Levothyroxine Might Not Benefit Euthyroid Women with Recurrent Pregnancy Loss
Studies have shown that thyroid autoimmunity is associated with pregnancy loss, as maternal thyroid hormones (TH) play a critical role in the development of both fetus and placenta. Pregnancy loss in women with positive thyroid autoantibodies occurs within the first trimester of gestation when the fetus is dependent on maternal thyroid hormone. In a recent study, researchers have reported that intake of levothyroxine failed to improve pregnancy outcomes in euthyroid women with recurrent pregnancy loss who were positive for thyroid peroxidase antibodies (TPO-Ab). The study findings were published in The Lancet on March 14, 2022.
Women positive for TPO-Ab have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. Therefore, Prof Mariƫtte Goddijn, MD and her team conducted a study to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function.
The T4LIFE trial was an international, phase 3, double-blind, placebo-controlled trial. In this trial, the researchers included 187 women (18ā42 years) who were TPO-Ab positive, had two or more pregnancy losses and had a thyroid-stimulating hormone (TSH) concentration within the institutional reference range. Before conception women were randomized to either the levothyroxine group (n=94) or the placebo group (n=93) orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0Ā·5ā1Ā·0 Ī¼g/kg bodyweight. The researchers continued administration of levothyroxine or placebo until the end of pregnancy. The major outcome assessed was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population.
Key findings of the study:
- Upon analysis, the researchers found that 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1Ā·03; absolute risk difference 1Ā·6%).
- They reported 7 adverse events from each group, among which none of them was directly related to the study procedure.
The authors concluded, "Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function."
In an accompanying editorial, Dr Tim Korevaar and Dr Rima Dhillon-Smith wrote, "This study suggests that there is no routine place for levothyroxine treatment in euthyroid women who are TPO-Ab positive who are actively trying for a pregnancy".
They further added, "Whether TPO-Abs should be assessed routinely when screening for hypothyroidism in women at high risk for adverse fertility or obstetric outcomes cannot be determined on the basis of the available data, although thyroid function test follow-up in women known to be TPO-Ab positive seems warranted".
For further information:
DOI: https://doi.org/10.1016/S2213-8587(22)00045-6
Keywords: Thyroid peroxidase antibodies, TPO-Abs, recurrent pregnancy loss, abnormal thyroid function, T4LIFE trial, levothyroxine, euthyroid women, The Lancet, TSH concentration,
