Importance of iodide sufficiency and normal thyroid function in fertility and during gestation.

Appropriate management of thyroid dysfunction in pregnancy is challenging in both its primary, secondary and tertiary forms of the disease. Primary hypothyroidism is by far most prevalent globally. Main causes are insufficiency of iodide supplementation in developing countries and autoimmunity in developed countries. However, after a very successful global implementation by World Health Organisation over decades accompanied by specific recommendations for management of the iodide supplementation during pregnancy, recent studies found that women both in USA and EU are again mild to moderately iodide deficient during pregnancy or going through assisted fertility treatment. This poses a disturbing risk in relation to foetal neurological and brain development. The diagnosis and treatment monitoring of the thyroid function during pregnancy are very challenged due to the extensive physiological as well as pathophysiological adaptations of the thyroid axis hormones to encompass a sufficient foetal supply. This is distorting the hormone measurements, since the normal limits are exceeded, and current biochemical methods are not calibrated for the adapted concentrations. Even though clinical guidelines exist there are still gaps in the evidence-based recommendations to guide clinicians to thyroid function management during pregnancy. Debut of hypothyroidism during pregnancy requires immediate diagnosis as it can lead to poor foetal outcome with intrauterine growth restriction and foetal demise on top of the risk for the neurocognition. Hypothyroidism in stable replacement treatment needs careful monitoring during pregnancy to adapt to the physiological changes in the requirement of the thyroid hormone thyroxine, and combination therapy with triiodothyronine is contraindicated. The frequent use of assisted reproduction technology (ART) with controlled ovarian hyperstimulation in these patient groups having disease induced low fertility has created an unrecognised risk of under-replacement due to accelerated oestrogen stimulation with increased risk of severe complications for both the woman and foetus. Longitudinal studies of the thyroid function bridging pre-ART, through ART to pregnancy and postpartum in different clinical settings are recommended. The area needs consensus recommendations between gynaecologists and endocrinologists in specialised centres to alleviate such increased gestational risk. There is a strong need of more research on improvement of thyroid hormone replacement, and biomarkers for treatment optimisation in this field of non-communicable diseases, which suffers from both limited attention from the health authorities and poor funding.