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Sperm Chromatin Structure Assay

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Sperm Chromatin Structure Assay (SCSA)

In the early days of in-vitro fertilization (IVF), couples with a male factor where sperm count, motility or morphology was decreased, achieved lower levels of success with IVF than couples where the sperm parameters were normal. Then, in 1992, along came intracytoplasmic sperm injection (ICSI) which allowed us to inject one single sperm into each egg, and we were able to achieve fertilization rates and pregnancy rates appropriate for the age of the egg provider.

Successful birth still continues to elude some couples in spite of good fertilization, the transfer of good quality embryos and the exclusion of immunological problems that could cause implantation failure. These patients may present with repeated negative tests with IVF or they may achieve implantation with losses either at the chemical stage or further along in the first and even in the second trimester.

Working in South Dakota, Don Evenson Ph.D. appears to have identified problems with the deoxyribonucleic acid (DNA) in sperm which may predict a lower fertility potential for some men. The basis of the test is the evaluation of the integrity of the DNA in sperm and also an estimation of the proportion of sperm carrying immature DNA. This test is called the Sperm Chromatin Structure Assay (SCSA).

The SCSA is a rapid, highly technological, flow cytometry-based measurement of DNA fragmentation in 5000 individual spermatozoa, randomly selective by non-biased machine criteria, thereby providing the most statistically robust and objective assessment of sperm DNA quality for the andrology clinic.

The single SCSA measurement provides:

The percentage of spermatozoa with Moderate and High DNA fragmentation (% DFI). Most healthy men in their 20's have <15% DFI. In clinical studies (n>1000) semen samples with >30% DFI have a dramatically reduced probability of producing a term pregnancy.
The percentage of spermatozoa with High DNA Stainability (HDS) with a threshold of >15% HDS which correlates with reduced fertility status.
The SCSA does not measure mutations and translocations unless they directly affect the DNA/chromatin integrity and also does not measure aneuploidy, like Down Syndrome unless it represents a significant amount of the total DNA content.

The SCSA has many advantages including the fact that it measures 5000 or more individual sperm in a very short space of time while also sampling all cell types in semen and also removing a lot of the subjective bias of the human eye measurements. Data have a higher level of repeatability (0.98-0.99) than those of any currently used semen parameter and these data correlate significantly with male factor infertility. The SCSA test therefore provides not only diagnostic but also prognostic evaluation of a man's potential for fertility. The SCSA appears to be stable over time with a high degree of repeatability.

Men with SCSA results with DFI >30% and HDS >15% appear to have a lower chance of producing a live birth in natural conception. The decrease in potential appears to be as much as 70%. Fertilization does not appear to be adversely affected when SCSA is abnormal as long as ICSI is performed when indicated by the usual parameters of total motile sperm and morphology. Thus, the egg does not appear to care if the sperm carries a genome with fragmented DNA or not. However, comparing the poor category relative to the excellent category, the blastocyst rate is about half, the pregnancy rate is reduced by 2/3 and the spontaneous abortion rate is doubled.

In summary, the SCSA data predicts a significantly reduced probability for in vivo and possibly in vitro fertility when the DFI is greater than 30%. In over 700 IVF related samples evaluated 73% of samples fell into the <30% category. In men with >30% DFI, it is likely that the remaining 70% of sperm also contain a lesser level of DNA abnormality but still sufficient DNA damage to prevent or decrease the chance of a live birth.

Procedures used in our program circumvent the negative outcomes associated with high DFI's. Only couples with recurrent spontaneous abortion will be considered for SCSA testing.