个体化与传统卵巢刺激用于体外受精：一项多中心、随机、对照、评估者盲法的3期非劣效性试验。
Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial.
作者信息
Nyboe Andersen Anders, Nelson Scott M, Fauser Bart C J M, García-Velasco Juan Antonio, Klein Bjarke M, Arce Joan-Carles
机构信息
Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
School of Medicine, University of Glasgow, Glasgow, United Kingdom.
出版信息
Fertil Steril. 2017 Feb;107(2):387-396.e4. doi: 10.1016/j.fertnstert.2016.10.033. Epub 2016 Nov 29.
OBJECTIVE
To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF.
DESIGN
Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1).
SETTING
Reproductive medicine clinics.
PATIENT(S): A total of 1,329 women (aged 18-40 years).
INTERVENTION(S): Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH ≥15 pmol/L: 0.10-0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d).
MAIN OUTCOMES MEASURE(S): Ongoing pregnancy and ongoing implantation rates; noninferiority margins -8.0%.
RESULT(S): Ongoing pregnancy (30.7% vs. 31.6%; difference -0.9% [95% confidence interval (CI) -5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; -0.6% [95% CI -6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; -0.9% [95% CI -5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8-14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg).
CONCLUSION(S): Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation.
CLINICAL TRIAL REGISTRATION NUMBER
NCT01956110.
目的
比较新型人重组促卵泡素δ（根据血清抗苗勒管激素（AMH）和体重进行个体化给药）与传统促卵泡素α给药用于体外受精（IVF）女性卵巢刺激的疗效和安全性。
设计
随机、多中心、评估者盲法、非劣效性试验（ESTHER-1）。
地点
生殖医学诊所。
患者
共1329名女性（年龄18 - 40岁）。
干预措施
促卵泡素δ（AMH <15 pmol/L：12 μg/d；AMH≥15 pmol/L：0.10 - 0.19 μg/kg/d；最大12 μg/d），或促卵泡素α（150 IU/d，持续5天，后续可能调整剂量；最大450 IU/d）。
主要观察指标
持续妊娠率和持续着床率；非劣效性界值为 - 8.0%。
结果
个体化促卵泡素δ与传统促卵泡素α的持续妊娠率（30.7%对31.6%；差异 - 0.9% [95%置信区间（CI） - 5.9%至4.1%]）、持续着床率（35.2%对35.8%； - 0.6% [95% CI - 6.1%至4.8%]）和活产率（29.8%对30.7%； - 0.9% [95% CI - 5.8%至4.0%]）相似。个体化促卵泡素δ使更多女性获得目标反应（8 - 14个卵母细胞）（43.3%对38.4%），低反应者更少（AMH <15 pmol/L的患者中少于4个卵母细胞）（11.8%对17.9%），高反应者更少（AMH≥15 pmol/L的患者中≥15个或≥20个卵母细胞）（分别为27.9%对35.1%和10.1%对15.6%），且预防卵巢过度刺激综合征采取的措施更少（2.3%对4.5%），尽管卵母细胞产量相似（10.0±5.6对10.4±6.5）、囊胚数量相似（3.3±2.8对3.5±3.2），且促性腺激素使用量更少（90.0±25.3对1
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