Objectives To evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and perinatal complications is increased compared with cleavage stage embryo transfers during in vitro fertilisation (IVF) treatment. Design Multicentre randomised controlled trial. Setting 21 hospitals and clinics in the Netherlands, 18 August 2018 to 17 December 2021. Participants 1202 women with at least four embryos available on day 2 after oocyte retrieval were randomly assigned to either blastocyst stage embryo transfer (n=603) or cleavage stage embryo transfer (n=599). Interventions In the blastocyst group and cleavage group, embryo transfers were performed on day 5 and day 3, respectively, after oocyte retrieval, followed by cryopreservation of surplus embryos. Analysis was on an intention-to-treat basis, with secondary analyses as per protocol. Main outcome measures The primary outcome was the cumulative live birth rate per oocyte retrieval, including results of all frozen-thawed embryo transfers within a year after randomisation. Secondary outcomes included cumulative rates of pregnancy, pregnancy loss, and live birth after fresh embryo transfer, number of embryo transfers needed, number of frozen embryos, and obstetric and perinatal outcomes. Results The cumulative live birth rate did not differ between the blastocyst group and cleavage group (58.9% (355 of 603) v 58.4% (350 of 599; risk ratio 1.01, 95% confidence interval (CI) 0.84 to 1.22). The blastocyst group showed a higher live birth rate after fresh embryo transfer (1.26, 1.00 to 1.58), lower cumulative pregnancy loss rate (0.68, 0.51 to 0.89), and lower mean number of embryo transfers needed to result in a live birth (1.55 v 1.82; P<0.001). The incidence of moderate preterm birth (32 to <37 weeks) in singletons was higher in the blastocyst group (1.87, 1.05 to 3.34). Conclusion Blastocyst stage embryo transfers resulted in a similar cumulative live birth rate to cleavage stage embryo transfers in women with at least four embryos available during IVF treatment. Trial registration International Clinical Trial Registry Platform NTR7034. Restricted access to the study data can be arranged on request to the corresponding author. Written proposals will be assessed by the ToF study group. A data sharing agreement including terms and conditions for authorship and publication will need to be signed before data are available.

中文翻译：

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预后良好的女性体外受精期间囊胚与卵裂期胚胎移植政策的累积活产率：多中心随机对照试验


目的 评估囊胚期胚胎移植（包括新鲜移植和冻融移植）是否能提高卵母细胞取出后的累积活产率，以及与体外受精过程中卵裂期胚胎移植相比，产科和围产期并发症的风险是否增加。体外受精）治疗。设计多中心随机对照试验。 2018 年 8 月 18 日至 2021 年 12 月 17 日，在荷兰 21 家医院和诊所进行研究。参与者 1202 名在卵母细胞取出后第 2 天至少有四个胚胎的女性被随机分配到囊胚期胚胎移植 (n=603) 或卵裂期胚胎转移（n=599）。干预措施囊胚组和卵裂组分别在卵母细胞取出后第5天和第3天进行胚胎移植，然后冷冻保存剩余胚胎。分析以意向治疗为基础，并根据方案进行二次分析。主要结果指标 主要结果是每次取卵的累积活产率，包括随机分组后一年内所有冻融胚胎移植的结果。次要结局包括新鲜胚胎移植后的累积妊娠率、流产率和活产率、所需胚胎移植数量、冷冻胚胎数量以及产科和围产期结局。结果 囊胚组和卵裂组的累积活产率没有差异（58.9%（603 例中的 355 例）v 58.4%（599 例中的 350 例；风险比 1.01，95% 置信区间 (CI) 0.84 至 1.22）。新鲜胚胎移植后的活产率较高（1.26、1.00至1.58），累积流产率较低（0.68、0.51至0.89），并且导致活产所需的胚胎移植平均数量较低（1.55 v 1.82；P<0.001）。单胎中度早产（32 至 <37 周）的发生率在囊胚组中较高（1.87、1.05 至 3.34）。结论 对于在 IVF 治疗期间至少有四个胚胎的女性，囊胚期胚胎移植与卵裂期胚胎移植的累积活产率相似。试验注册国际临床试验注册平台NTR7034。可以根据通讯作者的要求安排对研究数据的限制访问。书面提案将由 ToF 研究小组进行评估。在数据可用之前，需要签署一份数据共享协议，包括作者身份和出版的条款和条件。