Wang Zheng, Liu Fang, Hu Kailun, Tian Tian, Yang Rui, Wang Yuanyuan, Li Rong, Mol Ben W, Qiao Jie
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
Hum Reprod. 2024 Dec 1;39(12):2702-2710. doi: 10.1093/humrep/deae245.
Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle?
In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle.
The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies. Evidence regarding the outcomes of transferring two cleavage-stage embryos in a single fresh cycle versus transferring one cleavage-stage embryo in one fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle is scarce.
STUDY DESIGN, SIZE, DURATION: This study is a retrospective matched cohort study, where data were gathered from the clinical database of women who underwent IVF treatment at the Reproductive Center of Peking University Third Hospital between January 2011 and December 2019, with follow-up extending until December 2021.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study group included cycles with a fresh cleavage-stage SET and a subsequent frozen-thawed blastocyst-stage SET (2xSET, N = 976). Fresh cleavage-stage DET was the control group (DET, N = 976). Included cycles were divided into subgroups based on age (≥38 years vs <38 years) and total number of utilizable (transferred or cryopreserved) embryos (=2 vs >2).
The duration of infertility, prevalence of unexplained infertility, and controlled ovarian stimulation regimes differed significantly between the two groups and were adjusted for in the further analysis. We observed a significant increase in clinical pregnancies (55.5% vs 42%, adjusted odds ratio (OR) 1.87 [1.55-2.26]) and live births (44.8% vs 34.5%, adjusted OR 1.63 [1.35-1.97]) in favor of the 2xSET group. The preterm birth rate was lower in the study group (adjusted OR 0.64 [0.42-0.96]). Neonatal birth weight of singletons was similar between the two groups (adjusted B 4.94 g [-84.5 to 94.4]). The beneficial effect on the live birth rate disappeared in cases where aged 38 years and older or when only two embryos were utilizable.
LIMITATIONS, REASONS FOR CAUTION: This study is limited by differences in baseline characteristics of the two groups. Analyzing two consecutive SETs at the cleavage stage was not feasible. Additionally, the homogeneous population limits generalizability to other ethnic groups, which should be considered when interpreting the results broadly.
We recommend a combination strategy for women under 38 years old and with more than two embryos available: transfer one cleavage-stage embryo in the fresh cycle, followed by one blastocyst-stage embryo in the subsequent frozen-thawed cycle. This strategy reduces the risk of blastocyst culture failure while maintaining a high success rate. It offers hope to families seeking additional children and avoids unnecessary embryo disposal.
STUDY FUNDING/COMPETING INTEREST(S): B.W.M. had received grants from NHMRC, Ferring, Merck, and Guerbet, consulting fees and stock options from ObsEva, is on the advisory board of ObsEva, and reports consultancy for Guerbet, none of which are in relation to the present manuscript. All other authors have no conflict of interest to declare.
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在单个新鲜周期移植两个卵裂期胚胎，与在新鲜周期移植一个卵裂期胚胎并在随后的冻融周期移植一个囊胚期胚胎相比，生育结局是否存在显著差异？
对于年龄小于38岁且有两个胚胎可供移植的女性，与在单个新鲜周期移植两个卵裂期胚胎相比，在新鲜周期移植一个卵裂期胚胎并在随后的冻融周期移植一个囊胚期胚胎可提高活产率并降低多胎活产率。
重复单胚胎移植（SET）策略已成为解决每个周期SET相关活产率降低问题的一种方法。有大量证据表明，重复SET后的累积活产率与双胚胎移植（DET）相当，同时显著降低了多胎妊娠的发生率。关于在单个新鲜周期移植两个卵裂期胚胎与在一个新鲜周期移植一个卵裂期胚胎并在随后的冻融周期移植一个囊胚期胚胎的结局的证据很少。
研究设计、规模、持续时间：本研究是一项回顾性匹配队列研究，数据来自2011年1月至2019年12月在北京大学第三医院生殖中心接受体外受精治疗的女性的临床数据库，随访至2021年12月。
参与者/材料、设置、方法：研究组包括新鲜卵裂期SET及随后冻融囊胚期SET的周期（2xSET，N = 976）。新鲜卵裂期DET为对照组（DET，N = 976）。纳入的周期根据年龄（≥38岁与<38岁）和可利用（移植或冷冻保存）胚胎总数（=2与>2）分为亚组。
两组之间不孕持续时间、不明原因不孕患病率和控制性卵巢刺激方案存在显著差异，并在进一步分析中进行了调整。我们观察到临床妊娠（55.5%对42%，调整优势比（OR）1.87 [1.55 - 2.26]）和活产（44.8%对34.5%，调整OR 1.63 [1.35 - 1.97]）显著增加，有利于2xSET组。研究组的早产率较低（调整OR 0.64 [0.42 - 0.96]）。两组单胎新生儿出生体重相似（调整B 4.94 g [-84.5至94.4]）。在38岁及以上或仅有两个可利用胚胎的情况下，对活产率的有益影响消失。
局限性、谨慎原因：本研究受两组基线特征差异的限制。分析两个连续的卵裂期SET不可行。此外，同质人群限制了对其他种族群体的普遍性，在广泛解释结果时应予以考虑。
我们建议对于年龄小于38岁且有两个以上胚胎可供移植的女性采用联合策略：在新鲜周期移植一个卵裂期胚胎，随后在冻融周期移植一个囊胚期胚胎。该策略降低了囊胚培养失败的风险，同时保持了高成功率。它为寻求更多孩子的家庭带来了希望，并避免了不必要的胚胎丢弃。
研究资金/利益冲突：B.W.M.曾获得NHMRC、辉凌、默克和吉比的资助，从ObsEva获得咨询费和股票期权，是ObsEva的顾问委员会成员，并报告为吉比提供咨询服务，所有这些均与本手稿无关。所有其他作者均无利益冲突声明。
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