What are the causes of Sperm DNA Fragmentation?

The aetiology of SDF is multifactorial. Its accurate clinical implication remains poorly understood. Currently, there seems to be insufficient evidence to support the routine use of SDF in male factor evaluation. This test offers a possible further explanation for un-explained infertility. The results of a sperm DNA damage test may impact slightly on the management of your treatment but may identify why you are struggling to get pregnant.

In men, the major contributing factor for sperm DNA fragmentation is oxidative stress, which can be associated with one or more of the following:

• Infection
• Fever
• Elevated testicular temperature
• Recreational drugs
• Smoking
• Alcohol
• Stress
• Diet
• Environmental and occupational pollutants
• Advanced age (>40 years)
• Varicocele

What are the advantages of the sperm DNA fragmentation test?

• Provides a reliable analysis of sperm DNA integrity that may help to identify men who are at risk of subfertility
• Provides information that helps in the clinical diagnosis, management and treatment of male fertility
• Provides prognostic value in assessing the outcome of assisted conception treatment
• DFI testing may help better select varicocelectomy candidates among men with borderline or normal semen analysis parameters.
• It may also provide possible explanation in couples with unexplained infertility or recurrent pregnancy loss or IUI failures.
• DFI may provide prognostic information in couples that have previously failed IVF/ICSI.
• Additionally, high DFI may be a reason to consider using testicular sperm rather than ejaculated sperm with IVF/ICSI.

High rates of sperm DNA fragmentation and pregnancy potential

• Normal, healthy pregnancies do occur in couples where the male partner has high percentage of sperm with fragmented DNA, although the chances are significantly reduced.
• Embryos derived from sperm with highly fragmented DNA have poor prognosis
• DNA fragmentation could result in initiation of apoptosis and mutations resulting in blastocyst arrest, miscarriage and abnormalities in the offspring.
• Sperms with high DNA fragmentation fertilising younger oocytes than older oocytes carry a better prognosis of successful pregnancy, as they are much more efficient at DNA repair of defective sperm

What are the indications for men who may benefit from doing sperm DFI test?

• Unexplained infertility
• Arrested embryo development
• Poor blastocyst development
• Multiple failed IVF/ICSI treatments
• Recurrent miscarriage
• Advanced chronological age (>40 years)
• Varicocele

• Poor semen parameters
• Exposure to harmful substances

How is sperm DNA tested?

Sperm DNA fragmentation is tested by different techniques. The mostly commonly used SDF tests include comet assay, sperm chromatin structure assay (SCSA), sperm chromatin dispersion (SCD) test (or halo assay) and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) assay

A sperm sample is collected, analysed using Sperm chromatin Dispersion (SCD) testing technique, where the sperms undergo acid denaturation, removal of nuclear protein content, followed by different staining process and fixation. SCD test is based on the principle that sperm with fragmented DNA fail to produce the characteristic halo of dispersed DNA loops that is observed in sperm with non? fragmented DNA. The amount of DNA damage is calculated using DFI (DNA FRAGMENTION INDEX). A DFI of 20% or more significantly reduces the success rates after ICSI.

Sperm that have been tested for their DNA integrity cannot then be used for treatment, they are destroyed by the test.

What is the treatment of high sperm DNA fragmentation?

It depends essentially on the cause. If the damage is caused by free radicals, a change in lifestyle and diet designed to protect against oxidative stress may help reduce the levels of DNA fragmentation. Other treatment options include:

• Antibiotics in the co-existence of an infection
• Life style changes – Avoid drugs, smoking and occupation
• Diet – Eat fresh foods, particularly those containing antioxidants and vitamin C & E
• Varicocele surgery
• Testicular aspiration of sperm (DNA damage occurs at the post-testicular level, hence testicular sperm may have a better DNA integrity than ejaculated sperm)
• ICSI rather than IVF

Initiatives to reduce the levels of fragmentation can be assessed by undertaking a second test three months later.

Medicinal antioxidant treatments have not been shown to be effective so far, but this is one area of research that is continuing.

SUMMARY:

Despite suggestions that sperm DNA fragmentation could be a marker of sperm quality and predictor of fertility treatment outcome, this has not generally been supported by the evidence so far. 

It cannot be regarded as part of the routine semen assessment at the current time.

Sperm DNA fragmentation may vary considerably over time in a single individual.

The best way to reduce sperm DNA fragmentation is to eat fresh foods, particularly those containing antioxidants or vitamin C and E, and to stop smoking.