Zhang Sudan, Yang Mingdong, Li Teng, Yang Min, Wang Wei, Chen Yunqing, Ding Yu, Liu Jianxin, Xu Xiaohui, Zhang Jian, Wang Zheng, Liu Jiane
Department of Reproductive Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Rheumatology and Immunology, Shouguang People's Hospital, Shouguang, Shandong, China.
Mol Reprod Dev. 2023 Apr;90(4):218-226. doi: 10.1002/mrd.23677. Epub 2023 Mar 15.
Thyroid autoimmunity (TAI) triggered by genetic and epigenetic variation occurs mostly in women of reproductive age. TAI is described mainly by positivity of anti-thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). TPO-Ab, but not TG-Ab, was suggested to be associated with pregnancy outcome in euthyroid women undergoing assisted reproductive technology (ART), but their results are conflicting. This meta-analysis was performed to decide whether the presence of TPO-Ab-in a concentration dependent manner-correlates with the success of ART. A systematic literature search was performed in the PubMed, Web of Science, and EMBASE databases for relevant articles published from January 1999 to April 2022, and these studies focused on the effect of TAI on pregnancy outcomes of women who underwent in vitro fertilization, intracytoplasmic sperm injection and intrauterine insemination and met the inclusion criteria: (i) the studies were prospective or retrospective study; (ii) all patients undergoing ART were tested for thyroid-related antibodies; (iii) the assessed ART outcomes included miscarriage rate (MR) or delivery rate (DR). The exclusion criteria were: (i) female congenital uterine malformation, chromosomal diseases and other infectious diseases; (ii) overt hypothyroidism or pre-existing thyroid disease; (iii) thrombus tendency. We divided the included patients into three groups according to the TPO-Ab threshold they defined: (i) TPO-Ab (-), threshold <34 IU/mL; (ii) TPO-Ab-34, threshold >34 IU/mL; (iii) TPO-Ab-100, threshold >100 IU/mL. We then extracted necessary relevant data, including MR and DR. Egger's test was used to evaluate the risk of publication bias. This meta-analysis included a total of 7 literatures involving 7466 patients with TAI (-) and 965 patients with TAI (+) and revealed that there was no significant difference between group TPO-Ab-34 and group TPO-Ab (-) in MR [risk ratio (RR): 0.61 (0.35, 1.08), p = 0.09] and DR [RR: 0.97 (0.83, 1.13), p = 0.69]. By contrast, compared to TPO-Ab (-) group, TPO-Ab-100 patients showed markedly higher MR [RR: 2.12 (1.52, 2.96), p = 0.0046], and lower DR [RR: 0.66 (0.49, 0.88), p < 0.0001] with high degree of statistical significance. This meta-analysis suggests that, for euthyroid patients, high level of TPO-Ab (>100 IU/mL) could adversely influence the pregnancy outcome of ART.
由基因和表观遗传变异引发的甲状腺自身免疫（TAI）主要发生在育龄女性中。TAI主要通过抗甲状腺过氧化物酶抗体（TPO-Ab）和/或甲状腺球蛋白抗体（TG-Ab）呈阳性来描述。在接受辅助生殖技术（ART）的甲状腺功能正常的女性中，有人提出TPO-Ab而非TG-Ab与妊娠结局相关，但他们的结果相互矛盾。进行这项荟萃分析是为了确定TPO-Ab的存在是否以浓度依赖的方式与ART的成功率相关。我们在PubMed、科学网和EMBASE数据库中进行了系统的文献检索，以查找1999年1月至2022年4月发表的相关文章，这些研究聚焦于TAI对接受体外受精、卵胞浆内单精子注射和宫内人工授精的女性妊娠结局的影响，且符合纳入标准：（i）研究为前瞻性或回顾性研究；（ii）所有接受ART的患者均检测了甲状腺相关抗体；（iii）评估的ART结局包括流产率（MR）或分娩率（DR）。排除标准为：（i）女性先天性子宫畸形、染色体疾病和其他传染病；（ii）显性甲状腺功能减退或既往存在的甲状腺疾病；（iii）血栓倾向。我们根据所定义的TPO-Ab阈值将纳入的患者分为三组：（i）TPO-Ab（-），阈值<34 IU/mL；（ii）TPO-Ab-34，阈值>34 IU/mL；（iii）TPO-Ab-100，阈值>100 IU/mL。然后我们提取了必要的相关数据，包括MR和DR。使用Egger检验评估发表偏倚风险。这项荟萃分析共纳入7篇文献，涉及7466例TAI（-）患者和965例TAI（+）患者，结果显示TPO-Ab-34组和TPO-Ab（-）组在MR[风险比（RR）：0.61（0.35，1.08），p = 0.09]和DR[RR：0.97（0.83，1.13），p = 0.69]方面无显著差异。相比之下，与TPO-Ab（-）组相比，TPO-Ab-100患者的MR显著更高[RR：2.12（1.52，2.96），p = 0.0046]，而DR更低[RR：0.66（0.49，0.88），p < 0.0001]，具有高度统计学意义。这项荟萃分析表明，对于甲状腺功能正常的患者，高水平的TPO-Ab（>100 IU/mL）可能会对ART的妊娠结局产生不利影响。
