Thyroid function in early pregnancy following frozen embryo transfer: analysis from a randomized controlled trial

To investigate the impact of different frozen embryo transfer regimens on maternal thyroid function during early pregnancy and subsequent thyroid function in the newborns.

A secondary analysis of a randomized controlled trial including women aged 18-40 years with a body mass index ≤ 35 kg/m² undergoing frozen embryo transfer at Copenhagen University Hospital - Herlev (April 2021-May 2024). Ovulatory participants were randomized to modified natural or programmed cycle, and anovulatory participants to gonadotrophin-stimulated or programmed cycle. Maternal thyroid-stimulating hormone, free thyroxine, total thyroxine, and total triiodothyronine were measured. Neonatal thyroid-stimulating hormone was evaluated through the neonatal screening program.

In total, 251 cycles were analyzed: 94 modified natural and 99 programmed in the ovulatory group, and 29 gonadotrophin-stimulated and 29 programmed in the anovulatory group. Total triiodothyronine and thyroxine levels were significantly higher in programmed cycles during endometrial preparation and early pregnancy. Free thyroxine was elevated at gestational age 4 + 2 in programmed vs. modified natural cycles, but not compared to gonadotrophin-stimulated cycles. Thyroid-stimulating hormone levels were comparable at all time points. Neonatal thyroid-stimulating hormone did not differ between groups.

Although significantly higher maternal levels of total triiodothyronine, thyroxine, and free thyroxine were observed in programmed cycle, both maternal and neonatal thyroid-stimulating hormone levels were unaffected. These findings provide reassuring evidence for the endocrine health of women conceiving through programmed cycle and their newborns. The trial was prospectively registered in EudraCT with identification no. 2020-001218-39, registration date: 17 November 2020. Date of first patient's enrollment: 20 April 2021.