Recombinant follicle-stimulating hormone (follitropin alfa) versus purified urinary follicle-stimulating hormone in a low-dose step-up regimen to induce ovulation in Japanese women with anti-estrogen-ineffective oligo- or anovulatory infertility: results of a single-blind Phase III study.

Purpose: We aimed to compare the efficacy and safety of recombinant human follicle-stimulating hormone (follitropin alfa) and purified urinary human follicle-stimulating hormone (urofollitropin) for ovulation induction in Japanese women with anovulatory infertility;also to verify the noninferiority (in terms of ovulation rate) of follitropin alfa versus urofollitropin.

Methods: In a Phase III, multicenter, single-blind, parallel-group study, we enrolled 265 Japanese women aged 20-39 years. The patients were menstruating without apparent ovulation or were amenorrheic (with a positive progestin challenge test), and had failed to conceive with anti-estrogen ovulation-induction therapy. The patients underwent a low-dose step-up regimen using follitropin alfa or urofollitropin with a starting dose of 75 IU. The primary endpoint was the proportion of patients who ovulated (mid-luteal serum progesterone ≥5 ng/mL and/or confirmed clinical pregnancy). Secondary endpoints included the proportion of patients with a dominant follicle (≥18 mm) and the duration of stimulation.

Results: Ovulation occurred in 79.1% and 82.6% of the patients who received follitropin alfa and urofollitropin, respectively, in the full-analysis set ( = 261), and in 79.2% and 82.5% of the per-protocol set ( = 251). The predefined noninferiority criteria for the primary endpoint were achieved. No significant differences were observed in any secondary endpoint. Treatment-emergent adverse events were reported by a similar proportion of patients in each group (follitropin alfa, 53.5%; urofollitropin, 50.0%).

Conclusions: No significant difference in the primary efficacy endpoint (rate of ovulation) was observed between follitropin alfa and purified urofollitropin in women with anovulatory infertility who were menstruating or had progestin-positive amenorrhea. The use of treatment holidays in this study prevents comparison of the data with previous trials that utilized consecutive daily doses.