GnRH antagonists may affect endometrial receptivity

Abstract

Study objective-HOXA10 is an essential regulator of endometrial receptivity. To determine the effect of gonadotropin releasing hormone (GnRH) antagonists on endometrial receptivity we assessed endometrial HOXA10 expression in GnRH antagonist, GnRH agonist, and natural cycles. Design-Prospective case-control study Setting-University academic medical centerPatients-Nineteen subjects were included: 12 subjects underwent controlled ovarian hyperstimulation (COH) with recombinant follicle stimulating hormone (rFSH) and used either a GnRH antagonist or a GnRH agonist; 7 control subjects underwent natural cycles.Interventions-Pipelle endometrial biopsies were obtained 11 days after human chorionic gonadotropin (hCG) administration or spontaneous luteinizing hormone (LH) surge in untreated cycles, respectively. Immunohistochemistry was used to assess HOXA10 protein expression in endometrial glands and stroma. Main outcome measure(s)-Endometrial HOXA10 protein expressionResults-HOXA10 expression was significantly decreased in endometrial stromal cells in GnRH antagonist treated cycles compared with GnRH agonist treated cycles or natural cycle controls. There was no significant difference in glandular cell HOXA10 expression among the three groups.Conclusions-Use of GnRH antagonists may be associated with impaired HOXA10 expression in endometrial stromal cells, and thus may affect endometrial receptivity.

Early pregnancy loss rates were different among singleton gestations conceived by ICSI using GnRH agonist and antagonist

“…In this regard, a recent meta analysis comparing outcomes between antagonist and agonist cycles, including 13 randomized clinical trials with a range of 2-101 pregnant cases for each study, miscarriage rates were not found to be different (11.7% vs 11.5%) [18]. However, the studies in this meta analysis in the Cochrane review did not take into account the plurality of gestations and the definitions of miscarriage were not uniform [5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

“…In order to determine whether this subtle clinical outcome difference between those GnRH analogues could be integral to endometrial microenvironment, some studies addressed endometrium as a confounding factor. Histologically no apparent differences were found enough to detect any deleterious effects of GnRH antagonists; others found significant ultrastructural differences such as different expressions of growth factors and chemokins from endometrial cells exposed to GnRH agonists and antagonists [9][10][11][12]. Bearing in mind that GnRH receptors exist on endometrium, it may be speculated that endometrial factor could be related to this clinical outcome difference between GnRH agonists and antagonists.…”

A prospective randomised study comparing a GnRH-antagonist versus a GnRH-agonist short protocol for ovarian stimulation in patients referred for IVF

“…The study of Rackow showed that endometrial receptivity is decreased in cycles with GnRH antagonist use (Rackow et al, 2008). This could also explain why this effect is not observed in oocyte donation cycles.…”

Clinical view of the ineffectiveness of IVF problem with endometrial receptivity

“…Shapiro и соавторы, оценивая эндометрий в стимули-рованных циклах ЭКО в сравнении с натуральным циклом, обнаружили преждевременную секреторную трансфор-мацию и изменение экспрессии маркеров рецептивности в постовуляторной и ранней лютеиновой фазе, что, воз-можно, приводит к несинхронному взаимодействию меж-ду жизнеспособным эмбрионом и рецептивным или суб-рецептивным эндометрием [23]. Кроме того, по данным исследователей, в лютеиновой фазе стимулированного цикла изменяется профиль экспрессии генов эндометрия [24]. В описанных протоколах с антагонистом гонадотро-пин-рилизинг гормона (ГнРГ) снижается экспрессия генов НОХА 10 в строме эндометрия.…”

“…При анализе экспрессии НОХА 10 в эндометрии в стиму-лированных циклах в протоколах с ант-ГнРГ и а-ГнРГ изменения экспрессии этого гена обна-ружены не были [12]. Вместе с тем известные исследователи B. Rackow и коллеги предпола-гают, что ант-ГнРГ снижают экспрессию НОХА 10 в строме эндометрия [24]. Поэтому пациент-кам с неудачами имплантации в анамнезе перед проведением программы ВРТ ЭКО не-обходимо провести анализ всех индукторов, влияющих на эндометрий, морфологический пейзаж эндометрия, экспрессию рецепторов Е2 и прогестерона, пиноподии, интегрины, молекулярно-генетические аспекты эндомет-рия в стимулированных циклах.…”