Women with epilepsy may have a higher-than-average risk of fertility problems, particularly those on multiple anti-seizure drugs, a study published Monday suggests.

Researchers in India found that among 375 women with epilepsy who were trying to become pregnant, 62 percent successfully conceived, usually within two years. The rest, 38 percent, remained infertile over an average of three years of follow-up.

That compared with an infertility rate of 15 percent among married women in the surrounding Indian state of Kerala, according to the researchers.

The findings, reported in the journal Neurology, strengthen the evidence that women with epilepsy have a higher-than-average risk of fertility problems. They also indicate that women taking multiple anti-epilepsy drugs may be particularly at risk.

Of women on just one medication, 32 percent failed to conceive during the study period. That figure was 41 percent among women on two epilepsy drugs, and 60 percent among those on three or more drugs. Only 7 percent of those not taking any anti-seizure medication failed to conceive during the study.

The results do not prove, however, that the drugs themselves are to blame, or at least fully to blame.

Since women on multiple epilepsy drugs are likely to have more severe epilepsy, it’s possible that the severity of the disorder plays a role, according to Dr. Alison M. Pack, a neurologist at Columbia University Medical Center in New York and author of an editorial published with the study.

Whatever the reasons for the association, Pack told Reuters Health, “This suggests that women with epilepsy should be advised that they may have a higher-than-average risk of infertility.”

She suggested that women who are planning a pregnancy talk with their doctors; if possible, those on multiple epilepsy drugs may want to trim their drug regimen down.

Guidelines from the American Academy of Neurology and American Epilepsy Society already suggest that during pregnancy, women take only one anti-seizure medication whenever possible to lower the chances of birth defects.

In particular, women are advised to avoid the older epilepsy drug valproate (Depakene, Epival) during pregnancy; two other older medications - phenobarbital (Luminal) and phenytoin (Dilantin) - should also be limited.

It is not clear which drugs in particular may be related to fertility problems. In the current study, phenobarbital was the only individual drug associated with an increased infertility risk.

Phenobarbital and some other older epilepsy medications, like carbamazepine (Carbatrol, Tegretol), induce liver enzymes that affect blood levels of estrogen and other reproductive hormones. So it’s possible that they could affect a woman’s ability to become pregnant, said Pack, who is also a consultant to Pfizer, Inc., maker of the epilepsy drug Neurontin (gabapentin).

She noted that too few women were on any of the newer drugs commonly used in developed countries for the researchers to assess their association with fertility. Those include medications like topiramate (Topamax), levetiracetam (Keppra), lamotrigine (Lamictal) and oxcarbazepine (Trileptal).

More research is still needed into how the various epilepsy drugs might affect fertility, Dr. Sanjeev V. Thomas, the senior researcher on the study, told Reuters Health in an e-mail.

What the current findings do is solidify a connection between epilepsy and infertility, according to Thomas, of the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Trivandrum, India.

Some past studies have found that women with epilepsy have lower-than-average pregnancy rates, but it has been suggested that lower marriage rates or women’s personal decisions against pregnancy might explain the connection.

“This is probably the first time that it has been demonstrated that women with epilepsy who intend to become pregnant may experience increased risk of infertility,” Thomas said.

The findings are based on 375 women with epilepsy who were planning a pregnancy and were followed for an average of almost three years, and up to 10 years in some cases. All were seen at the researchers’ medical center, which specializes in treating neurological disorders.

Overall, 38 percent of the women failed to conceive during the study period. The researchers lacked a control group of women without epilepsy; instead they used data reported for the general population of Kerala, indicating that about 15 percent of married women were infertile.

The comparison of epileptic women from a hospital-based sample with statistics for the general population is not a perfect one, the researchers acknowledge, adding that larger studies are still needed.

Besides multiple-drug therapy, lower education levels and older age were also related to a greater risk of infertility in the epilepsy group.

“Putting all these factors together,” Thomas said, “it appears that more-difficult epilepsy that is drawn over longer period of time and requiring treatment with multiple anti-epileptic drugs is associated with increased risk.”

Thomas also said it is important to keep in mind that the majority of women with epilepsy in this study, particularly those with milder epilepsy requiring only one drug, successfully became pregnant.

SOURCE:  Neurology, October 12, 2010.