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The genetic integrity of the spermatozoan is essential for normal embryo development. A high level of DNA fragmentation in sperm cells may represent a cause of male infertility that conventional examinations - sperm concentration, motility analysis, morphology assessment - cannot detect. Results reported in the scientific literature show regardless of the assisted reproductive technology used, elevated levels of DNA fragmentation above the critical threshold will significantly compromise the possibility of a successful pregnancy.
This test provides a reliable analysis of sperm DNA integrity that may help to identify men who are at risk of failing to initiate a healthy ongoing pregnancy. Information about sperm DNA integrity may help in the clinical diagnosis, management and treatment of male infertility and may be of prognostic value in assessing outcome of assisted conception treatment.
Normal, healthy pregnancies do occur in couples where the male partner has a high percentage of sperm with fragmented DNA, although the chances are significantly reduced, as the percentage of sperm bearing low levels of DNA fragmentation is much lower. Embryos derived from sperm whose DNA is highly fragmented have a poor prognosis. Evidence suggests that this could result in initiation of apoptosis and mutations resulting in blastocyst arrest, miscarriage, abnormalities in the offspring and an increased susceptibility to childhood cancer. Protection against high DNA fragmentation may be afforded by younger oocytes which are much more efficient at DNA repair of defective sperm than older oocytes. Couples undergoing fertility treatment where sperm DNA fragmentation is high have a better prognosis if the female partner is young.
A major causative factor for sperm DNA damage is oxidative stress. Other factors include abnormalities in the regulation of apoptosis, or defects in topoisomerase activity. Increased sperm DNA fragmentation is also associated with:
Some causes of DNA fragmentation cannot be treated, but if the damage is caused by free radicals, then a change in lifestyle and a diet designed to protect against oxidative stress may help reduce the levels of DNA fragmentation in some of these cases. Treatment of infection with antibiotics would also be expected to reduce DNA fragmentation. There is some evidence to show that varicocoele repair may improve sperm DNA integrity. Initiatives to reduce the levels of fragmentation can be assessed by undertaking a second test three months after the first. Initial reports suggest that DNA damage occurs at the post-testicular level, so that testicular sperm may have a healthier DNA integrity than ejaculated sperm. Furthermore, studies show that ICSI may be a more effective treatment than IVF for sperm with a high DNA fragmentation.
This test is an effective method for measuring thousands of sperm in an ejaculate. Sperm are stained with a fluorescent probe that interacts with the DNA molecule. The fluorescence signal changes when the DNA is fragmented, and this is monitored using a flow cytometer. The SCSA® test has been developed over the last 20 years and is one of the most robust tests available for sperm DNA fragmentation. It is CLIA approved.
The results are reported showing 4 statistical categories of fertility potential :
≤ 15% DFI = excellent to good sperm DNA integrity
> 15 to < 25% DFI = good to fair sperm DNA integrity
> 25 to < 50% DFI = fair to poor sperm DNA integrity
≥ 50% DFI = very poor sperm DNA integrity
Note: The above values relate to natural and IUI conceptions
The statistically significant DFI threshold for subfertility has been established at > 25 %.Normal full-term pregnancies are possible with an elevated DFI, but the higher the level of fragmentation, the greater the incidence of reduced term pregnancies and miscarriage. The above values relate to natural and IUI conceptions. When % DFI is above 25 %, current literature suggests that the patient either try to reduce the DFI by medical intervention or change of lifestyle, or skipping IUI and go on to IVF ICSI for greatest success (www.scsatest.com for details)
Hypothesis: A high ratio of moderate DFI to high DFI sperm may be the most negative since moderate DFI sperm have normal nuclear morphology and will likely fertilise but may have DNA damage beyond the repair capacity of eggs.
High DNA stainability (HDS): % sperm with immature chromatin and abnormal proteins. Levels in the > 25% range are considered negative for pregnancy outcome
Additional information downloads:
Sperm DNA Fragmentation and Aneuploidy/Sample Information Sheet and Request Form (Word doc, 56Kb)
Osman A, Alsomait H, Seshadri S, El-Toukhy T, Khalaf Y (2014) The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis. Reprod Biomed Online. Nov 13. pii: S1472-6483(14)00603-8. doi: 10.1016/j.rbmo.2014.10.018. [Epub ahead of print] Review.
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