A randomized dose-response trial of a single injection of corifollitropin alfa to sustain multifollicular growth during controlled ovarian stimulation

Abstract

Background: This study primarily investigated the dose-response relationship of corifollitropin alfa to initiate multifollicular development for the first 7 days of controlled ovarian stimulation (COS).

Methods: Women aged 20-39 years undergoing COS for in vitro fertilization or intracytoplasmic sperm injection were randomized to a single dose of corifollitropin alfa 60, 120 or 180 microg, or daily injections of 150 IU recombinant follicle-stimulating hormone (rFSH). Patients treated with corifollitropin alfa started fixed daily treatment with 150 IU rFSH on stimulation Day 8. Patients received a GnRH antagonist (ganirelix 0.25 mg/day) from stimulation Day 5 until the day of human chorionic gonadotrophin.

Results: Pharmacokinetics of corifollitropin alfa were dose-proportional. The main reason for not having embryo transfer was insufficient ovarian response in 30.8, 2.6, 3.8 and 7.4% of patients in the corifollitropin alfa 60, 120, 180 microg and rFSH groups, respectively. On Day 8, the mean (standard deviation) number of follicles >or=11 mm was 6.8 (4.4), 10.1 (6.1) and 12.8 (7.5), respectively. The number of cumulus-oocyte complexes retrieved showed a clear dose-response relationship (P < 0.0001), being 5.2 (5.5), 10.3 (6.3) and 12.5 (8.0) in the three dose groups, respectively.

Conclusions: A single injection of corifollitropin alfa induces dose-related increase in multifollicular development and in the number of retrieved oocytes. The optimal dose for a 1-week interval is higher than 60 microg and lower than 180 microg and will be selected based on modelling and simulation taking into account insufficient stimulation as well as overstimulation. Clinical Trials gov: NCT00598208.