Preconception thyroid function optimization and pregnancy outcomes in women with recurrent pregnancy loss: a real-world cohort study.

Abstract

Background: The management of subclinical hypothyroidism with thyroid-stimulating hormone (TSH) levels between 2.5 and 4.0 mIU/L in women with recurrent pregnancy loss (RPL) remains controversial, as guidelines derived from general populations conflict. While a recent randomized trial confirmed the benefit of initiating levothyroxine (LT4) during early pregnancy, whether a more proactive strategy of preconception thyroid optimization improves outcomes in this high-risk group remains unknown.

Methods: We conducted a retrospective cohort analysis of 896 women with RPL and elevated TSH (2.5-4.0 mIU/L) during pre-pregnancy, from the Recurrent Pregnancy Loss Cohort Study. Based on clinical records, participants were categorized into two groups: treated group (n = 636) and untreated group (n = 260). The primary outcome was miscarriage. Associations were assessed using Firth's penalized-likelihood regression to address small-sample bias, with propensity score matching as a sensitivity analysis.

Results: After adjustment for antiphospholipid syndrome, degree of education, gravidity, and parity, LT4 treatment was associated with a significantly lower risk of miscarriage (adjusted odds ratio (aOR) = 0.33; 95% CI: 0.20, 0.54; P < 0.001). A reduced risk was also observed for threatened abortion (aOR = 0.49; 95% CI: 0.35, 0.71; P < 0.001). Results were robust in the propensity score-matched analysis.

Conclusion: In women with RPL and elevated TSH (2.5-4.0 mIU/L), a clinical care pathway involving preconception LT4 treatment was significantly associated with a reduced risk of miscarriage. This finding provides real-world evidence supporting the potential value of proactive preconception thyroid optimization in RPL, highlighting it as a priority strategy worthy of prospective investigation versus post-conception treatment initiation.