DNA FRAGMENTATION ASSESSMENT ON SPERM

Sperm Chromatin Structure Assay (SCSA) is a tool for measuring clinically important properties of sperm nuclear chromatin integrity. The results correlate well with the potential of sperm from a given male to produce embryos that would be sufficiently “competent to produce a live birth. The SDIA utilizes the metachromatic features of acridine orange (AO), a DNA probe, and the principles of flow cytometry (FCM).
SCSA data are not well correlated with classical sperm quality parameters and have been solidly shown to predict sub/infertility and poor reproductive performance. The SCSA measures DNA damage. The degree of abnormalities in the genetic material of the sperm is expressed numerically as the DNA Fragmentation Index (DFI). DNA damage may be present in sperm from both fertile and infertile men. Therefore, this sperm DNA damage analysis may reveal a hidden abnormality of sperm DNA in infertile men classified as unexplained based on apparently normal standard sperm parameters. Infertile men with abnormal sperm characteristics exhibit increased levels of DNA damage in their sperm. Sperm from infertile men with normal-appearing sperm may have DNA damage to a degree comparable to that of infertile men with abnormal-appearing sperm. The data suggests that an abnormal SDI assay is more likely to occur in cases of abnormal semen parameters. Thus the assay is ideally suited to fertility clinics to assess male sperm DNA integrity as related to fertility potential and embryo development as well as effects of reproductive toxicants. Since SCSA assay parameters are independent of conventional semen parameters, results may allow physicians to identify male patients for whom IVF or intracytoplasmic sperm injection ( ICSI) are necessary.

Cancer treatments are well known to adversely affect male fertility. Reduction of sperm output arises from the cytotoxic effects of chemo-or radiotherapy upon the spermatogenic epithelium. However, even if the epithelium survives there is a hazard to reproduction as the transgenerational in expression and present with effects ranging from “infertility" to miscarriage and there is an association with infertility and reproductive performance. Optimal sperm chromatin packaging seems necessary for full expression of the male fertility potential. SDI assays emerge as predictors of the probability to conceive and carry the pregnancy to viability
The improvement seen in sperm motility after sperm separation and sperm washing with IUI processing is not associated with a similar improvement in sperm DNA integrity. These data suggest that sperm processing techniques will not minimize sperm DNA damage and the potential transmission of genetic mutations in assisted reproductive cycles.

Data suggests the following :

• The viable (>12 weeks) IVF pregnancy rate (and thus presumably also the birth rate) could be as much as 2 times lower in women under 33yrs of age, whose husbands have abnormal SCSA assays ( with a DFI of <30%).>
• Although it is possible for abnormal SCSA results to sometimes spontaneously revert back to normal, this probably occurs quite infrequently.
• Although abnormal SCSA results are detected in men with apparently normal semen analyses, abnormal results are more commonly seen in cases of men who have abnormal sperm parameters (abnormal sperm count, motility and/or morphology)
• There is some suggestion that the use of antioxidant therapy ( Pycnogenol 200mg daily, L-Carnitine 3 grams per day, acetyl carnitine 500mg per day, Vitamin C 1,000mg per day and Vitamin E 800IU per day) taken for 6-8 weeks , can causes the SCSA assay to revert to normal in many cases. There is some suggestion that men who have varicoceles ( a collection of distended veins in the scrotum) associated with an abnormal SDI assay may experience a reversion of the SDI assay back to normal, 3-6 months following surgical or radiological ablation of the varicocele.

In summary, an abnormal SCSA assay augurs poorly for the outcome of non IVF (IUI or natural conception) fertility treatment in general but not IVF/ICSI in specific. In such cases, the fertilization rate and pregnancy rates are reduced and the chance of early pregnancy loss appears to be increased significantly. An abnormal SCSA result of course does not totally preclude a successful pregnancy. The prognosis worsens progressively as other factors come into play like female age.

The SDIA or the SCSA has become regarded as required baseline tests (to performed, regardless of their basic traditional semen analysis parameters (count, motility and sperm morphology) as the results are independently predictive of non IVF treatment outcomes. This obviously is important in decision making for the couple on what treatments to do and what expectations should then be on success.