Center for Reproductive Medicine, Shandong University, Jinan, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China.
Front Endocrinol (Lausanne). 2022 Jul 11;13:949123. doi: 10.3389/fendo.2022.949123. eCollection 2022.
Serum cytokine profile and T helper (Th)1/Th2 cell balance are related to the success of embryo implantation, although not yet firmly linked to recurrent implantation failure (RIF), a repeated failure to achieve clinical pregnancy following multiple high-quality embryo transfer. In this prospective study, comprehensive bioinfomatic analysis and logistic regression analysis were used to compare the serum cytokine profiles of 41 RIF patients with those of 29 subjects with first-cycle successful pregnancy in the mid-luteal phase and to assess the alterations of cytokine profiles in patients with clinical pregnancy at five weeks post-transplantation. We found several elevated pro-inflammatory cytokines, decreased anti-inflammatory cytokines, and increased Th1/Th2 cytokine ratios in RIF patients compared to control subjects. Specifically, the receiver operating characteristic (ROC) curve generated using multiple indicators provides a high predictive value for diagnosing RIF (area under the curve [AUC] = 0.94, 95% confidence interval [CI] 0.87-1.00, < 0.0001), with a sensitivity of 96.55% and a specificity of 87.50%. Meanwhile, at five weeks post-transplantation, patients in both groups diagnosed with clinical pregnancy exhibited increased levels of several cytokines compared with pre-pregnancy levels, and a gradual shift in Th1/Th2 balance toward Th2. These findings suggest that inflammatory serum cytokines and the predominance of Th1 cells likely contribute to RIF and possibly reflect the immune environment at the maternal-fetal interface, suggesting their value as outcome indicators in assisted reproductive therapy.
血清细胞因子谱和辅助性 T 细胞（Th）1/Th2 细胞平衡与胚胎着床成功有关，尽管尚未与反复着床失败（RIF）明确相关，即多次进行高质量胚胎移植后仍无法获得临床妊娠。在这项前瞻性研究中，我们使用综合生物信息分析和逻辑回归分析比较了 41 例 RIF 患者和 29 例在黄体中期首次周期成功妊娠的受试者的血清细胞因子谱，并评估了移植后 5 周时临床妊娠患者细胞因子谱的变化。与对照组相比，我们发现 RIF 患者存在几种升高的促炎细胞因子、降低的抗炎细胞因子和升高的 Th1/Th2 细胞因子比值。具体而言，使用多个指标生成的受试者工作特征（ROC）曲线对 RIF 的诊断具有较高的预测价值（曲线下面积 [AUC] = 0.94，95%置信区间 [CI] 0.87-1.00，<0.0001），灵敏度为 96.55%，特异性为 87.50%。同时，在移植后 5 周，两组临床妊娠患者的几种细胞因子水平均高于妊娠前水平，Th1/Th2 平衡向 Th2 倾斜。这些发现表明，炎症性血清细胞因子和 Th1 细胞优势可能导致 RIF，可能反映了母体-胎儿界面的免疫环境，表明它们作为辅助生殖治疗结局指标的价值。
