If you’ve met with a fertility specialist or you’re going through treatments, you may feel like you’ve had every test in the book. But the one test that you may not have completed may potentially be among the most important, especially for couples with male-factor or unexplained infertility: sperm DNA fragmentation analysis, an evaluation of the genetic health of sperm.

According to Dr. Ramy Abou Ghadya, urologist and chief medical officer at Legacy, “Most experts consider the DNA fragmentation index to be one of the missing pieces of the male infertility puzzle. This data is an invaluable diagnostic tool.”


What is sperm DNA fragmentation?

Put simply, sperm DNA fragmentation, or “SDF,” is the degree of damage to the genetic material inside sperm.

Sperm contain 23 chromosomes—molecules of DNA—that are supposed to combine with the egg’s 23 chromosomes to create an embryo. However, this DNA is fragile and is susceptible to damage due to age, illness or fever, varicocele (swollen veins in the testicles), medical treatments such as chemotherapy, exposure to toxins, and lifestyle choices such as smoking. This damage can happen while sperm is produced, or while it waits in “storage” in the testicles.

Sperm DNA fragmentation is evaluated using the “DNA fragmentation index” (DFI), a measurement of the percentage of sperm that contain damaged DNA. While there isn’t a consensus on specific cut-off values (and different tests have different scales of measurement), a DFI over 30–50% is generally considered high and may impact fertility.


How can sperm DNA fragmentation affect fertility or the outcome of fertility treatments?

The fertility field has known for quite a while that egg quality, the genetic health of an egg, is a key factor in female fertility. Now, emerging research is illuminating the role that sperm’s genetic health plays. A high DNA fragmentation index is associated with:

  • Lower pregnancy rates. In a study of fertility patients, couples who were not able to achieve pregnancy had an average of 51.7% sperm with DNA fragmentation, as opposed to 39.5% in the pregnant couples. (All other semen parameters were equal.)

  • Higher risk of infertility. In one study, men presenting for infertility evaluation—who had not been able to achieve a pregnancy for a year or more—had, on average, over twice as many sperm with DNA fragmentation than fertile men (27.6% vs. 13.3%).

  • Poorer outcomes from fertility treatments. In one study of IUI, IVF, and ICSI, it was found that high DFI had the power to predict whether or not a couple would achieve pregnancy with infertility treatment; pregnancy rates for couples with high DFI were less than half that of low-DFI couples (14% vs. 29%). In other studies, embryo quality and implantation rates have been negatively correlated with high DFI.

  • Higher risk of pregnancy loss. Multiple studies have tied higher miscarriage rates to high DFI. In one, couples in which the male partner had high levels of sperm DNA fragmentation were significantly more likely to experience a miscarriage—they had a 50% miscarriage rate vs. 16% for couples without a high level of SDF. DNA fragmentation may also be implicated in recurrent pregnancy loss.

  • Adverse health conditions for the child. Because of the many factors that contribute to the development of disease, it’s tricky to pin it to one specific cause, but experts believe that “loss of sperm DNA integrity… increases childhood disease burden.” Increasing paternal age and higher levels of sperm DNA fragmentation have been associated with the offspring’s increased chances of cancer, cleft palate, heart defects, schizophrenia, autism, and epilepsy.


How can you test for sperm DNA fragmentation?

Sperm DNA fragmentation is not evaluated as part of a typical semen analysis that looks at sperm count, motility, and morphology. Interestingly, in one estimate, 15% of infertile men have normal results from a traditional semen analysis. A sperm DNA fragmentation analysis is an important supplement to a semen analysis, providing a more complete understanding of male infertility.

There are several available tests for sperm DNA fragmentation that use high-tech methods to identify sperm cells with significant DNA damage. These tests are performed in a specialized laboratory; even if a patient provides a semen sample at their fertility clinic, the sample will be mailed to an outside laboratory for sperm DNA fragmentation testing.

To make this important testing more accessible, Legacy has introduced a first-of-its-kind mail-in sperm DNA fragmentation analysis, alongside their mail-in semen analysis kit. Legacy’s kits allow clients to produce a semen sample in the privacy and comfort of their own home—as opposed to the awkward experience of the clinic collection room—and get a clinic-grade analysis and report. Legacy clients also receive personalized, evidence-based recommendations to improve their sperm health.

Legacy’s labs use Halosperm sperm chromatin dispersion (SCD) testing, a well-established technique for identifying sperm DNA damage. During this test, normal spermatozoa can be identified by their glowing “halos,” formed by loops of DNA at the head of the sperm. These halos will not be present in sperm with highly damaged DNA.


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When should you test for sperm DNA fragmentation?

This is a question that’s getting a lot of attention in the fertility space as of late. Often, sperm DNA fragmentation isn’t tested until a couple has gone through one or more failed fertility treatments. But in multiple studies, researchers have concluded that DNA fragmentation “can predict ART outcome,” and that it’s a “significant predictor for future [miscarriage] and infertility.”

This predictive power, along with the probable impact of sperm DNA fragmentation on the health outcomes of the child, has prompted experts to call for universal SDF testing, earlier in the fertility journey. As two leading andrologists (sperm experts) wrote in a recent article, there is a strong argument to be made that sperm DNA fragmentation should be tested prior to starting any fertility treatments.

Purchase the test now and learn about your sperm DNA fragmentation in less than a week.

Who should do a sperm DNA fragmentation test?

  • All fertility patients, especially:

    • Patients with unexplained infertility.

    • Patients diagnosed with male-factor infertility of an unknown cause.

    • Patients with a history of miscarriages.

    • Patients with poor embryo quality during IVF treatment.

  • Men over 40.

  • Men with a history of cancer.

  • Men under treatment with prescription medications.

  • Men with lifestyle habits that may affect sperm health, such as smoking.

  • All men who want a more thorough understanding of their sperm health.


The good news: Sperm DNA fragmentation can often be improved, typically with simple lifestyle changes, such as quitting smoking, decreasing excess body weight, or having more frequent intercourse. Testing sperm DNA fragmentation proactively allows couples to address and resolve issues on their own, potentially saving time, money, and energy—all of which are often in short supply for fertility patients—as well as improving outcomes for both the parents and the child.