Sperm DNA Fragmentation

A man’s fertility is determined through a semen analysis that measures the sperm count, sperm motility and sperm morphology. However, this test does not give any information about the genetic constitution of the sperm, which is necessary for normal development of the embryo. Hence a high level of DNA damage in sperm cells may be a cause of male infertility that routine examinations through semen analysis cannot detect.

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Sperm Dna Fragmentation

What Is Sperm Dna Fragmentation?

Sperm DNA fragmentation is defined as the amount of damage seen in the sperm DNA. i.e. the amount of abnormal genetic material present within the sperm cell, which in turn may be a reason for male subfertility, IVF failure and miscarriage. One must consider the impact of DNA damage on the sperm because half of the DNA in the offspring comes from the father’s side.

Sperm DNA fragmentation is found to be higher in infertile men. So, men who have poor semen parameters are more prone to have high sperm DNA fragmentation, but high sperm DNA fragmentation can also be found in men with normal semen parameters, and the reason for their infertility is usually given as unexplained infertility.

What Is Sperm Dna Fragmentation Test?

To measure DNA damage in a semen sample we do the sperm chromatin structure assay. This test is used to measure the amount of DNA damage in thousands of sperm in an ejaculate. It measures the sensitivity of sperm DNA, how it denatures when exposed to heat or acids. To perform this test, the sperm is stained with a fluorescent probe that goes and interacts with the DNA molecule. If the DNA is fragmented, the fluorescence signal will change, and this change in signal is monitored using a flow cytometer. This sperm chromatin structure assay (SCSA) is standardised, validated CLIA (Clinical Laboratory Improvement Amendments) approved test.

When Is Sperm Dna Fragmentation Test Suggested?

The indications which might prompt a fertility specialist to recommend a sperm DNA test are:

  • Poor semen parameters
  • Presence of varicocele
  • Unexplained infertility
  • Arrested embryo development
  • Poor blastocyst development
  • Multiple failed IVF/ICSI treatment
  • Recurrent miscarriage in partner
  • Advanced chronological age
  • Exposure to harmful substances

The Role Of Dna Fragmentation In Embryo Development

Embryos, when formed from sperm whose DNA is highly fragmented, have a poor prognosis. Damaged DNA in sperms is more likely to affect embryos from Day 2 of development when the paternal genome is switched on, and it results in poor blastocyst development. There are some studies which act as a shred of evidence that suggests: DNA fragmentation in the embryo can result in cell degeneration and gene mutations, which could lead to arrested embryo development, miscarriage, abnormalities in the baby and increased susceptibility to childhood cancers.

The Relation Between Sperm Dna, Pregnancy And Miscarriage

Many extensive studies have indicated that the chances of successful natural pregnancy and assisted reproduction pregnancy rates are significantly reduced when the male partner has a high percentage of sperm with fragmented DNA. Also, sperm with high DNA fragmentation leads to higher miscarriage rates from natural conceptions as well as for those who opt for assisted reproductive treatment. So, it is always better to go for testing for sperm DNA fragmentation and identify the possible causes for unexplained infertility, failed IVF treatment cycles or recurrent miscarriage.

What Are The Causes Of Sperm Dna Fragmentation?

The main cause of sperm DNA fragmentation is said to be oxidative stress. Other probable factors include defects in sperm chromatin packaging and DNA repair mechanisms and abnormalities in the regulation of programmed cell death which is essential for regulating sperm production. Increase in sperm DNA fragmentation is also linked with a variety of extrinsic factors that are mentioned below:

  • Stress
  • Poor diet
  • Obesity
  • High fever
  • Infection
  • Presence of excess White Blood Cells in the semen
  • Varicocele
  • Elevated testicular temperature
  • Excessive smoking
  • Excessive alcohol consumption
  • Recreational drugs
  • Advanced chronological age
  • Environmental & occupational pollutants

What Is The Treatment For Sperm Dna Fragmentation?

If the reason for infertility is due to the presence of high level of Sperm DNA fragmentation in the male partner due to oxidative stress, then he should try to decrease it through lifestyle modifications, dietary changes, antioxidant treatment, and by ensuring an appropriate duration of abstinence.

Varicocele is one of the most known causes of male infertility and is usually linked to sperm DNA damage. Studies say that varicocele repair may improve sperm DNA integrity. After the varicocele surgery, a repeat test can be done after three months to check if the level of sperm DNA damage has reduced or not.

Treatment of infection (leucocytospermia)with antibiotics may also be beneficial in reducing sperm DNA damage, but before prescribing antibiotics, it is necessary to diagnose the cause of the infection, whether it is bacterial or not.

In the meanwhile, the specialist should treat the underlying cause of DNA damage in the sperm. If lifestyle management and treatment with proper medicines cannot treat the condition, then other methods, such as micromanipulation-based sperm selection or testicular sperm extraction, should be used to select healthy sperm with nuclear DNA integrity.

The testicular sperm may have a healthy DNA integrity than ejaculated sperm because studies suggest that DNA damage occurs at the post-testicular level. So, a testicular sperm aspiration (TESA) can be done, and the extracted sperms can be used for ICSI. ICSI may be a more effective treatment than IVF for sperm with high DNA damage since its fertilisation rate is found to be higher when compared to IVF. And ICSI treatment is not seen to be affected by the quality of the sperm.

What Is The Advantage Of Sperm Dna Damage Test Over Semen Analysis?

The difference between a semen analysis and sperm DNA fragmentation test is: A sperm DNA fragmentation test provides the genetic information from sperm cells, whereas a semen analysis report provides us with the simple information like the count, shape and motility of the sperm, but does not give us any insight regarding the quality of the sperm. Research on methods for selecting sperm with undamaged DNA in ART should be conducted in the future. Moreover, fertility specialists and embryologists who are working in the field of ART must continue to make efforts to obtain healthy sperm which has nuclear DNA integrity to minimise the adverse effects that may arise in children conceived from sperm with DNA damage.

CONCLUSION

To know about sperm DNA damage and its impact on male fertility can help infertility specialists in the diagnosis, management and treatment of male infertility cases. It may also help us to know the outcome in assisted reproduction techniques. Repeated findings of high levels of DNA fragmentation in the sperm may give the clinicians a thought whether to opt for sperm donation. The Sperm DNA fragmentation test can help couples to make an informed choice regarding their course of treatment.

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