STUDY QUESTION

研究问题

Do embryos displaying abnormal cleavage (ABNCL) up to Day 3 have compromised live birth rates and neonatal outcomes if full blastulation has been achieved prior to transfer?

如果在移植前已经实现完全囊胚形成，那么在第3天内出现异常卵裂（ABNCL）的胚胎是否会影响活产率和新生儿结局？

SUMMARY ANSWER

总结答案

ABNCL is associated with reduced full blastulation rates but does not impact live birth rates and neonatal outcomes once full blastulation has been achieved.

ABNCL与完全囊胚形成率降低有关。然而一旦达到形成囊胚，就不会影响活产率和新生儿结果。

WHAT IS KNOWN ALREADY?

现有研究证据

It is widely accepted that ABNCL is associated with reduced implantation rates of embryos when transferred at the cleavage stage. However, evidence is scarce in the literature reporting birth outcomes from blastocysts arising from ABNCL embryos, likely because they are ranked low priority for transfer.

人们普遍认为，ABNCL与卵裂期胚胎植入率降低有关。然而，有关来自ABNCL胚胎的囊胚出生结果的文献证据很少，这很可能是因为它们在移植时被排在较低的优先级。

STUDY DESIGN, SIZE, DURATION

研究设计、规模、持续时间

This retrospective cohort study included 1562 consecutive autologous in vitro fertilization cycles (maternal age 35.1 ± 4.7 years) performed at Fertility North, Australia between January 2017 and June 2022. Fresh transfers were performed on Day 3 or 5, with remaining embryos cultured up to Day 6 before vitrification. A total of 6019 embryos were subject to blastocyst culture, and a subset of 664 resulting frozen blastocysts was included for live birth and neonatal outcome analyses following single transfers.

这项回顾性队列研究包括2017年1月至2022年6月在澳大利亚北部生育中心进行的1562个IVF-ET周期（母亲年龄35.1±4.7岁）。新鲜胚胎移植在取卵后第3天或第5天进行，剩余胚胎在玻璃化冷冻前培养至第6天。总共对6019个胚胎进行了囊胚培养，并对664个冷冻囊胚中的一组进行单次移植后的活产和新生儿结果分析。

PARTICIPANTS/MATERIALS, SETTING, METHODS

参与者/材料、设置、方法

ABNCL events were annotated from the first mitotic division up to Day 3, including direct cleavage (DC), reverse cleavage (RC) and <6 intercellular contact points at the 4-cell stage (<6ICCP). For DC and RC in combination, the ratios of affected blastomeres over the total number of all blastomeres up to Day 3 were also recorded. All pregnancies were followed up until birth with gestational age, birthweight, and sex of the baby being recorded.

ABNCL事件的观察时间从第一次有丝分裂开始，一直持续到第三天。观察内容包括直接分裂（DC）、反向分裂（RC）和4细胞阶段的<6个细胞间接触点（<6ICCP）。对于DC和RC的组合，我们还记录了受影响的胚胎细胞数与所有胚胎细胞总数的比例，直到第三天。所有妊娠都进行了随访，直到分娩，记录了孕龄、出生体重和婴儿的性别。

MAIN RESULTS AND THE ROLE OF CHANCE

主要结果和偶然性作用

Full blastulation rates for embryos showing DC (19.5%), RC (41.7%), <6ICCP (58.8%), and mixed (≥2) ABNCL types (26.4%) were lower than the rates for those without ABNCL (67.2%, P < 0.01 respectively). Subgroup analysis showed declining full blastulation rates with increasing ratios of combined DC/RC affected blastomeres over all blastomeres up to the 8-cell stage (66.2% when 0 affected, 47.0% when 0.25 affected, 27.4% when 0.5 affected, 14.5% when 0.75 affected, and 7.7% when all affected, P < 0.01). However, once full blastulation had been achieved, no difference was detected between DC, RC, <6ICCP, and no ABNCL blastocysts following single frozen transfers in subsequent live birth rates (25.9%, 33.0%, 36.0% versus 30.8%, P > 0.05, respectively), gestational age (38.7 ± 1.6, 38.5 ± 1.2, 38.3 ± 3.5 versus 38.5 ± 1.8 weeks, P > 0.05, respectively) and birthweight (3343.0 ± 649.1, 3378.2 ± 538.4, 3352.6 ± 841.3 versus 3313.9 ± 509.6 g, P > 0.05, respectively). Multiple regression (logistic or linear as appropriate) confirmed no differences in all of the above measures after accounting for potential confounders.

显示 DC（19.5%）、RC（41.7%）、<6ICCP（58.8%）和混合（≥2种）ABNCL 类型（26.4%）的胚胎的完全囊胚形成率低于无 ABNCL 的胚胎（67.2%，P < 0.01）。亚组分析显示，随着 DC/RC 联合受累的胚泡占8 细胞期所有胚泡比例增加，完全囊胚形成率下降（0 受累时为 66.2%，0.25 受累时为 47.0%，0.5 受累时为 27.4%，0.75 受累时为 14.5%，全部受累时为 7.7%，P < 0.01）。然而，一旦形成完全囊胚，单次冷冻胚胎移植后，DC、RC、<6ICCP 和无 ABNCL囊胚之间的后续活产率（分别为 25.9%、33.0%、36.0% 和 30.8%，P > 0.05）孕周（分别为 38.7 ± 1.6、38.5 ± 1.2、38.3 ± 3.5 和 38.5 ± 1.8 周，P > 0.05）和出生体重（分别为3343.0 ± 649.1、3378.2 ± 538.4、3352.6 ± 841.3 和 3313.9 ± 509.6 克，P > 0.05）均无差异。多元回归（视情况而定逻辑或线性）证实，在考虑潜在混杂因素后，上述所有指标均无差异。

LIMITATIONS, REASONS FOR CAUTION

局限性、谨慎原因

Our study is limited by its retrospective nature, making it impossible to control every known or unknown confounder. Embryos in our dataset, being surplus after selection for fresh transfer, may not represent the general embryo population.

我们的研究具有回顾性，因此无法控制所有已知或未知的混杂因素。我们数据集中的胚胎是在选择新鲜胚胎移植后剩余的胚胎，可能无法代表一般胚胎群体。

WIDER IMPLICATIONS OF THE FINDINGS

研究结果的广泛意义

Our findings highlight the incremental impact of ABNCL, depending on the ratio of affected blastomeres up to Day 3, on subsequent full blastulation. The reassuring live birth and neonatal outcomes of ABNCL blastocysts imply a potential self-correction mechanism among those embryos reaching the blastocyst stage, which provides valuable guidance for clinical practice and patient counseling.

我们的研究结果强调了ABNCL对随后的完全囊胚形成的影响，这取决于第3天受影响的胚泡的比例。ABNCL胚泡囊胚的活产率和新生儿结果令人放心，这意味着在达到胚泡阶段的胚胎存在潜在自我矫正机制，这为临床实践和患者咨询提供了宝贵的指导。

参考文献：

Tammy Lee, Kelli Peirce, Jay Natalwala, Vincent Chapple, Peter J Mark, Katherine Sanders, Yanhe Liu, Abnormal cleavage up to Day 3 does not compromise live birth and neonatal outcomes of embryos that have achieved full blastulation: a retrospective cohort study, Human Reproduction, Volume 39, Issue 5, May 2024, Pages 955–962, https://doi.org/10.1093/humrep/deae062