Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility

J Clin Endocrinol Metab. 2018 Feb 1;103(2):632-639. doi: 10.1210/jc.2017-02120.


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 including women evaluated at a large academic health system between 1 January 2000 and 31 December 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asymptomatic Diseases
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Hyperthyroidism / blood
  • Hyperthyroidism / complications
  • Hyperthyroidism / diagnosis
  • Infertility / blood*
  • Infertility / diagnosis
  • Infertility / etiology
  • Male
  • Middle Aged
  • Reference Values
  • Thyroid Function Tests / standards*
  • Thyrotropin / blood*
  • Young Adult


  • Thyrotropin