一项35523例双胚胎新鲜移植的全国队列分析！

Study question

研究问题

Should a national embryo transfer (ET) policy designed in the era of cleavage stage transfers be adapted for blastocyst transfers to avoid twin pregnancies?

卵裂期胚胎移植时代制定的全国性胚胎移植政策是否应该针对囊胚移植进行调整，以避免双胎妊娠？

Summary answer

结论

Double embryo transfer policy results in unacceptable high twin rates at all ages and treatment ranks which is significantly more pronounced after double blastocyst transfer.

双胚胎移植政策导致了在所有年龄和治疗级别中难以接受的高双胎妊娠率，且在双囊胚移植后更加明显。

What is known already

已知情况

In 2003, authorities in Belgium implemented a law to reduce multiple pregnancies after ART by tailoring ET policies based on age, embryo quality, and cycle rank. A choice between SET or Double Embryo Transfer (DET) depending on embryo quality is allowed in the second cycle for patients under 36y with SET being mandatory with top quality embryos. DET is allowed as of the first cycle for patients aged 36y or more regardless of embryo quality. Blastocyst transfer results in significantly higher live birth rates, implying an increased risk of multiple pregnancies after multiple blastocyst transfers.

2003年，比利时当局颁布了一项法律，根据年龄、胚胎质量和周期数制定移植政策，以减少ART实施后的多胎妊娠。36岁以下的患者在第二周期才可以根据胚胎质量选择单胚胎移植（SET）或双胚胎移植(DET)；对于年龄≥36岁的患者，无论胚胎质量如何，从第一个周期开始都允许进行DET。囊胚移植后显著升高的活产率，但是也意味着多囊胚移植后多胎妊娠的风险也增加。

Study design, size, duration

研究设计、规模、持续时间

A analysis of 35,523 double embryo fresh transfer cycles over a period of 10 years from 2012 to 2021 from the Belgian national BELRAP (Belgian Registry on Assisted Procreation) registry was performed. The study included 26,930 double cleavage stage transfers (DET-CL) and 8,593 double blastocyst transfers (DET-BL).

对2012—2021年10年期间比利时国家BELRAP(比利时辅助生殖登记系统，Belgian Registry on Assisted reproductive)登记系统中的35,523个双胚胎新鲜移植周期进行了分析。本研究包括26930例双卵裂期移植(DET-CL)和8593例双囊胚移植(DET-BL)。

Participants/materials, setting, methods

参与者/材料、环境、方法

The primary outcomes were delivery rate (DR) per transfer and twin delivery rate (TDR). DR includes all deliveries with a least one live birth per transfer; the TDR includes all twin deliveries as a proportion of all deliveries. For analysis, the data were categorized into the following age groups: 18-25 years, 26-29 years, 30-35 years, 36-39 years and 40-45 years. Cycle ranks were categorized as follows: rank 1, rank 2 and cycle 3- ≥ 6.

主要结局指标为单个移植周期的分娩率(delivery rate，DR)和双胎分娩率(twin delivery rate，TDR)。DR指单次移植至少有1胎活产的所有分娩数；TDR包括所有双胎分娩数占总的分娩例数的比例。为进行分析，按年龄分组：18-25岁组、26-29岁组、30-35岁组、36-39岁组和40-45岁组。按周期分为：第1周期，第2周期和第3-6周期。

Main results and the role of chance

主要结果和意义

For all age groups and cycle ranks, delivery rate per transfer and twin delivery rate per delivery were significantly higher after DET-Bl compared to DET-Cl (26.0% versus 19.9%; p < 0.0001 and 28.0% versus 20.6%; p < 0.0001, respectively). In the age groups 26-29 years, 30-35 years and 36-39 years, a significantly higher TDR was observed in DET-Bl compared to DET-Cl, respectively (34.4% versus 24.2%, p = 0.0005; 33.5% versus 24.9%, p < 0.0001 and 24.3% versus 17.3%, p = 0.0002). TDR after DET-Bl was significantly lower in women aged 40-45 years compared to all other age groups, 18-25 years, 26-29 years, 30-35 years and 36-39 years, respectively (11.3% versus 32.8%, p < 0.0001; 11.3% versus 34.4%; p < 0.0001; 11.3% versus 33.5%; p < 0.0001 and 11.3% versus 24.3%; p < 0.0001), respectively).

DR was significantly lower in cycle rank 1 compared to cycle rank 2 (22.5% versus 25.5%; p < 0.0001) and compared to cycle rank 3 - > 6 rank 1 and (22.5% versus 27.1%; p < 0.0001). After DET-Bl, a significantly lower TDR was observed in cycle rank 1 compared to cycle rank 2 (15.6% versus 30.0%; p < 0.0001) and compared to cycle rank 3 - > 6 (15.6% versus 29.7%; p < 0.0001).

在所有年龄组和周期级别中，DET-BL组的单周期移植的分娩率和双胎分娩率显著高于DET-CL组(分娩率为26.0%＞19.9%，p＜0.0001；双胎分娩率为28.0%＞20.6%，p＜0.0001)。在26-29岁，30-35岁和36-39岁年龄组中，DET-BL的TDR显著高于DET-CL(分别是34.4%＞24.2%，p= 0.0005;33.5%＞24.9%，p＜0.0001；24.3%＞17.3%，p=0.0002)。40-45岁组女性的DET-BL后的TDR显著低于所有其他年龄组，与18-25岁组相比（11.3%＜32.8%，p＜0.0001），与26-29岁组（11.3%＜34.4%，p＜0.0001），与30-35岁组（11.3% ＜33.5%，p＜0.0001），与36-39岁组(11.3%＜24.3%，p＜0.0001)。

第1周期DR显著低于第2周期(22.5%＜5.5%，p＜0.0001)，与第3-6周期相比(22.5%＜27.1%，p＜0.0001)。在DET-BL后，第1周期与第2周期相比(15.6%＜30.0%，p＜0.0001)，和周期3-＞6相比(15.6%＜29.7%，p＜0.0001),TDR显著降低。

Limitations, reasons for caution

局限性及原因

The retrospective design is a limitation. Outcomes might be influenced by clinical and laboratory improvements over the years. The registry does not collect embryo quality data making it impossible to assess the effect of embryo quality on the ET policy and outcome.

回顾性研究设计的局限性，且结局可能受到多年来临床和实验室改善的影响。该登记系统不收集胚胎质量相关数据，因此无法评估胚胎质量对ET政策和结局的影响。

Wider implications of the findings

研究结果的更广泛意义

This data indicates that a double blastocyst transfer should only be considered from the age of 40 onwards. In the first cycle, regardless of age, we observe a significantly lower twin delivery rate, suggesting that a double ET is performed when only poor-quality blastocysts are available.

这些数据表明，只有在40岁及以上的年龄段才应考虑进行双胚胎移植。在第一次周期中，无论年龄如何，我们观察到双胎的分娩率显著较低，这表明只有当只有质量较差的囊胚可用时才进行双胚胎移植。

参考文献：

I De Croo, A Delbaere, S Lie Fong, L Henry, A Van de Vijver, E Anagnostou, C Autin, M De Vos, D Stoop, P-763 Twin births in Belgium: a national cohort analysis of 35 523 double fresh embryo transfers between 2012 and 2021, Human Reproduction, Volume 39, Issue Supplement_1, July 2024, deae108.040, https://doi.org/10.1093/humrep/deae108.040