Background and Aim: Theophylline acts as a cyclic-AMP phosphodiesterase inhibitor which elevates cAMP dependent sperm motility, however it can also damage sperm DNA integrity. Moreover, Zinc sulfate as an antioxidant can prevent sperm DNA damages. Objective:We investigated the effect of co-administration of theophylline and zinc sulfate on the improvement of sperm parameters and DNA integrity in asthenoteratozoospermic men. Methods: 120 asthenoteratozoospermic patients participated in a double-blind, randomized clinical trial study and were randomly divided into four groups: Placebo, theophylline, theophylline+zinc sulfate and zinc sulfate. After 3 months of Oral treatment, the sperm parameters were analyzed using the CASA system and the DNA fragmentation was also analyzed using sperm chromatin dispersion test at the beginning of the trial and at the end of the treatment. Data was analyzed statistically using the Repeated measurements ANOVA and the means were considered significantly different at P<0.05. Results: sperm motility and count and also the number of sperms with normal morphology increased significantly in all three groups compared to the placebo group but this increase was significantly higher in the theophylline + zinc sulfate group than the theophylline and zinc sulfate groups. Sperm DNA fragmentation increased significantly in the Theophylline group, while it showed a significant reduction in the zinc sulfate group compared to the placebo. There was no significant difference in the mean sperm DNA fragmentation in the theophylline + zinc sulfate group compared to the placebo. Conclusion: Co-administration of theophylline and zinc sulfate, as an antioxidant, could improve the sperm parameters and protect the sperm DNA from the undesirable effects of theophylline. Therefore, this drug combination can be prescribed in cases of infertile men with asthenoteratozoospermia.
