DIFFERENTIAL OVARIAN RESPONSE TO GONADOTROPIN PREPARATIONS DESPITE SIMILAR OVARIAN RESERVE: MENOPUR IN GNRH (GONADOTROPIN RELEASING HORMONE) ANTAGONIST SINGLE EMBRYO TRANSFER - HIGH RESPONDER (MEGASET-HR) TRIAL ANALYSIS

Abstract

Assess possible interactions between treatment group [highly-purified human menopausal gonadotropin (HP-hMG) or recombinant follicle stimulation hormone (r-FSH)] and ovarian reserve as indicated by baseline levels of anti-Müllerian Hormone (AMH) on the number of oocytes retrieved. Post-hoc analysis of a randomized, open-label, assessor-blind, non-inferiority trial conducted at 31 U.S. trials sites. 620 ovulatory women aged 21-35y with BMI 18-30 kg/m2 and serum anti-Müllerian hormone (AMH) ≥5 ng/mL were randomized 1:1 to a 150 IU start dose of HP-hMG (N=311) or rFSH (N=309) in a GnRH antagonist cycle with dose adjustments based upon response from day 6 onward. Human chorionic gonadotropin (hCG) was used to trigger oocyte maturation (GnRH agonist if at high risk of ovarian hyperstimulation syndrome [OHSS]). Central laboratory serum hormone measurements were measured at baseline and stimulation days: 6, day of/after trigger. Fresh transfer of a single blastocyst was performed in hCG-triggered cycles; all embryos were frozen if the risk of OHSS was high. Live births resulting from all fresh and any frozen transfers occurring within 6 months of randomization were collected. A normal regression model was used to explore interactions between treatment group and baseline AMH on the number of oocytes retrieved. Demographics across treatment arms were similar (mean patient age: 30 years for both; HP-hMG, rFSH mean [SD] BMI: 24.4 [3.3], 24.3 [3.4] kg/m2; AMH: 7.8 [3.6], 7.5 [2.4] ng/mL; antral follicle count: 30.5 [15.5], 31.0 [12.2]). The average number of oocytes per patient in the rFSH arm (22.2 [11.54]) was significantly higher than in the HP-hMG arm (15.1 [10.12]) as were serum estradiol levels at stimulation days 6 and trigger and OHSS rates, described previously.1 Cumulative live birth rates were similar between treatment groups at 51.5% and 50.6% in rFSH and HP-hMG arms respectively. A positive effect of baseline AMH levels on the number of oocytes retrieved was identified and differed statistically by treatment group (p value=0.032); subjects with higher baseline level of AMH had a larger ovarian response to rFSH versus HP-hMG. For every 1.6 ng/ml (11.1 pmol/L) increase in baseline AMH, rFSH stimulation results in one extra oocyte versus HP-hMG in predicted high-responders. Increasing baseline AMH was associated with higher oocyte yields but no difference in cumulative live birth rates in rFSH vs HP-hMG treated patients, with an accompanying increase in OHSS rates also observed in the rFSH arm. This unexpectedly exaggerated ovarian response, which is positively correlated with increasing ovarian reserve based upon the well-established biomarker AMH, highlights a key distinction between the gonadotropin preparations evaluated, creating opportunities for further optimization of stimulation.