Purpose Infertile men possess substantially more sperm DNA damage than do fertile men, damage that may impact negatively on reproductive outcomes. In this era of assisted reproductive technologies there is mounting concern regarding the safety of utilizing DNA-damaged spermatozoa in this setting. Therefore, it is important to identify strategies that may reduce sperm DNA damage. The purpose of this review is to discuss the rationale for antioxidant therapy in men with sperm DNA damage and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm DNA damage. Methods We reviewed the literature on antioxidants and sperm DNA damage. Results To date, the data suggest that dietary antioxidants may be beneficial in reducing sperm DNA damage, particularly, in men with high levels of DNA fragmentation. However, the mechanism of action of dietary antioxidants has not been established and most of the clinical studies are small. A beneficial effect of in vitro antioxidant supplements in protecting sperm DNA from exogenous oxidants has been demonstrated, however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established.

There is evidence from retrospective studies that varicocelectomy can improve sperm DNA damage in infertile men with a clinical varicocele. The objective of this prospective study was to examine further the effect of varicocelectomy on sperm chromatin and DNA integrity. We evaluated a consecutive series of infertile men (n = 25) who underwent microsurgical varicocelectomy for treatment of clinical varicocele. We examined conventional sperm parameters and sperm chromatin structure assay parameters (percentage DFI--DNA fragmentation index and percentage HDS--high DNA stainability, an index of chromatin compaction) before and 4 and 6 months after microsurgical varicocelectomy. Sperm DNA integrity improved significantly after surgery (percentage DFI decreased from 18 ± 11% before surgery to 10 ± 5%, and 7 ± 3%, at 4 and 6 months after surgery respectively). Sperm chromatin compaction also improved significantly after surgery (percentage HDS decreased from 11 ± 7% before surgery to 8 ± 6%, and 7 ± 5%, at 4 and 6 months after surgery, respectively). Sperm concentration and progressive motility improved after surgery, although the differences were not statistically significant when compared with that before surgery. The data show that varicocelectomy is associated with an improvement in sperm DNA integrity and chromatin compaction. These findings support the concept that correction of a varicocele can improve spermatogenesis, particularly spermiogenesis (the stage in spermatogenesis where compaction and stability of the sperm DNA and chromatin occur).

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Background Sperm DNA damage is associated with male infertility but whether normozoospermic infertile men also have DNA damage is unknown. Objective To evaluate sperm DNA and chromatin integrity in men with mild male factor infertility. Design, setting and participants Prospective study of 102 consecutive men (78 normozoospermic, 15 asthenozoospermic, 9 oligozoospermic) enrolled for intrauterine insemination (IUI) and 15 fertile controls. Outcome measurements and statistical analysis Standard semen parameters and sperm chromatin and DNA integrity were assessed and compared between groups. Sperm chromatin quality was assessed by (1) aniline blue staining (AB is specific to histone lysines), (2) iodoacetamide fluorescein fluorescence (IAF targets free protamine sulfhydryl groups) and (3) sperm chromatin structure assay (SCSA) with the results expressed as % DNA fragmentation index (%DFI). Results and limitationsThe mean (±SD) percentage of spermatozoa with positive IAF fluorescence was significantly higher in the IUI population compared to fertile controls (17 %±10 % vs. 8 %±6 %, P =0.0011) and also in the normozoospermic subset (n = 78) compared to controls (16 %±9 % vs. 8 %±6 %, P <0.0001, ANOVA). We also observed a trend toward lower %progressive motility, and higher %AB staining and %DFI in the IUI group compared to controls. We observed significant relationships between sperm %DFI and progressive motility (r =−0.40, P <0.0001) and between positive AB staining and IAF fluorescence (r =0.58, P <0.0001). Conclusions The data indicate that sperm chromatin integrity may be abnormal in men enrolled in IUI treatment cycles, despite the fact that most of these men are normozoospermic.

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These findings support the concept that correction of a varicocele can improve spermatogenesis and sperm function, as mitochondrial DNA copy number has been suggested to reflect the efficiency of spermatogenesis and has been inversely related to sperm motility.

The data demonstrate that infertile men have a higher proportion of spermatozoa with diffuse histone H2B than do fertile men and suggest that sperm DNA damage might, at least in part, be due to abnormally high histone H2B levels.