Comparison of reproductive outcomes in subclinical hypothyroidism women with high-normal versus low-normal thyroid-stimulating hormone levels after treatment with levothyroxine

Abstract

Objective: Reproductive outcomes in euthyroid women with high-normal thyroid-stimulating hormone (TSH) levels are comparable to those in euthyroid women with low TSH levels; however, few studies have investigated whether strictly controlled TSH levels after levothyroxine (LT4) treatment impair reproductive outcomes in infertile women with subclinical hypothyroidism (SCH). This study aimed to investigate the impact of high-normal versus low-normal TSH levels on reproductive outcomes in women undergoing their first in vitro fertilisation and embryo transfer (IVF-ET) cycle.

Design: This was a retrospective cohort study. Patients were divided into low-normal (TSH < 2.5 mIU/L, and ≥0.27 mIU/L) and high-normal (TSH ≥ 2.5 mIU/L, and <4.2 mIU/L) groups based on TSH levels after LT4 treatment. TSH levels after LT4 treatment and before ovarian stimulation were recorded. Reproductive outcomes were compared between the low-normal and high-normal TSH groups and between the euthyroid and LT4-treated groups.

Results: A total of 6002 women, 548 of whom were LT4-treated women, were finally included in this study. Among the LT4-treated women, 129 women had low-normal TSH levels, and 167 women had high-normal TSH levels. The clinical pregnancy rate, miscarriage rate, and live birth rate were comparable between the low-normal and high-normal groups (all p > .05). When adjusted by age, anti-Mullerian hormone (AMH) levels, infertility duration, transferred embryos, and dose and duration of LT4 treatment, high-normal TSH levels neither significantly decreased miscarriage (adjusted odds ratio [aOR] = 2.27, 95% confidence interval [CI] = 0.77-6.69, p = .14) nor increased clinical pregnancy (aOR = 1.15, 95% CI = 0.70-1.89, p = .57 or live birth (aOR = 0.97, 95% CI = 0.60-1.59, p = .92). Similar obstetric outcomes were observed between the low-normal and high-normal TSH groups after LT4 treatment and between the euthyroid and LT4-treated groups (all p ≥ .05).

Conclusions: High-normal TSH levels did not have adverse effects on clinical and obstetric outcomes when compared with low-normal TSH levels after LT4 treatment. However, whether it is appropriate to set 2.5 mIU/L as the goal of treatment before IVF/ICSI remains to be determined in further well-designed studies.

Keywords: IVF-ET; LT4; high-normal TSH; reproductive outcomes; subclinical hypothyroidism.