title: Defective soil for a fertile seed? Altered endometrial development is detrimental to pregnancy success.
abstract: BACKGROUND
  Synchronous development of the endometrium (to achieve a receptive state) and of the embryo is essential for successful implantation and ongoing pregnancy. Endometrial receptivity exists only for a finite time in a menstrual cycle and the endometrium is refractory to embryo implantation outside of this window. Administration of hormones to stimulate multifollicular development within the ovary, integral to the majority of assisted reproduction (ART) protocols, dramatically alters the hormonal milieu to which the endometrium is exposed versus normal menstrual cycles. Endometrial maturation may be profoundly affected by this altered endocrine environment.
  
  
  OBJECTIVE
  Compare endometrial histology in fertile women, fertile women undergoing hormonal stimulation for oocyte donation and infertile women undergoing fresh embryo transfers in an ART cycle with further comparisons between women who did or did not become pregnant. Examine the presence of leukocytes and markers of endometrial maturation.
  
  
  METHODS
  Endometrial histology was examined by hematoxylin and eosin staining with a semi quantitative scoring method developed to compare histological appearance of tissues. The presence of leukocytes and developmental markers was examined by immunohistochemistry and scored.
  
  
  RESULTS
  Endometrial histology was dramatically altered upon stimulation for ART. However, those women who became pregnant presented with significantly less alterations in histological endometrial maturation. Numbers and activation status of leukocyte populations were also altered within the endometria stimulated for ART, with neutrophils undergoing degranulation, usually observed only pre-menstrually.
  
  
  CONCLUSIONS
  We propose that such developmental changes render the endometrium hostile to the embryo and that modifications to ART protocols should be considered to take account of the requirement for endometrial receptivity and hence increase pregnancy rates.
authors.affiliation: Prince Henry's Institute of Medical Research, University of Melbourne, Melbourne, Victoria, Australia. jemma.evans@princehenrys.org
authors.forename: Jemma
authors.initials: J
authors.lastname: Evans
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Hannan
authors.forename: Cassandra
authors.initials: C
authors.lastname: Hincks
authors.forename: Luk J F
authors.initials: LJ
authors.lastname: Rombauts
authors.forename: Lois A
authors.initials: LA
authors.lastname: Salamonsen
mesh_terms: D000328:Adult; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D018873:Pregnancy Rate; D011388:Prolactin / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D011980:Receptors, Progesterone; D011388:Prolactin