Natural ovulation versus programmed regimens before frozen embryo transfer in ovulatory women: multicentre, randomised clinical trial.

Methods

Multicentre, randomised, parallel group, assessor blinded clinical trial.

多中心、随机、平行组、评估者盲法临床试验。

24 academic fertility centres in China.

中国24个学术生育中心。

4376 ovulatory women (aged 20-40 years) planning to undergo a frozen single blastocyst transfer.

4376名有排卵的女性（年龄在20-40岁之间），计划进行冷冻单囊胚移植。

Eligible participants were randomised (1:1) to receive a natural ovulation regimen or a programmed regimen of hormone replacement for endometrial preparation.

符合条件的参与者被随机分配（1:1），接受自然排卵方案或激素替代的程序化方案进行子宫内膜准备。

Endometrial preparation and frozen embryo transfer timing were determined in the natural ovulation regimen group by monitoring natural follicle development and measuring serum levels of luteinising hormone, oestradiol, and progesterone.

在自然排卵方案组中，通过监测自然卵泡发育和测量血清中的黄体生成素、雌二醇和孕酮水平来确定子宫内膜准备和冻胚移植的时机。

In the programmed regimen group, endometrial preparation was achieved by sequential administration of oestrogen and progesterone.

在程序化方案组中，通过顺序给予雌激素和孕激素来实现子宫内膜准备。

main_outcomes_and_measures

Primary outcomes were a healthy live birth and pre-eclampsia or eclampsia after a frozen embryo transfer.

主要结果是冻胚移植后的健康活产以及子痫前期或子痫。

Secondary outcomes were cycle cancellation, biochemical pregnancy, clinical pregnancy, ongoing pregnancy, pregnancy loss, ectopic pregnancy, live birth, birth weight, and maternal, fetal, and neonatal complications.

次要结果包括周期取消、生化妊娠、临床妊娠、持续妊娠、妊娠丢失、异位妊娠、活产、出生体重以及母体、胎儿和新生儿并发症。

Results

In the intention-to-treatanalyses, 910 (41.6%) of 2185 patients in the natural ovulation regimen group and 890 (40.6%) of 2191 in the programmed regimen group achieved a healthy live birth (relative ratio 1.03 (95% confidence interval(CI) 0.96 to 1.10); P=0.49).

在意向治疗分析中，自然排卵方案组的2185名患者中有910名（41.6%），而程序化方案组的2191名患者中有890名（40.6%）实现了健康的活产（相对比率1.03（95%置信区间（CI）0.96至1.10）；P=0.49）。

The risk of pre-eclampsia was lower in the natural ovulation regimen group among patients who achieved clinical pregnancy than in the programmed regimen group (2.9% (38 of 1302) v 4.6% (61 of 1326); 0.63 (0.43 to 0.94); P=0.02).

在实现临床妊娠的患者中，自然排卵方案组的子痫前期风险低于程序化方案组（2.9%（38/1302）对比4.6%（61/1326）；0.63（0.43至0.94）；P=0.02）。

The incidences of early pregnancy loss (12.1% (158 of 1302) v 15.2% (201 of 1326); 0.80 (0.66 to 0.97)), placental accreta spectrum (1.8% (24 of 1302) v 3.6% (48 of 1326); 0.51 (0.31 to 0.83)), caesarean section (69.5% (776 of 1117) v 75.6% (831 of 1100); 0.92 (0.87 to 0.97)), and postpartum haemorrhage (2.0% (22 of 1117) v 6.1% (67 of 1100); 0.32 (0.20 to 0.52)) were lower in the natural ovulation regimen group.

自然排卵方案组的早期妊娠丢失（12.1%（158/1302）对比15.2%（201/1326）；0.80（0.66至0.97））、胎盘粘连谱系（1.8%（24/1302）对比3.6%（48/1326）；0.51（0.31至0.83））、剖宫产（69.5%（776/1117）对比75.6%（831/1100）；0.92（0.87至0.97））和产后出血（2.0%（22/1117）对比6.1%（67/1100）；0.32（0.20至0.52））的发生率均低于程序化方案组。

No differences between groups were observed for birth weight or neonatal complications.

两组间在出生体重或新生儿并发症方面未观察到差异。

The rate of cycle cancellation was higher in the natural ovulation regimen (16.2% (354 of 2185) v 11.5% (251 of 2191), P<0.001).

自然排卵方案的周期取消率更高（16.2%（354/2185）对比11.5%（251/2191），P<0.001）。

The prespecified per protocol and subgroup analyses yielded results consistent with the intention-to-treatanalyses.

预先设定的按方案和亚组分析结果与意向治疗分析结果一致。

Conclusions

In ovulatory women, a natural ovulation regimen for endometrial preparation was as effective as programmed regimen in terms of achieving a healthy live birth after frozen embryo transfer, but with a lower risk of maternal complications during pregnancy.

在排卵妇女中，自然排卵方案在子宫内膜准备方面与程序化方案一样有效，都能在冷冻胚胎移植后实现健康活产，但前者在怀孕期间的母体并发症风险较低。

trial_registration

Chinese Clinical Trial Registry ChiCTR2200057990.

中国临床试验注册中心ChiCTR2200057990。