The influence of thyroid disorders on adverse pregnancy outcomes

This thesis explores the association between thyroid disorders and adverse pregnancy outcomes, the underlying pathophysiology and treatment possibilities. The association between thyroid disorders and adverse pregnancy outcomes is investigated in a systematic review and two retrospective cohort studies. Women with subclinical hypothyroidism and/or thyroid autoimmunity in pregnancy have an increased risk for unexplained subfertility, (recurrent) miscarriage, preterm birth, pre-eclampsia, breech presentation, perinatal mortality and maternal post-partum thyroiditis. Observational data show that thyroid function disorders and thyroid peroxidase antibodies are associated with disturbed folliculogenesis, spermatogenesis, lower fertilisation rates and lower embryo quality. Available evidence shows that thyroid hormone transporters and receptors are expressed in the ovary, the early embryo, endometrium, uterus and placenta suggesting that thyroid hormone has a direct effect on reproduction and pregnancy. However, the exact underlying pathophysiology of these associations remains unclear. There are no data on the mechanisms underlying the association between thyroid peroxidase autoantibodies and reproduction. Treatment possibilities of thyroid disorders in pregnancy have been studied in a systematic review and a retrospective cohort study. Treatment of hyperthyroidism reduces the risk of preterm delivery, pre-eclampsia and low birth weight. Levothyroxine is effective in reducing the risk of miscarriage and preterm delivery. Current evidence is insufficient to advise treatment of subclinical hypothyroidism or thyroid autoimmunity. To further investigate the effect of levothyroxine treatment in pregnant women with thyroid autoimmunity, a multicentre, international, randomized controlled study has been started and the study protocol is described in this thesis.