Articles written by professionals from The Wellington Hospital for Healthcare Professionals.
Thyroid disease is associated with subfertility which affects between 1% and 5% of couples.
Thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) have key roles in growth and development. Thyroid disease is common in women of reproductive age, and changes in thyroid function can impact greatly on reproductive function before, during and after conception.
Overt hypothyroidism affects 0.5% of women of reproductive age. Mild thyroid failure or subclinical hypothyroidism has a prevalence of approximately 2–4%. It is characterised by raised serum thyroid-stimulating hormone (TSH) of >4.5mU/l in combination with a normal free T4 (9–25pmol/l) and no clinical symptoms or signs of hypothyroidism. Women with subfertility have raised mean serum TSH levels and increased rates of subclinical and overt hypothyroidism compared with controls. Raised serum TSH >2.5mU/l may be associated with reduced rates of fertilisation during assisted conception and reduced pregnancy rates. Improvements in implantation, pregnancy and live birth rates are reported following treatment with levothyroxine (L-T4) in overt and subclinical hypothyroidism. However, even following L-T4 replacement therapy, egg numbers and fertilisation rates, and implantation, pregnancy and live birth rates appear to be reduced compared with euthyroid controls. Serum TSH levels <2.5mU/l are recommended pre-conceptually in the subfertility setting, in line with the guidelines for first trimester serum TSH.
Autoimmune conditions are implicated in subfertility and there has been longstanding speculation over the importance of thyroid autoantibodies in subfertility. Autoimmune thyroid disease (AITD) is the most common cause of hypothyroidism in women of reproductive age. Thyroid autoantibodies are present in almost all patients with Hashimoto’s thyroiditis, two-thirds of those with post-partum thyroiditis and three-quarters of those with Graves’ disease. Thyroid autoimmunity is present in 25% of the general population and is consistently increased in the subfertile population, compared with fertile controls. A proportion of people with AITD have normal serum TSH.
Thyroid autoantibodies are an early sign of lymphocytic infiltration and therefore a predictor of thyroid disease. Increased rates of subfertility are seen in euthyroid women with AITD and it is the management of this group that has created the greatest debate among clinicians. There is little evidence to suggest whether treating euthyroid women with AITD with L-T4 in the assisted reproduction setting improves outcome.
It seems reasonable to measure thyroid function routinely in women presenting with subfertility initially by a serum TSH measurement. Given that improvements in reproductive outcomes are observed in serum TSH <2.5mU/l, serum TSH levels should be maintained <2.5mU/l for those with clinical and subclinical hypothyroidism. Subclinical hypothyroidism (serum TSH >2.5mU/l) should prompt a repeat serum TSH level and for thyroid autoantibodies to be checked. If the serum TSH persists >2.5mU/l, treatment with L-T4 is warranted to bring the TSH <2.5mU/l. The dose of L-T4 should be titrated until the serum TSH is brought to 2.5mU/l or less, and during this period monitoring of free T4 and serum TSH every six weeks is warranted. The evidence is lacking over the benefit of commencing L-T4 in those who are euthyroid with AITD. It should, however, prompt close monitoring of thyroid function if pregnancy does result, with monitoring of foetal wellbeing and, subsequently, neonatal review.
Hypothyroidism, reproductive health, Dr Mark Vanderpump, endocrinology, thyroid disease, subfertility, reproductive age, autoimmune, post-partum thyroiditis
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