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

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

Author information

Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts.



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.


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.


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.


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.

[Available on 2019-02-01]
[Indexed for MEDLINE]

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