Women with epilepsy who want to have children may find it hard to become pregnant — a prospective study from India has found a high rate of infertility among epileptic women.
The study, which followed 375 women with epilepsy for up to 10 years, found that 38.4% failed to conceive, according to Sanjeev Thomas, MD, of the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Trivandrum, India, and colleagues.
Factors associated with a greater likelihood of being infertile included being older than 25, less than 10 years of education, and the use of three or more antiepileptic medications (P<0.05 for all), Thomas and co-authors reported in the Oct. 12 issue of Neurology.
“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,” wrote Alison Pack, MD, of Columbia University, in an accompanying editorial.
Thomas and colleagues followed women with epilepsy who enrolled in India’s Kerala Registry of Epilepsy and Pregnancy in the preconception phase (within 15 days of their last menstrual period) from 1998 to 2007. All of the women planned to get pregnant.
Over a follow-up of one to 10 years, among the 375 women included in the analysis, 231 became pregnant and 144 did not. Pregnancy occurred within two years for most of the women who did conceive.
Although the study did not include a control group, the researchers compared the infertility rate with that of a similarly-aged group of married women living in Kerala, finding it to be more than twice as high in the women with epilepsy (38.4% versus 15.13%).
Among the study cohort, only 3.7% were not taking any antiepileptics; most (56.2%) were on monotherapy, 22.9% were taking two drugs, and 15.5% were taking at least three epilepsy medications.
The rate of infertility increased linearly as exposure to antiepileptics increased from none (7.1%) to three or more (60.3%) (P=0.001 for trend).
Polytherapy was associated with a greater likelihood of infertility compared with monotherapy (OR 1.33, 95% CI 1.11 to 1.60).
When looking at specific drugs, the researchers found that only phenobarbital had a definite relationship with the likelihood of infertility — both as monotherapy (OR 1.52, 95% CI 0.94 to 2.46) and as either monotherapy or polytherapy (OR 1.43, 95% CI 1.09 to 1.87).
Other antiepileptics, including valproate, did not appear to be related to infertility.
“The enzyme-inducing antiepileptic drugs like phenobarbital and carbamazepine may influence the concentration of steroid hormones and the sex hormone binding globulin, resulting in decreased bioavailability of estradiol, which in turn may lead to menstrual irregularity,” Thomas and co-authors explained.
Low educational levels and being age 25 or older were both determined to be significant predictors of infertility (P<0.05 for both).
In addition, using at least three antiepileptics was associated with a greater likelihood of infertility, which “may be due to the direct adverse effect of polytherapy or the indirect effect of underlying refractory epilepsy that required polytherapy,” according to the researchers.
The latter explanation was supported by Steven Pacia, MD, director of the Comprehensive Epilepsy Center at Lenox Hill Hospital in New York City.
In a statement, he said that “patients with more severe epilepsy can be expected to have a higher incidence of cognitive problems, mood disorders, and hyposexuality, which may also lead to higher rates of infertility.”
Thomas and colleagues acknowledged that their study was limited by the lack of a control group, and urged that larger studies addressing demographic factors such as age and educational status need to be carried out.
The study was sponsored by the Indian Council of Medical Research.
Thomas reported serving as editor of Annals of Indian Academy of Neurology.
Pack reported serving as a consultant to Pfizer and receiving funding from the NIH.