Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Clin Endocrinol (Oxf). 2023 Mar;98(3):426-435. doi: 10.1111/cen.14802. Epub 2022 Aug 17.
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.
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.
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).
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.
甲状腺刺激激素（TSH）水平处于正常高值的甲状腺功能正常女性的生殖结局与 TSH 水平处于低值的甲状腺功能正常女性相当；然而，很少有研究调查左旋甲状腺素（LT4）治疗后严格控制 TSH 水平是否会损害亚临床甲状腺功能减退（SCH）女性的不孕患者的生殖结局。本研究旨在调查高正常 TSH 水平与低正常 TSH 水平对首次体外受精和胚胎移植（IVF-ET）周期的女性的生殖结局的影响。
这是一项回顾性队列研究。根据 LT4 治疗后 TSH 水平，患者被分为低正常（TSH<2.5mIU/L，且≥0.27mIU/L）和高正常（TSH≥2.5mIU/L，且<4.2mIU/L）组。记录 LT4 治疗后和卵巢刺激前的 TSH 水平。比较低正常 TSH 组和高正常 TSH 组之间、甲状腺功能正常组和 LT4 治疗组之间的生殖结局。
共有 6002 名女性，其中 548 名是 LT4 治疗的女性，最终纳入本研究。在 LT4 治疗的女性中，129 名女性 TSH 水平处于低正常范围，167 名女性 TSH 水平处于高正常范围。低正常组和高正常组的临床妊娠率、流产率和活产率相似（均 p>0.05）。在调整年龄、抗苗勒管激素（AMH）水平、不孕持续时间、移植胚胎数量以及 LT4 治疗的剂量和时间后，高正常 TSH 水平既不会显著降低流产率（调整优势比[aOR]为 2.27，95%置信区间[CI]为 0.77-6.69，p=0.14），也不会增加临床妊娠率（aOR 为 1.15，95%CI 为 0.70-1.89，p=0.57）或活产率（aOR 为 0.97，95%CI 为 0.60-1.59，p=0.92）。LT4 治疗后低正常 TSH 组和高正常 TSH 组之间以及甲状腺功能正常组和 LT4 治疗组之间的产科结局相似（均 p≥0.05）。
与 LT4 治疗后的低正常 TSH 水平相比，高正常 TSH 水平对临床和产科结局没有不良影响。然而，在进一步设计良好的研究中，仍需要确定是否应该将 2.5mIU/L 设定为 IVF/ICSI 前的治疗目标。
