Research in context
Evidence before this study
We searched PubMed for studies published between the inception of the database and Nov 1, 2021, using the search terms (“recurrent miscarriage” OR “recurrent pregnancy loss”) AND (“thyroid peroxidase antibodies” OR “thyroid autoimmunity”) to find randomised trials and meta-analyses of randomised trials, published in English, that evaluated the effectiveness of levothyroxine supplementation on live birth rates in women with thyroid peroxidase antibodies (TPO-Ab) and recurrent pregnancy loss. We did not find any randomised trials that included women with recurrent pregnancy loss, but we did find a meta-analysis of 2263 women who were TPO-Ab positive enrolled in six randomised trials. None of the included studies in this meta-analysis focused on women with recurrent pregnancy loss. No differences in pregnancy loss rates and live birth were found in women positive for TPO-Ab who received levothyroxine compared with control groups. The large randomised TABLET trial, included in the meta-analysis, did a subgroup analysis of women with recurrent pregnancy loss. No effect of levothyroxine was seen on live birth rates in women positive for TPO-Ab and recurrent pregnancy loss compared with placebo (RR 1·04 [95% CI 0·72–1·51). However, the TABLET trial did not exclude women with other risk factors for recurrent pregnancy loss besides TPO-Ab, which reduced the likelihood of a beneficial effect of levothyroxine for this subgroup. In the TABLET trial a fixed dose of levothyroxine was used, which did not reduce the number of abnormal thyroid function tests during pregnancy in comparison with placebo.
Added value of this study
Our international, double-blind randomised trial focussed on women with recurrent pregnancy loss who were positive for TPO-Ab. Levothyroxine was dosed depending on the participant's body weight and thyroid stimulating hormone concentration. There was no significant difference in live birth rate between the levothyroxine and placebo groups. There was also no evidence of a difference in any of the secondary outcomes, including pregnancy losses, ongoing pregnancy rates, and preterm birth.
Implications of all the available evidence
Routine use of levothyroxine in women with recurrent pregnancy loss, normal thyroid function, and positive for TPO-Ab is not recommended.