Too much of a good thing? Experimental evidence suggests prolonged exposure to hCG is detrimental to endometrial receptivity

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Does prolonged exposure of the endometrium to hCG, as experienced after ovulation induction in an assisted reproduction technology (ART) cycle, affect functional measures of endometrial receptivity? SUMMARY ANSWER: Prolonged endometrial hCG exposure detrimentally affects the manner in which the endometrium can respond to hCG secreted by the blastocyst. WHAT IS KNOWN ALREADY: Prolonged hCG exposure down-regulates endometrial LH-CG receptor (LHCGR) expression in a baboon model. HCG exposure during the proliferative phase of oocyte-donation cycles and frozen embryo transfer cycles is associated with a lower pregnancy rate. STUDY DESIGN, SIZE, DURATION: LHCGR was examined in endometria of women undergoing ART cycles (GnRH agonist/antagonist) and across the menstrual cycle in normally cycling fertile women. To determine whether prolonged hCG exposure affects the subsequent endometrial response to hCG, endometrial epithelial cells (HES cell line and primary cultures of human endometrial epithelial cells) were exposed to a low dose of hCG (0.5-5 IU) for up to 5 days, to mimic the chronic exposure during an ART cycle, and subsequently exposed to an acute blastocyst mimic dose of hCG (20 IU). PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial tissues were collected at hCG + 2 (n = 37) from women undergoing ART between August 2006 and August 2008, and across the cycle from women with known fertility (n = 40). LHCGR localization and staining intensity were determined by immunohistochemistry and semi-quantitative scoring. HES cells were treated with hCG as above and analyzed for LHCGR localization (immunocytochemistry), phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 (western immunoblotting), adhesion to trophoblast-like matrices (adhesion assays) and tight junction integrity (trans-epithelial resistance assessment). MAIN RESULTS AND THE ROLE OF CHANCE: Endometrial epithelial LHCGR staining was significantly lower in women stimulated with
Original languageEnglish
Pages (from-to)1610 - 1619
Number of pages10
JournalHuman Reproduction
Issue number6
Publication statusPublished - 2013

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