Thyroid Autoimmunity and Reproductive Outcomes: Antibody-Specific Associations in a National Cohort from the All of Us Research Program

BACKGROUND: Thyroid autoimmunity (TAI) is the most common autoimmune condition affecting women of reproductive age. Prior studies have linked TAI to adverse reproductive outcomes; however, antibody-specific effects and their relative clinical significance remain incompletely defined. OBJECTIVE: To evaluate antibody-specific associations between TAI and adverse reproductive outcomes in reproductive-age women using a large national biobank. METHODS: This retrospective cohort study utilized data from the NIH All of Us Research Program (Controlled Data Repository version 8). Reproductive-age women were categorized as antibody-negative or antibody-positive for any thyroid autoantibody (AnyAb), thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), or thyrotropin receptor antibodies (TRAbs). Outcomes included disorders of menstruation, female infertility, endometriosis, and recurrent miscarriage (evaluated in a pregnancy-restricted subset). Associations were assessed using pre-specified pairwise comparisons with Holm-Bonferroni adjustment. RESULTS: TAI was associated with adverse reproductive outcomes in an antibody-specific manner. Disorders of menstruation were more prevalent among women with TPOAb and TgAb positivity compared with controls. Female infertility and recurrent miscarriage were the most robust findings, with strong associations with the AnyAb, TPOAb, and TgAb groups. Endometriosis demonstrated moderate associations driven by TPOAb positivity and overall antibody (AnyAb) positivity. TRAb-specific associations were not consistently significant. Findings varied by antibody type, highlighting heterogeneity within TAI. CONCLUSIONS: In this large population-based cohort, TAI was associated with adverse reproductive outcomes, particularly infertility and recurrent miscarriage. These findings refine prior literature by distinguishing confirmatory from novel associations and emphasize the importance of antibody-specific interpretation when evaluating reproductive risk in women with TAI.