DNA, the genetic blueprint in humans and other organisms, consists of two intertwined chains called DNA strands, each made up of sugars and phosphate. This DNA holds information in the form of a code composed of four types of molecules called bases, which are attached to the strands like the rungs of a ladder. Although all humans have the same bases, their sequence determines the genetic instructions for building and maintaining an organism. Just as different letter combinations form different words, the unique order of these bases makes each person’s DNA distinct. Sperm DNA fragmentation occurs when there is a change in these bases or a physical break in one or both DNA strands of the chromosomes in the sperm.

What Causes Sperm DNA Fragmentation?

Oxidative stress is a primary cause of sperm DNA fragmentation. This stress results from the accumulation of damage caused by free radicals—atoms with unpaired electrons—not adequately neutralized by antioxidants. Factors contributing to sperm DNA fragmentation include infections, smoking, drug use, exposure to environmental and occupational pollutants, aging, varicocele (enlarged veins in the scrotum), high fevers, elevated testicular temperature (from laptop use or hot tubs), chronic diseases like diabetes and cancer, and poor diet and obesity. Additionally, fragmentation can occur when the body cannot repair DNA breaks or lacks proteins that keep DNA in a compact, protected form.

Why Would Sperm DNA Fragmentation Testing Be Useful?

Although semen analysis is the most common test for assessing male infertility, it does not reliably predict fertility or the likelihood of pregnancy with infertility treatment. Therefore, researchers have sought other methods to determine male fertility. Successful embryo development requires undamaged DNA from both the egg and sperm. Studies have shown that sperm DNA damage is more common in infertile men and may affect reproductive outcomes. Many infertile men exhibit increased DNA fragmentation even with normal semen analysis results. These findings have led to testing DNA integrity as another way to assess fertility potential.

What Does Testing for Sperm DNA Fragmentation Involve and Who Should Have It Performed?

Several tests can assess sperm DNA fragmentation, with the most studied ones being the sperm chromatin structure assay (SCSA), the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay (TUNEL), the single-cell gel electrophoresis assay (COMET), and the sperm chromatin dispersion test (SCD). These tests estimate the extent of DNA damage in a semen sample, usually performed at an external laboratory using a sample obtained through ejaculation.

Despite numerous studies, the 2013 American Society for Reproductive Medicine Practice (ASRM) committee concluded that there is insufficient data to support a consistent link between increased DNA fragmentation and reproductive outcomes. This is likely because millions of sperm are produced, and unless there is complete DNA fragmentation, it is unlikely to be the sole cause of infertility. Currently, there is not enough evidence to recommend routine DNA fragmentation testing to predict pregnancy rates during fertility treatment. However, a reproductive urologist can determine if this testing would be useful in specific cases to develop a treatment plan.

Can You Treat Sperm DNA Fragmentation?

Because new sperm are produced every 72 days, reducing exposure to oxidative stress can decrease sperm DNA fragmentation. Recommendations to reduce oxidative stress include:

– Have varicoceles evaluated by a urologist to see if surgical repair is necessary.
– Avoid hot tubs and tight-fitting underwear.
– Maintain a healthy diet rich in fruits, vegetables, and antioxidants.
– Exercise regularly.
– Avoid smoking, illicit drugs, and limit alcohol intake.
– Consult a urologist to review medications and adjust if necessary (e.g., SSRIs).
– Consider supplements containing vitamins and antioxidants.

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