One of the main factors affecting male-factor infertility is sperm DNA fragmentation, which refers to abnormal genetic material within sperm. In addition to infertility, DNA fragmentation has also been associated with higher rates of miscarriage and in vitro fertilization (IVF) failure. While a semen analysis can help detect issues with sperm quality, including sperm count, morphology, and motility, a separate sperm DNA fragmentation analysis is recommended to identify these genetic issues.
Find out what causes sperm DNA fragmentation, how to test for it, and what you should do if you receive abnormal results.
Key takeaways
- Sperm DNA fragmentation refers to the amount of genetic damage seen in sperm DNA. This may consist of a change or deletion of bases, or a break or separation in one or both strands of DNA contained within sperm.
- Because sperm DNA integrity is crucial for fertilization and development of healthy offspring, high levels of genetic damage can contribute to male-factor infertility, miscarriage, and IVF failure.
- Causes of sperm DNA fragmentation include oxidative stress, errors during the sperm production process, varicocele, and advanced age.
- Making lifestyle changes, like cutting back on alcohol, giving up smoking, and maintaining a healthy weight, can all help reverse sperm DNA damage.
What is sperm DNA fragmentation?
DNA is made of two linked strands that wind around each other in a staircase-like structure called a “double helix.” Contained within the strands are pairs of chemicals known as nucleotides. The different combinations of these base pairs are what determine each person’s unique genetic sequence.
Sperm DNA fragmentation refers to the amount of genetic damage seen in sperm DNA. This may consist of a change or deletion of bases, or a break or separation in one or both strands of DNA contained within sperm. Because sperm DNA integrity is crucial for fertilization and development of healthy offspring, high levels of genetic damage can contribute to male-factor infertility, miscarriage, and IVF failure.
A crucial indicator in evaluating semen quality is the “DNA fragmentation index,” or DFI, which refers to the percentage of sperm in a particular semen sample with fragmented DNA. A higher DNA fragmentation index means there is a larger percentage of a person’s sperm containing genetic damage.
Factors that cause sperm DNA fragmentation
From extrinsic factors, like oxidative stress, to intrinsic errors during the sperm production process, there are a number of reasons why a person may have a higher sperm DNA fragmentation index.
Oxidative stress
Oxidative stress refers to an imbalance between free radicals and antioxidants in your body. Some factors that contribute to this imbalance include exposure to environmental toxins such as pesticides, heavy metals, pollution, radiation, certain infections, and lifestyle habits like smoking and drinking.
Research has shown oxidative stress is a major cause of sperm DNA fragmentation. As oxidative stress increases, sperm exhibit elevated levels of DNA damage, and at the highest levels of oxidative stress, a high DNA fragmentation index can be observed in addition to a loss of sperm motility (sperm movement). In this 2019 study, researchers cite the connection between unexplained infertility and recurrent pregnancy loss with elevated levels of oxidative stress and sperm DNA fragmentation.
Errors during condensation or apoptosis
During the sperm production process, the genetic material within sperm condenses, allowing large amounts of DNA to occupy a very small space. In some cases, this process results in physical breaks in the DNA.
While this is all happening, the body is busy discarding faulty cells through a natural process called apoptosis, which is a type of cell death that serves as a “self-cleaning” mechanism. Sometimes, this process gets interrupted along the way and damaged sperm are able to escape. This is known as abortive apoptosis, another error leading to a higher DFI.
Varicocele
A varicocele is a medical condition in which the veins of the scrotum become enlarged. Studies have found a higher prevalence of DNA fragmentation in varicocele patients and a correlation between the presence of varicocele and impaired sperm DNA integrity. This damage can be reversed with a varicocelectomy — a surgical procedure that treats a varicocele and has been associated with improved sperm concentration, progressive motility, and morphology (sperm shape).
Advanced age
This 2020 study found a correlation between age and sperm DNA fragmentation. Those above the age of 50 presented a statistically significant increase in DNA damage and were 4.58 times more likely to present sperm DNA fragmentation than men aged 21–30. The researchers pointed to mitochondrial damage as the culprit.
Sperm DNA fragmentation and fertility
Having high levels of sperm DNA fragmentation does not mean conception is impossible — as proven in this 2004 study. However, research does indicate that men with a high DFI are at an increased risk for infertility. In one study, couples experiencing infertility or miscarriage were more likely to have a male partner with moderate or high levels of sperm DNA fragmentation, leading researchers to conclude that damaged DNA was the “best predictor” for whether a couple would not achieve pregnancy.
