Levothyroxine before conception in women with thyroid antibodies: a step forward in the management of thyroid disease in pregnancy

Studies suggesting an association between thyroid autoimmunity and pregnancy-related adverse outcomes, particularly miscarriage and preterm delivery, date to nineties. The postulated causes for these associations were attributed to a direct or indirect effect of autoimmunity and/or to a mild thyroid impairment. Since then, small trials and several meta-analyses confirmed a detrimental effect of thyroid autoimmunity and suggested that patients with thyroid autoimmunity who wish to conceive or are pregnant might benefit from levothyroxine treatment to decrease the rate of miscarriage and preterm delivery. A recently published large trial investigated the hypothesis that the administration of levothyroxine in euthyroid antibody-positive women seeking pregnancy might increase the live birth rate. Women who were trying to conceive and had a history of miscarriage or infertility were tested for TSH and thyroperoxidase antibodies. Euthyroid antibody positive women were randomized to receive 50 μg/day of levothyroxine or placebo and were tested for thyroid function throughout pregnancy. In patients with thyroid function test results outside of assay-specific reference limits, the trial agent was discontinued. 56.6% in the LT4 group and 58.3% in the placebo group became pregnant and the live birth rates were similar in the two groups (37.4% vs 37.9%, respectively). There was also no difference in pre-term delivery rate and other maternal and neonatal outcomes between the two groups. The present commentary discusses the main findings of the trial and implications for clinical practice.