Are GnRH antagonists comparable to agonists for use in IVF?

Abstract

We believe that appropriate comparison of optimal GnRH agonist and antagonist regimens has not been performed yet. Currently available meta-analyses included all comparative studies between GnRH agonists and antagonists performed so far, including less than optimal GnRH antagonist regimens. After critical appraisal of the various studied GnRH antagonist regimens in terms of follicular development and IVF outcome, we postulate that early suppression of endogenous FSH results in optimal follicular development. Additionally, stable and early suppression of LH and progesterone levels during the entire period of stimulation may be an advantage for implantation and pregnancy outcome. In this respect, single dose and particularly flexible protocols seem to be less advantageous. Early FSH and LH suppression can be achieved by early GnRH antagonist administration (stimulation day 1) or by oral contraceptive (OC) pretreatment. More studies comparing long GnRH agonist protocols with 'long' GnRH antagonist protocols, with enough power to identify differences in pregnancy rates, are required before appropriate comparison can be made.

Rescue in vitro fertilization using a GnRH antagonist in hyper-responders from gonadotropin intrauterine insemination (IUI) cycles

“…This appears to be independent of whether a GnRH agonist or antagonist protocol is used [9,10]. For a number of years, a long mid-luteal GnRH agonist protocol for IVF was the standard of care, until research showed the feasibility of IVF with antagonist protocols.…”

“…This treatment is on the one hand associated with an increased number of ovarian cysts, and on the other hand, with an increased prevalence of side effects, most notably, estrogenic deprivation symptoms. In contrast, GnRH antagonists cause immediate and rapid gonadotropin suppression, by competitive occupancy of the GnRH receptor, and thus intuitively make a more logical choice to use in IVF for the prevention premature LH surges, especially since they reduce the duration of treatment [10]. Therefore, GnRH antagonists could be administered at any time during the early or mid-follicular phase of a treatment cycle to prevent a premature LH surge [10].…”

“…In contrast, GnRH antagonists cause immediate and rapid gonadotropin suppression, by competitive occupancy of the GnRH receptor, and thus intuitively make a more logical choice to use in IVF for the prevention premature LH surges, especially since they reduce the duration of treatment [10]. Therefore, GnRH antagonists could be administered at any time during the early or mid-follicular phase of a treatment cycle to prevent a premature LH surge [10]. Conversion of high-response gonadotropin-IUI cycles to "rescue" IVF could not prevent the prevalence of multiple pregnancy rates without single or double embryo transfer policies in place [5].…”

Clomiphene Citrate plus Modified GnRH Antagonist Protocol for Women with Poor Ovarian Response Undergoing ICSI Treatment Cycles: Randomized Controlled Trial

“…It has been postulated that elevated endogenous FSH underline the synchronization of early antral follicles [10]. Follicular size heterogeneity has been shown to be negatively affecting the reproductive outcomes, GnRH agonists and OCP pills are used to abolish this discrepancy [11].…”

The state of “freeze-for-all” in human ARTs

“…The introduction of GnRH antagonists seemed to open up a new way to more Bfriendly IVF^ [23]. Unlike indirect pituitary suppression induced by GnRH agonists, administration of GnRH antagonists causes immediate and dose-related suppression of gonadotropin release by competitive occupancy of GnRH receptors in the pituitary [24], which results in a much shorter duration of stimulation and absence of side effects caused by profound hypoestrogenemia [25,26]. A meta-analysis by AlInany et al demonstrated that the live birth rates between the use of GnRH antagonists and agonist protocols were comparable [27], but the majority of trials clearly support GnRH antagonists resulting in a significantly lower incidence (50 %) of OHSS compared with GnRH agonists [27][28][29].…”