Actions of GnRH antagonists on IGF-II, IGF-binding protein-2 and pregnancy-associated plasma protein-A in human granulosa-lutein cells

Abstract

Objective: Recently, GnRH antagonists (GnRHants) have been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). Here we investigated whether the GnRHants cetrorelix and ganirelix exert effects on the human ovarian IGF system. Since controversy exists on the action of GnRH agonists in the human ovary, we also tested the effect of triptorelin on IGF-II, IGF-binding protein-2 (IGFBP-2) and pregnancy-associated plasma protein-A (PAPP-A) in cultured human granulosa-lutein cells. Design: In vitro cell culture study in a research laboratory of a university hospital. Patients: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin or cetrorelix. Cells were treated with triptorelin, cetrorelix or ganirelix, 1 nmol/l each, for 48 h. IGF-II, IGFBP-2 and PAPP-A were measured by RIA and enzyme immunoassay respectively. Results: GnRHants and triptorelin did not affect IGF-II, IGFBP-2 or PAPP-A. Conclusions: We conclude that GnRHants do not exert any significant effects on the IGF system of granulosa-lutein cells and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Follicular fluid anti-Müllerian hormone and inhibin B concentrations: comparison between gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist cycles

“…Recent studies with human granulosa-lutein cells demonstrated that GnRH antagonist did not exert any significant effects on the ovarian insulin-like growth factor (IGF) system (37). In addition, Asimakopoulos et al (38) showed no difference in intrafollicular levels of E 2 , P, IGF-I, and epidermal growth factor between GnRH-a and GnRH antagonist protocols.…”

Cryopreserved blastocyst transfer: impact of gonadotropin-releasing hormone agonist versus antagonist in the previous oocyte retrieval cycles

“…These potential extrapituitary effects of GnRH antagonist have been claimed to be the cause of a lower pregnancy rate (6,13). However, studies on the effects of GnRH antagonists on individual reproductive organs have produced controversial results (12,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), so it is still unclear which of the extrapituitary effects of GnRH antagonists (e.g., on oocyte quality, embryo development, or endometrial maturation) could be the main cause of a lower pregnancy rate.…”

“…This hypothesis is based on in vitro studies demonstrating that GnRH antagonists negatively affect the biosynthesis of growth factors such as insulin-like growth factor (IGF) and epidermal growth factor (EGF), which are important for oocyte maturation (35). However, recent studies with human granulosa-lutein cells demonstrated that GnRH antagonists did not exert any significant effects on ovarian steroidogenesis and the IGF system (22,23). In addition, Asimakopoulos et al (24) showed no difference in intrafollicular levels of estradiol, progesterone, IGF-I, or EGF when comparing GnRH-agonist with GnRH-antagonist protocols.…”

Comparison of preovulatory follicular concentrations of epidermal growth factor, insulin-like growth factor-I, and inhibins A and B in women undergoing assisted conception treatment with gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists

“…Similarly, the follicular levels of inhibin A in women undergoing IVF with GnRH antagonists were not found to be different from those in women undergoing natural-cycle IVF (16). Moreover, granulosa cells treated in vitro with a GnRH antagonist did not differ from cells treated with a GnRH agonist in secretion of IGF-II or insulin-like growth factor binding protein (17).…”