To assess whether morphokinetic features at the cleavage stage together with specific gene expression in cumulus cells (CCs) may be used to predict whether human embryos are able to achieve the expanded blastocyst stage on day 5. Eighty-one embryos were cultured using the Geri plus® time-lapse system. Twenty-seven embryos progressing to the expanded blastocyst stage (BL group) were compared with thirty-five embryos showing developmental arrest (AR group) and nineteen reaching the stage of early or not fully expanded blastocyst (nBL group). The analyzed morphokinetic variables were pronuclear appearance (tPNa), pronuclear fading (tPNf), and completion of cleavage to two, three, four, and eight cells (t2, t3, t4, and t8). CCs were analyzed by RT-qPCR for bone morphogenetic protein 15 (BMP15), cytochrome c oxidase subunit II (COXII), ATP synthase subunit 6 (MT-ATP6), connexin 43 (Cx43), and heme oxygenase-1 (HO-1). Embryos of BL group showed a significantly faster kinetic. BMP15, COXII, and MT-ATP6 mRNA expression was significantly higher in CCs of BL group embryos, whereas Cx43 and HO-1 mRNA levels were higher in AR group. Kinetic parameters and gene expression were not significantly different between either the BL and nBL groups or the AR and nBL groups. ROC curves showed that the most predictive cut-offs were t2 < 26.25 for morphokinetics and COXII > 0.3 for gene expression. Multivariable logistic regression analysis showed that morphokinetic variables and gene expression were both valuable, independent predictors of embryo development to expanded blastocyst. Our results suggest the possibility of developing integrated prediction models for early embryo selection at the cleavage stage.

中文翻译：

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卵裂期胚胎的形态动力学分析和卵丘细胞中特定基因表达的评估独立预测人类胚胎发育为扩大囊胚：一项初步研究。

为了评估卵裂阶段的形态动力学特征以及卵丘细胞 (CC) 中的特定基因表达是否可用于预测人类胚胎是否能够在第 5 天达到扩大的囊胚阶段。使用 Geri plus 培养了 81 个胚胎® 延时系统。将 27 个进展到囊胚扩张阶段（BL 组）的胚胎与 35 个发育停滞的胚胎（AR 组）和 19 个达到早期或未完全扩张囊胚阶段的胚胎（nBL 组）进行比较。分析的形态动力学变量是原核出现（tPNa）、原核褪色（tPNf）以及分裂成两个、三个、四个和八个细胞（t2、t3、t4和t8）的完成。通过 RT-qPCR 分析 CC 中的骨形态发生蛋白 15 (BMP15)、细胞色素 c 氧化酶亚基 II (COXII)、ATP 合酶亚基 6 (MT-ATP6)、连接蛋白 43 (Cx43) 和血红素加氧酶-1 (HO-1) ）。BL组的胚胎表现出明显更快的动力学。BL组胚胎的CC中BMP15、COXII和MT-ATP6 mRNA表达显着较高，而AR组胚胎中Cx43和HO-1 mRNA水平较高。BL 和 nBL 组或 AR 和 nBL 组之间的动力学参数和基因表达没有显着差异。ROC 曲线显示，对于形态动力学，最具预测性的截止值是 t2 < 26.25；对于基因表达，最具预测性的截止值是 t2 < 26.25，COXII > 0.3。多变量逻辑回归分析表明，形态动力学变量和基因表达都是胚胎发育至囊胚扩张的有价值的独立预测因子。我们的结果表明开发用于卵裂阶段早期胚胎选择的综合预测模型的可能性。