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Sperm DNA fragmentation testing

Date: 2-12-2008

SCSA-Sperm DNA fragmentation testing

SCSA Definition
SCSA Background
How SCSA is performed
Clinical significance of SCSA

SCSA Definition

SCSA stands for sperm chromatin structure analysis. Other names describing the same test are: sperm DNA fragmentation test, sperm chromatin fragmentation test.

SCSA Background

Recently, there has been increased emphasis on the evaluation of sperm quality. This is due, in part to the fact that a sperm test or semen test by itself is of limited value. Sperm counts, for example, fluctuate significantly from day to day in most men. When you think about it, sperm are nothing more than transport vehicles to get DNA from the male into the female egg. Since sperm are very small, a large amount of DNA must be "crammed" into a very small container. In order to accomplish this feat, the DNA is wound and twisted on itself and wrapped around blocks of protein. The combination of DNA and protein blocks is referred to as chromatin. Part of the function of the protein blocks is to protect the sperm DNA from damage during its long journey from where it is produced (in the testicles) to where it hopefully arrives (the egg). However, it seems that some DNA will remain susceptible to damage and that DNA can become fragmented.

How SCSA is performed

There are several different tests that have been developed to assess the percentage of sperm with significant DNA fragmentation. One test is called the TUNNEL assay. Another is called the COMET assay. The test that has received the most attention recently however, is called the SCSA or sperm chromatin structure analysis. During the SCSA test, sperm are treated with a chemical to allow entry of a special dye into the sperm cell. The dye sneaks its way into crevices in the DNA molecule. In theory, sperm with fragmented DNA take up more of the dye. Then, using a procedure called flow cytometry, the sperm that took up lots of dye (the sperm with fragmented DNA) can be differentiated form the sperm that took up only a little dye (sperm with normal DNA). Finally, using a computer program, each sperm can be graphed out or the percentage of sperm with fragmented DNA can be determined.

Clinical significance of the SCSA test

Some of the early clinical data involving SCSA suggested that men with more than 30% of their DNA with fragmentation had extremely poor pregnancy rates (1% or less) even with aggressive techniques such as in vitro fertilization - IVF.Current data proves that this was not true! In 2004, several research abstracts were presented at the annual meeting of the American Society for Reproductive Medicine - ASRM. The results of these studies were quite different than the original studies.

 

In Colorado, 128 couples going through an IVF cycle had sperm frozen for SCSA. The pregnancy rate in patients with a SCSA showing less than 30% fragmentation (the normal group) was 62%. The pregnancy rate in patients with an SCSA greater than 30% (the abnormal group) was 81%. In the abnormal group, the average SCSA result was a fragmentation index of 40%.
 
Another study performed in North Carolina and since published in the journal Fertility and Sterility involved 100 couples undergoing IVF. SCSA testing was performed on the same semen specimen that was used for fertilization of the eggs. Nine of nineteen couples achieved clinical pregnancy when the DFI (DNA fragmentation index) was greater than 27 %.

 

The best conclusions that can be made today about an abnormal SCSA test are:
  • All men, whether fertile or infertile, have some sperm with fragmented DNA
  • Men with a normal semen analysis can have an abnormal SCSA.
  • A SCSA test result is very consistent over time. The SCSA is more consistent than a semen analysis. Some things can cause an abnormal test, however, such as a high fever or certain medications. Certain steps in preparing to do the test can affect the results of the SCSA.
  • The best evidence to dates suggests that men with an abnormally high percentage of sperm with DNA fragmentation, have a pregnancy rate similar to men with a normal percentage of sperm DNA fragmentation when using techniques such as IVF.