Short gonadotropin-releasing hormone agonist versus flexible antagonist versus clomiphene citrate regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial.

OBJECTIVE: Poor responders represent a frustrating condition for couples undergoing IVF and clinicians, and their treatment remains disputed. To assess the efficacy and the most suitable protocol, we conducted a randomized controlled trial comparing three different protocols of ovarian stimulation in poor responder women: clomiphene citrate (CC) plus a high dose of gonadotropins and GnRH antagonist, flexible GnRH antagonist protocol and a short GnRH agonist protocol.

PATIENTS AND METHODS: Between July 2014 and December 2015 we enrolled 250 poor responders in a previous IVF cycle at least 3 months before. We divided into three groups: group A, 68 women treated with clomiphene citrate and FSH plus antagonist; Group B, 71 patients treated with FSH plus antagonist; Group C, 75 patients treated with FSH plus GnRH agonist.

RESULTS: The GnRH agonist protocol showed a significantly higher pregnancy rate (29.3% vs. 5.9% vs. 14.1% respectively) than the clomiphene and the GnRH antagonist protocol, number of mature oocytes collected, estradiol levels and endometrial thickness. The cost of medications for each baby born was lower for the GnRH agonist protocol than for the others; the implantation rate was significantly lower in the clomiphene group (4.8%) than in the GnRH antagonist group (9.3%) and the GnRH agonist groups (19.2%). No significant differences emerged for total FSH administered, days of stimulation, numbers of oocytes retrieved and embryos transferred.

CONCLUSIONS: This study demonstrates that short GnRH agonist protocol should be the first choice in poor responders; instead, clomiphene citrate should be avoided due to its very low success rate and high costs.