Diagnostic accuracy of sperm DNA degradation index (DDSi) as a potential noninvasive biomarker to identify men with varicocele-associated infertility.

Purpose: Varicocele is a frequent cause of impaired testicular function that has been associated with increased levels of sperm DNA fragmentation (SDF). Sperm with degraded DNA (DDS), as observed using the sperm chromatin dispersion (SCD) test, represent a subpopulation of spermatozoa with extensive DNA and nuclear protein damage. The aim of this work was to determine the usefulness of sperm DNA degradation index (DDSi) as a novel noninvasive biomarker to identify infertile men with varicocele.

Methods: A total of 593 semen samples obtained from men attending infertility clinics were analyzed for SDF and DDS with the SCD test. These samples were classified as: (1) fertile donors; (2) infertile patients with least two failed assisted reproduction cycles; (3) leukocytospermia; (4) Chlamydia trachomatis infection; (5) testicular cancer, and (6) infertile men with varicocele. The DDSi was obtained by determining the proportion of DDS in the whole sperm population presenting with fragmented DNA. The diagnostic accuracy of DDSi was evaluated by correlation coefficient and receiver operating characteristics analyses.

Results: A positive correlation (r ≥ 0.52) was observed between the SDF and the frequency of degraded sperm in all patient groups. The sperm DNA degradation index (DDSi) was at least twice as higher in infertile men with varicocele (mean: 0.54) compared with other clinical conditions and fertile donors (means ranging from 0.02 to 0.21; P < 0.0001). A DDSi ≥ 0.33 identified patients with varicocele with 94 % accuracy.

Conclusion: Although DDS is not pathognomonic of varicocele, the DDSi is a useful noninvasive biomaker to identify infertile individuals with varicocele when examining sperm DNA damage during a routine semen analysis. This finding may alert practitioners and laboratories performing semen analysis that in the presence of an abnormal DDSi it is likely that a given patient has varicocele. It is therefore strongly recommended that such patients be referred to urologists in order to undergo a full andrological examination and be properly counseled.