SWOT analysis of Sperm DNA Fragmentation (SDF) testing

Male infertility contributes to a high percentage of those couples who are unable to conceive after 12 months of regular and unprotected sexual intercourse. The basic and essential evaluation or diagnostic test for men is the semen analysis. However, on its own, it cannot provide additional information about the functional capability of the sperm. Neither can it tackle the problem of idiopathic or UI (unexplained infertility).

Recently, in the 6th published edition of the WHO Laboratory Manual, the limitations of examination of human semen have been acknowledged. It has underlined the importance of sperm function testing and, as an additional examination, has recommended the sperm DNA fragmentation (SDF) or DNA fragmentation index (DFI) assessment test.

When nuclear DNA (the cells containing the genetic instructions for the development of all living organisms) are damaged by various factors and cannot be properly repaired, SDF occurs in these sperm cells. The importance of sperm DNA integrity is relevant due to the fact that infertile men have shown elevated levels of SDF.

Cause: SDF can be caused by factors such as ROS leading to oxidative stress, abortive apoptosis, deficiencies in recombination and imbalances in protamine ratios. Generally, DNA fragmentation is categorised into SSBs (single strand breaks) and DSBs (double strand breaks). Although each may have different effects on reproduction, most studies investigating the effect of SDF on male infertility do not distinguish between the two types of breaks.

Tests: There are 4 different tests recommended for SDF testing. They are the SCSA (sperm chromatin structure assay, TUNEL, SCD (sperm chromatin dispersion test) and Comet assay (single cell gel electrophoresis). The SCSA is based on AO (Acridine Orange) used as a fluorescent staining agent to detect the amount of damage to the sperm. The amount of fluorescence in the sperm identifies with DFI (DNA fragmentation index) which shows the percentage of cells with broken DNA. It requires a highly accurate laser instrument called a flow cytometry on which the analysis can be done. The uniqueness of this method is that in addition to providing a measurement on the DFI value in the semen sample, it can also report on the nuclear maturity of the sperm cell – by measuring the staining intensity and is reported as high DNA stainability (HDS) percentage. It shows the extent of stainability of the sperm nucleus which indicates immature spermatozoa. Having a standardized protocol and proprietary software for all users is an advantage of the SCSA.

SWOT analysis on DFI testing – Strengths, weaknesses, opportunities and threats. A recent study by experts analysed the current status of research on SDF testing by applying the SWOT method to see if it was a useful method of testing.
Strengths: It was found that SDF does have a negative impact on male fertility – thereby making it a biomarker of male fertility potential.

  • High SDF levels have been associated with an increased risk of failure to conceive naturally.
  • Similarly, high SDF scores have been found in many idiopathic infertile couples and with those men suffering with varicocele (varicose veins in the spermatic cord).
  • Higher levels of SDF were found in couples with RPL (recurrent pregnancy loss) when compared with fertile couples.
  • Interventions such as varicocelectomy and lifestyle changes can have a positive effect on SDF.

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Weaknesses: Despite SDF being a valid indication for infertility, there are still no standardized cut off/threshold values for each testing method apart from the SCSA test which is based on clinical data. Each type of test sets its own standards. Also, it is still not very clear which group of infertile couples would benefit most from the test.

Opportunities: Immense opportunities lie open now that the link between SDF and male infertility has been proved. Further research can:

  • strengthen the clinical value of SDF
  • clarify the type of infertile couples who would most benefit by SDF testing
  • provide standardization of testing methods
  • offer methods of reducing high levels of SDF which could result towards the treatment of infertility
  • develop the link between SDF testing and oocyte capacity
  • offer sperm selection techniques to patients for better fertility treatment outcomes.

Threats: In spite of the recommendations of SDF assay as an extended test of semen analysis, some uncertainties still exist. The test should not be misused. Long term use of antioxidants could result in reductive stress. Expensive equipment and highly trained professionals are required.

Conclusion: Despite some uncertainties, the importance of SDF or DFI testing cannot be undermined. Many conditions can contribute to high levels of SDF, such as varicocele, age, lifestyle habits, genital tract infections and environmental exposure. With tests to verify the percentage of SDF, some solutions to reduce the levels can be recommended. We, at Andrology Center, are the only licensed laboratory in India authorised to offer the genuine SCSA test. We offer both semen analysis and SDF or sperm DFI (sperm DNA fragmentation index) tests. Our equipment is of high standard and the technology used ensures accurate results. Based on the test results, a Fertility Specialist can advise the best treatment method.