A randomized, assessor-blind, dose-response trial in patients undergoing controlled ovarian stimulation for IVF/ICSI with a novel recombinant FSH preparation (FE 999049) derived from a human cell-line

Abstract

To establish the relationship between the dose of FE 999049, a novel recombinant FSH derived from a human cell-line (PER.C6) and the number of oocytes retrieved, and to characterize it according to serum AMH. Randomized, controlled, assessor-blind, multicentre, dose-response trial in 265 IVF/ICSI patients undergoing controlled ovarian stimulation with one of five doses of FE 999049 (Ferring Pharmaceuticals) or one dose of follitropin alfa (GONAL-F, EMD Serono) (NCT01426386). Patients were randomized to fixed doses of 5.2, 6.9, 8.6, 10.3 or 12.1 μg/day FE 999049 (N=222) or follitropin alfa 11 μg/day (150 IU/day) (N=43). Randomization was stratified by serum AMH (low: 5.0-14.9 pmol/L, high: 15.0-44.9 pmol/L; Beckmann-Coulter Gen 2 ELISA). Stimulation was carried out in a GnRH antagonist cycle (ganirelix 0.25 mg/day from day 6). Triggering was done when ≥3 follicles ≥17 mm. Ongoing pregnancy was determined 10-11 weeks after compulsory single blastocyst transfer. There was a significant (p<0.001) dose-response relationship for FE 999049 with respect to number of oocytes retrieved; overall and for each AMH strata. Increasing the FE 999049 dose with 10% led to an increase of 1 oocyte (95% CI: 0.65-1.30) in the high AMH stratum and 0.5 oocyte (95% CI: 0.22-0.72) in the low AMH stratum. The dose-response curves were significantly (p<0.05) different for the two strata, with 31-97% more oocytes in the high AMH stratum across FE 999049 doses. The percentage of FE 999049 patients with extreme responses (i.e. <4 or ≥20 oocytes) followed a U-shaped dose-response curve. No linear relationship was observed between FE 999049 dose and number of blastocysts, but rather a threshold relationship. The ongoing pregnancy rate was 35% for FE 999049 and unrelated to dose. A significant dose-response relationship was established between FE 999049 and number of oocytes retrieved with significantly different slopes for the low and high AMH strata.