What is Sperm DNA Fragmentation?

DNA fragmentation testing is a type of male fertility test which measures the amount of damaged DNA in a sperm sample. All men have some amount of damage to their sperm DNA, but high percentages of damage may indicate greater difficulty achieving pregnancy with IUI and IVF.

Testing for Sperm Quality

For decades, fertility testing for men has relied almost solely on a basic semen analysis, which examines sperm concentration, morphology and motility. Still, around 30% of the 5 million men in the US who are facing infertility still do not know why they are infertile. This suggests that a semen analysis is inadequate when it comes to evaluating male fertility potential. While it can check for the presence of motile sperm that are shaped normally, it does not provide much insight on the sperm’s ability to contribute to a successful pregnancy.

Sperm Quality Testing. Easy, Mail-in Kit.

More recently, there is a growing recognition of the need for better sperm quality testing. Full disclosure: Path provides an advanced sperm quality test, which looks at sperm epigenetics, but in this post we are going to talk about a different type of test which looks at sperm DNA fragmentation.

Sperm DNA Fragmentation

Sperm DNA fragmentation refers to the amount of damage seen in sperm DNA. Essentially, calculating what percentage of the sperm has breaks in the DNA.  Sperm are very small yet they need to carry massive amounts of genetic information to the egg. With so much DNA getting packed into a tiny sperm cell, it turns out not everything arrives intact as intended.

Over the last few decades, significant research has been done to look at how the amount of damage observed in sperm DNA can be used as a marker for male infertility. While our understanding of sperm DNA damage has grown, the exact cause remains unknown. One important observation is that the amount of sperm damage detected does not always correlate with semen parameters. In other words, you can have a normal sperm count, motility, and morphology, and still have large amounts of sperm DNA damage. Interestingly, the egg has some capacity to repair damaged sperm DNA upon fertilization, however, scientists believe there may be a threshold of DNA damage beyond the repair capacity of eggs.

Sperm Chromatin Structure Analysis (SCSA) Testing

Many tests have been developed to measure sperm DNA damage, but they all use slightly different procedures and result in different standards of measurement. The SCSA test is the most widely used method. It involves treating sperm with a chemical dye; broken sperm DNA turns red, normal sperm DNA turns green.

Afterwards, the sample is run through a computerized machine with a special software which reads about 5,000 sperm cells categorizing the ratio of green-to-red sperm cell to figure out the Fragmentation Index (DFI). It is possible that SCSA testing can detect damage in some 20% of couples that have previously had no explanation for infertility. 

Understanding DNA Fragmentation Results

Like any test ordered by your doctor, it is important to consult with your physician or other qualified health care provider regarding specific questions you may have about your DNA fragmentation results. However, on the SCSA report you will likely see a key with 4 values to help you understand your results:

a.) Excellent to Good (less than or equal to 15% DFI)

b.) Good to Fair (greater than 15% to less than 25% DFI)

c.) Fair to Poor (greater than or equal to 25% to less than 50% DFI)

d.) Very Poor (greater than or equal to 50% DFI)

Therefore, a patient with a DFI of 8.2% would fall into the “excellent to good” category with 8.2% of the sperm cells containing DNA damage. The SCSA test recommends that patients with a % DFI above 25% should skip IUI and go straight to IVF/ICSI for greatest success.

Clinical Utility of DNA Fragmentation

At least one recent study found that patients who have DFI% greater than or equal to 29% have a significantly improved blastocyst transfer outcome when they opted for fertility intervention (e.g. TESE/TESA, PICSI, IMSI) compared to no intervention (Bradley et al. 2016). 

However, other research suggest there is little difference in IVF pregnancy rates between sperm with normal and abnormal DNA fragmentation.

Although DNA fragmentation testing has been around for several decades and the largely accepted belief is that infertility and sperm DNA fragmentation are linked, this test is not yet a standard tool in fertility clinics. Although high percentages of DNA fragmentation can be a good indicator of problems on the male side, we can’t use this test to accurately predict IVF success.

New Option for Advanced Sperm Quality Testing

It is clear that more studies need to be conducted on the clinical utility of DNA fragmentation. Although DNA fragmentation testing provides an additional option to test male fertility, it certainly has limitations–it can calculate the % of broken DNA in the sperm, however, where these breaks are occurring and in what genes specifically cannot be answered.

The Path Test is a completely different way to evaluate the quality of sperm. Rather than look at overall DNA damage, our test looks for epigenetic abnormalities. Abnormalities that correlate with male infertility, and knowing your sperm epigenetics may give you new insight into why problems are occurring.

Kristin Brogaard, PhD

Kristin Brogaard, PhD is Co-founder and COO of Inherent Biosciences, a molecular diagnostics company at the intersection of epigenetics and AI. Dr. Brogaard is an experienced molecular biologist, study director, and operations manager for early stage biotech startups. She received her PhD in Molecular Biology from Northwestern University developing novel epigenetic technologies. She subsequently worked with Dr. Leroy Hood, a pioneer in personalized medicine technologies, first as a post-doc and then as a colleague launching a novel scientific wellness start-up, Arivale. Dr. Brogaard has broad business experience that includes launching and scaling the health startup, Arivale. Additionally, Dr. Brogaard was the Director of Program Management at Arivale managing all strategic projects with a highly qualified team of program and project managers.

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