Conventional semen analysis doesn’t always flag sperm abnormalities that could lead to decreased fertility. As a result, men who fall within normal ranges set by the World Health Organization may still have significant DNA damage. In the search for improved sperm quality identification techniques, sperm DNA fragmentation (SDA)—which examines the number of nicks and breaks present in the sperm’s DNA—may fit the bill, Whitney J. Palmer writes in the latest issue of Clinical Laboratory News.

“The results can guide treatment option selections and fertility services. But reservations remain about how widely applicable and accepted SDF should be,” writes Palmer.

Four available tests identify a man’s DNA Fragmentation Index (DFI):

  • Sperm chromatin structure assay, which uses a chemical dye to stain broken sperm red and normal sperm green;
  • Sperm chromatin dispersion, which treats sperm with acid denaturation after which normal sperm produce halos;
  • Terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphates (dUTP) nick end labeling, which employs fluorescent dUTP to label single- and double-strand breaks; and
  • SpermComet, a single-cell gel electrophoresis technique in which only fragmented sperm travel through the gel.

“SDF is the only test that allows us to look at anything other than bulk semen parameters …  It lets us look at that quality of the DNA packaging critical for early embryo development,” said James Hotaling, MD, assistant professor of surgery and co-director of the Fertility Integrated Practice Unit at the University of Utah School of Medicine in Salt Lake City.

Environmental factors such as ultraviolet light and lifestyle factors such as obesity and diabetes can lead to DNA imperfections. Varicoceles—enlarged testicular veins that cause overheating and injure sperm—is another condition often seen in infertile men. According to Ashok Agarwal, PhD, director of the Cleveland Clinic Clinical Andrology Lab and Sperm Bank, an SDF test can guide both lifestyle changes and fertility treatment options that offer the greatest chances of success, reducing a man’s DNA damage and thus avoiding pricey reproductive treatments. 

Several factors are impeding SDF’s widespread use in clinical practice. Access is one problem: Only a select number of labs offer the test. Consistency and translatability pose other barriers. “Not only does each SDF test assess DNA fragmentation differently, each also has its own cut point to diagnose sperm quality levels,” Palmer writes. Some experts are calling for a standardization of the test’s procedures and results reporting. Others say it needs to be vetted in larger clinical trials.

This isn’t a silver bullet for every man struggling with infertility. “It’s one way to examine, look for, and find hidden problems that aren’t told by semen analysis, and that’s a big thing,” Agarwal says.

Pick up the January/February issue of CLN to learn more about the new frontier of fertility testing with SDF.