Sperm DNA fragmentation

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. I agree with Agarwal et al. (1) that sperm DNA fragmentation (SDF) should be included in the evaluation of male factor infertility, along with semen analysis. Although there exist divergent views on this topic, our group has routinely employed SDF (TUNEL assay) and other methods for identification of sperm DNA damage (Chromomycin A3, MitoTracker Green, Annexin V) during the investigation of male factor infertility over the last 10 years. We call this global assessment sperm DNA integrity (SDI), and during this time we analyzed some clinical implications, as below. (I) Are there age thresholds for increased SDI? The effect of aging on SDF was evaluated in 2,178 semen samples. SDF deteriorated with aging (SDF: ≤35 years, 14.7%; ≥36 years, 16%; P<0.05), and this seems to be associated with mitochondrial damage (2). Sperm apoptosis, measured using Annexin V, is not correlated with aging (apoptosis: ≤35 years, 19.1%±8.0%; 36–39 years, 19.3%±7.9%; P>0.05) (2). Evidence suggests that there are declines in semen quality and male fertility associated with increasing male age. Advanced paternal age has been implicated in a higher frequency of miscarriages, autosomal dominant diseases, aneuploidy, and other disorders. Advanced male age has also been correlated with infant mortality (3-5). One plausible explanation for these outcomes is that older men may have more sperm with damaged DNA. Chromatin damage has been associated with male infertility, conception problems, and difficulties to sustain a pregnancy. There is also evidence linking sperm DNA damage with the risk of mutations and birth defects (6-9). The age-related increase in sperm DNA damage suggests that delaying childbearing, not only for women but also for men, may jeopardize the couple’s reproductive capacity. (II) Does varicocele affect SDI? SDI is considered a marker of male fertility potent ia l . High leve l s o f SDF have been significantly linked to lower rates of natural conception and assisted reproductive pregnancies (1,10). Varicocele has been associated with increased levels of reactive oxygen species and decreased seminal antioxidant capacity, increased SDF and defective spermatogenesis in affected patients. A cross-sectional study was carried out with semen samples from 2,399 men, randomly selected from couples who attended an infertility clinic. A total of 16.3% (391/2,399) of the men had a varicocele (11). Physical examination was used to diagnose varicocele. Individuals with varicocele have increased SDF associated with an increase in abnormal mitochondrial activity and an increase in abnormal chromatin packaging (SDF with varicocele, 16.3%±8.8%; SDF without varicocele, 15.3%; OR: 1.02, 95% CI, 1.01–1.03, P=0.03) (11). (III) Is overweight/obesity associated with a decrease in sperm quality and impaired SDI? Obesity appears to have a negative influence on the male fertility and reproductive function overall. Overweight and obesity have been associated with significant reductions in the levels of total testosterone, free testosterone, and sex hormoneCommentary