Effect of extra-low dose levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism undergoing in vitro fertilization and embryo transfer

Objective: This study was undertaken to test the therapeutic effect of extra-low dose of levothyroxine (LT4; 25 mcg/day) to preconception and pregnant women with subclinical hypothyroidism (SCH). Materials and methods: This is a retrospective study, SCH women who succeeded in their first in vitro fertilization (IVF) cycle between January 1, 2018, to December 31, 2020 were included. SCH is defined as normal serum free thyroxine (T4) level and an elevated serum thyroid stimulating hormone (TSH) level >4 mIU/L. Extra-low dose of levothyroxine (LT4; 25 mcg/day) was prescribed to the SCH women from the establish of diagnosis of SCH to the end of pregnancy. The pregnancy outcomes (miscarriage, live birth, preterm birth, and small for gestational age baby) were compared to the euthyroid pregnant women. Results: Totally, 589 women were screened, and 317 cases received their first time IVF treatment. 167 women were clinically pregnant after IVF treatment, 155 of them were euthyroid and 12 of these women were diagnosed to have SCH. The average age of the participants was 35 years old. There were no significant differences in age, body mass index (BMI), anti-müllerian hormone (AMH), types of embryo transfer, number of embryos to transfer, or embryo stage during transfer between two groups. The live birth rate, miscarriage rate, and preterm birth rate in women with SCH supplemented with extra-low dose of LT4 were non-inferior to euthyroid patients (miscarriage rate: P = 0.7112; live birth rate: P = 0.7028; preterm delivery: P = 0.2419; small for gestational age: P = 0.2419). Conclusion: Our result demonstrated that supplementation with extra-low dose of levothyroxine at 25 mcg/day to SCH women can produce the comparable obstetrical and neonatal outcome as that in euthyroid pregnant women. Accordingly, we suggest extra-low-dose of levothyroxine may be considered as a safe and effective alternative for those SCH pregnant women who were not tolerated to the standard dose of levothyroxine.