Yi Hongliang, Yu Minyan, Dai Yu, Zhang Chanyu
Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China; The Reproductive Medical Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Center for Reproductive Medicine, The Affiliated Hospital of Nantong University, Nantong University, Nantong, China.
Eur J Obstet Gynecol Reprod Biol. 2025 Aug;312:114521. doi: 10.1016/j.ejogrb.2025.114521. Epub 2025 Jun 10.
Cytokines are important modulators secreted by many cell types that are involved in multiple biological functions, including human embryo development and implantation. Recently, several studies have confirmed that cytokines in most body fluids are predictive of pathophysiological processes. The purpose of this study was to explore whether the cytokines in the culture medium of single pre-implantation blastocysts could be used as non-invasive predictors of embryo implantation potential in frozen embryo transfer (FET) cycles. Seventy-eight culture medium samples were collected on day 5 from single blastocysts with different morphological scores between January 2023 and December 2023. All the blastocysts were cryopreserved through vitrification and transferred in subsequent FET cycles. The expression levels of cytokines were detected and measured using the Luminex's xMAP assay. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to analyze predictors. Cytokine candidates were subjected to multivariate logistic regression analysis to build a prediction model for blastocyst implantation potential. Among the 6 cytokines screened by LASSO regression analysis, there were marked differences in the expression levels of IL-18 and TRAIL between the groups with and without pregnancy. None of the clinical variables were identified as influencing the blastocyst implantation. The ROC curve analyses demonstrated that joint assessment of IL-18 and TRAIL levels has better predictive ability than each separately. The measurement of the specific cytokines in pre-implantation blastocyst culture medium may provide a new direction for research focusing on developing a precise, non-invasive method for predicting of embryo implantation potential with high sensitivity and specificity.
细胞因子是由多种细胞类型分泌的重要调节剂，参与多种生物学功能，包括人类胚胎发育和着床。最近，多项研究证实，大多数体液中的细胞因子可预测病理生理过程。本研究的目的是探讨单胚胎植入前囊胚培养基中的细胞因子是否可作为冷冻胚胎移植（FET）周期中胚胎着床潜力的非侵入性预测指标。在2023年1月至2023年12月期间，从形态学评分不同的单囊胚中于第5天收集了78份培养基样本。所有囊胚均通过玻璃化冷冻保存，并在随后的FET周期中进行移植。使用Luminex的xMAP检测法检测并测量细胞因子的表达水平。进行最小绝对收缩和选择算子（LASSO）回归分析以分析预测指标。对细胞因子候选物进行多因素逻辑回归分析，以建立囊胚着床潜力的预测模型。在LASSO回归分析筛选出的6种细胞因子中，妊娠组和未妊娠组之间IL-18和TRAIL的表达水平存在显著差异。未发现任何临床变量影响囊胚着床。ROC曲线分析表明，联合评估IL-18和TRAIL水平比单独评估具有更好的预测能力。测量植入前囊胚培养基中的特定细胞因子可能为开发一种精确、非侵入性的高灵敏度和特异性预测胚胎着床潜力的方法的研究提供新方向。
