# Lack of difference in thyroid hormone profile between offspring conceived naturally and through ART

## TL;DR

Children conceived through ART have similar thyroid function to naturally conceived children, according to a large cohort study in China.

## Contribution

This study provides the first large-scale evidence that ART does not affect long-term thyroid function in children.

## Key findings

- No significant differences in thyroid hormone levels were found between ART and naturally conceived children.
- A slight difference in TSH levels during toddlerhood in the ET group was not significant in older children.
- ART-conceived children show comparable thyroid profiles to naturally conceived children across all age groups.

## Abstract

Does the thyroid function of children conceived through ART differ from that of naturally conceived (NC) children?

Our study results indicate that both children conceived through fresh embryo transfer and frozen embryo transfer exhibit a thyroid function profile similar to that of NC children.

Few studies have compared thyroid function between ART-conceived and NC children, and conflicting conclusions have been reported.

This study was based on a cohort at a tertiary health centre in China. The prospective cohort study included 9450 children born between 2005 and 2021 and followed up until June 2023. The outcomes of interest were the levels of the children’s thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin autoantibody (A-TG), and thyroid peroxidase antibody (A-TPO).

The participants were 3940 fresh embryo transfer conceived children (ET group), 4730 frozen embryo transfer conceived children (FET group), and 780 NC children. Their ages ranged from 1.5 to 10 years. Generalized estimating equations (GEE) was used to compare the main outcomes.

No significant between-group differences were observed in FT4 levels or the odds of TSH, FT3, FT4, A-TG, or A-TPO levels beyond the standard range. Further subgroup analysis indicated that the ET group exhibited a slightly higher TSH level than the NC group during the toddler age period (mean TSH: 2.93 vs. 2.72 µIU/ml). However, this difference was no longer significant among preschool and school-aged children. Additionally, there were no significant differences in FT4 levels between the ART and NC groups across all age subgroups.

Due to the inability to acquire urinary iodine data, we cannot adequately assess the influence of iodine intake on the study results. Both the unavoidable loss to follow-up in the cohort and the imbalance in the proportion of girls (higher in the NC group than in the ART group) may potentially introduce selection bias.

The study results indicate that ART-conceived children exhibit a thyroid function profile comparable to that of NC children. Furthermore, ART appears to be safe for long-term thyroid function in children.

National Key Research and Development Program of China (no. 2024YFC2706700), the National Natural Science Foundation of China (NSFC) Regional Innovation and Development Joint Fund (U24A20664), the National Key Technology Research and Developmental Program of China (2024YFC2706902), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Special Support Programme for High-level Talents, Taishan Scholars Programme for Young Experts of Shandong Province (tsqn202507388), Shandong Provincial Postdoctoral Innovation Project (no. SDCX-ZG-202502002), General Programme of Shandong Provincial Natural Science Foundation of China (ZR2022MH087), Young Talent of Lifting engineering for Science and Technology in Shandong, China (SDAST2024QTA071), Chinese Red Cross Foundation (2220025007). The authors declare no competing interests.

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