Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women Seeking Infertility Care

Abstract

Background: While overt thyroid disease is a well known risk factor for infertility, the potential consequences of mild thyroid dysfunction or thyroid autoimmunity remain unknown. Experimental studies suggest a considerable role for thyroid hormone in the physiological mechanisms of ovarian reserve, but translation of such findings to human studies remains rare. A potential role for thyroid function in female reproduction could be especially relevant when the cause of infertility remains unknown, such as in women with diminished ovarian reserve (DOR) or unexplained infertility. The aims of this study were to investigate the association of thyroid function and autoimmunity with markers of ovarian reserve day 3 follicle-stimulating hormone (FSH) concentrations and antral follicle count (AFC), and to investigate whether thyroid function or autoimmunity may have different effects in women with DOR or unexplained infertility.

Methods: Thyrotropin, free thyroxine, thyroxine, free triiodothyronine (fT3), triiodothyronine, thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs), as well as AFC and the day 3 FSH concentration, were measured among women seeking fertility treatment at the Massachusetts General Hospital Fertility Center. Multiple linear or mixed regression models were used to study the association of thyroid function or autoimmunity with AFC or day 3 FSH.

Results: In the total study population (436 women, 530 AFC measurements), there was no association of thyroid function or TPOAb positivity with AFC. However, TgAb positivity was associated with a higher AFC (mean difference = 3.4 [95% confidence interval (CI) 1.8-5.1], p < 0.001). In women with DOR or unexplained infertility, lower fT3 and TPOAb positivity were associated with a lower AFC (fT3: continuous nonlinear association, p = 0.009; TPOAb positivity: -2.3 follicles [confidence interval -3.8 to -0.5], p = 0.01), while TgAb positivity was not associated with AFC. Neither thyroid function nor thyroid antibody positivity was associated with the day 3 FSH concentration.

Conclusions: This study found that lower fT3 and TPOAb positivity are associated with a lower AFC in women with DOR or unexplained infertility. Future studies are required to replicate these findings and further elucidate the role of TgAbs and underlying mechanisms through which thyroid function and autoimmunity is associated with ovarian reserve.

Keywords: TPO antibody; antral follicle count; thyroid.

Conflict of interest statement

The authors have nothing to disclose.

Figures

FIG. 1.

Flow chart for final study population selection. *Excluded due to multicystic ovaries, difficult to visualize, or absent ovary.

FIG. 2.

Plots show the association of thyrotropin (TSH), free thyroxine (fT4), or free triiodothyronine (fT3) with the antral follicle counts as the predicted mean count (black lines) with confidence interval (gray area). All analyses were adjusted for age, body mass index (BMI), smoking, ethnicity, and infertility cause.

FIG. 3.

Plots show the association of TSH, fT4, or fT3 with the follicle-stimulating hormone (FSH) concentration measured at the third day of the menstrual cycle as the predicted mean count (black lines) with confidence interval (gray area). All analyses were adjusted for age, BMI, smoking, ethnicity, and infertility cause.

FIG. 4.

Plots show the association of TSH, FT4, or fT3 with the antral follicle count as the predicted mean count (black lines) with confidence interval (gray area). All analyses were adjusted for age, BMI, smoking, ethnicity, and infertility cause.

FIG. 5.

Plots show the association of day 3 FSH with the antral follicle count as the predicted mean count (black lines) with confidence interval (gray area), as modeled using the whole data set for women within the lowest 10% of fT3, TgAb-positive or TPOAb-positive women (all shown by continuous lines), or the highest 10% of fT3, TgAb-negative, or TPOAb-positive women (dotted lines). All analyses were adjusted for age, BMI, smoking, ethnicity, and infertility cause.