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January 5, 2018

Explaining "Unexplained" Infertility

For couples trying to get pregnant, fertility problems with no known cause are hard to take. Here's something new to consider.

Infertility is heartbreaking for women trying to become or remain pregnant and affects about 10 percent of women in the United States. A woman is labeled as being infertile when she has not been able to become pregnant after one year of unprotected intercourse. Couples often undergo extensive and expensive medical evaluations to search for a cause.

In women, the causes of infertility can include anatomic malformations as well as endocrine and ovarian problems. The causes of infertility in men include abnormal semen and sperm. Infertility treatment is based on the underlying cause, but may not always be effective, and in 10 to 20 percent of cases, no cause, in either the man or the woman, is found to explain a couple's inability to become pregnant: There is normal ovulation, healthy fallopian tubes, normal uterine cavity and normal semen analysis.

Women with otherwise unexplained infertility had significantly higher TSH levels than women whose infertility was linked to their partners' sperm count.

Low thyroid, or hypothyroidism, can affect fertility by causing irregular menstrual cycles and abnormal ovulation. But what about women whose thyroid function is within the normal range but who have levels drifting toward the abnormal limits? A recent study explored whether thyroid function, as estimated by Thyroid Stimulating Hormone (TSH) level, was related to infertility.

Thyroid stimulating hormone (TSH) is produced by the pituitary gland and serves to regulate the production of thyroid hormone by the thyroid gland. When thyroid hormone dips below normal, more TSH is produced, making TSH levels a good way to measure the adequacy of the body's thyroid hormone supply. A rising level of TSH can reflect an underactive thyroid gland and, in fact, is considered to be a more accurate indicator than measuring thyroid hormone itself. Women whose thyroid function is within the normal range but at the low end will show TSH levels that are creeping upward. The upper limit of normal for TSH is still being debated and an absolute number has not been agreed upon by all experts, but current guidelines suggest the normal level should be less than 4 mIU/L.

Researchers at Harvard Medical School wanted to see if women with unexplained infertility had TSH levels that, while still within the normal range, were somewhat high, making it likely that a subtle form of hypothyroidism was impacting their fertility. They looked at women with fertility problems who had no history of thyroid disease and normal thyroid function tests.

The TSH levels in nearly 200 women with unexplained infertility were compared with those of a control group of 57 women who had normal infertility work-ups themselves, but were infertile because of inadequate exposure to healthy sperm as a result of having to a male partner with a low or no sperm count.

The women with otherwise unexplained infertility had significantly higher TSH levels than controls. Nearly twice as many had TSH levels greater than or equal to 2.5 mIU/L. Although this level is within the normal reference range, it points to mild variations of thyroid dysfunction. The authors suggest that this shows that even TSH levels within the normal range may be an important factor in women with unexplained infertility.

At this point, the research shows an association between rising TSH and unexplained infertility, but does not prove cause and effect. More research is needed, but the findings may open up avenues of treatment for unexplained infertility, such as giving thyroid supplement, that may avoid the need for some patients to undergo more expensive and invasive evaluations.

The study is published in The Journal of Clinical Endocrinology & Metabolism.
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