Nianyu Li1,2,3,4,5, Yueshuang Lu1,2,3,4,5, Pinxin Si1,2,3,4,5, Zhuqing Li1,2,3,4,5, Yingying Qin1,2,3,4,5, Xue Jiao1,2,3,4,5,6. 1. Center for Reproductive Medicine, Shandong University, Jinan, China. 2. Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China. 3. Shandong Key Laboratory of Reproductive Medicine, Jinan, China. 4. Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China. 5. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China. 6. Suzhou Institute of Shandong University, Suzhou, China.
Abstract
Background: Thyroid dysfunction is prevalent in reproductive-age women and has been identified as a risk factor for female infertility. However, it remains largely unclear whether subtle thyroid dysfunction, as estimated by moderately high thyrotropin (TSH) levels within the normal range, is associated with ovarian reserve in infertile women before assisted reproductive technology (ART) treatment. Methods: This cross-sectional study involved 3501 euthyroid infertile women, including 2189 women with TSH levels ≤2.5 μIU/mL and 1312 women with high-normal TSH levels (2.51-4.20 μIU/mL). Ovarian reserve markers were compared between women with low- and high-normal TSH levels. Correlation analysis and regression models were used to estimate the association of TSH levels with ovarian reserve. In addition, the association of subtle thyroid dysfunction with ovarian reserve was further evaluated after stratification for different infertility diagnoses and statuses of thyroid autoimmunity (TAI). Results: In the total population, women with high-normal TSH levels had significantly decreased anti-Müllerian hormone (AMH) concentrations (p < 0.001), a lower bilateral antral follicle count (AFC) (p < 0.001), and a higher prevalence of diminished ovarian reserve (DOR) (p = 0.018) than women with low-normal TSH levels. The TSH levels showed a negative association with both AMH levels (r = -0.050, p = 0.003) and bilateral AFC (r = -0.071, p < 0.001). Furthermore, the association of high-normal TSH levels with decreased AMH and AFC was more prominent in infertile women with ovulation dysfunction (p = 0.002, p = 0.002), unexplained infertility (p = 0.020, p = 0.028), or negative TAI (both p < 0.001). Conclusions: These data suggested that subtle thyroid dysfunction was associated with DOR in infertile women before ART treatment, which will add evidence that strengthens the systematic screening of TSH levels/TAI in infertile women and will contribute to the discussion of specific TSH cutoff values in predicting ovarian reserve.
Background: Thyroid dysfunction is prevalent in reproductive-age women and has been identified as a risk factor for female infertility. However, it remains largely unclear whether subtle thyroid dysfunction, as estimated by moderately high thyrotropin (TSH) levels within the normal range, is associated with ovarian reserve in infertile women before assisted reproductive technology (ART) treatment. Methods: This cross-sectional study involved 3501 euthyroid infertile women, including 2189 women with TSH levels ≤2.5 μIU/mL and 1312 women with high-normal TSH levels (2.51-4.20 μIU/mL). Ovarian reserve markers were compared between women with low- and high-normal TSH levels. Correlation analysis and regression models were used to estimate the association of TSH levels with ovarian reserve. In addition, the association of subtle thyroid dysfunction with ovarian reserve was further evaluated after stratification for different infertility diagnoses and statuses of thyroid autoimmunity (TAI). Results: In the total population, women with high-normal TSH levels had significantly decreased anti-Müllerian hormone (AMH) concentrations (p < 0.001), a lower bilateral antral follicle count (AFC) (p < 0.001), and a higher prevalence of diminished ovarian reserve (DOR) (p = 0.018) than women with low-normal TSH levels. The TSH levels showed a negative association with both AMH levels (r = -0.050, p = 0.003) and bilateral AFC (r = -0.071, p < 0.001). Furthermore, the association of high-normal TSH levels with decreased AMH and AFC was more prominent in infertile women with ovulation dysfunction (p = 0.002, p = 0.002), unexplained infertility (p = 0.020, p = 0.028), or negative TAI (both p < 0.001). Conclusions: These data suggested that subtle thyroid dysfunction was associated with DOR in infertile women before ART treatment, which will add evidence that strengthens the systematic screening of TSH levels/TAI in infertile women and will contribute to the discussion of specific TSH cutoff values in predicting ovarian reserve.