Fertility

A Guide to Sperm DNA Fragmentation

Eloise Edington | 30 Jul 2021

Have you heard of sperm DNA fragmentation? If you have dipped your toes into the world of fertility testing, you’re probably familiar with the sperm basics: count, motility (or movement) and morphology (or shape/structure). These are the parameters tested in a semen analysis, typically the first step to understanding male fertility.

But these are not the only metrics that matter for sperm, and more advanced testing — like sperm DNA fragmentation analysis — can be used to identify deeper issues that may be affecting male (in)fertility. To help you better understand male fertility testing, Fertility Help Hub have reached out to Legacy, a digital fertility clinic, who can reveal all about the male fertility testing process.

Read on to understand what sperm DNA fragmentation is, how it affects fertility, and what testing can tell us.

Words by Legacy

Sperm DNA Fragmentation is Damage to Sperm’s Genetic Material

To explain, let’s go back to Bio 101. An embryo is created when a sperm and an egg join, called fertilisation. Sperm and eggs are both haploid cells, meaning they contain just one set of chromosomes (23 total). When a sperm fertilises an egg, its genetic material joins the egg’s to create a diploid cell with 46 chromosomes — one set of 23 from each parent. This process produces the child’s unique genetic code.

Unfortunately, this DNA is also fragile. Sperm DNA fragmentation is a measure of the degree of damage to the genetic material carried by sperm. Possible damage includes a change or deletion of bases — the building blocks of DNA — or a break or separation in one or both strands of DNA.

Because this DNA works as a sort of “blueprint” for protein and cell synthesis in the body, including embryo development, the genetic integrity of sperm is a key consideration in fertility. Sperm DNA fragmentation may be a contributor to infertility, recurrent pregnancy loss, and IVF failure.

Sperm DNA fragmentation analysis can identify this problem. Your DNA fragmentation index (DFI) is the percentage of sperm in a particular analysis sample that contains damaged genetic material. A higher DFI means that a larger proportion of sperm is genetically abnormal.

How does the DNA Inside Sperm get Damaged: Lifestyle Factors, Illness, and Age

How does the DNA inside sperm get damaged? There are a few possible explanations. It’s theorised that the genetic material can be broken or left unprotected after “chromatin condensation,” the scientific name for the process of squeezing a lot of DNA inside a very small sperm. It’s also possible that increased proportions of damaged sperm in a semen sample may be the result of a faulty QA system — the sperm cells with abnormal DNA should have been marked for self-destruction, called apoptosis, but for some reason were missed.

It’s likely that both of these mechanisms play a role in sperm DNA fragmentation, probably in combination with the effect of oxidative stress. Oxidative stress is damage to your body’s cells as a result of unchecked reactive oxygen species (ROS), also known as “free radicals.”

Free radicals are unstable molecules produced as normal byproducts of your body’s daily functions, and they are typically neutralised by antioxidants. (We produce some antioxidants naturally within our bodies, but usually take in more through diet and fertility supplements.) An increase in free radicals could be caused by exposure to environmental toxins, smoking, infection, or radiation, among other factors.

If there are too many free radicals, too few antioxidants, or both, we’re left with an imbalance that causes oxidative stress. Unchecked free radicals can cause damage to the DNA inside sperm. That’s why many of the risk factors for sperm DNA fragmentation are behaviours or experiences that are known to increase oxidative stress.

Risk Factors for Sperm DNA Fragmentation:

Smoking or using tobacco. One study found that smokers had, on average, more than twice as many sperm with abnormal chromatin condensation, compared to non-smokers
Illness, infection, or inflammation. Men with sexually transmitted infections, for example, have sperm DNA fragmentation levels around three times higher than healthy men, according to research. Fever can affect sperm DNA fragmentation for up to 3 months post-illness. And varicocele — an enlargement of the veins in the scrotum — is associated with increased levels of sperm DNA fragmentation
Chemical, toxin, or radiation exposure. The CDC reports that exposure to chemicals used in plastic production, pesticides/insecticides, lead, or benzene can all affect sperm DNA fragmentation. In one study, healthcare workers exposed to the radiation used in X-rays had nearly 20% higher average sperm DNA fragmentation than other men
Certain medical treatments including chemotherapy for cancer. One case study of a cancer patient reported a substantial increase in sperm DNA damage after 8 weeks of chemotherapy treatment for leukaemia, which persisted nearly a year later

Sperm DNA Fragmentation and Age

Research indicates that increasing age is associated with increased sperm DNA fragmentation, and the increase becomes especially significant for men in their late 40s and early 50s. One study found a 33% increase in sperm DNA fragmentation between people in their late 20s and people in their early 50s.

