What Is Sperm DNA Fragmentation? When Is the Test Requested?

The first test requested when male fertility is assessed is a semen analysis. It shows sperm count, motility and morphology, but it says nothing about the state of the genetic material the sperm carries. In some couples, conception does not occur even though the semen analysis values fall within the normal range, or pregnancies end in repeated miscarriage. This is where one particular test comes into consideration: the sperm DNA fragmentation test.

This article explains what the test measures, in which patients it is meaningful, how the result is assessed and what is done when it is found to be high.

What is sperm DNA fragmentation?

The head of the sperm carries the genetic information needed for the embryo to develop. DNA fragmentation means that there are breaks in that genetic chain. An increased proportion of breaks means that embryo development after fertilisation may be affected.

Two points deserve emphasis here. First, some degree of DNA breakage in every ejaculate is ordinary; a problem arises when the proportion rises markedly. Second, the egg cell has a capacity to repair a certain level of breakage, and that capacity is related to the woman's age. The same fragmentation value can therefore carry different meanings in different couples.

How does it differ from a semen analysis?

A semen analysis and a DNA fragmentation test are not interchangeable; they examine different things:

• A semen analysis assesses the count, motility and shape of sperm cells. What it measures is the capacity of sperm to reach the egg.
• A DNA fragmentation test assesses the integrity of the genetic material the sperm carries. What it measures is the capacity of sperm, once they arrive, to contribute to the formation of a healthy embryo.

This distinction explains a picture frequently seen in the clinic: even in a sample containing motile, normal-looking sperm, the proportion of DNA breaks can be high. The reverse is also possible. DNA fragmentation is therefore complementary to the semen analysis.

What causes fragmentation?

More than one mechanism plays a part in the formation of DNA breaks. The headings most often encountered in the clinic are as follows:

• Oxidative stress: An increase in free radicals and disruption of the protective antioxidant balance is the mechanism most often implicated.
• Varicocele: Dilation of the veins around the testicle can increase fragmentation through raised temperature and oxidative stress.
• Infection and inflammatory processes: Genital tract infections and chronic prostatitis may contribute.
• Smoking, alcohol and excess weight: Lifestyle factors that increase the oxidative burden.
• Heat exposure: Habits such as prolonged hot environments, sauna use and working with a laptop on the lap come into consideration.
• Febrile illness and certain medicines: A recent febrile illness can affect the result because of the production cycle.
• Age: Fragmentation tends to increase with advancing paternal age.
• Long abstinence: Sperm waiting a long time in the epididymis are exposed to more oxidative stress.

In which patients is it requested?

The DNA fragmentation test is not requested routinely in every infertility assessment. The situations in which it is meaningful are typically these:

• Unexplained infertility: No conception despite a normal female assessment and a normal semen analysis
• Recurrent pregnancy loss: Couples with a history of repeated early miscarriage
• Failed assisted reproduction attempts: Repeated failure with insemination or IVF
• Poor embryo quality: Embryo development arresting despite fertilisation
• Varicocele: Particularly where additional information is needed for a surgical decision
• Advanced paternal age and marked lifestyle risk factors

It is important that the decision to test is made at the level of the couple. The result takes on meaning not on its own, but together with the female partner's age, ovarian reserve and previous treatment history.

How is the test performed and how is the result read?

As with a semen analysis, the test is performed on a semen sample. A period of two to five days of abstinence is generally recommended before the sample is given; it should be remembered that very long abstinence can itself raise the fragmentation rate.

Laboratories use different methods, and each method has its own reference range. An assessment should therefore not be made without knowing which method was used and what that laboratory's reference range is. Comparing two results obtained with different methods directly is misleading.

The result is reported as a percentage and is usually classified as low, borderline or high. A high value does not mean that pregnancy will not occur; it indicates the presence of a factor that may affect the likelihood of pregnancy, and one that can be addressed.

What is done if the value is high?

High fragmentation is, in most cases, a finding that can be addressed. The path taken is determined by the cause:

• A correctable cause is sought: Where there is a varicocele, genital infection or hormonal problem, that is addressed first.
• Lifestyle is reviewed: Stopping smoking, weight management, reducing heat exposure and sleep patterns fall under this heading.
• Ejaculation frequency is adjusted: In some patients, shortening the abstinence period can change the result.
• Antioxidant support is considered: This comes into play in cases where oxidative stress is prominent; unlimited and unsupervised use is known to carry adverse effects of its own.
• The assisted reproduction plan is reviewed: Sperm selection methods applicable on the laboratory side during IVF, and in some cases retrieving sperm directly from the testicle, may be considered.

Because sperm production is completed over a cycle of roughly three months, the effect of any adjustments is usually seen in a follow-up test performed three months later. This waiting period does not mean the treatment is not working; it is a natural consequence of the production cycle.

Points that are commonly misunderstood

There are pieces of misinformation about this test that patients frequently encounter:

• "A high value means fatherhood is impossible" is not true. Pregnancies are seen in patients with high values too; the test is an indicator of likelihood, not a statement of outcome.
• "A normal semen analysis makes the test unnecessary" is not true. The group in which the test is most useful is precisely couples whose semen analysis is already normal and whose infertility is unexplained.
• "Taking antioxidants will lower the value" is not true on its own. Proceeding with supplements alone while a correctable cause exists can cost time.
• "A single result is enough" is not true. A follow-up test may be needed, because transient factors such as febrile illness, intense stress or the abstinence period can change the result.

When should a doctor be consulted?

A detailed assessment of the male factor is advised in the following situations:

• No conception after a year of regular, unprotected intercourse
• Six months having elapsed where the female partner is over 35
• Two or more early pregnancy losses
• Problems with fertilisation or embryo development during IVF attempts
• Noticing dilated veins or swelling in the testicle

Sperm DNA fragmentation is a complementary test that assesses an aspect of male fertility a semen analysis cannot show. Requested in the right patient, it can shed light on unexplained infertility and recurrent pregnancy loss, and where it is high, it is in most cases a finding that can be addressed. What matters is that the result is assessed together with the method used, the couple's history and the female partner's situation. Assoc. Prof. Zülfü Sertkaya practises in urology and andrology in Istanbul; assessment and treatment planning in male infertility are carried out with individual assessment and confidentiality.

Frequently Asked Questions