AT THE AAN 2016 ANNUAL MEETING
VANCOUVER (FRONTLINE MEDICAL NEWS) – Women with epilepsy have fertility rates comparable with healthy women in the general population, according to results from the first prospective observational cohort study to make the comparison.
During the year-long Women With Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study, 70% of women with epilepsy and 67% of healthy control women became pregnant, and there was no significant difference in the mean time to pregnancy between those with and without epilepsy (6 months vs. 9 months, respectively), Dr. Page Pennell reported at the annual meeting of the American Academy of Neurology.
Live births occurred in 82% of pregnancies of women with epilepsy and 80% of controls, while miscarriages occurred in 13% and 20%, respectively. Both of those rates are very similar to the general population. Another 5% of pregnancies in women with epilepsy were ectopic, terminated due to chromosomal abnormality, or lost to follow-up.
“These findings should reassure women with epilepsy and clinicians when counseling women with epilepsy who are planning pregnancy,” said Dr. Pennell, director of research for the division of epilepsy in the department of neurology at Brigham and Women’s Hospital in Boston. She is a primary investigator of the study along with Dr. Jacqueline French, professor of neurology at NYU Langone Medical Center and Dr. Cynthia Harden, system director of epilepsy services at Mount Sinai Beth Israel, both in New York.
“I think overall the findings are more in the light of myth busting. … We don’t necessarily see a lot of problems with fertility, yet the literature suggests that the birth rates are much lower,” Dr. Harden said in an interview.
“It’s really the first solid evidence, and it’s nice because in a sea of bad news for women when it comes to family planning and achieving pregnancy and pregnancy outcomes, I think this was very positive to say that their ability to achieve pregnancy was no different than what was reported by a control population without epilepsy,” Dr. Katherine Noe, an epilepsy specialist at the Mayo Clinic in Scottsdale, Ariz., said when asked to comment on the study.
“There was certainly reason to be concerned,” said Dr. Noe, who was not involved in the study. “We have a lot of data saying that babies exposed to antiepileptic drugs are more likely to have malformations, and so you could have a baby that already early in pregnancy has severe malformations that would be more likely to end in spontaneous abortion.”
Dr. Noe said that pregnancy registry data indicate that women with epilepsy may be more likely to have a pregnancy that ends in a miscarriage. Investigators for several studies published in 2015 reported that women with epilepsy face greater risk for morbidity and adverse outcomes at the time of delivery and during pregnancy than women without epilepsy ( JAMA Neurol. 2015;72:981-8 and Lancet. 2016;386:1845–52 ). Women with epilepsy also have been thought to be more prone to infertility for various reasons, including menstrual irregularities, polycystic ovarian syndrome related to antiepileptic medications, and early menopause, she said.
Three previous studies had reported that women with epilepsy had birth rates as low as only one-quarter to one-third that of women without epilepsy. There have been many reasons reported for why that might be the case, including lower marriage rates, sexual dysfunction, lower libido (in both men and women with epilepsy), and increased number of anovulatory cycles, or greater choice to not become pregnant, Dr. Pennell said.
The WEPOD study enrolled 89 women with epilepsy and 109 healthy controls who were seeking to become pregnant and had stopped using contraception within 6 months of enrollment or were about to stop using it. The investigators excluded women with infertility, polycystic ovarian syndrome, endometriosis, endocrine disorder, and heavy smoking, or who were not in an exclusive heterosexual relationship with a significant other or spouse.
Participants received iPod touch devices with an app with which they tracked menses and intercourse, as well as antiepileptic drug use and seizures in women with epilepsy. “This was a particularly novel part of the study,” Dr. Harden said. It allowed the investigators to track adherence very well. Participants logged about 87% of their days in the app, and the investigators could see when the entries were made.
Women in both groups had a mean age of about 31 years and mean body mass index of about 25 kg/m2. Overall, 52%-58% had undergone a prior pregnancy. Women with epilepsy, compared with controls, were less often Asian (17% vs. 6%) or African American (16% vs. 1%). The education level of participants was “fairly similar” between the groups, and slightly more women with epilepsy were unemployed (21% vs. 10%). Women with epilepsy also were more often married than were controls (89% vs. 75%).
During the study, 36% of women with epilepsy were still having seizures. At enrollment, most of the women’s seizure types were generalized (30%) or focal only (63%). Dr. Pennell noted that the antiseizure medications that the women were taking were typical for women of reproductive age: lamotrigine monotherapy (44%), levetiracetam monotherapy (28%), monotherapy with a strong enzyme-inducing drug (12%), other polytherapy (10%), polytherapy with a strong enzyme-inducing drug (6%), other monotherapy (3%), or no antiseizure medication (2%). A few women either added or stopped drugs during the study. A total of 18 women with epilepsy and 15 healthy controls dropped out.
As expected, age affected the likelihood of becoming pregnant, as well as number of prior pregnancies. Body mass index did not affect the likelihood of becoming pregnant, while white race and being married increased the likelihood.
In future analyses, the investigators are planning on checking whether ovulatory rates, frequency of intercourse, and time of intercourse had any impact on pregnancy, and in women with epilepsy, they will check the effect of the type of antiseizure medication and seizure-related factors.
“I think our findings will stand with future analyses.” Dr. Harden said. “The most interesting future findings may come from within the epilepsy group,” she said, noting that older antiepileptic medications have been previously associated with difficulty conceiving.
The WEPOD study was funded by the Milken Family Foundation, the Epilepsy Therapy Project, and the Epilepsy Foundation.