Human menopausal gonadotrophin in a pre-filled injection pen is non-inferior to the US-approved powder formulation

RESEARCH QUESTION: Is non-inferiority demonstrated for highly purified human menopausal gonadotrophin (HP-HMG) in an injection pen versus the US approved HP-HMG powder formulation for number of fertilized oocytes in women undergoing ovarian stimulation? DESIGN: Randomised, double-blind, double-dummy, parallel group, multicentre, non-inferiority trial at 19 US reproductive medicine centres enrolling 401 women ages 18‒42 years, randomised 1:1 to HP-HMG pen or HP-HMG powder. After downregulation in a gonadotropin-releasing hormone agonist (GnRHa) cycle, ovaries were stimulated with HP-HMG pen or HP-HMG powder at a starting dose of 225 IU for the first 5 days, with subsequent dose adjustments as needed. The number of fertilized (two pronuclei [2PN]) oocytes 19 ± 2 h after insemination was the primary end point. RESULTS: The primary end point was met, and HP-HMG pen was non-inferior to HP-HMG powder, with the mean ± SD number of fertilized 2PN oocytes 8.2 ± 5.5 and 6.6 ± 4.3, respectively (adjusted treatment difference: 1.50, 95% CI 0.57 to 2.42). The number of oocytes retrieved was 14.3 ± 8.1 with HP-HMG pen and 11.4 ± 6.3 with HP-HMG powder. The mean number of blastocysts was 4.8 ± 3.8 in the HP-HMG pen group and 3.9 ± 3.0 in the HP-HMG powder group. The ongoing pregnancy rate per started stimulation cycle was 45.0% in the HP-HMG pen group and 42.7% in the HP-HMG powder group and the live birth rate was 44.1% and 42.2% after fresh transfer, respectively. The incidence of early ovarian hyperstimulation syndrome was 3.5% in both groups. CONCLUSIONS: HP-HMG as a solution for injection in a pre-filled injection pen is an effective and safe alternative to the approved powder formulation.