The Sperm Chromatin Structure Assay (SCSA): A Measure of the Potential of Sperm to Help Propagate a Viable Pregnancy
In about 40% of infertility cases, male factor is the sole cause. In approximately another 40% it is solely a female factor and in the remainder (20%) both male and female factors are involved. In more than 80% of cases, performance of a semen analysis (sperm concentration, motility, and morphology) will be sufficient to diagnose male factor.
There is growing evidence to indicate that DNA damage is prevalent in many cases of male infertility and that this can impact fertility, even in the presence of a normal semen analysis. The latter occurs in 10% of cases when sperm parameters are normal. What remains unclear is at how the DNA damage should be measured, at exactly what level it would impact fertility and precisely, precisely what should be done when there is evidence of such damage and how effective treatment will be.
While assessing male factor by semen analysis (whether using conventional manual assessment or computer measurement is reliable in about 95% of cases, it tends to be more accurate when it comes to diagnosing normal male fertility, in about 20%-25% of cases where it diagnoses poor sperm parameters it is inaccurate.
A variety of conditions can cause sperm DNA damage. They include, malignant disease, irradiation, chemotherapy, varicoceles (a collection of surrounding varicose veins in scrotum), white blood cells in the sperm (leucocytospermia) ,cigarette smoking and even cryopreservation (freezing) of sperm.
Sperm chromatin structure Assay (SCSA).
Sperm chromatin has a highly specialized and compact structure that is essential for protection and subsequent transmission of the paternal genome.
The SCSA evaluate for Sperm DNA damage, expressing it as the percentage of sperm DNA fragmentation –(DFI-small breaks in the sperm chromosomes). A DFI of <15% is considered normal while a value of >30% is regarded as abnormal. Fifteen percent (15%)-30% is “intermediate”. Couples where the man has sperm that registers a DFI of >30% reportedly have a four-fold reduction in term pregnancies and a doubling in the miscarriage rate.
What is true is that the SCSA is measure of sperm DNA damage and does predict male sub/infertility and poor reproductive performance. The SCSA/SDIA measures the degree of abnormalities in the genetic material of the sperm, expressing it numerically as the DNA Fragmentation Index (DFI).
This having been said, it is important to reemphasize that SCSA data will not always correlate well with standard sperm parameters (count, motility and morphology).
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 unveils infertility in cases where prior standard sperm parameters failed to reveal underlying male infertility. Optimal sperm chromatin packaging seems necessary for full expression of male fertility potential. SCSA emerge as predictors of the probability to conceive and carry the pregnancy to viability
Current information on the clinical role of the SCSA testing in patients undergoing IVF suggests the following:
- The IVF birth rate could be as much as 1.5-2 times lower in women under 33yrs of age, whose husbands have patently abnormal SCSA assays (with a DFI of >30%). Results seem to become progressively worse with advancing maternal age such that at 35y+, the viable pregnancy rate could be as much as 2-3 times lower.
- It is possible for abnormal SCSA results to spontaneously revert back to normal, this occurs infrequently. One study reported that even without treatment, 37% of patients with an abnormal result on first SCSA (DFI >30%) were subsequently found to have normal result (DFI < 30%) on a second SCSA test.
- 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)
- Abnormal SCSA augers 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 result does not preclude a successful pregnancy. In fact we have seen many IVF pregnancies occur in spite of abnormal SCSA results….even when the DFI was > 60%
- The likelihood of a successful outcome with IVF/ICSI in cases where the SCSA is abnormal worsens progressively as the age of the egg provider advances beyond 35yrs.
- While abnormal SCSA 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 male fertility blends such as “Proxeed or, Proceptin if taken for 2-3 months can improve the SCSA. In fact, in a relatively recent study, 38 men with an increased percentage of DNA fragmented sperm who received antioxidants, were followed for 2 months after one failed ICSI attempt. A second ICSI cycle was then performed which demonstrated a marked improvement of clinical pregnancy rates (48.2% vs. 6.9%) when compared with pretreatment ICSI outcomes.[
While the SCSA is not a measure of the sperm’s ability to fertilize an egg, results tend to correlate well with the potential of the fertilized egg, to develop into “competent” embryos (i.e. ones that are capable of propagating live births). As such the introduction of SCSA in the diagnostic armamentarium represents an important advance