Sperm DNA Fragmentation – Causes & Effect on Fertility

Sperm DNA fragmentation refers to the presence of sperm with damaged (broken) DNA, which affects male fertility.

Alterations of any kind in sperm DNA are likely to cause infertility in the man affected, as integrity of sperm DNA is key to obtaining viable embryos and subsequently a healthy baby.

So, to sum up, the higher the sperm DNA damage index, the lesser the chances of achieving an ongoing pregnancy.

Sperm DNA fragmentation & infertility

Male fertility and sperm quality are evaluated by means of a sperm test or semen analysis report. However, there exist other sperm parameters that are not usually evaluated and can have an impact on fertility as well.

A good example would be sperm DNA fragmentation. It is estimated that about 10-15% of childless males have alterations in the genetic material of the sperm they produce, whilst common parameters like count, motility, and morphology are normal.

Fragmented DNA in sperm

In order for fertilization to result in viable embryos with implantation potential, it is necessary that the DNA of both egg and sperm are free from damage and other lesions.

High DNA fragmentation rates can translate into:

• Reduced fertilization rates
• Poor embryo quality
• Reduced implantation rates
• Increased miscarriage rates

It should be noted that implantation failure and miscarriage risk are present in all cases of patients who undergo fertility treatment as long as the male partner has sperm DNA fragmentation, let alone if this alteration has never been diagnosed before.

DNA fragmentation test for sperm

As explained above, many males have normal sperm test results but the sperm DNA fragmentation index is considerably high. Nevertheless, the most likely is that sperm DNA damage is detected along with other sperm disorders.

In any case, in order to evaluate the quality of sperm DNA, one should undergo a specific test known as sperm DNA fragmentation test.

Oftentimes, a couple undergoes DNA fragmentation testing when pregnancy is not achieved after several unsuccessful attempts. The following is a list of the most frequent indications:

• Unexplained infertility
• Repeated implantation failure
• Poor-quality embryos
• Varicocele
• Recurrent pregnancy loss
• Men who are 45 or older
• Chronic diseases like diabetes
• Men who smoke cigarettes
• Abnormal semen analysis results, especially in cases of necrospermia and hypospermia

There exist several methods for evaluating the level of sperm DNA fragmentation at the laboratory. Nonetheless, the following are the most important ones:

TUNEL Assay

The TUNEL Assay (Terminal deoxynucleotidyl transferase dUTP nick end labeling) is a technique used for detecting sperm DNA fragmentation by using bench top flow cytometer.

The TUNEL method involves staining the sperms using a fluorescence microscopy that detects DNA-fragmented spermatozoa only.

When the sample is observed under the flow cytometer or fluorescence microscopy, DNA-fragmented spermatozoa can be seen with greater fluorescent intensity.

SCD test

Sperm Chromatin Dispersion (SCD) test is used to measure the degree of sperm chromatin decondensation.

To this end, sperms are treated using an acid and other substances that prevent DNA loops from forming.

As a result, sperms with intact DNA will have larger sperm chromatin dispersion rates, while those with damaged DNA will have low or non-existent halos of dispersed DNA around the head.

Sperm Chromatin Dispersion (SCD) Test

Causes

Over the past few years, evidence has shown that about 25% of infertile men have high levels of sperm DNA fragmentation after doing a sperm DNA fragmentation test.

Many factors can cause sperm DNA to be damaged, including:

High scrotal temperature

Due to episodes of high fever, presence of a varicocele, or wearing too tight clothes.

Seminal infections

Caused by Chlamydia trachomatis, a bacteria that affects sperm quality.

Pharmaceutical medications

Pesticides and high levels of air pollution can affect sperm DNA.

Tobacco consumption

Men who smoke have a decreased sperm quality. In fact, smoking can increase the concentration of sperm with damaged DNA.

Advanced age

Sperm DNA fragmentation increases dramatically with age, especially from age 45 onwards.

Aside from these causes, sperm DNA fragmentation can occur during the sperm production process (spermatogenesis), including failure to identify sperm with defects to eliminate them from the testis, as well as an incomplete sperm maturation process in the epididymis.

Causes of sperm DNA fragmentation

Treatment

Not all causes of sperm DNA fragmentation are treatable or can be cured. In all other cases, a treatment based on antioxidants is typically enough to improve sperm quality.

