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Euthyroid Hyperthyrotropinemia in Children Born after in Vitro Fertilization

Division of Endocrinology, Metabolism, and Diabetes (S.D.S., G.P.C., C.K.-G.), First Department of Pediatrics; Second Department of Obstetrics and Gynaecology (A.M.-P.); and Division of In Vitro Fertilization (D.L.), First Department of Obstetrics and Gynaecology, Athens University Medical School, 11527 Athens, Greece

Address all correspondence and requests for reprints to: Sophia D. Sakka, M.D., First Department of Pediatrics, Athens University Medical School, "Aghia Sophia" Children’s Hospital, Thivon, Levadias Street, 11527 Athens, Greece. E-mail: ssakka{at}med.uoa.gr or sophiasakka{at}yahoo.gr.

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.