Low-Normal Thyroid Implicated in Unexplained Infertility

Becky McCall

December 27, 2017

A slightly underactive thyroid gland, the low end of normal, may help to explain some infertility of unknown cause, according to findings of a cross-sectional study published online in the Journal of Clinical Endocrinology & Metabolism.

Specifically, nearly twice as many women with unexplained infertility (26.9%) had a thyroid-stimulating hormone (TSH) level greater than 2.5 mIU/L compared with control patients with normal fertility (13.5%) (P < .05), and on average, those with unexplained infertility showed higher than normal levels of TSH, which is usually elevated in women with underactive thyroid glands.

The study was led by Tahereh Orouji Jokar, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts.

Importantly, write the authors, "All of the subjects in this study had TSH levels within the normal, pre-pregnancy reference range, suggesting that even mild variations of thyroid dysfunction within the normal range may be an important factor in fertility in women who have no known cause for their infertility."

"When couples who are ready to start a family are unable to conceive despite extensive planning, multiple doctor's visits, and expensive treatments, it can be emotionally devastating," noted senior author Pouneh K. Fazeli, MD, also from Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts, in an Endocrine Society press release.

"Since our study shows that women with unexplained infertility have higher TSH levels compared to women experiencing infertility due to a known cause, more research is needed to determine whether treating these higher TSH levels with thyroid hormone can improve their chances of getting pregnant."

Thyroid Hormone Replacement May Help Some Infertile Women to Conceive

Up to 30% of infertile couples have unexplained infertility, defined as the inability to conceive after 12 months of unprotected intercourse with no diagnosed cause.

Results of prior studies that have looked at the relationship between TSH levels and conception rates or time to pregnancy have shown conflicting results, say Dr Jokar and colleagues.

To better understand the issue, they set out to compare TSH (and prolactin levels) in women with unexplained infertility with those in women with normal fertility except for the fact their male partner had no, or low, sperm in their semen (control group).

In this way, their study differed from the prior studies by using very strict criteria to ensure patients had regular menstrual cycles and completely normal fertility evaluations in the control group (other than azoospermia/severe oligospermia among the males) and no known history of thyroid disease or abnormal thyroid function tests.

They analyzed electronic records data from 187 women with unexplained infertility, a mean age of 31 years, and a median body mass index of 23 kg/m2 and compared the outcomes with 52 women in the control group. All women had a TSH measurement within the normal range (upper limit of normal, <5 mIU/L).

Women with unexplained infertility had a significantly higher median TSH level than control patients (1.95 vs 1.66 mIU/L; P = .003), even after controlling for age, body mass index, and smoking status. Prolactin levels did not differ between the groups.

Despite current practice guidelines not recommending treatment for patients with a high-normal TSH level who are attempting to conceive naturally, some clinicians do prescribe thyroid hormone replacement.

In the study, 22.8% of patients with a TSH of at least 2.5 mIU/L were started on thyroid hormone replacement after their initial evaluation; this means that three quarters were not, demonstrating the great variance in clinical practice and the important need for more data.

"Since we now know from our study that there is an association between TSH levels at the high end of the normal range and unexplained infertility, it is possible that a high-normal TSH level may negatively impact women who are trying to get pregnant," Dr Fazeli pointed out.

"This could open up new avenues for possible treatments. The next step will be to see if lowering TSH levels will help this group conceive."

The authors have disclosed no relevant financial relationships.

J Clin Endocrinol Metabol. Published online December 19, 2017. Abstract

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