title: Ovarian stimulation for in vitro fertilization alters the intrauterine cytokine, chemokine, and growth factor milieu encountered by the embryo.
abstract: OBJECTIVE
  To elucidate the impact of ovarian stimulation on the intrauterine milieu represented by the cytokine, chemokine, and growth factor profile in endometrial secretions aspirated before embryo transfer.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Fertility center in tertiary referral university hospital.
  
  
  METHODS
  Forty-two patients undergoing ovarian stimulation with GnRH analogues were recruited. They participated in both a natural and an ovarian-stimulated cycle for within patient comparisons.
  
  
  METHODS
  Endometrial secretion aspiration was performed immediately before embryo transfer.
  
  
  METHODS
  The concentrations of 17 mediators known to be involved in human embryo implantation were assessed by multiplex immunoassay.
  
  
  RESULTS
  After correction for multiple testing, significantly higher concentrations of interleukin (IL)-1β, IL-5, IL-10, IL-12, IL-17, tumor necrosis factor (TNF)-α, heparin-binding epidermal growth factor (HbEGF), eotaxin, and dickkopf homologue-1 were present in endometrial secretions obtained in stimulated compared with natural cycles.
  
  
  CONCLUSIONS
  Endometrial secretion analysis provides a novel means of investigating the effect of ovarian stimulation on the intrauterine milieu. The in vivo milieu encountered by the embryo after transfer is significantly altered by ovarian stimulation.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands. c.m.boomsma@umcutrecht.nl
authors.forename: Carolien M
authors.initials: CM
authors.lastname: Boomsma
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
mesh_terms: D000328:Adult; D054413:Chemokine CCL11 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism*; D004624:Embryo Transfer; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods*; D011446:Prospective Studies; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
chemical_list: D054413:Chemokine CCL11; D018925:Chemokines; D006063:Chorionic Gonadotropin; D016207:Cytokines; C501126:DKK1 protein, human; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha