Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
JAMA. 2023 May 2;329(17):1460-1468. doi: 10.1001/jama.2023.5302.
Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate.
To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure.
DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021).
Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy.
The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life.
Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights.
Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure.
Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.
背景：胚胎着床失败仍是体外受精的一个重大障碍。地塞米松作为一种免疫调节剂，被广泛用于提高着床和妊娠的概率，尽管其疗效证据不足。
目的：评估在反复着床失败的女性中，与安慰剂相比，10 mg 地塞米松对活产的疗效。
设计、地点和参与者：这是一项在中国 8 家生殖中心进行的双盲、安慰剂对照、随机临床试验。2018 年 11 月至 2020 年 8 月（最终随访时间为 2021 年 8 月）期间，招募了符合以下条件的女性：曾有 2 次或以上胚胎移植失败史，取卵时年龄小于 38 岁，计划进行冻融胚胎移植，且有优质胚胎可用。
干预措施：参与者被随机（1:1）分为两组，分别接受每日口服 10 mg 地塞米松（n=357）或匹配安慰剂（n=358），从开始冻融胚胎移植的子宫内膜准备到早孕。
主要结局和测量指标：主要结局是活产，定义为 28 周或以上有生命迹象的任何数量新生儿的分娩。
结果：在 715 名随机分组的女性中（平均年龄 32 岁），714 名（99.9%）有活产结局数据，纳入主要分析。地塞米松组活产率为 37.8%（135/357），安慰剂组为 38.8%（139/358）（绝对差异，-1.0%[95%CI，-8.1%至 6.1%]；相对比值[RR]，0.97[95%CI，0.81 至 1.17]；P=0.78）。地塞米松组生化妊娠丢失率为 17.3%，安慰剂组为 9.9%（绝对差异，7.5%[95%CI，0.6%至 14.3%]；RR，1.75[95%CI，1.03 至 2.99]；P=0.04）。地塞米松组早产率为 11.8%，安慰剂组为 5.5%（绝对差异，6.3%[95%CI，0.2%至 12.4%]；RR，2.14[95%CI，1.00 至 4.58]；P=0.04）。两组间生化妊娠、临床妊娠、着床、新生儿并发症、先天畸形、其他不良事件或新生儿平均出生体重发生率无统计学差异。
结论：在反复着床失败的患者中，与安慰剂相比，地塞米松治疗并未提高活产率。数据表明，地塞米松的使用可能增加早产和生化妊娠丢失的风险。我们的结果对临床实践中地塞米松治疗反复着床失败的价值提出了挑战。
临床试验注册：中国临床试验注册中心注册号：ChiCTR1800018783。
