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

Yuji Taketani; Eduardo Kelly; Yasunori Yoshimura; Hiroshi Hoshiai; Minoru Irahara; Hideki Mizunuma; Hidekazu Saito; Kazumichi Andoh; Takumi Yanaihara

doi:10.1007/s12522-010-0046-5

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

Reprod Med Biol. 2010 Feb 23;9(2):99-106. doi: 10.1007/s12522-010-0046-5. eCollection 2010 Jun.

Authors

Yuji Taketani¹, Eduardo Kelly^{2

3}, Yasunori Yoshimura⁴, Hiroshi Hoshiai⁵, Minoru Irahara⁶, Hideki Mizunuma⁷, Hidekazu Saito⁸, Kazumichi Andoh⁹, Takumi Yanaihara¹⁰

Affiliations

¹ Department of Obstetrics and Gynaecology, Graduate School of Medicine, Faculty of Medicine University of Tokyo Tokyo Japan.
² EMD Serono, Inc. Rockland MA USA.
³ Steptoe Therapeutics, Inc. Hingham MA USA.
⁴ Department of Obstetrics and Gynaecology, School of Medicine Keio University Tokyo Japan.
⁵ Department of Obstetrics and Gynaecology, School of Medicine Kinki University Osaka-Sayama Japan.
⁶ Department of Obstetrics and Gynaecology The University of Tokushima Faculty of Medicine Tokushima Japan.
⁷ Department of Obstetrics and Gynaecology, School of Medicine Hirosaki University Hirosaki Japan.
⁸ Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care National Center for Child Health and Development 157-8535 Tokyo Japan.
⁹ Department of Gynaecology Japanese Red Cross Medical Center Tokyo Japan.
¹⁰ Department of Obstetrics and Gynaecology Showa University School of Medicine Tokyo Japan.

Abstract

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 (n = 261), and in 79.2% and 82.5% of the per-protocol set (n = 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.

Keywords: Follitropin alfa; Infertility; Low‐dose step‐up; Ovulation induction; Urofollitropin.