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Sperm DNA Fragmentation – Factors, Causes, Significance, Tests, and Treatment

DNA fragmentation is a test for male fertility which measures the amount of damaged DNA in a given sperm sample. DNA fragmentation can occur spontaneously or intentionally by laboratory personnel. Spontaneous DNA fragmentation is fragmentation that gradually accumulates in a cell. DNA fragmentation is more common among men with sperm motility defects. It is helpful in predicting outcomes for In-vitro Fertilization (IVF) and its expansion intracytoplasmic sperm injection (ICSI). The main unit of measurement is the DFI (DNA Fragmentation Index). The abnormal genetic material present in the sperm can, in turn, lead to male subfertility, IVF failure, and miscarriage. A conventional semen analysis is done to

check the sperm concentration, while motility analysis and morphology assessment cannot analyze the sperm at the molecular level; hence, the DNA fragmentation test helps in finding faulty DNA in sperm. Sperms with high DNA fragmentation fertilizing younger oocytes carry a better prognosis of achieving a successful pregnancy. All men have some amount of damaged DNA in their sperms; more significant damage may indicate more incredible difficulty in achieving pregnancy with IVF and IUI. (1) (2)

Factors that Damage Sperm DNA

DNA damage increases with age; men in their 50s or 60s have a higher percentage of sperm fragmentation than men in their 30s or 20s. (3) Other factors that damage sperm DNA include the following:

  • Exposure to various chemicals or toxic agents
  • Excessive heat
  • Chronic infections in the prostate
  • Chemotherapy
  • Radiation or smoking

To prevent further damage to DNA, doctors may recommend drawing sperm directly from the testicle with a needle or suggesting antioxidant vitamins that help minimize the damage.

Causes of Sperm DNA Fragmentation

One of the major contributing aspects for sperm DNA fragmentation is stress oxidative, which can be related with one or more of the following:

  • Intrinsic causes, such as deficiencies in recombination during Spermatogenesis
  • Abnormal Spermatid Maturation
  • Infection and Pyrexia
  • Variations In Sperm Protamine Expression
  • Abortive Apoptosis
  • Elevated Testicular Temperature
  • Recreational drugs
  • Extrinsic causes like Lapse of Time from the Ejaculation
  • Excessive Smoking and Alcoholism
  • Oxidative Stress and Unhealthy Diet
  • Environmental and Occupational Pollutants
  • Advanced Chronological Age

Causes of sperm damage who can Benefit from Sperm Fragmentation Test

The need for a Sperm Fragmentation Test arises when there are:

  • Unexplained infertility
  • Arrested embryo development
  • Poor blastocyst development
  • Unsuccessful attempts for IVF and ICSI treatments
  • Miscarriage
  • Advanced chronological age
  • Varicocoele
  • Poor semen parameters
  • Exposure to harmful substances

The Significance of DNA Fragmentation Test

The fragmentation test can determine what percentage of sperms has fragmentation. Less than 15 per cent of damage means an excellent outcome, while 16 to 29 per cent means a moderate outcome. More than 30 per cent damage means higher sperm fragmentation, which indicates difficulty in achieving a healthy pregnancy, even with IVF. High sperm DNA fragmentation level affects blastocyst development and there are higher chances of failed assisted conception treatment and miscarriage.

Sperm DNA fragmentation is higher in subfertile men with abnormal sperm parameters; however, men with normal sperm parameters can also develop sperm abnormality.

Embryos from sperm with highly fragmented DNA are likely to have a poor

prognosis. High level of DNA fragmentation could result in the initiation of natural cellular death (apoptosis) and abnormalities in the offspring.

Different kinds of Test for Sperm DNA Fragmentation

There are different types of tests available to assess the percentage of sperms with DNA fragmentation, such as the SCSA, TUNNEL assay and COMET assay. However, the test that has received the most attention is the Sperm Chromatin Structure Analysis (SCSA). (7)

Sperm Chromatin Structure Analysis (SCSA)

During the SCSA test, a special dye is allowed to enter the sperm cell, and the sperm is treated with a chemical. Generally, sperms with fragmented DNA take up more of the dye once it makes its way into crevices in the DNA molecule. With the help of a procedure called flow cytometry, the sperm that takes up lots of dye can be easily be differentiated from the sperm that takes up only a little dye (sperm with normal DNA). Finally, the percentage of each sperm with fragmented DNA can be graphed by using a computer program. A patient with a result of 8.2 per cent comes under the excellent to a suitable category, with 8.2 per cent of the sperm cells containing DNA damage. The SCSA test recommends that patients with higher than 25 per cent should skip IUI and go straight to IVF/ICSI for better results.

Sperm Comet Test

The sperm Comet test is a second-generation DNA test that provides unique information by measuring the amount of DNA damage in individual sperm. Sperm Comet results predict the success of infertility treatments and the treatment type most likely to succeed. This test detects the percentage of sperm with DNA damage. If the result shows 45 percent damage, it shows an average of 45 percent DNA damage in each sperm that was assessed. A flow cytometer is used to monitor a fluorescent probe that relates with the DNA molecule.

Advantages of Sperm DNA Fragmentation Test

Sperm DNA fragmentation test offers a consistent analysis of sperm DNA veracity that may help to find men who are at risk of infertility. It also provides information for clinical diagnosis, management, and treatment of male fertility.

Treatment of High Sperm DNA Fragmentation

The treatment of High Sperm DNA Fragmentation depends essentially on its causes. If the DNA damage is due to free radicals, lifestyle changes and a healthy diet designed to shield against oxidative stress may help decrease the levels of DNA fragmentation.