The expression of cytokines IFN-γ, IL-4, IL-17A, and TGF-β1 in peripheral blood and follicular fluid of patients testing positive for anti-thyroid autoantibodies and its influence on in vitro fertilization and embryo transfer pregnancy outcomes

Abstract

The aim of this work was to study the expression of the cytokines IFN-γ, IL-4, IL-17 A, and TGF-β1 in peripheral blood and follicular fluid (FF) of patients positive for antithyroid autoantibodies (ATA⁺) with normal thyroid gland function and the influence of these autoantibodies on in vitro fertilization and embryo transfer (IVF-ET) pregnancy outcomes. Nineteen patients were in the ATA⁺ group, and 27 patients tested negative for anti-thyroid autoantibody (ATA⁻). Blood samples were drawn from the two groups of patients on the oocyte retrieval day and the 5th and 14th days of transplantation; in addition, FF was extracted on the oocyte retrieval day from both groups of patients and tested through enzyme-linked immunosorbent assay (ELISA) for IFN-γ, IL-4, IL-17 A, and TGF-β1. For the ATA⁺ group, the concentration of IFN-γ increased whereas the concentration of TGF-β1 decreased in peripheral blood on the oocyte retrieval day (p < .05); the concentration of IL-4 decreased in peripheral blood on the 5th and 14th days of transplantation for the ATA⁺ group (p < .05); further, the concentration of IL-17 A increased whereas that of TGF-β1 decreased in FF (p < .05). The ratio of IL-17 A/TGF-β1 in the ATA⁺ group significantly increased in FF and peripheral blood on the oocyte retrieval day and the 14th day of transplantation (p < .05). The ratio of IL-17 A/TGF-β1 in FF of the pregnant patients was significantly lower than in the non-pregnant patients (p < .05). The findings suggested that the ratio between pro-inflammatory and anti-inflammatory cytokines was adversely affected; therefore, adverse pregnancy outcomes of patients with ATA⁺ undergoing IVF-ET treatment may be attributed to immunological mechanisms.

摘要

这项工作的目的是研究甲状腺功能正常的抗甲状腺自身抗体阳性（ATA +）患者细胞因子IFN-γ, IL-4, IL-17A和TGF-b1在外周血和卵泡液（FF）中的表达, 以及探究这些自身抗体对体外受精和胚胎移植（IVF-ET）妊娠结局的影响。ATA +组中共计19名患者, 对照组为检测为抗甲状腺自身抗体（ATA-）阴性的27位患者。在取卵日, 移植后的第5天和第14天从两组患者中抽取血样, 另外, 在两组患者的取卵日提取卵泡液, 并通过酶联免疫吸附测定（ELISA）测量IFN-γ, IL-4, IL-17A和TGF-β1的表达水平。ATA +组在取卵日IFN-γ浓度增加, 外周血中TGF-β1浓度降低（p <.05）；ATA +组移植后第5天和第14天外周血中IL-4浓度降低（p <.05）; 在卵泡液中, IL-17A浓度增加而TGF-β1浓度降低（p <.05）。 在取卵日和移植后第14天, ATA +组卵泡液和外周血中IL-17A / TGF-β1的比例显著增加（p <.05）。 妊娠患者卵泡液IL-17 A / TGF-β1的比例显著低于非妊娠患者（p <.05）。 研究结果表明, ATA +患者促炎细胞因子和抗炎细胞因子比例受到了不利影响; 接受IVF-ET治疗的ATA +患者的不良妊娠结局可归因于免疫机制。

Keywords:

• Follicular fluid
• IFN-γ
• IL-4
• IL-17A
• TGF-β1

Acknowledgements

The authors are sincerely grateful for the help and support of teachers and colleagues at the reproductive medicine center in Yantai Yuhuangding Hospital. There are no relevant conflicts of interest.

Ethical approval

The study was approved by the Department of Reproductive Medicine of Yantai Yuhuangding Hospital ethics committee. Oral and written information was given to all potential patient representatives and written consent was collected before enrollment.

Disclosure statement

No potential conflict of interest was reported by the authors.