Research has also demonstrated that high levels of sperm DNA fragmentation increase the likelihood of having other abnormal semen parameters, such as poor sperm motility or morphology. This 2002 study found the average level of DNA damage was significantly higher among those with other abnormal semen parameters.
Furthermore, sperm DNA fragmentation affects the development of blastocysts and increases the chances of miscarriages or assisted reproductive technology (ART) failure, such as IVF and intracytoplasmic sperm injection (ICSI). In this study out of Saudi Arabia, which examined the relationship between sperm DNA fragmentation and ICSI cycles, researchers found there was no difference in ICSI outcome in low and moderate sperm DNA fragmentation. However, those with high sperm DNA fragmentation did not achieve pregnancy.
Testing for sperm DNA fragmentation
The first test doctors typically recommend when assessing male fertility is the semen analysis, but this type of assessment cannot detect sperm DNA fragmentation. Pairing a semen analysis with a sperm DNA fragmentation analysis is the best way to get a full picture of your fertility.
There are a number of tests that can help identify sperm DNA fragmentation, including sperm chromatin dispersion (SCD) testing, a single cell gel electrophoresis (SCGE) assay, a sperm chromatin structure assay (SCSA), and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Each of these tests must be conducted in a specialist lab as they use different types of technologies to detect and quantify damaged DNA.
Why test for sperm DNA fragmentation?
Testing for sperm DNA fragmentation can help you get a better understanding of your fertility and potentially help you avoid stressful and costly complications down the line. Knowing you have sperm DNA fragmentation can help you make decisions about your health that may reverse DNA damage and increase your chances of conceiving.
You should test for sperm DNA fragmentation if you:
- have unexplained infertility
- have a history of miscarriages
- have failed IVF treatments because of poor embryo quality
- are over 40
- have a history of cancer
- take prescription medications
- engage in lifestyle habits that may affect sperm health, such as smoking or excessive drinking
- have varicocele
- want a better understanding of your sperm health
At-home sperm DNA fragmentation analysis
Legacy’s first and only at-home sperm DNA fragmentation analysis allows you to test the DNA integrity of your sperm from the comfort and privacy of your home. Simply produce your sample via ejaculation, send it to our labs in a special transport media, and receive results in as little as a week.
Our labs use sperm chromatin dispersion (SCD) to identify sperm DNA damage and quantify your DFI. In this test, sperm are carefully denatured, or chemically degraded, proteins are removed, and sperm is examined under a high-powered microscope. If “halos” are detected, your sperm does not have DNA damage. If there are no halos detected, DNA fragmentation is present.
Your results will include context on what your numbers mean for you and your family-building plans. And if you have any questions, you can always book a virtual appointment with one of our male fertility specialist medical providers, to discuss your results and possible next steps.
Understanding your test result and treatment options
Some experts say a DNA fragmentation index over 30% is considered high and may impact fertility. However, those with a DNA fragmentation index of 15–30% can also experience subfertility, especially if their semen analysis results are also abnormal. It’s important to note that 15% of infertile patients have normal semen analysis results, making a case for a separate DNA fragmentation analysis.
If your sperm DNA fragmentation test result indicates your DFI is high, your doctor may need to test for and treat underlying diseases that may be contributing to the DNA damage, such as varicocele or male genital tract infections causing oxidative stress. Or, your doctor may recommend testicular sperm retrieval to use in ICSI as some studies show testicular sperm tend to have less DNA damage and better DNA integrity than ejaculated sperm.
There are also a number of lifestyle factors and supplement options you can pursue on your own to help improve your abnormal result and reverse sperm DNA damage.
How to improve an abnormal result
You already learned that oxidative stress is a major contributor to sperm DNA fragmentation. Making some adjustments to your lifestyle can help you improve your sperm integrity for better chances of conceiving. This includes:
- cutting back on alcohol
- giving up smoking
- following a nutritious diet and exercising to maintain a healthy weight
- wearing loose underwear
- avoiding environments with high temperatures such as saunas and hot tubs
- taking vitamins and minerals like vitamin C, vitamin E, zinc, selenium, and L-carnitine (which can all be found in Legacy’s Male Fertility Supplement)
If you use Legacy’s at-home sperm DNA fragmentation testing kit, you’ll also receive evidence-based recommendations for improving your sperm DNA and overall fertility health, based on your lifestyle and personal results, no appointment necessary.
Learn more about how to improve your sperm health in our sperm improvement guide.
