Bidirectional association between thyroid autoimmunity/thyroglobulin antibody and diminished ovarian reserve: a systematic review and meta-analysis of observational studies

Background Evidence suggests that thyroid autoimmunity (TAI) may be associated with ovarian dysfunction; however, most studies have focused primarily on thyroid peroxidase antibodies (TPOAb), while evidence regarding thyroglobulin antibodies (TgAb) remains limited and inconsistent. This study aimed to evaluate the association between TAI/TgAb and ovarian reserve. Methods A systematic literature search was conducted in PubMed, Embase, Web of Science, CNKI databases for Chinese- and English-language articles published from January 2014 to January 2025. A bidirectional validation design was employed: (1) forward analysis, quantifying between-group differences in serum anti-Müllerian hormone (AMH) levels between TAI-positive women and healthy controls using standardized mean differences (SMD); and (2) reverse analysis, quantifying differences in TgAb levels (SMD for continuous variables) and TgAb positivity rates (odds ratios OR for dichotomous variables) between women with diminished ovarian reserve (DOR) and healthy controls. This study was prospectively registered with PROSPERO (CRD420251207428) and conducted in accordance with the PRISMA 2020 guidelines. The reverse analysis denotes a reverse-direction cross-sectional comparison in which the grouping and outcome variables are exchanged; it does not imply temporal or causal reversal. Results Thirteen studies (total n = 4,286) were included. Forward analysis (4 studies, n = 870) demonstrated significantly lower serum AMH levels in TAI-positive women compared with controls (SMD=−0.20, 95% CI [−0.34, −0.06], P = 0.005, I 2 = 0%). Reverse analysis of continuous variables (5 studies, n = 1,496) revealed significantly elevated TgAb levels in women with DOR compared with controls (SMD=0.93, 95% CI [0.36, 1.50], P = 0.001, I 2 = 94%); however, this estimate should be interpreted with caution given the substantial heterogeneity. Reverse analysis of dichotomous variables (7 studies, n = 2,568) confirmed that women with DOR had significantly higher odds of TgAb positivity compared with controls (OR=1.65, 95% CI [1.29, 2.11], P < 0.0001, I 2 = 32%). Conclusions A significant bidirectional association exists between diminished ovarian reserve and TgAb/TAI positivity. TAI may impair ovarian reserve, while women with ovarian insufficiency exhibit a higher burden of thyroglobulin autoantibodies. These findings highlight the clinical importance of TgAb screening in the evaluation of ovarian function among reproductive-age women. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251207428 , identifier CRD420251207428.