Why does this happen? It’s possible that, with age, sperm cells are less able to repair their own DNA damage. Additionally, with age, you accumulate DNA damage in the testes, as well, which may impact the sperm cells created. The increased damage could also be due to structural degradation within the testicles or the sperm cells over time.

Sperm DNA Fragmentation is Associated with Infertility, Miscarriage and Poor Health Outcomes for the Child

Those with high levels of sperm DNA fragmentation are at an increased risk for 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. In another, couples experiencing infertility or miscarriage were more likely to have a male partner with moderate or high levels of DNA fragmentation.

This is true also for those using fertility treatments such as in vitro fertilisation (IVF). In one study of 360 couples undergoing IVF, higher sperm DNA fragmentation levels were associated with lower fertilisation rates, embryo quality, and pregnancy rates. The researchers concluded that DNA fragmentation “can predict ART [assisted reproductive technology] outcome.”

Sperm DNA fragmentation may also be a significant contributor to pregnancy loss. Several studies (1, 2, 3) have correlated higher DFI with increased incidence of miscarriage in fertility patients. In each of these studies, miscarriage rates are around three times higher among couples with high DFI, compared to those with low DFI.

Finally, emerging research suggests that sperm DNA damage may be a factor in the health of the offspring. For example, a strong correlation has been found between the development of retinoblastoma, a childhood eye cancer, and DNA fragmentation in paternal sperm. Advanced paternal age has also been associated with many conditions in offspring — including cleft palate, heart defects, schizophrenia, autism, and epilepsy — possibly due to increased sperm DNA fragmentation. The health of the next generation is what’s driving some experts to push for doctors to test and address sperm DNA fragmentation before any fertility treatment.

Sperm DNA Fragmentation Testing is Easier Now Than Ever

Sperm DNA fragmentation is not tested as part of a typical semen analysis. There are several methods and technologies for visualising and measuring damage to DNA inside the sperm nucleus, most of which involve using chemicals to break down the sperm membranes and high-powered microscopes to clearly identify damage. These tests are performed in a speciality lab — even if you collect your semen sample at your clinic, it will be shipped to the lab for DNA fragmentation testing.

Legacy has introduced the first and only easy mail-in sperm testing kit to analyse sperm DNA fragmentation. Our fertility clinics use the sperm chromatin dispersion (SCD) technique to assess sperm genetic health. During SCD testing, sperm are carefully denatured — or chemically degraded — and examined under a high-powered microscope to identify the “halos” formed by loops of intact DNA. (Sperm with damage will not produce a halo.)

Testing sperm DNA fragmentation at home, early in the process, can be game-changing, allowing you to address abnormalities early or work with your doctor to choose the best treatment for you. Legacy’s test kit makes this more accessible, affordable, and approachable.

Learn more about at-home sperm testing.

Who should consider sperm DNA fragmentation testing?

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
- People over 40
- People with a history of cancer
- People under treatment with prescription medications
- People with lifestyle habits that may affect sperm health, such as smoking
- Anyone who wants a more thorough understanding of their sperm health

Treatment for Sperm DNA Fragmentation can be Improving Your Lifestyle, Taking Supplements, or Treating the Underlying Cause

If the underlying cause is a lifestyle or occupational factor — such as smoking or toxin exposure — eliminating it should allow sperm’s genetic health to recover. Similarly, after an illness or infection, sperm health should recover, gradually, on its own. Treatment for medical causes can also improve sperm DNA fragmentation, whether that’s antibiotics to clear an infection or surgery to repair a varicocele.

Additionally, upping your antioxidant intake (in the form of supplements and/or improved diet) can help prevent oxidative stress and decrease sperm DNA damage. Fruits and vegetables are the most robust source of antioxidants in our diet, and unsurprisingly, fruit and vegetable consumption is positively correlated with improved sperm health. CoQ10, an antioxidant often taken as a fertility supplement, has been associated with a 13% reduction in sperm DNA fragmentation.

It takes 2–3 months to produce sperm, so it will take that long (or longer) to see changes in your sperm DNA fragmentation as a result of your efforts. Here’s a slightly more fun, and more immediate, way to decrease sperm DNA fragmentation: Have more frequent sex. Studies show that longer periods of abstinence (i.e. no ejaculation) can cause increased DNA damage in sperm.

These studies into sperm DNA fragmentation may be a great help to improving your fertility. Hopefully, this run-through of sperm DNA fragmentation has given you an insight into how the DNA inside of sperm gets damaged and you now have a better understanding of how to treat it through lifestyle changes. If you would like to order an at-home testing kit from the online fertility clinic, Legacy, to check out your sperm DNA and receive treatment advice, visit the Legacy website.

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