ArticleEndocrine connections2026
Preconception thyroid function optimization and pregnancy outcomes in women with recurrent pregnancy loss: a real-world cohort study.
Article in Endocrine connections, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe 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.
methodsWe 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.
resultsAfter 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.
conclusionIn 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.
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