在体外受精周期中，与标准人绒毛膜促性腺激素触发剂量相比，使用 1500IU 人绒毛膜促性腺激素加卵泡刺激素触发对卵母细胞能力的影响：一项随机、双盲、对照非劣效性试验。

Triggering with 1,500 IU of human chorionic gonadotropin plus follicle-stimulating hormone compared to a standard human chorionic gonadotropin trigger dose for oocyte competence in in vitro fertilization cycles: a randomized, double-blinded, controlled noninferiority trial.

机构信息

Division of Reproductive Endocrinology and Infertility, Center for Reproductive Health, University of California San Francisco, San Francisco, California.

出版信息

Fertil Steril. 2022 Aug;118(2):266-278. doi: 10.1016/j.fertnstert.2022.05.006. Epub 2022 Jun 12.

DOI:10.1016/j.fertnstert.2022.05.006

PMID:35705380

Abstract

OBJECTIVE

To assess if triggering with 1,500 IU of human chorionic gonadotropin (hCG) with 450 IU of follicle-stimulating hormone (FSH) induces noninferior oocyte competence to a standard dose of hCG trigger used in in vitro fertilization (IVF). The alternative trigger will be considered noninferior if it is at least 80% effective in promoting oocyte competence.

DESIGN

Randomized, double-blinded, controlled noninferiority trial.

SETTING

Academic infertility practice.

PATIENTS

Women aged 18-41 undergoing IVF with antral follicle count ≥8, body mass index ≤30 kg/m, and no history of ≥2 IVF cycles canceled for poor response were enrolled. Participants with a serum estradiol >5,000 pg/mL on the day of trigger were excluded because of high risk of ovarian hyperstimulation syndrome.

INTERVENTIONS

Participants were randomized to receive an alternative trigger of 1,500 IU of hCG plus 450 IU of FSH or a standard trigger dose of hCG (5,000 or 10,000 IU) for final oocyte maturation.

MAIN OUTCOME MEASURES

The primary outcome was total competent proportion, defined as the probability of 2 pronuclei from an oocyte retrieved. The alternative trigger will be considered noninferior to the standard trigger if a 1-sided 95% confidence interval (CI) of the relative risk (RR) is not <0.8. Secondary outcomes included oocyte recovery and maturity, intracytoplasmic sperm injection fertilization, embryo quality, pregnancy rates, as well as serum and follicular hormones. Secondary outcomes were compared using a 2-sided superiority test. Outcomes were analyzed by intention-to-treat and per-protocol.

RESULTS

A total of 105 women undergoing IVF were randomized from May 2015 to June 2018. The probability of the primary outcome was 0.59 with the alternative trigger and 0.65 with the standard trigger, with a RR of 0.91 and a 1-sided 95% CI of 0.83. Noninferiority of the alternative trigger was demonstrated. Live birthrate from all fresh transfers in the alternative trigger group vs. standard trigger was 46.9 vs. 46.4% (RR, 1.01; 95% CI, 0.62-1.62), respectively. Live birthrate per randomized participant was 48.1% in the alternative trigger group vs. 62.7% with the standard trigger (RR, 0.73; 95% CI, 0.48-1.11). No participants had a failed retrieval.

CONCLUSION

Triggering with 1,500 IU of hCG plus 450 IU of FSH promoted noninferior oocyte competence compared to a standard hCG trigger dose.

TRIAL REGISTRATION

NCT02310919.

摘要

目的

评估 1500IU 人绒毛膜促性腺激素（hCG）联合 450IU 卵泡刺激素（FSH）触发与体外受精（IVF）中标准剂量 hCG 触发相比，是否能诱导非劣效卵母细胞成熟。如果替代触发的有效性至少达到 80%，则可以认为其不劣于标准触发。

设计

随机、双盲、对照非劣效性试验。

地点

学术不孕不育实践。

患者

年龄在 18-41 岁之间，接受 IVF 治疗，窦卵泡计数≥8，体重指数（BMI）≤30kg/m²，且无≥2 个因反应不佳而取消的 IVF 周期史。因卵巢过度刺激综合征风险较高，血清雌二醇水平>5000pg/mL 的参与者被排除在外。

干预

参与者被随机分配接受替代触发剂 1500IU hCG 加 450IU FSH 或标准触发剂量 hCG（5000 或 10000IU）进行最终卵母细胞成熟。

主要结局指标

主要结局是总成熟比例，定义为从取回的卵母细胞中获得 2 个原核的概率。如果替代触发的相对风险（RR）的单侧 95%置信区间（CI）不<0.8，则替代触发将被认为不劣于标准触发。次要结局包括卵母细胞回收和成熟、胞浆内精子注射受精、胚胎质量、妊娠率以及血清和卵泡激素。次要结局采用双侧优效性检验进行比较。采用意向治疗和方案治疗进行分析。

结果

2015 年 5 月至 2018 年 6 月，共有 105 名接受 IVF 的女性随机分组。替代触发的主要结局概率为 0.59，标准触发的概率为 0.65，RR 为 0.91，单侧 95%CI 为 0.83。证明替代触发具有非劣效性。替代触发组和标准触发组的新鲜移植周期活产率分别为 46.9%和 46.4%（RR，1.01；95%CI，0.62-1.62）。替代触发组和标准触发组每位随机参与者的活产率分别为 48.1%和 62.7%（RR，0.73；95%CI，0.48-1.11）。没有参与者出现取卵失败。