STUDY QUESTION What is the relationship between sperm DNA fragmentation and oxidative stress (OS) with increasing male age? SUMMARY ANSWER Sperm DNA fragmentation increases with age and is likely related to both defective spermatogenesis and increasing OS levels. WHAT IS KNOWN ALREADY Sperm quality declines with age. The presence of DNA damage in a high fraction of spermatozoa from a raw semen sample is associated with lower male fertility in natural conception and intrauterine insemination. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of 16 945 semen samples analysed at a single reference laboratory between January 2010 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS All males were undergoing an infertility evaluation. The cohort was divided into seven age categories: <30, 30–34, 35–39, 40–44, 45–49, 50 to <54 and ≥55 years. The mean age was 37.6 years (SD 6.8). Sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) were calculated using flow cytometry. OS levels were measured using the oxidative stress adducts (OSA) test, by spectrophotometry. ANOVA with weighted polynomial contrast analysis was used to evaluate trends for DFI, OSA and HDS values across age categories. MAIN RESULTS AND THE ROLE OF CHANCE Mean DFI significantly increased across all age groups (Ptrend < 0.001). OSA was lowest in patients <30 years old (mean 3.6, SD 1.0) and also increased as age increased (Ptrend < 0.001). There was a statistically significant difference between age groups for each of the three parameters (P < 0.001). There was a significant linear trend for DFI, OSA and HDS across the seven age categories (P < 0.001). Among patients with high DFI, there was a decreasing age-dependent trend in the patients observed with high OSA (P < 0.001). LIMITATIONS, REASONS FOR CAUTION This is a retrospective study. All males included in the study were undergoing a work-up for infertility and may not be representative of a fertile population. Additional patient demographics and clinical data were not available. WIDER IMPLICATIONS OF THE FINDINGS DNA and/or oxidative damage in sperm may be just as important to understand as the chromosomal aberrations that are carried in the oocyte. Further studies are needed to evaluate the effect of advancing paternal age on the male genome and, ultimately, on the health of the offspring. STUDY FUNDING/COMPETING INTEREST(S) No funding was obtained for this study. V.D. is an employee of Reprosource/Quest Diagnostics. D.S. reports he was a Scientific Advisor to Cooper Surgical. TRIAL REGISTRATION NUMBER N/A

BackgroundTimed and frequent intercourse around the time of female ovulation is recommended to improve conception. Although a significant number of articles have examined how the length of abstinence affects these semen analysis, the effects of frequent (daily) ejaculation has not been rigorously studied.MethodsTwenty normal men were recruited for daily ejaculation over 14 consecutive days, after a 3–5 days abstinence period. Semen samples were collected at the beginning of the study (day 1) and then on days 3, 7 and 14. In addition to the standard semen analysis, markers of sperm DNA quality were assessed.ResultsThe mean age of men completing the study was 25 years (range, 23–33 years). Significant decreases were observed in mean semen volume, total motile count (TMC) and sperm concentration during the study period without significant changes in motility or morphology. A large initial change in ejaculate volume, TMC and sperm concentration provided the primary difference in these values over the study period, with a plateau in values after this initial decrease (after study day 3). Metrics of DNA integrity did not change in a statistically or clinically meaningful way during the study period.ConclusionsWhile a small study, this represents the most extensive examination of sperm quality with daily ejaculation. These findings generally support an approach of a short period of abstinence followed by daily copulation around ovulation to maximize the number of sperm available and optimize conception.

There are few data on the effects of methotrexate on reproductive capacity in men with inflammatory bowel diseases (IBDs). We performed a case-control study to determine the effects of methotrexate on sperm quality and genetic integrity. We compared sperm samples from 7 men with IBD who had been exposed to methotrexate for at least 3 months with sperm samples collected from 1912 age-matched men at fertility centers (controls) where sperm parameters would be expected to be worse than those of the general population. Sperm were evaluated by basic semen analysis and advanced sperm integrity testing. In samples from men with IBD, all basic semen analysis parameters were within normal limits. However, these samples had reduced sperm integrity, based on significant increases in levels of DNA fragmentation and damage from oxidative stress compared with controls. Our findings indicate that methotrexate can reduce DNA integrity in sperm and cause damage via oxidative stress.

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