Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
Hum Reprod. 2021 Jun 18;36(7):1832-1840. doi: 10.1093/humrep/deab071.
Is there any difference in the ongoing pregnancy rate after immediate versus delayed frozen embryo transfer (FET) following a stimulated IVF cycle?
Immediate FET following a stimulated IVF cycle produced significantly higher ongoing pregnancy and live birth rate than did delayed FET.
Embryo cryopreservation is an increasingly important part of IVF, but there is still no good evidence to advise when to perform FET following a stimulated IVF cycle. All published studies are retrospective, and the findings are contradictory.
STUDY DESIGN, SIZE, DURATION: This was a randomised controlled non-inferiority trial of 724 infertile women carried out in two fertility centres in China between 9 August 2017 and 5 December 2018.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women having their first FET cycle after a stimulated IVF cycle were randomly assigned to either (1) the immediate group in which FET was performed in the first menstrual cycle following the stimulated IVF cycle (n = 362) or (2) the delayed group in which FET was performed in the second or later menstrual cycle following the stimulated IVF cycle (n = 362). All FET cycles were performed in hormone replacement cycles. The randomisation sequence was generated using an online randomisation program with block sizes of four. The primary outcome was the ongoing pregnancy rate, defined as a viable pregnancy beyond 12 weeks of gestation. The non-inferiority margin was -10%. Analysis was performed by both per-protocol and intention-to-treat approaches.
Women in the immediate group were slightly younger than those in the delayed group (30.0 (27.7-33.5) versus 31.0 (28.5-34.2), respectively, P = 0.006), but the proportion of women ≤35 years was comparable between the two groups (308/362, 85.1% in the immediate group versus 303/362, 83.7% in the delayed group). The ongoing pregnancy rate was 49.6% (171/345) in the immediate group and 41.5% (142/342) in the delayed group (odds ratios 0.72, 95% CI 0.53-0.98, P = 0.034). The live birth rate was 47.2% (163/345) in the immediate group and 37.7% (129/342) in the delayed group (odds ratios 0.68, 95% CI 0.50-0.92, P = 0.012). The miscarriage rate was 13.2% (26 of 197 women) in the immediate group and 24.2% (43 of 178 women) in the delayed group (odds ratios 2.10; 95% CI 1.23-3.58, P = 0.006). The multivariable logistic regression, which adjusted for potential confounding factors including maternal age, number of oocytes retrieved, embryo stage at transfer, number of transferred embryos/blastocysts, reasons for FET, ovarian stimulation protocol and trigger type, demonstrated that the ongoing pregnancy rate was still higher in the immediate group.
LIMITATIONS, REASON FOR CAUTION: Despite randomisation, the two groups still differed slightly in the age of the women at IVF. The study was powered to consider the ongoing pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the observed differences between the treatment groups in terms of live birth rate should, therefore, be made with caution.
Immediate FET following a stimulated IVF cycle had a significantly higher ongoing pregnancy and live birth rate than delayed FET. The findings of this study support immediate FET after a stimulated IVF cycle.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was used and no competing interests were declared.
ClinicalTials.gov identifier: NCT03201783.
28 June 2017.
DATE OF FIRST PATIENT’S ENROLMENT: 9 August 2017.
在刺激体外受精（IVF）周期后，立即进行与延迟冷冻胚胎移植（FET）相比，持续妊娠率是否存在差异？
与延迟 FET 相比，刺激 IVF 周期后立即进行 FET 可显著提高持续妊娠率和活产率。
胚胎冷冻保存是 IVF 中越来越重要的一部分，但仍然没有很好的证据可以建议在刺激 IVF 周期后何时进行 FET。所有已发表的研究都是回顾性的，结果相互矛盾。
研究设计、规模、持续时间：这是在中国两家生育中心于 2017 年 8 月 9 日至 2018 年 12 月 5 日期间进行的一项 724 例不孕女性的随机对照非劣效性试验。
参与者/材料、设置、方法：在接受刺激 IVF 周期后的第一次 FET 周期中，将不孕女性随机分为（1）立即组，其中 FET 在刺激 IVF 周期后的第一个月经周期进行（n=362），或（2）延迟组，其中 FET 在刺激 IVF 周期后的第二个或以后的月经周期进行（n=362）。所有 FET 周期均在激素替代周期中进行。随机序列使用在线随机化程序生成，块大小为 4。主要结局是持续妊娠率，定义为超过 12 周妊娠的可存活妊娠。非劣效性边界为-10%。通过意向治疗和方案进行分析。
立即组的女性比延迟组的女性略年轻（分别为 30.0（27.7-33.5）与 31.0（28.5-34.2），P=0.006），但两组中≤35 岁的女性比例相似（308/362，立即组为 85.1%，延迟组为 303/362，83.7%）。立即组的持续妊娠率为 49.6%（171/345），延迟组为 41.5%（142/342）（优势比 0.72，95%CI 0.53-0.98，P=0.034）。活产率在立即组为 47.2%（163/345），在延迟组为 37.7%（129/342）（优势比 0.68，95%CI 0.50-0.92，P=0.012）。立即组的流产率为 13.2%（26/197 名女性），延迟组为 24.2%（43/178 名女性）（优势比 2.10；95%CI 1.23-3.58，P=0.006）。多变量逻辑回归，调整了潜在混杂因素，包括母亲年龄、取卵数、移植时胚胎阶段、移植胚胎/囊胚数、FET 原因、卵巢刺激方案和触发类型，表明立即组的持续妊娠率仍然更高。
局限性、谨慎原因：尽管进行了随机分组，但两组女性在 IVF 时的年龄仍略有差异。该研究有能力考虑持续妊娠率，但活产率可能更具临床意义。因此，应该谨慎地得出关于治疗组在活产率方面观察到的差异的结论。
刺激 IVF 周期后立即进行 FET 与延迟 FET 相比，持续妊娠率和活产率显著更高。本研究结果支持刺激 IVF 周期后立即进行 FET。
研究资金/利益冲突：未使用外部资金，不存在竞争利益。
ClinicalTrials.gov 标识符：NCT03201783。
2017 年 6 月 28 日。
2017 年 8 月 9 日。
