Male infertility: Possible association with valproate exposure

Purpose: To describe a potential association between male infertility and v alproate (VPA) exposure. VPA has been implicated in the development of poly cystic ovarian disease and subsequent menstrual and infertility problems in women with epilepsy. Infertility has been well described in population-bas ed studies of persons with epilepsy. The low marital rates for men with epi lepsy have previously been thought to play a major contributing role. Methods: We report a case of a 32-year-old man whose wife and he were able to bear a child before the development of his epilepsy. With VPA monotherap y, the family were unable to conceive despite 3 years of unprotected interc ourse. An infertility evaluation of the man revealed a very low sperm count of <50,000/ml, no motile sperm, <10% viability, and 100% with abnormal str ucture. Follicle-stimulating hormone, luteinizing hormone, and testosterone levels were normal. Results: Felbamate (FBM) was initiated and VPA discontinued for improved se izure control. Within 4 months, the couple conceived their second child. A seminal analysis revealed a sperm count of >16 million, 50% motility, 78% v iability, and 72% with abnormal structure. Conclusions: One must be cautious in extrapolating from a case report, but these findings strongly suggest a direct effect of VPA on spermatic structu re and function.