Effect of luteal phase support with progesterone on thyroid function: a sub-study of the FET optimizing trial.

ObjectiveInfertility is a major health issue, and fertility treatments, including frozen embryo transfer (FET), are common. Progesterone, essential for endometrium development and receptivity, is used to improve implantation rates. This study investigates the effect of luteal phase support with progesterone on thyroid function in modified natural FET cycles.MethodsThis is a sub-study of a randomized controlled trial (FET optimizing trial). Data were collected at two fertility centers from January 2019 to October 2022. Euthyroid women receiving single frozen-thawed embryo transfer in a modified natural cycle were included. The study participants were categorized into two groups: the luteal phase support (LPS) and the no LPS groups. The LPS group received vaginal progesterone 100 mg three times daily starting at day 4 after ovulation trigger with human chorionic gonadotropin (day 0). A pregnancy test was performed on day 16. Thyroid function was repeatedly measured. Linear mixed modeling was used to test the effect of progesterone on thyrotropin (TSH, primary outcome) and free thyroxine (fT4). Interaction with thyroid autoimmunity was tested.ResultsIn total, 85 women were included: 45 received progesterone LPS and 40 did not. Participants were 34 ± 4 years of age and had a BMI of 23 (IQR: 21; 26), and 25% were positive for thyroid autoimmunity. Serum progesterone increased with LPS, but TSH and fT4 levels were not affected by LPS. There was no interaction with thyroid autoimmunity. In the progesterone LPS group, 44% conceived compared with 55% in the no LPS group, P = 0.33.ConclusionProgesterone LPS does not affect thyroid function during the luteal phase.