Oxidative stress caused by an increased number of free radicals in the man's organism causes damage to sperm DNA. For this reason, leading a healthy lifestyle and a balanced is key to reduce the levels of sperm DNA fragmentation.

Some antioxidants that can boost sperm quality are vitamins C, E, and A, which are found in fruits, vegetables, vegetable oils, brown rice, soy, chocolate, oregano, tea, etc.

On the other hand, seminal infections should be treated with antibiotics to reduce the levels of sperm DNA fragmentation. Surgery to treat varicocele also improves sperm DNA integrity and subsequently boost male fertility.

Effect on pregnancy

The fact that a man has elevated levels of sperm DNA fragmentation does not mean that conceiving naturally is impossible. However, the chances of success decrease due to all the reasons explained above.

If the fragmentation index is rather low, it is possible that the egg fixes the damage by itself after fertilization. Although this mechanism of action is still to be studied, it depends highly on the type of damage and egg quality.

In spite of all this, patients with a percent of sperm DNA fragmentation above 30% should go directly for IVF with ICSI treatment, also known as IVF-ICSI.

Artificial Insemination (AI) presents lower success rates in patients with sperm DNA fragmentation. For this reason, this treatment option is not recommended in these cases.

FAQs from users

How does MACS in sperm selection work?

MACS stands for Magnetic-activated cell sorting and consists of discarding apoptotic sperm, or select sperm that do not have fragmented DNA.

It can be used in seminal samples of patients who are going to perform both in vitro fertilization (IVF), intracytoplasmic microinjection (ICSI) and artificial insemination (AI), although its limitation is that it must be used in samples with sufficient seminal quality for the result to be optimal, as the seminal concentration decreases.

It is indicated for patients with a high percentage of spermatozoa with fragmented DNA, repeated miscarriages, poor embryo quality and low fertilization rates.

Is it better to study single-stranded or double-stranded DNA breaks? And why?

Single stranded fragmentation produces different problems than double stranded fragmentation. While single stranded breaks are related to male sterility, double stranded breaks are related to a higher risk of abortion.

Single stranded fragmentation is mainly caused by oxidative stress (tobacco, alcohol...), and is a much more extensive error, affecting a large part of the spermatozoid DNA. This makes it very difficult to repair by the oocyte and, therefore, not even gestation occurs.

In the case of double-stranded fragmentation, breaks are produced at specific points that are unprotected by an enzyme called nuclease, so the damage is not so extensive and can even be repaired by a young egg. Otherwise, if this fragmentation is not repaired, it will give rise to an embryo with chromosomal alterations that will most probably end in a miscarriage.

Therefore, depending on the problem of the patients, we may find it more interesting to study one or another type of fragmentation. However, the ideal would be to study both types of fragmentation, given that there could be problems in both.

How much does a sperm fragmentation test cost?

The cost of this test is not covered by insurance and is $300, plus the home collection kit that cost $150.

Are tests of sperm DNA damage clinically useful?

Absolutely, especially in cases of pregnancy loss by IVF and ICSI, as well as to increase IUI pregnancy rates. However, the true clinical utility of these tests is still to be established, as available studies are still small and few in number.

Can sperm DNA fragmentation be improved?

Yes, following a treatment based on antioxidants, as well as vitamin supplements including vitamins C, E, and A. However, the chances of success depend on the level of DNA fragmentation. In the most severe cases, that is, when the percent of DNA fragmentation is above 30%, pregnancy can only be achieved by means of IVF/ICSI.

Can sperm with DNA fragmentation fertilize an egg?

Yes, it is not impossible, especially when the level of fragmentation is low or moderate. Sometimes, if the fragmentation index is low, it is possible that the egg cell compensates this alteration and fixes the damage after fertilization, which would result in a viable embryo.

Does sperm DNA fragmentation cause birth defects?

Actually, there is no human study showing a direct relationship between birth defects and sperm DNA fragmentation. However, damage in the sperm DNA increases the risks increases the risk of genetic mutations, thereby increasing the risk of miscarriage.

Suggested for you

In addition to this test, there exist other male fertility tests that can be done prior to starting a fertility treatment. Find them all in the following post: Male Fertility Testing – How Do You Know if a Man’s Sperm Is Fertile?

As explained above, IVF with ICSI is the most adequate fertility treatment for those couples who are trying to conceive without luck and testing has show high levels of sperm DNA fragmentation. Check out this for information: What Is ICSI Technique? – Process, Success Rates & Cost.