Objective

Repeated implantation failure (RIF) has been shown related to maternal immune imbalance. Many studies suggested that prednisone promoted the Th17/Treg balance shift to the direction of immune tolerance. Our study aimed to evaluate the role of prednisone in Th17/Treg balance and pregnancy outcome in RIF patients.

Study design and main outcome measures

Peripheral blood of healthy fertile controls and RIF patients were collected at the late proliferation phase. The population of Treg and Th17 cells, the expression of Foxp3 and RORC mRNA and the concentration of IL-17A, IL-23 and IL-10 were detected by flow cytometry, qRT-PCR and enzyme-linked immunosorbent assay. RIF patients were given oral prednisone 10 mg daily from the late proliferation phase of the cycle before FET. After one month of treatment, the above immune indicators were tested, and natural cycle frozen embryo transfer was performed.

Results

The Treg cells proportion and IL-10 concentration in peripheral blood of RIF patients was lower than that of NF group, while the proportion of Th17 cells and concentration of proinflammatory cytokine were significantly higher. After prednisone treatment, the indicators related to immune tolerance increased significantly. Five out of 19 RIF patients were successful pregnancy after FET, in which, one had an early miscarriage and four live births. No pregnancy complications and fetal abnormalities were observed.

Conclusions

We report the beneficial effect of prednisone on RIF patients. The underlying mechanism may attribute to shift the Treg/Th17 immune balance to a Treg bias, and enhance embryo implantation, ultimately improve pregnancy outcomes.

中文翻译：

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泼尼松通过增强调节性 T 细胞偏差改善重复植入失败的妊娠结局

客观的

重复植入失败 (RIF) 已被证明与母体免疫失衡有关。许多研究表明，泼尼松促进了Th17/Treg平衡向免疫耐受方向转移。我们的研究旨在评估泼尼松在 RIF 患者 Th17/Treg 平衡和妊娠结局中的作用。

研究设计和主要结局指标

在增殖后期收集健康可育对照和 RIF 患者的外周血。采用流式细胞术、qRT-PCR和酶联免疫吸附法检测Treg和Th17细胞数量、Foxp3和RORC mRNA的表达以及IL-17A、IL-23和IL-10的浓度。RIF 患者在 FET 前从周期的晚期增殖阶段开始每天口服 10 mg 泼尼松。治疗1个月后，检测上述免疫指标，进行自然周期冷冻胚胎移植。

结果

RIF患者外周血Treg细胞比例和IL-10浓度低于NF组，而Th17细胞比例和促炎细胞因子浓度显着升高。泼尼松治疗后，免疫耐受相关指标明显升高。19 名 RIF 患者中有 5 名在 FET 后成功怀孕，其中 1 名早产，4 名活产。未观察到妊娠并发症和胎儿异常。

结论

我们报告了泼尼松对 RIF 患者的有益作用。潜在机制可能归因于将 Treg/Th17 免疫平衡转变为 Treg 偏向，并增强胚胎着床，最终改善妊娠结局。