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Analyzing Sperm DNA Damage To Diagnose Male Infertility

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In over a third of infertile couples, male infertility is thought to play a role in the inability to conceive a child. Sperm DNA damage is a leading cause of male infertility but is a measure that is not analyzed by current fertility tests. The knock-on effect of this is a reduction in the potential success of fertility treatments such as In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI).

A recent collaborative study between Examen and the Lister Fertility Clinic in London used Examen’s COMET assay to measure sperm DNA damage in men with unexplained infertility. We spoke with Professor Sheena Lewis, CEO of Examen, to learn more about the study, the links between sperm DNA damage and infertility, and the value of adding this parameter to fertility testing.

Molly Campbell (MC): Why is it important to conduct sperm DNA damage analysis when exploring fertility and infertility treatment options?

Sheena Lewis (SL):
Our research shows that 80 percent of men attending fertility clinics, with normal sperm counts, had a high sperm DNA damage result measured using our Exact range of tests. This is extremely important as men with high levels of damaged sperm DNA are less likely to get their partner pregnant and have double the risk of miscarriage, plus they are less likely to be successful with fertility treatments, such as IVF and ICSI.

Up until now, such couples' issues with fertility were diagnosed as "unexplained" and they were offered IVF. Our research reports that these couples are more likely to have a family using ICSI.

It is so often the case that male infertility is under investigated, especially prior to fertility treatment. As such, couples may undergo IVF or ICSI and endure the stress and emotional toll this takes, as well as the cost, only to find the treatment is unsuccessful. Sperm DNA analysis using Exact tests powered by SpermCOMET®, provides men and healthcare professionals with the information they need to make the best treatment decisions for every individual.

Anna MacDonald (AM): What causes sperm DNA damage? If high levels are detected, are there any lifestyle changes or treatments that can help men produce sperm with lower levels of DNA damage?

DNA damage (fragmentation) is usually caused by oxidative stress. Oxidative stress produces free radicals which attack the DNA molecule causing breaks in the DNA strands. Sperm DNA damage is often associated with underlying medical conditions (including: varicocele, infection or fever), or certain lifestyle choices (including: drinking, smoking, recreational drugs or overweight). Sperm DNA damage can be significantly reduced by making healthy lifestyle changes including quitting smoking, reducing alcohol consumption, eating healthily, taking more exercise and reducing stress. As sperm production works best at lower temperatures, wearing compression shorts or tight underwear, spending all day sitting at a desk or even doing lots of cycling can damage a man’s sperm. Treating underlying conditions such as varicocele and infections can also have a significant impact in improving sperm quality. Even changes for as short a time as three months can make a big difference.

AM: How is male infertility currently diagnosed? What are some of the limitations of these methods?

The first step in testing male infertility is usually semen analysis but this only measures the quantity, morphology and motility of sperm and does not provide sufficient information about the quality. Many men with a normal sperm count cannot get their partners pregnant, whilst lots of men with a low count do conceive naturally. Sperm DNA analysis gives a vital measure of the health of the sperm which is fundamental to being able to determine the likelihood of fertilization and the possibility of having a baby.

MC: Please can you tell us more about the COMET technology? How does a fertility test utilizing this platform differ from currently available methods?

Conventional semen parameters are accepted to have limited diagnostic value for male infertility and poor prognostic value for Assisted Reproductive Therapy (ART) success. In contrast, sperm DNA fragmentation has been shown to be a robust biomarker of male infertility, ART failure and miscarriage. The Exact range of tests, Exact FertilityTM, Exact IVFTM and Exact ICSITM, utilize Examen’s proprietary SpermCOMET® technology to assess levels of DNA damage. The COMET assay uses single cell gel electrophoresis to measure the amount of single- and double-strand DNA fragments present in individual sperm, generating a picture of the extent of DNA fragmentation.

The tests provide the average COMET score (average percentage DNA damage), the proportion of sperm with high DNA damage and the proportion of sperm with low DNA damage which can be used to understand unexplained infertility as well as predict the success of both IVF and ICSI. The EXACT tests are the only tests to report the damage in individual sperm and how this impacts on IVF and ICSI.

MC: Please can you tell us more about your latest study in collaboration with the Lister Fertility Clinic? What were your most significant findings?

The average COMET score has previously been shown to have a strong correlation with all fertility checkpoints, including live birth rate. This study aimed to establish whether new, more detailed measures of the proportion of sperm with low or high DNA damage improve the power of the test in the diagnosis of male infertility and the prediction of the success of ICSI as well as IVF. The results confirm that the additional COMET measurements can be used to assist in the diagnosis of unexplained infertility as well as predicting the success of ICSI. These novel test parameters enable professionals to add to their male workups, make more informed clinical decisions and improve fertility treatment outcomes

AM: What future work do you have planned?

We are working on the impact of our EXACT tests on miscarriage. We are also developing another test for double strand breaks only. This will be particularly useful in men who have had failed treatment with ejaculated sperm and are now considering using their own testicular sperm rather than resorting to donor sperm.

Our goal is to help men become fathers and we will continue to work with fertility specialists and urologists to provide the scientific insights needed to inform clinical decisions that support all couples on their journey to parenthood.

Sheena Lewis was speaking with Molly Campbell and Anna MacDonald, Science Writers for Technology Networks.