Sperm DNA Fragmentation Testing
What is Sperm DNA Fragmentation Testing?
In a nutshell, a sperm DNA fragmentation test is a test to evaluate the amount of damaged DNA in a sperm sample. It’s normal to have a level of sperm DNA damage, but a high percentage of damage may be of concern and indicate greater difficulty achieving a pregnancy with fertility treatments, like IUI and IVF.
How is sperm tested?
Historically, when it comes to assessing male fertility, a basic semen analysis has been used. This test examines sperm concentration, morphology and motility. We now know that a basic semen analysis is inadequate when it comes to truly evaluating male fertility potential as while it can provide information on the morphology (shape) of the sperm, it does not provide much insight on the sperm’s ability to contribute to a successful pregnancy. A successful pregnancy needs genetic material from both egg and sperm and if the egg or sperm contains high levels of damage, it will inevitably contribute to the chances of a healthy conception. Let’s explain further……
Sperm DNA Fragmentation in detail
The genetic material provided by a male partner is responsible for half the genetic make-up of a child. This material is wrapped up tightly within the head of the sperm cell and needs to arrive to the egg intact. Sperm DNA is up to 6 times more tightly packed than a somatic cell DNA (for example a blood cell or skin cell). As a result, DNA damage can occur and the level of this damage is used as a marker for male infertility. Interestingly, the amount of sperm damage detected does not always correlate with semen parameters assessed through a basic semen analysis, so it’s an important test to consider doing when evaluating sperm.
The egg has the ability to repair some level of DNA damage in the early stages of embryo development (fertilisation and the first three days), however research has shown that the egg does not have the capacity to repair high levels of sperm DNA damage.
The Testing:
There are three different tests to assess sperm DNA damage and all using slightly differing methods which result in different standards of measurement.
the sperm chromatin structure assay (SCSA),
the COMET assay (the single-cell gel electrophoresis assay).
the TUNEL assay (Terminal Transferase dUTP Nick End Labelling)
Each test measures different aspects of sperm chromatin damage and as a result have variable levels of diagnostic and prognostic strength.
1) The Sperm Chromatin Structure Assay (SCSA)
The SCSA test is used most commonly and involves treating sperm with chemical dye; broken sperm DNA turns the colour of the dye (red), normal sperm DNA turns green.
After this, the sample is run through a computerised machine with a special software which reads about 5,000 sperm cells categorizing the ratio of green-to-red sperm cell to figure out the Fragmentation Index (DFI).
Understanding SCSA Sperm DNA Fragmentation Results
Always consult with your doctor when discussing results or another qualified health professional. Typically, on a SCSA report you will see the below values;
1) Excellent to Good (less than or equal to 15% DFI)
2) Good to Fair (greater than 15% to less than 25% DFI)
3) Fair to Good (greater than or equal to 25% to less than 50%n DFI)
4) Very Poor (greater than or equal to 50% DFI)
A patient with a DFI of 9% would be classified as “excellent to good” whereas a patient with a DFI of 30% would be classified as “fair to good”.
SCSA detect faults in the nuclear proteins protecting the DNA. Nuclear protein damage could make the DNA more vulnerable to damage, but this test is not a measure of the actual damage to the DNA molecule itself.
A study done by Bradley, et al (2016), showed that patients with a DFI > 29% have a significantly improved blastocyst transfer outcome when they opted for fertility intervention (e.g. TESE/TESA, PICSI, IMSI) compared to no intervention.
2) The COMET Sperm DAN Fragmentation Test
COMET technology is based on a technique known as single cell gel electrophoresis (SCGE)COMET detects single and double-strand DNA fragments present in individual sperm, making it a direct assay of damaged DNA. Average Sperm DNA Fragmentation is the average percentage of DNA fragmentation per sperm in the semen sample.
Understanding COMET Sperm DNA Fragmentation Results
If your result falls within 0 – 31%, you are within the fertile range. If your result falls between 31 – 100%, you are outside of the fertile range and have an increased risk of infertility.
3) The TUNEL Assay (Terminal Transferase dUTP Nick End Labelling)
The TUNEL assay is a highly sensitive method of assessing the integrity of Sperm DNA. It measures the number of breaks or nicks in the DNA of the sperm. Unlike the SCSA test mentioned above, requiring 1 million sperm,TUNEL can be performed on as fews as 1,000 sperm and from a sample retrieved by biopsy.
Understanding TUNEL Assay Sperm DNA Fragmentation Results
The established normal value is less than 10% of sperm with DNA damage.
What Causes Sperm DNA Fragmentation?
As we mentioned above, a small percentage of DNA fragmentation is normal but certain factors can contribute to this.
Medications such as selective serotonin re-uptake inhibitors (SSRIs), which are commonly prescribed for depression, anxiety, and other mental health conditions.
Varicoceles or the swelling of the veins that transport blood away from the testicles
Prolonged time between ejaculation
Infections including prostate, urinary tract and sexually transmitted diseases (STIs)
Smoking and drug use
There is acceptance that sperm DNA fragmentation testing can add value to the fertility work-up however, it is not standard test for clinicians to order this routinely. A high result can be a good indicator for fertility outcomes and provide an opportunity for further evaluation into lifestyle and general health, as these are interlinked.