Infertility Risk Higher for Women With Epilepsy

Emma Hitt, PhD

October 12, 2010

October 12, 2010 — Women with epilepsy, especially those taking multiple epilepsy drugs, may be at increased risk for infertility compared with women without epilepsy and those taking no epilepsy drugs, according to new research.

In a cohort of women with epilepsy, more than a third had infertility, with age, lower education, and exposure to multiple drugs being important predictors of infertility.

Sanjeev Thomas, MD, from the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Trivandrum, India, and colleagues report the findings in the October 12 issue of Neurology.

Dr. Thomas emphasized that two thirds of women with epilepsy do not have excess risk for infertility, but clinicians need to be aware of the risk for infertility in women with epilepsy and should make positive enquiries about plans for pregnancy. "All women should be initiated on folic acid in the preconception stage," he told Medscape Medical News.

Dr. Thomas added that clinicians need to reassess the need for antiepileptic drug therapy and consider switching to monotherapy if the clinical situation permits. In addition, a "more detailed work-up for infertility needs to be initiated if a woman fails to conceive in a year or 2," he said.

Complex Interaction

According to the researchers, the link between epilepsy and infertility has not been clearly demonstrated in previous studies. However, they note that some antiepileptic drugs, such as phenobarbital and carbamazepine, "are powerful inducers of hepatic enzymes that are involved in the metabolism of sex hormones," and therefore may interfere with reproductive function.

In the current study, researchers followed 375 women with an average age of 26 years who were anticipating becoming pregnant. The women were followed until they became pregnant or for up to 10 years. During that time, 62% became pregnant, and 38% did not, representing a much higher infertility rate compared with the average rate of about 15% in the local region of India where the study was conducted.

Women who were taking at least 3 epilepsy drugs were 18 times more likely to be infertile than those taking no epilepsy drugs (odds ratio, 17.9; 95% confidence interval, 2.14 - 149.48). Among those taking no epilepsy drugs, 7% were infertile compared with 32% of those taking 1 epilepsy drug, 41% of those taking 2 epilepsy drugs, and 60% of those taking 3 or more epilepsy drugs.

Of the epilepsy drugs, phenobarbital appeared to be associated with the greatest risk for infertility, but no trend was observed with valproate or other drugs. Most women achieved pregnancy within the first 1 to 2 years of follow-up, and older age and lower education were important predictors.

According to Dr. Thomas, the association between infertility and epilepsy may be social, biological, and/or pharmacological and is likely a "complex interaction" that is not yet been adequately understood.

"Some of the antiepileptic drugs are likely to alter the reproductive hormonal balance and predispose to polycystic ovarian syndrome, which in turn is associated with infertility," he told Medscape Medical News. "We have also noticed that spontaneous abortions occur in several women with epilepsy," he said.

Important Contribution

In a related editorial, Alison M. Pack, MD, from Columbia University, in New York City, notes that the researchers have made an "important contribution to our understanding of the risk of infertility in women with epilepsy."

She added that based on the findings of this study, women with epilepsy "should be counseled about the potential risk of infertility and referred for an infertility evaluation if there is a failure to conceive."

The study was sponsored by the Indian Council of Medical Research. The authors and editorialist have disclosed no relevant financial relationships.

Neurology. 2010;75:1351-1355.

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