DNA Fragmentation Testing and ZyMot

Approximately 15% of men with unexplained infertility have a clinical normal Semen Analysis. It is important to understand the basics before rushing into treatment such as IVF. This could either optimise a single cycle of IVF or reduce the need for assisted reproduction entirely.

Sperm DNA fragmentation testing is now recognised as an important part of fertility assessments and is increasingly recommended by leading organisations worldwide.

These guidelines emphasise the critical role of SDF testing in improving clinical decision-making and fertility treatment outcomes.

  • World Health Organization (WHO): Includes SDF testing in its 2021 extended examination list.

  • European Association of Urology (EAU): Recommends SDF testing for couples with recurrent pregnancy loss (RPL) from natural conception, failure of assisted reproductive technology (ART), or men with unexplained infertility1

  • Global Andrology Forum (GAF): Highlights SDF testing for unexplained and idiopathic male infertility, recurrent miscarriage, clinical varicocele, and ART failure, including recurrent implantation or fertilisation failure2.

What is Sperm DNA Fragmentation?

  • Every cell in our bodies, except for red blood cells, contains DNA in its nucleus. This DNA holds all the information needed for each cell to function. To fit into the nucleus, DNA is carefully packed onto chromosomes (23 pairs in total). However, this packing must strike a balance – tight enough to protect the DNA but loose enough to access the genetic information when needed.

  • Sperm cells are unique. Their sole purpose is to deliver 50% of the baby’s genetic blueprint (one set of 23 chromosomes) from the father to the egg, which contains the other 50% from the mother. To ensure the DNA reaches the egg safely, sperm cells are tightly packed and strip away everything unnecessary, including the machinery that repairs DNA damage.

  • DNA exists as two strands arranged in a double helix, resembling a spiral staircase. Damage to this structure can occur in two ways:

    • Single-strand breaks (ssDB): More common and less impactful.

    • Double-strand breaks (dsDB): Less common but more challenging for the sperm to overcome.

  • At LCRH double-stranded DNA fragmentation testing is often pursued after unexplained recurrent miscarriage or repeated IVF failure of euploid embryos.

  • Sperm cells are particularly vulnerable to DNA damage because they lack the repair mechanisms found in other cells. This vulnerability is due to the dense packing of DNA and the absence of cellular machinery that prevents or repairs damage. Factors such as lifestyle choices, stress, and medical conditions can exacerbate this damage.

What may be included in the causes of high single-stranded sperm DNA fragmentation?

  • Oxidative stress (from smoking, infections, varicocele, poor diet, obesity etc.) 

  • Advanced paternal age 

  • Environmental toxins (pollution, radiation) 

  • Illnesses (e.g., diabetes, febrile illness)

  • Lifestyle factors (stress, heat exposure, alcohol, caffeine, smoking, vaping)

What might the consequences of high sperm DNA fragmentation include?

  • Reduced Fertility 

    • Natural conception is less likely: Even if sperm count and motility are normal, high DNA fragmentation can impair the sperm's ability to fertilize an egg or support embryo development.

  • Higher time to pregnancy

    • Couples may take significantly longer to conceive naturally.

  • Poor Embryo Development

    • DNA damage in sperm can lead to defective embryonic development that results in poor blastocyst formation in IVF cycles.

  • Increased Risk of Miscarriage

    • Embryos derived from sperm with fragmented DNA have a higher likelihood of early pregnancy loss, particularly first-trimester miscarriages.

  • Lower Success Rates in Assisted Reproductive Technologies (ART)

    • IVF and ICSI (intracytoplasmic sperm injection) success may be reduced.

What are the types of DNA fragmentation tests used by LCRH and how much does they cost?

LCRH routinely recommends the Sperm Comet® Exact, Sperm Comet® Extend and/or the Sperm Comet® Extensiv DNA fragmentation tests:

DNA Fragmentation Testing

You can find out more at: https://examenlab.com

  • The Exact® test’s function is to measure the level of DNA fragmentation in a sperm sample. It measures both single strand DNA breaks (ssDB) and double strand DNA breaks (dsDB). £500

  • The Extend® test exclusively measures double strand DNA breaks (dsDB). Double-strand DNA damage seems to be particularly associated with frequent, early miscarriages, often when the semen analysis and ordinary DNA fragmentation tests are normal or near-normal. £600

  • The Extensiv® test is a combination of both the Exact and Extend tests. £1,000

What can I do about high single-stranded DNA fragmentation? How can I improve my sperm DNA Quality?

Sperm are created in a cycle that takes about 90 days. Simple, positive changes to your lifestyle can significantly improve the health of your sperm DNA.

1. Varicoceles – diagnose and repair

  • Particularly for large and palpable varicoceles.

2. Treatment of infections and inflammation 

  • Addressing conditions such as prostatitis or microbiome imbalances.

3. More frequent ejaculation

  • Intervals ≤2days appear to reduce oxidative burden and yield sperm populations with decreased sperm DNA fragmentation.

4. Quit Smoking or Vaping

  • Tobacco contains thousands of chemicals toxic to sperm. Smoking generates “free radicals” – unstable molecules that attack and damage sperm DNA.

