Taketani Yuji, Kelly Eduardo, Yoshimura Yasunori, Hoshiai Hiroshi, Irahara Minoru, Mizunuma Hideki, Saito Hidekazu, Andoh Kazumichi, Yanaihara Takumi
Department of Obstetrics and Gynaecology, Graduate School of Medicine, Faculty of Medicine University of Tokyo Tokyo Japan.
EMD Serono, Inc. Rockland MA USA.
Reprod Med Biol. 2010 Feb 23;9(2):99-106. doi: 10.1007/s12522-010-0046-5. eCollection 2010 Jun.
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.
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.
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%).
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.
我们旨在比较重组人促卵泡激素（follitropin alfa）和纯化尿促卵泡激素（urofollitropin）对日本无排卵性不孕症女性进行促排卵的疗效和安全性；同时验证follitropin alfa相对于urofollitropin在排卵率方面的非劣效性。
在一项III期、多中心、单盲、平行组研究中，我们纳入了265名年龄在20 - 39岁的日本女性。这些患者月经周期正常但无明显排卵或闭经（孕激素激发试验阳性），且抗雌激素促排卵治疗未能受孕。患者采用起始剂量为75 IU的follitropin alfa或urofollitropin进行低剂量递增方案治疗。主要终点是排卵患者的比例（黄体中期血清孕酮≥5 ng/mL和/或确诊临床妊娠）。次要终点包括优势卵泡（≥18 mm）患者的比例和刺激持续时间。
在全分析集（n = 261）中，接受follitropin alfa和urofollitropin治疗的患者排卵率分别为79.1%和82.6%；在意向性分析集（n = 251）中，分别为79.2%和82.5%。达到了主要终点的预定义非劣效性标准。在任何次要终点上均未观察到显著差异。每组中报告治疗中出现不良事件的患者比例相似（follitropin alfa组为53.5%；urofollitropin组为50.0%）。
在月经周期正常或孕激素阳性闭经的无排卵性不孕症女性中，follitropin alfa和纯化尿促卵泡激素在主要疗效终点（排卵率）上无显著差异。本研究中使用治疗假期妨碍了将数据与之前使用连续每日剂量的试验进行比较。
