Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis

Objective: To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves outcomes.

Design: Systematic review and meta-analysis.

Setting: University obstetrics and gynecology departments.

Patient(s): Women with RPL and overt/subclinical hypothyroidism, and/or thyroid autoimmunity.

Intervention(s): None.

Main outcome measure(s): Associations between RPL and overt/subclinical hypothyroidism and/or thyroid autoimmunity and any effects of treatment.

Result(s): After our review of articles from PubMed, EMBASE, Web of Science, and CENTRAL, we found two interventional studies in which levothyroxine did not improve the subsequent live-birth rate in women with subclinical hypothyroidism with or without thyroid antibodies. A meta-analysis of five studies revealed the prevalence of subclinical hypothyroidism in RPL to be 12.9% (95% confidence interval [CI], 0%-35.2%). A meta-analysis of 17 studies revealed a statistically significant association between RPL and thyroid autoimmunity (odds ratio 1.94; 95% CI, 1.43-2.64). However, a randomized study suggested that levothyroxine does not benefit euthyroid women with thyroid autoimmunity.

Conclusion(s): Based on the limited observational studies available, no association exists between RPL and subclinical hypothyroidism, nor does levothyroxine improve subsequent pregnancy outcomes. An association exists between RPL and thyroid autoimmunity, but levothyroxine does not improve subsequent pregnancy outcomes. Women with RPL should be screened/treated for overt thyroid disease but not thyroid autoimmunity. Thyroid antibody screening is not supported by the published studies, and further randomized studies are needed. No recommendation regarding the treatment of subclinical hypothyroidism can be made at this time; prospective and randomized studies are urgently needed.