  • Studies show a clear link between smoking and reduced fertility, including lower sperm counts, more abnormal-looking sperm, and low motility. 

5. Limit Alcohol Consumption

  • Excessive alcohol intake can reduce sperm count and motility. To give yourself the best chance, it’s wise to keep alcohol to a minimum for at least three months before trying to conceive.

  • UK guidelines suggest no more than 3-4 units per week.

6. Manage Chronic Stress

  • Long-term stress can disrupt hormone levels and contribute to sperm DNA damage. 

  • While stress is a part of life, finding healthy ways to manage it -through exercise, mindfulness, or hobbies- can support both your mental well-being and your sperm production.

7. Understand Age-Related Factors

  • While it was once thought male fertility didn’t decline with age, we now know that’s not true. As men get older, the natural processes that protect sperm DNA become less efficient. 

  • For men over 45, understanding your sperm DNA health is especially important, as damage can affect conception and the long-term health of your child.

8. Avoid Recreational Drugs

  • Substances like cannabis can negatively affect sperm in several ways, slowing them down and altering their ability to fertilise an egg. 

  • Long-term cannabis use can have a lasting impact on sperm production.

9. Maintain a Healthy Weight

  • A Body Mass Index (BMI) of over 25 can negatively affect both the quality and quantity of your sperm.

  • A combination of regular, moderate exercise and a balanced diet is the best strategy for maintaining a healthy weight and supporting optimal sperm production.

10. Avoid Excess Heat

  • Sperm production works best at a slightly cooler temperature than the rest of your body. Frequent exposure to high heat can damage developing sperm. 

  • Avoid tight-fitting underwear or compression shorts.

  • Limit long periods of sitting or cycling.

  • Avoid hot tubs, saunas, and placing laptops directly on your lap.

11. Fuel Your Body with a Balanced Diet

  • Your sperm need the right nutrients to thrive. Focus on a diet rich in fruits, vegetables, lean proteins (fish, eggs, beans), and whole grains. Limit your intake of processed foods high in fat, sugar, and salt. 

  • Essential foods: Lots of fruit and steamed vegetables; some starchy foods like bread, rice, potatoes, and pasta; and some protein like meat, fish, eggs, and beans.

  • Limit intake of fat, sugar, or salt.

12. Consider antioxidant supplementation 

  • Too few antioxidants are sub-optimal for DNA repair, but too many also causes problems (a "reductive stress" effect). This is an area where talking to your consultant or andrologist is genuinely useful rather than self-prescribing.

What can I do about high double-stranded DNA fragmentation? 

At LCRH double-stranded DNA fragmentation testing is often pursued after unexplained recurrent miscarriage or repeated IVF failure of euploid embryos.

  • Microfluidic sperm sorting (such as ZYMot) is seen to reduce these levels of double stranded DNA fragmentation to within the normal range in approximately 80% of men tested. (studies ongoing)

  • There is evidence that as a woman gets older, her eggs lose their ability to repair the DNA fragmentation.

Who are Fertility Solutions and how might they be involved in our care?

Fertility Solutions is a company based in Beaconsfield and are one of our closest partners, particularly around male factor fertility. Patients who contact Fertility Solutions directly can seamlessly book initial consultations with LCRH and patient care will remain well co-ordinated. 

We commonly work closely with Fertility Solutions around investigating sperm health including DNA fragmentation.  If the location is convenient for you, we may refer you directly to them. 

We also specifically use Fertility Solutions to investigate whether the use of ZyMot may improve successful embryo development. A typical cost journey may be:

  1. Initial Sperm Comet Extend DNA fragmentation test - £699 (paid directly to Fertility Solutions) 

  2. Investigation of whether ZyMot might lower or optimise the DNA fragmentation £1,190 (£290 paid directly to Fertility Solutions)

  3. If indicated, the inclusion of ZyMot on the day of fertilisation - £300. 

What is Sperm ZyMot and when might it be used?

The ZyMot sperm separation device is a microfluidic technology designed to select the healthiest sperm with high motility and low DNA fragmentation for IVF/ICSI, mimicking natural selection. It avoids harmful centrifugation, resulting in higher quality sperm samples. This tool is ideal for high DNA fragmentation or previous failed IVF cycles. 

Key Benefits of ZyMot Sperm Selection:

  • Reduced DNA Damage: By avoiding centrifugation, the device minimizes mechanical stress and potential DNA fragmentation.

  • Superior Selection: It uses a membrane filter that simulates natural barriers, allowing only high-motility sperm to pass through.

  • Improved Outcomes: Studies suggest better fertilization rates, higher quality embryo development, and improved blastulation, particularly in cases with high DNA fragmentation.

  • Ideal Candidates: It is recommended for couples with high sperm DNA fragmentation, repeated IVF failures, poor embryo quality, or recurrent miscarriages. 

The Procedure:

  1. Loading: Semen is injected into the bottom chamber of the device.

  2. Migration: Motile sperm swim up through a microfluidic membrane, leaving behind dead cells and debris.

  3. Collection: After approximately 30 minutes of incubation, high-quality sperm are collected from the top outlet for use in ICSI. 

You can find out more at: https://www.coopersurgical.com/product/zymot-multi-sperm-separation-device

Using ZyMot in a cycle costs £300.