Where does sperm DNA fragmentation testing stand?

Have you ever considered genetic issues with males particularly in sperm DNA when there is an unexplained infertility between couples? Yes, it is true that male infertility is a common cause of infertility in today’s age, yet it has always been sidetracked when it has come to unexplained infertility issues or unexplained miscarriages.

Over 15% of married couples worldwide experience fertility problems, and 50% of these cases are caused by male factor infertility. Couples trying to start the family late in life and adverse changes in the lifestyle, have increased infertility issues and the causes of male infertility.¹

The integrity of genetic material in the sperm or sperm DNA is very important for fertilization and embryo development. Sperm DNA fragmentation is a term used to denote abnormal genetic material within the sperm, which in turn may lead to male subfertility, IVF failure and miscarriage.²

When it comes to detecting male infertility, conventional semen analysis remains the routine test, however it has limitations to identify sperm DNA damage in men.¹

Why Testing Sperm DNA Damage is Important?
A plethora of studies have confirmed that sperm DNA damage including DNA fragmentation has strong associations with infertility. These include impaired fertilization, slow early embryo development, reduced implantation and miscarriage.¹

Consequently, there is a need for a technique that provides more detailed information about sperm quality. A sperm DNA fragmentation (SDF) has emerged as a possible tool to measure the level of molecular damage present in a man’s sperm.³

Sperm DNA testing will provide essential information and help couples with treatment strategies tailored for their particular needs. These include couples with unexplained infertility, semen analysis prior to embarking on IVF, couples who  have had unsuccessful IVF and couples who have had miscarriages.¹

What Tests is Currently Available for Sperm DNA Damage?
The most often used tests include the comet assay, sperm chromatin structure assay, the terminal transferase dUTP nick end labeling (TUNEL) assay, and the sperm chromatin dispersion (SCD or Halo) test. All these sperm DNA tests are different as they measure different aspects of DNA damage and have different sensitivities.¹

The Sperm Chromatin Structure Assay (SCSA)
A fluorescence cell sorter test, which measures the susceptibility of sperm DNA to denaturation after exposure to heat or acid conditions.¹

• • Measures only single stranded fragments¹
  • Can detect sperm DNA damage in ~20% of unexplained couple¹
  • The clinical threshold for DNA fragmentation index (DFI) is 30% – meaning 30% of the sperm have damage and 70% have no detectable damage. Couples with > 30% damage are less likely to have success with IVF and probably they need other options like intracytoplasmic sperm injection (ICSI)¹

The TUNEL Assay – Detects ‘nicks’ (free ends of DNA) by incorporating fluorescently stained nucleotides. This allows the detection of single and double stranded damage of DNA.¹

• • Viability stain measures DNA damage in live sperm¹

The Sperm Chromatin Dispersion (SCD) Test – Measures the absence of damage rather than the damaged DNA in sperm.¹

• • Cheap and convenient form of sperm DNA testing¹
  • Available in a kit form at fertility centers¹
  • Simple and inexpensive assay¹
  • Limitation includes relatively faint low-density nucleoids, with less contrasting images¹

The Comet assay – It quantifies the actual amount of DNA damage per sperm. As the mass of DNA fragments stream out from the head of unbroken DNA, they resemble a ‘heavenly comet’ tail, hence the name.¹

• • Uses only 5000 sperm, so is suitable for the assessment of small samples¹
  • Can measure both single and double strand breaks¹
  • Can even measure altered bases¹
  • Is sensitive, repeatable and capable of detecting damage in every sperm (even those of fertile donors)¹

Sperm Defragmentation Test Explains the Unexplained
As we all know, unexplained infertility causes a great distress to the couple as well to the clinic. It has been observed that 80% of couples with unexplained infertility later on get diagnosed with sperm DNA damage) This suggests that sperm DNA damage is the cause of infertility in a substantial number of men.¹

In couples with poor results with IVF, it has been observed that 40% of the men had high sperm DNA damage (> 50%).¹

It is essential to do sperm DNA testing before offering IVF, or IUI, and without sperm DNA testing can lead to treatments with very low chances of success. From the infertility clinic’s point of view, using IVF in the couples diagnosed with sperm DNA damage can lead to reduced overall IVF success rates.¹

Where Does Sperm DNA Fragmentation Testing Stand in Current Day Fertility Management
Sperm DNA fragmentation testing plays a very important role in couples who would like to avoid the loss of valuable biological time, the cost of failed cycles and the heartache of repeatedly unsuccessful cycles of IUI and IVF treatment. It will help getting a diagnosis, appropriate treatment and better-informed couples.

These novel tests (particularly sperm DNA testing) are increasingly used by fertility clinics as they provide robust data to support them. Sperm DNA fragmentation testing is crucial to check male infertility, particularly when there is an unexplained infertility or a series of unsuccessful IVF procedure involved.

References: 1. Sharif K. Sperm DNA fragmentation testing: To do or not to do? Middle East Fertil Soc J. 2013;18(2):78-82.
2. Sperm DNA fragmentation test [Internet]. Available at: https://www.reproductivehealthgroup.co.uk/fertility-treatments/assessments/men/dna-fragmentation/. Accessed on Sep 23, 2020.
3. Palmer WJ. Sperm DNA fragmentation: The new frontier of fertility testing [Internet]. Available at: https://www.aacc.org/publications/cln/articles/2019/janfeb/sperm-dna-fragmentation-the-new-frontier-of-fertility-testing. Accessed on Sep 23, 2020.