The use of GnRH antagonists in ovarian stimulation

GnRH antagonists induce a rapid decrease in LH and FSH, preventing and interrupting LH surges. Their properties do not require a desensitization period, and this allows their use in the late follicular phase. GnRH antagonists could replace GnRH agonists in controlled ovarian stimulation without their side-effects and their long desensitization period. Two protocols for assisted reproduction technology (ART) cycles were designed: the single-dose protocol allies simplicity and efficacy, while the multiple-dose protocol is efficient and could reduce monitoring of the cycle, though compliance is mandatory. A review of the available literature on GnRH antagonists in ART cycles is presented, focusing on phase III controlled trials and ART results. Both protocols using GnRH antagonists were associated with the need for a smaller dose of gonadotrophin, a shorter stimulation period and a lower incidence of ovarian hyperstimulation syndrome (OHSS), albeit with statistically comparable pregnancy rates. A trend is observed in all studies showing a lower pregnancy rates in GnRH antagonist cycles as compared with GnRH agonist cycles. The role of the lower number of embryos, and the potential adverse effects of GnRH antagonists on endometrium or follicle must be studied. More cycles using GnRH antagonists are necessary to confirm their equivalent pregnancy rates. There is room for improvement in both protocols with regard to scheduling, antagonist dose level and the timing of its administration. Until further studies have been conducted, luteal support seems to remain mandatory. Perinatal outcome appears similar to that with other stimulation regimens. Triggering of ovulation can be obtained with GnRH agonist for patients at risk of OHSS. With regard to GnRH antagonists, questions remain regarding pregnancy rates, the indications of their use in patients with polycystic ovary syndrome or poor responders, and in ovarian stimulation outside IVF.