Morphokinetic parameter S2 predicts early embryo developmental potential and associated metabolic pathways.

IF 2.7 3区医学 Q2 GENETICS & HEREDITY

Journal of Assisted Reproduction and Genetics Pub Date : 2025-10-13 DOI:10.1007/s10815-025-03709-w

Xuehua Chen, Huanhua Chen, Guiting Huang, Ruoyun Lin, Hong Zhou, Xiaojing Fan, Zhulian Wu, Kongrong Xu, Jinhui Shu, Caizhu Wang

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引用次数: 0

Abstract

Purpose: The aim of this study was to determine the predictive value of the morphokinetic parameter S2 (the duration between cleavage from the 3-cell to 4-cell stage in the absence of direct cleavage) for early embryo developmental potential, establish its optimal cutoff value, and explore associated metabolic pathways.

Methods: This prospective study analyzed 662 embryos from 65 patients (September 2023-October 2024) which were cultured in time-lapse incubators. S2's predictive value for blastocyst formation/quality was assessed, with a cutoff value calculated through receiver operating characteristic (ROC) analysis. Subsequently, metabolomic profiling of spent culture media (SCM) from 20 patients was stratified by S2 cutoff using liquid chromatography-tandem mass spectrometry (LC-MS).

Results: Among 662 embryos cultured in time-lapse incubators, 474 were analyzed to evaluate the association between S2 and developmental potential. Significant differences in S2 values were observed between the blastocyst formation vs. non-formation groups and high- vs. low-quality blastocyst groups (both median 0.5 vs. 0.8, P < 0.05). Logistic regression analysis showed that S2 predicted available blastocyst formation with an area under the curve (AUC) of 0.622 (95%CI = 0.559-0.685, P < 0.001) and blastocyst quality with an AUC of 0.645 (95% CI = 0.569-0.722), with an optimal cutoff of 0.7 h. Based on this cutoff, the day 3 (D3) SCM from 20 patients was divided into two groups (S2 < 0.7 and S2 ≥ 0.7) for metabolomic analysis. The results revealed 98 differentially expressed metabolites (59 upregulated and 39 downregulated), enriched in protein digestion/ absorption, aminoacyl-tRNA biosynthesis, fatty acid metabolism, central carbon metabolism in cancer, and glutamatergic synapse.

Conclusions: The S2 parameter (optimal cutoff = 0.70 h) shows moderate predictive capacity for embryo developmental potential (AUC = 0.64), with its regulation by specific metabolic pathways, supporting its inclusion in future multifactorial embryo evaluation models.

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形态动力学参数S2预测早期胚胎发育潜能和相关代谢途径。

目的：本研究旨在确定形态动力学参数S2（在无直接卵裂的情况下，从3细胞阶段到4细胞阶段的卵裂间隔时间）对早期胚胎发育潜力的预测价值，确定其最佳截断值，并探索相关代谢途径。方法：本前瞻性研究分析了65例患者（2023年9月- 2024年10月）在延时培养箱中培养的662个胚胎。评估S2对囊胚形成/质量的预测价值，并通过受试者工作特征（ROC）分析计算截止值。随后，使用液相色谱-串联质谱（LC-MS）对20例患者的废培养基（SCM）进行S2切断分层。结果：在662个延时培养的胚胎中，分析了474个胚胎S2与发育潜能的关系。S2值在囊胚形成组与未形成组、高质量囊胚质量组与低质量囊胚质量组之间存在显著差异（中位数分别为0.5和0.8，P）。结论：S2参数（最佳截止时间= 0.70 h）对胚胎发育潜力具有中等预测能力（AUC = 0.64），受特定代谢途径的调控，支持将其纳入未来的多因子胚胎评估模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Assisted Reproduction and Genetics 医学-妇产科学

CiteScore

5.70

自引率

9.70%

发文量

286

审稿时长

1 months

期刊介绍： The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.