子宫内膜异位症不孕患者发生自身免疫甲状腺炎的活性氧相关机制的研究

Endometriosis and autoimmune thyroiditis (AIT) are common diseases that cause infertility in women, the rate of oviposition, fertilization, high quality embryo rate, implantation rate, and clinical pregnancy rate were significantly reduced in patients with endometriosis after IVF-ET. The incidence of AIT increased in the patients with endometriosis, and AIT increased the rate of early pregnancy abortion. The presence of high level reactive oxygen (ROS) may promote the occurrence of AIT in patients with endometriosis, but there is no study to directly verify the association between the two diseases. Our previous studies suggest an increase in the incidence of AIT in patients with endometriosis and Recent study by applicant published on JAMA suggest that levothyroxine treatment in AIT patients with low risk of abortion does not improve the IVF-ET outcome of infertile women the incidence of endometriosis in patients with antithyroid antibody rate increased, two kinds of diseases are closely related in the pathogenesis of the disease, but there is no study exploring two kinds of disease mechanisms on contact. Endometriosis patients may have high levels of ROS promoting the onset of autoimmune thyroiditis. This study use a prospective research method for IVF patients with follicular fluid and peripheral blood of ROS and antioxidant experiments to explore the role of ROS in apoptosis and the relationship of the two disease and granule cells. It is of great significance for the improvement of IVF outcome in patients with endometriosis to provide new ideas for the use of antioxidants to improve embryo improvement in AIT patients

子宫内膜异位症与自身免疫甲状腺炎（AIT）均是导致女性不孕的常见疾病，内异症患者行IVF后优质胚胎率、着床率、临床妊娠率显著降低。内异症患者中AIT发病率升高，AIT增加妊娠早期流产率。内异症患者可能存在高水平活性氧（ROS）促进AIT的发生，但尚未有研究直接验证两种疾病发病机制上的联系。申请人既往研究提示内异症患者中AIT发病率升高、近期在JAMA上发表的研究提示甲状腺功能正常的AIT患者予甲状腺素治疗不能改善不孕妇女IVF结局。本研究拟探究内异症通过ROS通路促进AIT发生机制。留取内异症IVF助孕的合并及不合并AIT患者卵泡液及外周血，测定其中ROS及抗氧化能力、细胞因子、DNA损伤标记物，测量颗粒细胞内ROS水平、细胞内来源，运用流式细胞技术等测定颗粒细胞凋亡及通路。通过本研究可对合并内异症及AIT患者运用抗氧化剂培养胚胎改善提供新思路，对改善内异症患者IVF结局有重要意义。

自身免疫性甲状腺炎（AIT）是育龄期女性最常见的自身免疫性疾病，大量临床研究发现AIT患者中不孕症的发生率明显增加，但对AIT影响不孕症发生的分子机制尚不明确。基于我们的临床研究，我们发现虽然AIT并未影响不孕症女性的妊娠结局包括临床妊娠率、流产率、活产率和单胎出生体重，但AIT患者行促排卵治疗后的获卵数明显少于非AIT女性。我们的研究进一步检测了AIT女性和非AIT女性卵泡液中的免疫因子，结果显示AIT女性卵泡液中炎性趋化因子CXCL9，CXCL10，CXCL11和炎性细胞因子IL-4，IL-5，IL-6，IL-10， IFN-gamma较非AIT女性明显升高。其CXCR3+的T细胞数量也明显增加。我们的研究明确了AIT女性卵泡液微环境存在免疫紊乱，此外，我们的研究首次论证了AIT女性卵泡液中存在IFN-gamma-CXCL9/10/11-CXCR3+T细胞通路的激活。