Publication:

Endocrine interventions and live birth outcomes in women with recurrent pregnancy loss: a meta-analysis

Recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder for which endocrine therapies are frequently considered, although their effects on live birth remain uncertain. This meta-analysis assessed the effectiveness of progesterone and levothyroxine on pregnancy outcomes in women with RPL. Following PRISMA 2020 guidance, PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were searched from January 2015 to the final search date without language restrictions. Eight studies involving 7,749 participants were included in the systematic review; quantitative synthesis was restricted to randomized controlled trials with comparable data. Mantel-Haenszel fixed-effect meta-analyses generated pooled risk ratios (RRs) with 95% confidence intervals (CIs), heterogeneity was assessed using I², and risk of bias was evaluated with Cochrane RoB 2. For progesterone versus placebo, two large trials (PROMISE and PRISM; n=4,864) showed no statistically significant improvement in live birth (RR=1.03, 95% CI=1.00-1.07; I²=0%; p=0.08). For levothyroxine, pooled analysis suggested a non-significant trend toward improved live birth (RR 1.25, 95% CI 0.90-1.73; I²=74%), but substantial heterogeneity limited confidence in the estimate. Differences in thyroid status and study populations may explain part of this variability. Current evidence does not support routine empirical progesterone or levothyroxine use in unselected women with RPL. Progesterone may offer modest benefit in selected higher-risk subgroups, particularly women with multiple previous miscarriages; treatment should therefore be individualized according to clinical characteristics and endocrine profiles.