Relationships between the age of 25,445 men attending infertility clinics and sperm chromatin structure assay (SCSA®) defined sperm DNA and chromatin integrity

Fertil Steril. 2020 Aug;114(2):311-320. doi: 10.1016/j.fertnstert.2020.03.028. Epub 2020 Jul 9.


Objective: To determine relationships between age of men with potential male factor infertility and sperm chromatin structure assay (SCSA) measures of sperm DNA fragmentation (SDF) and high DNA stainable sperm (HDS), and to compare these data with those obtained from healthy donor men without reproductive issues.

Design: Retrospective study.

Setting: Infertility clinics and diagnostic laboratory.

Patients: A total of 25,445 men attending infertility clinics. Donors were 87 men working at Lawrence Livermore National Laboratory.

Intervention: None.

Main outcome measures: SCSA measures (% DNA fragmentation index (DFI), X DFI, SD DFI, and %HDS) of men aged 21-80 years.

Results: In the study population, advancing paternal age was associated with increased sperm DNA fragmentation (SDF) scored as increased percentage of sperm in semen ejaculates with measurable DNA strand breaks (%DFI). The slope of increase in %DFI prior to age 41.6 years was 0.39, which increased after age 41.6 to more than double at a slope of 0.86. These changes in DNA/chromatin in more than 25,000 aging men attending infertility clinics are similar to those seen over the same age span (20-80 years) in 87 nonpatient, healthy men without reproductive issues. For the age group 20-50 years, there was no major significant difference in %DFI between patients and donor men. According to a logistic regression model, the estimated probability is that, for example, a 40-year-old and a 50-year-old man have a 20% and 40% chance, respectively, to have a pathological DFI ≥25% by age factor alone. The condensation of sperm chromatin in patients increased with age in a linear fashion, from a mean of 12.2 %HDS at age 20-25 to a mean of 7.9 %HDS at age 60-65. Patients had a greater %HDS than donors across all ages.

Conclusions: The great heterogeneity of both DFI and HDS values at a specific age prevents the automatic translation of age into an index of DNA fragmentation. However, it reinforces the idea that both DFI and HDS evaluation can play a role in detecting potential male infertility in cases that are not resolved by routine testing and in cases of multiple miscarriages. DFI and HDS data can help clinicians to predict a man's fertility potential, to consider corrective therapeutic approaches, as well as to assess the risk to the offspring's health.

Keywords: Male infertility; SCSA test; age; healthy donors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chromatin / pathology*
  • DNA Fragmentation*
  • Fertility
  • Fertility Clinics
  • Flow Cytometry*
  • Humans
  • Infertility, Male / pathology*
  • Infertility, Male / physiopathology
  • Infertility, Male / therapy
  • Male
  • Middle Aged
  • Paternal Age*
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Semen Analysis*
  • Spermatozoa / pathology*
  • Young Adult


  • Chromatin