Effect of levothyroxine on the pregnancy outcomes in recurrent pregnancy loss women with subclinical hypothyroidism and thyroperoxidase antibody positivity: a systematic review and meta-analysis

Objective This study aimed to explore the effects of levothyroxine on pregnancy outcomes and thyroid function in recurrent pregnancy loss (RPL) women with subclinical hypothyroidism (SCH) or thyroperoxidase antibody positivity (TPOAb+).Methods Literature search was performed from inception to 24 June 2022. The heterogeneity for each outcome was evaluated using Cochran's Q test and quantified with I-squared (I2). Pooled effect sizes were expressed as relative risk (RR) and weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Stability of the results were assessed using the sensitivity analysis.Results Fifteen eligible studies with 1911 participants were included in this meta-analysis. The pooled data showed that levothyroxine decreased premature delivery rate (RR = 0.48, 95%CI: 0.32, 0.72), miscarriage rate (RR = 0.59, 95%CI: 0.44, 0.79), premature rupture of membranes (PROM) rate (RR = 0.44, 95%CI: 0.29, 0.66), and fetal growth restriction rate (RR = 0.33, 95%CI: 0.12, 0.89) in RPL women with TPOAb+. In RPL women with SCH, live birth rate was elevated (RR = 1.20, 95%CI: 1.01, 1.42) and miscarriage rate was reduced (RR = 0.65, 95%CI: 0.44, 0.97) by levothyroxine. In addition, levothyroxine substantially decreased TSH level (WMD = −0.23, 95% CI: −0.31, −0.16) and TPO level (WMD = −23.48, 95%CI: −27.50, −19.47).Conclusions Levothyroxine improved pregnancy outcomes and thyroid function in RPL women with TPOAb+ or SCH, indicating that levothyroxine may be beneficial for RPL women if TPOAb+ or SCH occurs. Future studies are needed to verify our findings.