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Embryo implantation and GnRH antagonists: GnRH antagonists do not activate the GnRH receptor
1Organon, Oss, The Netherlands. b.mannerts@organon.oss.akzonobel.nl
Abstract:
Recent suggestions that gonadotrophin-releasing hormone (GnRH) antagonists activate the GnRH receptor are discussed. Most of the studies cited in support of this suggestion are in-vitro studies, testing supra-pharmacological doses of GnRH analogues in cancer cell lines, whereas GnRH antagonists, e.g. ganirelix or cetrorelix, do not affect the steroidogenesis of human granulosa cells in vitro. In patients treated with GnRH antagonists prior to IVF or intracytoplasmic sperm injection (ICSI), oocyte maturity and fertilization rates are equal to those achieved following a long protocol of GnRH agonists. Although there is a tendency towards a lower pregnancy rate (not statistically significant) in the initial trials using GnRH antagonist with either recombinant FSH or human menopausal gonadotrophin (HMG) for ovarian stimulation, this new treatment option of GnRH antagonists facilitates short and simple treatment and improves the convenience and safety for the patient. As with GnRH agonists in the past, the clinical outcome of GnRH antagonist treatment will improve with time as more clinical experience is gained (learning curve) and the treatment protocol is optimized. Moreover, a GnRH agonist instead of human chorionic gonadotrophin (HCG) may be used for triggering ovulation and will decrease the cancellation rate and minimize the risk for developing ovarian hyperstimulation syndrome (OHSS).
Insights
Gonadotrophin-releasing hormone (GnRH) antagonists do not activate the GnRH receptor, contrary to some in-vitro studies. GnRH antagonists offer a convenient and safe option for IVF/ICSI patients, with outcomes expected to improve with clinical experience.
Area of Science:
- Reproductive Endocrinology
- Pharmacology
Background:
- Recent in-vitro studies suggest gonadotrophin-releasing hormone (GnRH) antagonists may activate the GnRH receptor.
- However, these studies often use supra-pharmacological doses in cancer cell lines, which may not reflect clinical reality.
Purpose of the Study:
- To discuss the current understanding of GnRH antagonist activity at the GnRH receptor.
- To evaluate the clinical efficacy and safety of GnRH antagonists in assisted reproductive technologies.
Main Methods:
- Review of in-vitro studies on GnRH analogues and cancer cell lines.
- Analysis of clinical data from patients undergoing IVF/ICSI using GnRH antagonists for ovarian stimulation.
- Comparison of outcomes with GnRH agonists and assessment of safety profiles.
Main Results:
- GnRH antagonists (e.g., ganirelix, cetrorelix) do not affect steroidogenesis in human granulosa cells in vitro.
- Oocyte maturity and fertilization rates in patients treated with GnRH antagonists are comparable to those achieved with GnRH agonists.
- Initial trials show a non-significant trend towards lower pregnancy rates, but improved treatment convenience and safety.
Conclusions:
- GnRH antagonists are a safe and convenient option for IVF/ICSI, with no evidence of GnRH receptor activation in relevant cell types.
- Clinical outcomes are expected to improve with increased clinical experience and protocol optimization.
- Using GnRH agonists for ovulation triggering can reduce cancellation rates and the risk of ovarian hyperstimulation syndrome (OHSS).