Abstracts

Few studies have investigated the effects of valproate (VPA) and carbamazepine (CBZ) on human sperm, and decreased sperm motility was one of the findings. Our aim was to further study the effects of CBZ and VPA on human sperm motility, including sperm ability to penetrate cervical mucus, a functional test not hitherto studied in relation to antiepileptic drugs (AEDs). VPA was dissolved in PBS, CBZ in 2.5% ethanol + PBS. Normal semen from healthy human donors (sperm count[gt]20 million/mL, [gt]50% motile, progressive type of movement) was incubated for 2hr with several dilutions of VPA or CBZ. Parameters analyzed included sperm motility (% motile cells), EC50, motility quality grade (1-6), identification of abnormal motiltity patterns, and ability of spermatozoa to penetrate into bovine cervical mucus after 10 min contact (number of cells penetrating, depth of penetration). Statistical analysis was performed using the Wilcoxon Signed Ranks Test. VPA significantly (p[lt]0.05) decreased sperm motility at concentrations [ge]3125mg/L, with EC50=12500mg/L. Motility quality grade was decreased at concentrations [ge]12500mg/L. Cervical mucus penetration was inhibited at concentrations [ge]6250mg/L. [quot]Shaking[quot], an abnormal motility pattern, was observed at [ge]12500mg/L.
CBZ significantly (p[lt]0.05) decreased sperm motility at concentrations [ge]156mg/L, with EC50=312mg/L. Motility quality grade was decreased at concentrations [ge]312mg/L. Cervical mucus penetration was also inhibited at concentrations [ge]312mg/L. The [quot]shaking[quot] pattern was observed at [ge]156mg/L. Both VPA and CBZ impair sperm motility, quantitatively and qualitatively, at concentrations well above the therapeutic range. These concentrations also impair the ability of human spermatozoa to penetrate into bovine cervical mucus, the composition and properties of which are similar to human cervical mucus. This finding implies impairment of the physiologic function of spermatozoa by high concentrations of these AEDs.