Sperm DNA Integrity Assay (SDIA)

The Sperm DNA Integrity assay (SDIA) is a tool for measuring clinically important properties of sperm nuclear chromatin integrity.

The results correlate fairly 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).

SDIA data are not well correlated with classical sperm quality parameters (bulk semen parameters) and have been solidly shown to predict sub/infertility and poor reproductive performance. The SDIA 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 SDI/ SCS assay parameters are independent of conventional semen parameters, results may allow physicians to identify male patients for whom IVF and intracytoplasmic sperm injection ( ICSI) will be far less likely to result in initiation of viable (>12 weeks) pregnancy

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 potential hazard to reproduction 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 Percol processing is not associated with a similar improvement in sperm DNA integrity (SDIA assay results). These data suggest that sperm processing techniques will not minimize sperm DNA damage and the potential transmission of genetic mutations in assisted reproductive cycles. Most current data available on the significance of abnormal SDIA results in infertile couples seeking treatment has emanated from non-IVF pregnancies. IVF 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 SDI assays ( with a DFI of <30%). Results become progressively worse with advancing maternal age such that at 35 yrs+, the viable pregnancy rate could be as much as 3-4 times lower.

Although it is possible for abnormal SDIA results to sometimes spontaneously revert back to normal, this probably occurs quite infrequently.

Although abnormal SDIA 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 SDI assay to improve or even revert to normal. 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 SDI assay augers rather poorly for the outcome of fertility treatment in general and 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. However, it is important to emphasize that an abnormal SDIA result does not totally preclude a successful pregnancy. The prognosis worsens progressively as the age of the egg provider advances beyond 33yrs. Although abnormal SDIA results rarely revert to normal spontaneously this can and does happen on occasion. Selective surgical ligation of a varicocele and medical anti-oxidant treatment may be effective in restoring the SDIA to normal.

If an abnormal SDIA result fails to revert to normal in spite of treatment, the use of donor sperm should be seriously considered, especially when the egg provider is over 35 and facing a “rapidly ticking” biological clock. Another approach would be to divide eggs in half in an IVF cycle and use donor sperm for some of the eggs and husband’s sperm for the others.