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DNA Fragmentation Testing: What Is It and When Should It Be Used?

Luke Machen, MD

What is DNA fragmentation?

Typically, one of the first tests in the evaluation of an infertile male is a semen analysis, which includes semen volume, sperm concentration, and sperm motility. While there is frequently a relationship between semen parameters and pregnancy rates, a semen analysis is an imperfect test; it is not predictive of pregnancy and it does not evaluate all aspects of sperm functionality.

Recently, there has been a push to develop complementary testing to the semen analysis that may help characterize sperm dysfunction. One such test is sperm DNA fragmentation, which is the percent of broken or fragmented DNA in a sperm. Multiple studies have shown that poor DNA integrity can be associated with infertility through a reduction in fertilization rates or embryo quality, and/or an increase in miscarriage rates.

What causes increased DNA fragmentation?

Sperm DNA may become damaged either during formation of the sperm, or while sperm are being stored and maturing in the epididymis. This is most likely due to increased levels of reactive oxygen species and oxidative stress. The levels of oxidative stress can be exacerbated by many factors, some external lifestyle factors and some internal. The following is a list of common causes of increased DNA fragmentation:


  • Lifestyle factors
    • Obesity
    • Drugs
    • Smoking
    • Pollution
    • Advanced age
    • Occupational exposures


  • Illnesses
    • Diabetes
    • Cancer
    • Systemic infections
  • Reproductive tract pathologies
    • Varicoceles
    • infections

When should DNA fragmentation testing be considered?

As mentioned above, studies thus far have shown that there seems to be an association between DNA fragmentation and infertility. However, at this time there is not sufficient evidence to routinely perform DNA fragmentation on all men with fertility issues, which is reflected in the latest guidelines of the American Urological Association and the American Society for Reproductive Medicine. Thus, it can be challenging to identify clinical scenarios where DNA fragmentation testing should be utilized. The strongest evidence exists to check DNA fragmentation in the following scenarios:

  • Varicoceles — varicoceles are dilated testicular veins which may be associated with testicular dysfunction. While there is a well-established relationship between varicoceles and infertility, many men with varicoceles are able to conceive without difficulty. DNA fragmentation may help determine which men would benefit from treatment of the varicoceles.
  • Unexplained infertility — some couples have difficulty conceiving despite normal semen analyses and no identifiable female issues. DNA fragmentation may be elevated in these individuals and could be worth checking.
  • Recurrent pregnancy loss — the likelihood of natural pregnancy has been shown to be reduced with elevated DNA fragmentation, and has been linked to recurrent miscarriages
  • Recurrent IUI/IVF failures — intrauterine insemination and in-vitro fertilization success rates may be lower in men with increased DNA fragmentation, both in terms of achieving pregnancy and loss of pregnancy
  • Preponderance of lifestyle risk factors — as mentioned above, lifestyle factors such as smoking or obesity may be associated with DNA fragmentation; testing may reinforce the need for lifestyle alterations and monitor the effects of these modifications

What are the treatment options?

If someone is found to have elevated DNA fragmentation, there are several potential treatment options. In the setting of a modifiable risk factor, the first step should be to eliminate the risk factor — e.g. weight loss, eliminate tobacco use, etc. Otherwise, perhaps the most conservative treatment is oral antioxidant supplementation. Oral antioxidants may be of benefit to some men, and the risks are minimal, although not all patients may experience a decrease in their DNA fragmentation. In the setting of elevated DNA fragmentation with a varicocele, treatment of the varicocele may be of benefit, and has been shown to produce modest reductions in fragmentation indices. Another treatment option in select individuals would be the utilization of testicular sperm with assisted reproductive techniques. In some studies, the DNA quality of sperm harvested directly from the testicle has been shown to be superior to ejaculated sperm. However, this is not a first-line treatment, and is typically reserved for patients who have failed IVF with ejaculated sperm.


While not yet recommended to routinely evaluate in men with infertility, sperm DNA fragmentation has been shown to be a useful adjunct to a traditional semen analysis in select individuals. Discuss with your physician if you have any of the aforementioned risk factors to see if DNA fragmentation testing could be of benefit for you and your spouse.


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