Robinson Institute, University of Adelaide, Australia.
Hum Reprod. 2011 Aug;26(8):2200-8. doi: 10.1093/humrep/der163. Epub 2011 May 27.
One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles.
In this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs).
First, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9-20.8%), headache (9.1%, 95% CI: 7.0-11.5%) and pelvic pain (7.6%, 95% CI: 5.7-9.9%). Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56-65%) after censoring for patients who discontinued.
Treatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity. The trial was registered under ClinicalTrials.gov identifier NCT00696878.
单次注射促卵泡素阿尔法可替代控制性卵巢刺激（COS）周期中的前 7 天每日 FSH 注射。治疗性蛋白的重复治疗可能会引起免疫反应或过敏反应。我们评估了在最多三个 COS 周期中使用促卵泡素阿尔法治疗的免疫原性和安全性。
在这项多中心、III 期非对照试验中，体重超过 60kg 的患者在月经周期第 2 或 3 天开始接受一次 150µg 促卵泡素阿尔法注射，并在刺激第 5 或 6 天接受 0.25mg ganielix。主要观察指标为针对促卵泡素阿尔法的抗体形成（使用高度敏感的放射免疫沉淀测定法）、过敏反应、局部耐受性和不良事件（AE）。
分别有 682、375 和 198 名患者开始了第一、第二和第三个 COS 周期。未观察到临床相关的免疫原性或与药物相关的过敏反应。对于 192 名接受第三个周期治疗的患者，治疗后血液样本在抗促卵泡素抗体检测中呈阴性，导致单侧 95%置信区间（CI）上限为 1.5%。最常见的 AE 为程序性疼痛（17.7%，95%CI：14.9-20.8%）、头痛（9.1%，95%CI：7.0-11.5%）和骨盆疼痛（7.6%，95%CI：5.7-9.9%）。在对停药患者进行删失后，三个周期后的累积持续妊娠率（包括冷冻胚胎移植周期和自然妊娠）为 61%（95%CI：56-65%）。
在接受最多三个治疗周期的正常反应患者中，促卵泡素阿尔法治疗可安全有效地启动和维持 COS 前 7 天的卵巢刺激，且无需担心免疫原性。该试验在 ClinicalTrials.gov 标识符 NCT00696878 下注册。
