Association of serum anti-Müllerian hormone levels with early miscarriage: a retrospective cohort and mendelian randomization study

While anti-Müllerian hormone (AMH) serves as a well-established biomarker of ovarian reserve, its association with early miscarriage risk remains inconsistently characterized across previous research. To address this evidence gap, our investigation systematically evaluates the relationship between serum AMH concentrations and early miscarriage through a combination of retrospective cohort study and mendelian randomization analysis. The retrospective cohort study enrolled women who achieved intrauterine clinical pregnancies through in vitro fertilization cycles at Peking University Third Hospital between January 2019 and December 2023 (N = 19,154). These women were subsequently divided based on their anti-Müllerian hormone levels. Logistic regression and restrictive cubic spline regression models were applied to investigate the association between anti-Müllerian hormone levels and early miscarriage. Additionally, a two-step Mendelian randomization approach was utilized to investigate the causal relationship between anti-Müllerian hormone levels and miscarriage. Exposure traits were extracted from a meta-GWAS dataset (N = 9,968), while outcome traits were obtained from three separate GWAS datasets (N = 135,962, N = 360,044, and N = 150,215, respectively). In the in vitro fertilization (IVF) cohort, there were 2,780 women with AMH<1.1ng/ml, 6,666 women with 1.1 < AMH ≤ 2.6 ng/ml, and 9,708 women with AMH ≥ 2.6ng/ml. Compared to women with AMH ≥ 2.6ng/ml, women with AMH < 1.1 ng/mL (17.7% vs. 10.9% reference; aOR = 1.26 [1.11–1.44], p < 0.001) and women with AMH 1.1–2.6 ng/mL (13.8% vs. 10.9%; aOR = 1.13 [1.02–1.25], p = 0.018) exhibited significantly higher rates of early miscarriage. The aOR of early miscarriage showed a decreasing trend as AMH levels increased in restrictive cubic spline (p < 0.001). MR analysis did not detect a causal relationship between AMH levels and spontaneous miscarriage or recurrent miscarriage. Women with low AMH levels who conceive naturally do not need to worry excessively about early miscarriage. However, in the IVF population, low AMH levels warrant caution regarding the risk of early miscarriage. Future studies are necessary to confirm the causal relationship between AMH and early miscarriage in IVF cycles.