Autoimmune Thyroid Disease and Female Fertility: Does Anti-TPO Accelerate Ovarian Aging?

Background: Thyroid autoimmunity, particularly anti-thyroid peroxidase antibodies (anti-TPO), has been implicated in female infertility and premature ovarian insufficiency, yet its effect on quantitative ovarian-reserve parameters across clinical subgroups remains uncertain. Methods: This retrospective cross-sectional study included 1,460 euthyroid infertile women (18–45 years) evaluated at a tertiary reproductive endocrinology center between 2022–2025. Participants were stratified by anti-TPO (≥9 vs < 9 IU/mL), body-mass-index (BMI ≥ 30 vs < 30 kg/m²), and PCOS status. Linear and logistic regression analyses were used to assess associations between anti-TPO and ovarian-reserve markers—anti-Müllerian hormone (AMH), antral follicle count (AFC), and follicle-stimulating hormone (FSH)—adjusting for age, BMI, and TSH. Results: Anti-TPO positivity (17.6%) was associated with significantly reduced AMH (1.47 ± 1.52 vs 3.33 ± 3.03 ng/mL; p < 0.0001), lower AFC (8.18 ± 5.06 vs 15.88 ± 8.18; p < 0.0001), and higher FSH (9.40 ± 6.21 vs 8.06 ± 4.79 mIU/mL; p = 0.001). Effects were strongest in non-obese, PCOS-negative, and < 35-year-old women. Logistic regression confirmed anti-TPO ≥ 9 IU/mL as an independent predictor of diminished ovarian reserve (AMH < 1 ng/mL: OR = 3.13; AFC < 5: OR = 6.48). Structural-equation modeling showed direct, TSH-independent effects of anti-TPO on AMH and AFC. Conclusions: Elevated anti-TPO antibodies are independently associated with reduced ovarian reserve in euthyroid women, particularly among younger, non-obese, and PCOS-negative individuals. Anti-TPO screening may serve as an early biomarker for reproductive aging and guide individualized fertility counseling.