Higher TSH levels within the normal range are associated with unexplained infertility

Abstract

Context: Unexplained infertility (UI), defined as the inability to conceive after 12 months of unprotected intercourse with no diagnosed cause, affects 10% to 30% of infertile couples. An improved understanding of the mechanisms underlying UI could lead to less invasive and less costly treatment strategies. Abnormalities in thyroid function and hyperprolactinemia are well-known causes of infertility, but whether thyrotropin (TSH) and prolactin levels within the normal range are associated with UI is unknown. Objective: To compare TSH and prolactin levels in women with UI and women with a normal fertility evaluation except for an azoospermic or severely oligospermic male partner. Design, Setting, and Participants: Cross-sectional study includingwomen evaluated at a large academic health systembetween 1 January 2000 and 31December 2012 with normal TSH (levels within the normal range of the assay and < 5 mIU/L) and normal prolactin levels (< 20 ng/mL) and either UI (n = 187) or no other cause of infertility other than an azoospermic or severely oligospermic partner (n = 52). Main Outcome Measures: TSH and prolactin. Results: Women with UI had significantly higher TSH levels than controls [UI: TSH 1.95 mIU/L, interquartile range: (1.54, 2.61); severe male factor: TSH 1.66 mIU/L, interquartile range: (1.25, 2.17); P = 0.003]. This finding remained significant after we controlled for age, body mass index, and smoking status. Nearly twice as many women with UI (26.9%) had a TSH > 2.5 mIU/L compared with controls (13.5%; P < 0.05). Prolactin levels did not differ between the groups. Conclusions: Women with UI have higher TSH levels compared with a control population. More studies are necessary to determine whether treatment of high-normal TSH levels decreases time to conception in couples with UI.