The standard sperm analysis which measures sperm count, motility and morphology has been around for more than one hundred years. In years gone by, the method of choice was to count the sperm on a grid (“Coulter Counter”) under a microscope, assess sperm movement and progression from one point to another to determine “motility,” then observe the sperm’s appearance to rate the “morphology” (shape). Today we rely on the computer to define these parameters for us much more accurately and reliably. What has NOT changed is that that while an overtly abnormal sperm analysis (regardless of how it is performed) allows for the diagnosis of male infertility, intermediate values are often difficult to interpret. And what makes matters even worse is the fact that some men having perfectly normal standard sperm parameters are nevertheless infertile.

The introduction of the Sperm Chromatin Structure Assay (SCSA) and the Sperm DNA Integrity Assay (SDIA) (both of which measure sperm nuclear integrity) has vastly improved the ability to accurately evaluate male fertility, when interpreted in association with standard sperm parameters (count, motility and morphology). And when it comes to Assisted Reproduction, SCSA/SDIA results have been found to correlate well with the potential of sperm to propagate embryos that would be “competent” to produce a live birth. As such, the introduction of these tests into the IVF arena represents an important advance.

This having been said, it is important to know that SCSA/SDIA data will not always correlate well with standard sperm parameters (count, motility and morphology). In most (but certainly not all) cases of overtly abnormal sperm parameters, the SCSA/SDIA results will be abnormal. In some cases, even where the standard sperm analysis is normal, we find overtly abnormal SCSA/SDIA results.

The SCSA/SDIA measures sperm DNA damage and does predict male sub/infertility and poor reproductive performance. It measures the degree of abnormalities in the genetic material of the sperm, expressing it numerically as the DNA Fragmentation Index (DFI). It is true that varying degrees of DNA damage may be present in sperm from both fertile and infertile men. However, a quantitative expression of the DFI often will reveal a hidden abnormality of sperm DNA and as such, unveil infertility in cases where prior standard sperm parameters failed to reveal such issues. Optimal sperm chromatin packaging seems necessary for full expression of male fertility potential. SCSA/SDI assays emerge as predictors of the probability to conceive and carry the pregnancy to term.

Since an abnormal SCSA/SDI assay is more likely to occur in cases of abnormal standard semen parameters, it is ideally suited to assessing the fertility potential and predicting embryo development as well as effects of reproductive toxicants. Since SCSA/SDIA parameters are independent of conventional semen parameters, results may allow physicians to identify those cases of male infertility where the performance IVF and intracytoplasmic sperm injection (ICSI) would be less likely to result in “competent” embryos that are likely to result in successful pregnancies.

Certain cancer treatments involving chemotherapy and radiation therapy are known to adversely affect male fertility. In such cases, a reduction of sperm output may arise from cytotoxic effects upon the sperm-producing cells in the testicles. However, even if these cells survive such cancer therapy, there remains a risk to reproduction that could express in a variety of forms of reproductive dysfunction ranging from infertility to miscarriage. Such risk could theoretically even be trangenerational (i.e. expressed in the sperm or eggs of the offspring of patients so treated).

Current information on the clinical role of the SCSA/SDIA testing in patients undergoing IVF suggests the following:

• The IVF birth rate could be as much as 2 times lower in women under 33 years of age, whose partners have patently abnormal SDI assays (with a DFI of >30%). Results seem to become progressively worse with advancing maternal age such that at 35 years and up, the viable pregnancy rate could be as much as 3 times lower.
• Although it is possible for abnormal SCSA/SDIA results to sometimes spontaneously revert back to normal, this occurs quite infrequently in my experience.
• Although abnormal SCSA/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)
• Abnormal SCSA/SDIA augurs poorly for the outcome of fertility treatments in general and for IVF/ICSI in specific. In the latter cases, fertilization and pregnancy rates are reduced, and the chance of early pregnancy loss appears to be increased. However, it is important to stress that an abnormal SCSA/SDIA result does not preclude a successful pregnancy. In fact, we have seen many IVF pregnancies occur in spite of abnormal SCSA/SDIA results….even when the DFI was elevated above 60%
• The likelihood of a successful outcome with IVF/ICSI in cases where the SCSA/SDIA is abnormal worsens progressively as the age of the egg provider advances beyond 35 years.
• While abnormal SCSA/SDIA results rarely revert spontaneously to normal, this can and does happen on occasion, especially following surgical or interventional radiological treatment of varicoceles (a collection of distended veins surrounding one or both testicles in the scrotum). In addition, there is some suggestion that the use antioxidant/vitamin blends such as Proxeed or Proceptin if taken for 8-12 weeks (the sperm life cycle) will sometimes improve the SCSA/SDIA.

It is likely that the SCSA/SDIA will become a standard adjunct to the basic semen analysis, especially for cases of established male infertility, “unexplained” infertility, and “unexplained” IVF failures.