The reduction in total motile sperm count and the increase in sperm DNA fragmentation are associated with paternal age in normozoospermic men

Aging Male. 2026 Dec 31;29(1):2612794. doi: 10.1080/13685538.2026.2612794. Epub 2026 Jan 10.

Abstract

Background: Normozoospermia does not guarantee fertility. Sperm DNA fragmentation (SDF) reflects intrinsic sperm quality and adverse reproductive outcomes, and double-strand breaks (DSBs) indicate more severe DNA damage.

Methods: From July 2021 to February 2025, semen parameters, total motile sperm count (TMSC), and SDF from 534 normozoospermic men at National Cheng Kung University Hospital were retrospectively analyzed. Total DNA fragmentation (Total DFI) was measured using the sperm chromatin dispersion (SCD) test, and DSB DFI was assessed using the SDF Releasing (SDFR) assay.

Results: Paternal age correlated negatively with ejaculatory volume (ρ = -0.214, p < 0.001), progressive motility (ρ = -0.184, p < 0.001), and TMSC (ρ = -0.118, p = 0.003), but positively with total DFI (ρ = 0.186, p = 0.025). Although Total DFI did not differ significantly across the three age groups (p = 0.081), men ≥ 40 years had higher Total DFI than those < 40 years (p = 0.032). DSB DFI showed no difference. Total DFI correlated with DSB DFI (ρ = 0.298, p = 0.005). Oligoasthenoteratozoospermic men exhibited higher total DFI than normozoospermic men (p = 0.048).

Conclusion: Advancing paternal age is associated with reduced semen quality and increased sperm DNA fragmentation even among normozoospermic men.

Keywords: Paternal age; double-strand breaks; male infertility; normozoospermia; sperm DNA fragmentation.

Plain language summary

Advancing paternal age, even in normozoospermic men, is associated with reduced semen quality and increased sperm DNA fragmentation, indicating potential risks to reproductive outcomes.Routine semen analysis alone may overlook age-related sperm DNA damage, underscoring the value of incorporating the sperm DNA fragmentation (SDF) test in infertile men with normozoospermia.

MeSH terms

  • Adult
  • DNA Fragmentation*
  • Humans
  • Male
  • Middle Aged
  • Paternal Age*
  • Retrospective Studies
  • Semen Analysis
  • Sperm Count*
  • Sperm Motility*
  • Spermatozoa*