Euthyroid Hyperthyrotropinemia in Children Born after in Vitro Fertilization

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 T-3, T-4, 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 mu IU/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 T-3 or T-4 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. (J Clin Endocrinol Metab 94: 1338-1341, 2009)