2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction

Abstract

Severe thyroid dysfunction may lead to menstrual disorders and subfertility. Fertility problems may persist even after restoring normal thyroid function, and then an assisted reproductive technology (ART) may be a solution. Prior to an ART treatment, ovarian stimulation is performed, leading to high oestradiol levels, which may lead to hypothyroidism in women with thyroid autoimmunity (TAI), necessitating levothyroxine (LT4) supplements before pregnancy. Moreover, women with the polycystic ovarian syndrome and idiopathic subfertility have a higher prevalence of TAI. Women with hypothyroidism treated with LT4 prior to ART should have a serum TSH level <2.5 mIU/L. Subfertile women with hyperthyroidism planning an ART procedure should be informed of the increased risk of maternal and foetal complications, and euthyroidism should be restored and maintained for several months prior to an ART treatment. Fertilisation rates and embryo quality may be impaired in women with TSH >4.0 mIU/L and improved with LT4 therapy. In meta-analyses that mainly included women with TSH levels >4.0 mIU/L, LT4 treatment increased live birth rates, but that was not the case in 2 recent interventional studies in euthyroid women with TAI. The importance of the increased use of intracytoplasmic sperm injection as a type of ART on pregnancy outcomes in women with TAI deserves more investigation. For all of the above reasons, women of subfertile couples should be screened routinely for the presence of thyroid disorders.

Keywords: Assisted reproductive technology; In vitro fertilization; Intracytoplasmic sperm injection; Radioactive iodine; Subclinical hypothyroidism/hyperthyroidism; Subfertility; Thyroid autoimmunity; Thyroid cancer.

Fig. 1

Algorithm for workup and management of thyroid disorders in women of subfertile couples starting an ART procedure. ¹If not possible for local terms, then measure TgAb in case TSH >2.5 mIU/L and negative TPOAb/look for sonographic criteria of TAI if available. ²Or above/below the reference range of the assay for non-pregnant women or institutional population-specific values. ³LT4 dose depending on baseline TSH level and body weight; start 25 μg when TSH 2.51–4.0 mIU/L → target TSH <2.5 mIU/L. ^#Decide to treat on a case-by-case basis (cf text for details). *In case of pregnancy, the day of the second/confirmatory hCG measurement. TAI, thyroid autoimmunity; TgAb, thyroglobulin antibodies; TPOAb, thyroid peroxidase antibodies; LT4, levothyroxine; hCG, human chorionic gonadotropin; OS, ovarian stimulation; ART, assisted reproductive technology. The figure is reproduced from Unuane and Poppe (Female infertility: do we forget the thyroid? J Endocrinol Invest. 2015) with permission from Springer.