Should thyroxine hormone be started in women having fertility concerns with high-normal TSH and negative TPO antibody?

This landmark NEJM trial showed no benefit in women with TPO antibodies and a TSH > 2.5 of starting levothyroxine. However, most IVF centers start low-dose levothyroxine since subclinical hypothyroidism is associated with an increased risk of miscarriages especially if TSH > 5 or TSH > 2.5 with positive antibodies. There is no harm in starting the med but the benefit is unclear.

In addition to the TABLET trial in NEJM, there are two additional recent negative trials in the literature: POSTAL and T4LIFE.

While there is likely no harm to using low-dose LT4 for TPO Ab-positive euthyroid women pre-conception, there does not appear to be any benefit. However, it is important to follow thyroid function tests in those women throughout the first half of gestation as TPO Ab positivity confers an increased risk for the development of hypothyroidism in pregnancy.