Sperm DNA fragmentation can lead to male infertility, failed ICSI, or recurrent miscarriage because embryonic development is strongly linked to the integrity of the genetic material, known as DNA, present in sperm. But what exactly is sperm DNA fragmentation, and how does it affect fertility?

What is sperm DNA fragmentation?

DNA, or deoxyribonucleic acid, is the genetic material in humans and living organisms, consisting of two long strands that coil around each other. Sperm DNA fragmentation refers to breaks in the genetic material (DNA) present in the sperm. These breaks can affect either one or both of the DNA strands. This damage usually occurs after the sperm has left the testicle.

DNA fragmentation in spermatozoa can cause fertility problems such as decreased fertilization rates and pregnancy rates, decreased embryo quality, and increased miscarriage rates, even in cases where the semen sample analysis is normal in terms of count, motility, and morphology.

Sperm DNA fragmentation is not tested as part of the traditional semen analysis. However, performing a semen analysis with sperm DNA fragmentation testing allows for a comprehensive assessment of overall sperm health.

What causes sperm DNA fragmentation?

Oxidative stress is one of the primary causes of sperm DNA fragmentation due to the damage caused by free radicals. The body uses antioxidants to prevent free radical damage. Antioxidants are naturally produced by our bodies and can be obtained from food or dietary supplements. Semen also contains high levels of antioxidants such as vitamins E and C and glutathione, which protect sperm from oxidative stress. Antioxidants are also produced in other parts of the male reproductive system where sperm are stored.

However, certain behaviors can lead to increased levels of free radicals beyond what the body can manage, such as:
• Exposure to environmental toxins like pesticides, heavy metals, exhausts, and general environmental pollution.
• Radiation.
• Infections.
• Smoking.
• Alcohol consumption.

On the other hand, if antioxidant levels are very low, possibly due to poor nutrition, they may not be able to adequately counteract the free radicals.

Sperm DNA fragmentation is also associated with the following:
• Aging.
• Varicocele (enlarged veins within the scrotum).
• Diseases accompanied by a high fever.
• Elevated testicular temperature (due to laptops and hot baths).
• Diseases like diabetes and obesity.
• Cancer and cancer treatments.

Sperm DNA fragmentation also occurs when the body cannot repair the DNA breaks and when there is a deficiency in the proteins that bind DNA to be less susceptible to damage.

What is the importance of the genetic material of sperm?

The purpose of sperm is to carry the genetic material (DNA) from the husband to combine with the genetic material of the wife’s egg to form the embryo’s genetic material.

Most cells in the human body contain 46 chromosomes, while reproductive cells (eggs and sperm) contain only 23 chromosomes each. When they combine, they create a complete living organism with the appropriate number of chromosomes.

Therefore, the genetic integrity of sperm is a key consideration in fertility. Any damage to the DNA of sperm can interfere with its ability to properly fertilize the egg or develop into a healthy embryo, and this is why the issue of sperm DNA fragmentation is important. Therefore, sperm DNA fragmentation testing should be performed when attempting to conceive.

Dr. Adham Zaazaa, Consultant in Andrology and ICSI and Professor of Andrology and Fertility Surgery at Cairo University, was the first to introduce sperm DNA fragmentation testing in Egypt in 2008, just one year after it was approved abroad. His master’s thesis focused on diagnosing and treating DNA fragmentation in sperm, and due to its importance, it was discussed in the presence of Professor DP Evenson, the inventor of sperm DNA fragmentation testing worldwide.

Why is sperm DNA fragmentation testing useful?

Results from semen analysis alone cannot definitively confirm male fertility or the likelihood of achieving pregnancy with fertility treatment. As a result, doctors have sought other methods to determine male fertility.

Successful embryonic development requires undamaged genetic material from both the egg and sperm. Studies have shown that sperm DNA damage is more common in infertile men and may contribute to impaired reproductive ability. It has also been found that a significant proportion of infertile men have increased DNA fragmentation despite normal semen analysis results, highlighting the importance of sperm DNA fragmentation testing as another means of complete and integrated fertility assessment.

What does sperm DNA fragmentation testing involve?

Various tests for sperm DNA fragmentation provide an estimate of the extent of DNA damage present in a semen sample. Typically, sperm DNA fragmentation testing is performed using a semen sample obtained through ejaculation.

When should sperm DNA fragmentation testing be performed?

Sperm DNA fragmentation testing should be conducted before starting any fertility treatments, as it provides a more comprehensive assessment of sperm health in addition to the results of semen analysis.

Candidates for DNA fragmentation testing are:
• All infertile men, especially those diagnosed with unexplained infertility, a history of recurrent miscarriages, or poor embryo quality during intracytoplasmic sperm injection (ICSI).
• Individuals over the age of 40.
• Those with a history of cancer.
• Individuals with daily habits that may affect sperm health, such as smoking.

Is sperm DNA fragmentation treatable?

Since new sperm are created every 72 days, reducing oxidative stress may decrease the degree of sperm DNA fragmentation. Here are some recommendations from Dr. Adham Zaazaa, MD, Consultant in Andrology, to reduce oxidative stress:

• Evaluate testicular varicocele to determine if surgical treatment is necessary.
• Avoid hot baths and tight underwear.
• Follow a healthy diet full of fruits and vegetables rich in antioxidants.
• Avoid smoking and drugs.
• Switch or modify any medications that may contribute to oxidative stress.
• Take nutritional supplements containing vitamins and antioxidants.

There are many treatment options available when sperm DNA fragmentation is detected. However, your first step is consulting a trusted and experienced doctor, such as Dr. Adham Zaazaa, a consultant in ICSI and professor of andrology and fertility surgery at Cairo University, who can provide an accurate diagnosis and guidance based on the results of the sperm DNA fragmentation test. Dr. Adham Zaazaa has developed a non-surgical technique called SIVCA to directly retrieve sperm from the testicle for ICSI, reducing the chances of sperm DNA fragmentation.