P-088 The Paternal Clock: Shedding Light on the Relationship Between Paternal Age and Sperm DNA Fragmentation

Abstract

Abstract Study question What is the impact of advanced paternal age (APA) on sperm DNA fragmentation index (DFI)? Summary answer Sperm DFI levels remain relatively stable until the age of 35 and increase progressively beyond that age. What is known already APA can have a negative impact on male fertility and the health of offspring. Previous studies have shown that APA is linked to poor conventional sperm parameters, including decreased semen volume, sperm count, motility, morphology, as well as poor sperm DNA integrity. Additionally, APA has been associated with reduced natural or assisted reproduction and perinatal outcomes and a higher risk of genetic and chromosomal abnormalities in the offspring. Study design, size, duration A retrospective cohort study of 4250 consecutive semen samples from men undergoing infertility evaluation at the OVO clinic, in Montreal, Canada, between April 2016 and December 2022. Participants were stratified into seven age groups: <26 (n = 36; 0,8%), 26-30 (n = 500; 11,8%), 31-35 (n = 1269; 29,9%), 36-40 (n = 1268; 29,8%), 41-45 (n = 732; 17,2%), 46-50 (n = 304; 7,2%), >50 years (n = 141; 3,3%). The mean age was 37.4 ± 6.4 years (range 18-71 years). Participants/materials, setting, methods The study was population-based and included male patients from all ages, ethnicities, and medical histories. Semen samples were collected after 2-3 days of abstinence. For patients who underwent more than one DFI testing, only the first sample was included, and any duplicates were excluded. DFI was evaluated by flow-cytometry based TUNEL assay using the APO-Direct Kit. Data were analyzed using one-way ANOVA and T3 Dunnett post-hoc multiple comparison test, as well as Pearson’s correlation coefficient. Main results and the role of chance The results show a significant positive correlation between %DFI and age (r = 0.19, p < 0.001). Mean %DFI levels were relatively stable in men aged <26 to 35 years (17.9%, 18.1% and 18.1% in men aged <26, 26-30 and 31-35, respectively), with %DFI increasing progressively beyond age 35 (20.7%, 22.5%, 25.7% and 27.9% in men aged 36-40, 41-45, 46-50 and >50, respectively). The mean %DFI in the 36-40 age group was significantly higher than in the 31-35 age group (p < 0,001). Our study has uncovered that %DFI follows an exponential curve starting at age 35, indicating that the %DFI accelerates significantly as men age beyond their mid-30s. Limitations, reasons for caution This retrospective analysis has inherent limitations that may introduce confounding variables. The patient clinical background, such as medical history and lifestyle factors was not assessed. Also, the studied cohort consisted of a population under investigation for infertility and may not be representative of the general male population. Wider implications of the findings The study demonstrates the age-related increase in sperm %DFI and suggests that there may be an age cut-off below which sperm %DFI is stable and beyond which sperm %DFI increases. This information may be useful to medical specialists that offer sperm DNA testing to infertile couples. Trial registration number not applicable