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Women with epilepsy have high infertility rates. Marriage and childbirth later in life, neuroendocrine effects of seizures, and use of antiepileptic drugs (AEDs) all might underlie this association. The epilepsy and pregnancy registry in Kerala, India, initiated in 1998, prospectively enrolled women with epilepsy who were attempting to conceive. To determine rates and predictors of infertility, researchers followed 375 enrollees for >1 year.
Among 369 women with epilepsy who had known AED status, 14 (4%) were not using AEDs, 211 (57%) received monotherapy, 86 (23%) took 2 AEDs, and 58 (16%) took ≥3 AEDs. During a mean follow-up of 997 days, 38% of women with epilepsy were identified as infertile because they were unsuccessful at conceiving. The infertility rate in Kerala's general population is 15%. Compared with no exposure, use of any AED raised risk for infertility (odds ratio, 1.5; 95% confidence interval, 1.3–1.8); compared with monotherapy, polytherapy was associated with higher risk (OR, 1.3; 95% CI, 1.1–1.6). Multivariable analysis showed that, compared with no AEDs, adjusted ORs for infertility were 5.3 for one AED, 7.3 for two AEDs, and 17.9 for three AEDs. Phenobarbital (whether in monotherapy or polytherapy) was associated with higher rates of infertility, phenytoin did not show a definitive effect, and neither carbamazepine nor valproate was linked to infertility.
Sukumaran SC et al. Polytherapy increases the risk of infertility in women with epilepsy. Neurology 2010 Oct 12; 75:1351.
Pack AM. Infertility in women with epilepsy: What's the risk and why? Neurology 2010 Oct 12; 75:1316.
Comment
These results show that AED use, particularly as polytherapy, contributes to infertility in women with epilepsy. Infertility in women who require polytherapy could be a reflection of underlying epilepsy severity rather than (or in addition to) being caused by the regimens. Surprisingly, phenobarbital, but not carbamazepine or valproate, was associated with infertility (carbamazepine, like phenobarbital, is a hepatic enzyme inducer that can interfere with metabolism of reproductive hormones, and valproate has been associated with polycystic ovary syndrome). This might be explained by the small numbers of phenobarbital users relative to carbamazepine and valproate users, which underscores the need for larger studies of infertility in women with epilepsy. Notably, few or no women with epilepsy were using the newer AEDs (lamotrigine, oxcarbazepine, and topiramate), thereby limiting applicability of these findings to U.S. practice.