  al.  2014  

Pundir et  al.  2014  

Conclusions Ø  The  evidence  from  RCTs  is  insufficient  to  draw  any  conclusions   Ø  More  RCTs  are  needed  to  assess  whether  the  hysteroscopy  is  likely  to   benefit  women  with  otherwise  unexplained  subfer.lity  associated  with  suspected   uterine  pathologies   Ø  There  are  knowledge  gaps  concerning  the  effects  of  the  number,              size  or  extent  and  localisa.on  of  major  uterine  cavity              on  the  main  outcomes  in  ART   Ø  Future  randomised  studies  should  report  on  primary  outcomes              such  as  live  births  and  adverse  events  such  as  miscarriage  and  hysteroscopic              complica.ons.  

Conclusions Ø Hysteroscopy  in  asymptoma.c  women  prior   to  their  the  first  IVF  cycle  could  improves   treatment  outcome  when  performed  just   before  commencing  the  IVF  cycle   Ø Robust  and  high-­‐quality  randomized  trials  to   confirm  this  finding  are  warranted.  

L7 h fatemi le ap  
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