Treatment for High Levels of Sperm DNA Fragmentation and Nuclear Decondensation: Sequential Treatment with a Potent Antioxidant Followed by Stimulation of the One-Carbon Cycle vs One-Carbon Cycle Back-up Alone

Current lifestyle can have a negative impact on spermatogenesis via fragmentation of sperm DNA. Attempting to limit generation of ROS-related DNA damage through anti-oxidant supplementation is a tempting option, but current antioxidant treatments are inefficient, and lead to degradation of tertiary structures in sperm nuclear DNA (decondensation) by opening protaminecystine bridges. We investigated the effects of two different treatment regimes in patients, with no major semen anomalies and partners with no female factor detected. All the male partner had a very high level of sperm DNA fragmentation and de condensation: sequential treatment with a potent antioxidant followed by support of the one carbon cycle was compared with one-carbon cycle support alone. These two groups were also compared with a third (control) group of men who chose not to take these supplements. All of the patients who received sequential treatment showed a decrease in their fragmentation index, without concomitant increase in nuclear decondensation. However, patients treated with one-carbon cycle support alone showed similar results. The pregnancy rates reached 50% and over in the treated groups vs 27% in the control group. This confirms a strong correlation between methylation, homocysteine recycling and oxidative stress (Hoffman 2011, Ménézo et al. 2011).