Yuji Taketani1, Eduardo Kelly2,3, Yasunori Yoshimura4, Hiroshi Hoshiai5, Minoru Irahara6, Hideki Mizunuma7, Hidekazu Saito8, Kazumichi Andoh9, Takumi Yanaihara10. 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.
RCT Entities:
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.
Authors: Nienke S Weiss; Elena Kostova; Marleen Nahuis; Ben Willem J Mol; Fulco van der Veen; Madelon van Wely Journal: Cochrane Database Syst Rev Date: 2019-01-16