Euthyroid Hyperthyrotropinemia in Children Born after in Vitro Fertilization
Abstract Context: Assisted reproduction techniques are now commonly used. Although classic in vitro fertilization (IVF) started almost 30 yr ago, few long-term systematic prospective studies of children conceived with assisted reproduction have been performed. Objective: Our objective was to investigate thyroid function in children conceived after IVF vs. naturally conceived controls. Populations and Methods: A total of 106 children conceived after classic IVF and 68 naturally conceived controls, aged 4–14 yr, were studied. All children were thoroughly examined, and serum T3, T4, TSH, anti-thyroid peroxidase, and anti-thyroglobulin antibodies were measured. A second TSH determination and a thyroid ultrasound were performed for TSH higher than 5 μIU/ml, and children were considered to have persistent hyperthyrotropinemia, if the TSH elevation was confirmed. Results: Seven IVF children but none of the controls had persistent elevations of circulating TSH, suggesting euthyroid hyperthyrotropinemia or subclinical primary hypothyroidism (P = 0.044). TSH was significantly higher in the IVF group than in controls (P = 0.046), whereas no significant differences in the concentrations of T3 or T4 were observed. None of the children had detectable circulating antithyroid antibodies in either group. Conclusions: A significant elevation of serum TSH compatible with a mild TSH resistance of the thyroid were found in IVF children compared with controls. This was not due to the presence of antithyroid autoantibodies. We suggest that this might represent a slight epigenetic developmental abnormality related to the preimplantation manipulation of the embryo. Further studies are needed to confirm these findings and to better determine their etiopathogenesis and clinical significance.