OBJECTIVES To assess if segmental aneuploid embryos display unique morphokinetic patterns DESIGN: Retrospective multicentre study including a total of 7,027 embryos cultured between 2016 and 2021 in 3 European IVF centres. Analysis was performed on aggregated multicentre data and separately for data from each centre. Embryos with no more than 4 chromosomal alterations were considered in the analysis, resulting in 3,040 euploids, 2,818 whole-chromosome and 697 segmental aneuploids. Overall, the dataset contained 3,742 distinct euploid-segmental sibling pairs. SUBJECTS Standard morphokinetic features were annotated using various time-lapse systems. Blastocysts were subjected to comprehensive chromosomal screening via PGT-A. EXPOSURE Morphokinetic patterns were compared among euploid, whole-chromosome aneuploid, and segmental aneuploid embryos. MAIN OUTCOMES MEASURES Morphokinetic timings across groups were compared using statistical analysis and associations with cleavage features were assessed. Multi-centre and centre-specific multivariate logistic regression models were calibrated, and their predictive performance was evaluated on independent test set data using Area-Under-ROC curve metrics. RESULTS Segmental aneuploid embryos cleaved significantly slower than their euploid siblings across the first three cell cycles, with a delay reaching the blastocyst stage of development. Specifically during these early cell cycles, segmental aneuploid embryos were also shown to be significantly slower than their aneuploid siblings . A logistic model based on morphokinetic data from the multicentre dataset and regressed against type of aneuploidy displayed modest predictive performance on an independent test set (train-AUROC=0.58; test-AUROC=0.57). Predictive performance improved based on data from a single centre displaying adequate predictive performance on an independent test set from the same centre (train-AUROC=0.74; test-AUROC=0.64). However, the predictive value diminished when tested on data from other centres (AUROC=0.52-0.55). Finally, the presence of multinucleation and blastomere exclusion at cleavage stage, were associated with segmental aneuploidies. The combination of morphokinetic features and these discrete embryo morphological features into the logistic regression model (train AUROC=0.71) provided an improved prediction of segmental aneuploidy, supporting future investigations using more comprehensive annotation systems. CONCLUSION The developed predictive framework might help improve decision-making in PGT-A cycles, helping in the evaluation of embryos showing segmental aneuploidy and distinguishing which embryos are more likely to not have lethal uniform aneuploidies for transfer.

中文翻译：

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具有节段性非整倍体的人类胚胎表现出延迟的早期发育：多中心形态动力学分析。


目的 评估节段性非整倍体胚胎是否表现出独特的形态动力学模式设计： 回顾性多中心研究，包括 7,027 年至 2016 年间在 3 个欧洲 IVF 中心培养的共 2021 个胚胎。对聚合的多中心数据进行分析，并分别对来自每个中心的数据进行分析。分析考虑了不超过 4 个染色体改变的胚胎，产生了 3,040 个整倍体、2,818 个全染色体和 697 个节段非整倍体。总体而言，该数据集包含 3,742 个不同的整倍体节段兄弟姐妹对。受试者 使用各种延时系统注释标准形态动力学特征。通过 PGT-A 对囊胚进行全面的染色体筛选。暴露 比较了整倍体、全染色体非整倍体和节段非整倍体胚胎之间的形态动力学模式。主要结局指标 使用统计分析比较各组的形态动力学时间，并评估与卵裂特征的关联。校准多中心和中心特异性多变量 logistic 回归模型，并使用 Area-Under-ROC 曲线指标在独立测试集数据上评估其预测性能。结果 在前三个细胞周期中，节段性非整倍体胚胎的切割速度明显慢于其整倍体兄弟姐妹，延迟到达囊胚发育阶段。特别是在这些早期细胞周期中，节段性非整倍体胚胎也被证明比它们的非整倍体兄弟姐妹明显慢。基于来自多中心数据集的形态动力学数据并针对非整倍体类型进行回归的 logistic 模型在独立测试集上显示出适度的预测性能 （train-AUROC=0.58;test-AUROC=0.57）。 基于来自单个中心的数据，预测性能得到改善，这些数据在来自同一中心的独立测试集上显示出足够的预测性能 （train-AUROC=0.74;test-AUROC=0.64）。然而，当对来自其他中心的数据进行测试时，预测价值降低 （AUROC=0.52-0.55）。最后，卵裂期多核化和卵裂球排除的存在与节段性非整倍体有关。将形态动力学特征和这些离散的胚胎形态学特征结合到 logistic 回归模型 （train AUROC=0.71） 中，提供了对节段性非整倍体的改进预测，支持未来使用更全面的注释系统进行研究。结论 开发的预测框架可能有助于改善 PGT-A 周期的决策，有助于评估显示节段性非整倍体的胚胎，并区分哪些胚胎更有可能没有致命的均匀非整倍体进行移植。