The advance of molecular biology and genomics made a quantum change in the management of many medical conditions. Although their  role in infertility lacks clarity, many fertility specialists apply them to improve success. These tools and tests are very useful in conditions like cystic fibrosis, non-obstructive azoospermia. In addition a sperm DNA fragmentation test helps tp predict the probability of success in IVF treatment. These are diagnostic tests, but their role in therapy are still under evaluation. 

What happens when you have high DNA fragmentation?

      A DNA fragmentation test shows the percentage of spermatozoa in the semen with damaged DNA. DNA is the component of the cell that decides all features and transmits the same to the offspring. This test indicates the fertility potential of a given semen sample. But unfortunately, it is difficult to determine the quantity of unfragmented sperm for natural conception.

Usually in patients,  more than 50% good spermatozoon is required for natural conception. DNA fragmentation is a physiological process in sperm cells. Aging sperms undergo a type of intracellular degeneration called apoptosis. Not all but a certain proportion are bound to undergo this process at any time. Upto 50% of cells showing DNA fragmentation is natural rather than any disease process. Unless the sample has 100% DNA fragmentation, it may be impossible to call the sample sterile.  

What causes DNA  Fragmentation?

Sperm DNA damage may occur by any of these processes:

  • Apoptosis during formation of sperm cells 
  • Defective chromatin condensation during maturation of sperm
  • Oxidative stress during the transport of sperm cells through the male genital tract. 

In men, the major contribution is sperm in fertility. The factors for sperm DNA fragmentation is oxidative stress, which can be associated with one or more of the following:

  • Infection
  • Pyrexia
  • Elevated testicular temperature
  • Recreational drugs
  • Smoking
  • Alcohol 
  • Stress 
  • Diet
  • Environmental and occupational pollutants
  • Advanced chronological age
  • Varicocele

How is the test done?     

 The interior of a sperm cell contains genetic material which mixes with the egg cell DNA for successful fertilization and normal embryo development. If the fertilizing sperm has high DNA fragmentation it may not fertilize with the egg. In short it may lead to male subfertility, IVF failure and miscarriage. Routinely a semen analysis does not check the percentage of fragmentation in DNA.  It requires a special test which can differentiate between normal  and fragmented DNA.

A number of sperm DNA fragmentation tests are available at present. These are available at reproductive health hospitals and fertility centers. Some of them are:

  • Sperm chromatin dispersion (SCD) 
  • Single cell gel electrophoresis assay (SCGE) or the comet assay
  • Sperm chromatin structure assay (SCSA)
  • Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay

Why is this test done?

  • This test reliably analyzes sperm DNA integrity and helps to identify men who are at risk of subfertility
  • Provides information which helps in the clinical diagnosis, management and treatment in the male fertility
  • It has prognostic value where you can predict the success of treatment
  • High sperm DNA fragmentation affects advanced embryo culture or blastocyst development 
  • Failure of assisted conception treatment and miscarriage are common with these abnormal sperms
  • Sperm DNA fragmentation is higher if  basic semen analysis is abnormal 
  • Men with normal sperm parameters can have abnormal sperm DNA fragmentation test reports. 

Can you get pregnant with high sperm DNA fragmentation?

Spermatozoa cannot repair its damaged DNA. But egg cells and embryos have the potential to repair after the fertilization process.

  • Normal, healthy pregnancies can occur with a high percentage of sperm with fragmented DNA. Although the chances are significantly reduced in these men, sperm bearing high DNA fragmentation can also fertilize an egg.
  • Embryos from sperm with highly fragmented DNA may not implant and give pregnancy.
  • DNA fragmentation can result in initiation of natural cellular death. Hence these embryos can show arrest of growth, miscarriage and abnormalities in the baby.
  • Sperm with high DNA fragmentation fertilizing younger eggs have better chances. These cells are much more efficient at DNA repair of defective sperms.

When should you do this test?

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

How costly is sperm DNA fragmentation test?

Most commonly applied method to check the DNA is the Sperm chromatin dispersion (SCD) test. Usually this test utilizes a kit which has reagents to stain the sperms. After the staining your embryologist can differentiate between the abnormal and normal ones. They count the percentage of abnormal sperm cells and prepare the report. This kit costs around 20,000 INR. On the other hand, a single kit can be utilized to check 5-6 samples your laboratory may charge 5000 to 6000 rupees per test.

Sperm DNA fragmentation test results:

The fertility specialist will review DNA fragmentation test results with you and make appropriate recommendations based on the specific situation. Accordingly, your doctor may determine the fertility potential likewise:

  • 15% or less fragmentation – Excellent sperm DNA integrity
  • 15-25% DFI – Good to fair
  • 25-50% DFI – Fair to poor
  • 50% or more DFI – Extremely poor sperm DNA integrity.

The DNA fragmentation rates are high when it is more than 30%. Furthermore, These patients have less pregnancy rate compared to those with excellent sperm DNA integrity. 

How to reduce DNA fragmentation in sperm?

It depends 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 level of DNA fragmentation. 

Other treatments are:

  • Antibiotics in co-existence of infection
  • Lifestyle changes like avoid drugs, smoking and heat place occupation
  • Diet like fresh foods, particularly those containing antioxidants and vitamin C & E.
  • Varicocele surgery
  • Testicular aspiration of sperm during ART procedure
  • ART  procedure  to conceive

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

Which ART procedure is preferable – ICSI or IVF?

When performing ICSI, your embryologists will try to select spermatozoa with normal morphology and rapid motility. These sperms tend to have less DNA damage. Hence ICSI is preferable to conventional IVF where sperm selection occurs naturally. Embryologists use various techniques to select the healthy sperm. Some of them are

  • Selecting sperms with high progressive motility
  • Intracytoplasmic morphologically selected sperm injection (IMSI) , hyaluronic acid-bound sperm selection
  • The electrophoretic separation technique
  • Density gradient centrifugation 
  • Magnetic-activated cell sorting 
  • Density gradient with magnetic activated cell sorting 

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