Effect of isotretinoin on sperm quality in humans: an in vitro model

Isotretinoin is a retinoid widely used for severe acne, known for its teratogenicity, but with an unclear impact on male fertility and the risk of fetal exposure through semen. This study evaluated in vitro the effect of different concentrations of isotretinoin (therapeutic and extremely high) on the motility, vitality, and integrity of human sperm DNA.

For this purpose, human semen samples (n=17) were exposed to isotretinoin concentrations of 22 nM, 660 nM, 66,000 nM, and 660,000 nM. Sperm motility and vitality were assessed up to 5 hours post-exposure, while DNA fragmentation was evaluated at 2 hours.

Concentrations of 22 nM, 660 nM, and 66,000 nM did not significantly affect the sperm assessed parameters. However, the highest concentration (660,000 nM) induced immediate cytotoxicity in human sperm, resulting in 100% immotile and nonviable sperm cells, as well as increased sperm DNA fragmentation.

Knowing that the concentrations achieved clinically in semen and blood are considerably lower than the cytotoxic concentration, these findings suggest that treatment with therapeutic doses of isotretinoin does not compromise human sperm function in vitro.