Sperm chromatin structure assay (SCSA): a tool in diagnosis and treatment of infertility

Abstract

Diagnosis of male infertility has mainly been based on the World Health Organization (WHO) manual-based semen parameter's concentration, motility and morphology. It has, however, become apparent that none of these parameters are reliable markers for evaluation of the fertility potential of a couple. A search for better markers has led to an increased focus on sperm chromatin integrity testing in fertility work-up and assisted reproductive techniques. During the last couple of decades, numerous sperm DNA integrity tests have been developed. These are claimed to be characterized by a lower intraindividual variation, less intralaboratory and interlaboratory variation and thus less subjective than the conventional sperm analysis. However, not all the sperm chromatin integrity tests have yet been shown to be of clinical value. So far, the test that has been found to have the most stable clinical threshold values in relation to fertility is the sperm chromatin structure assay (SCSA), a flow cytometric test that measures the susceptibility of sperm DNA to acid-induced DNA denaturation in situ. Sperm DNA fragmentation as measured by SCSA has shown to be an independent predictor of successful pregnancy in first pregnancy planners as well as in couples undergoing intrauterine insemination, and can be used as a tool in investigation, counseling and treatment of involuntary childlessness. More conflicting data exist regarding the role of sperm DNA fragmentation in relation to fertilization, pre-embryo development and pregnancy outcome in in vitro fertilization and intracytoplasmic sperm injection (ICSI).

Figure 1

Histogram of an SCSA analysis of a sperm sample with a high DFI. The normal population of sperm (66% of all spermatozoa) is indicated by the arrow. Thirty-four percent of the sperm have abnormal packaged DNA why DFI is 34%. DFI, DNA fragmentation index; SCSA, sperm chromatin structure assay.

Figure 2

OR for infertility in vivo in relation to standard sperm parameters and different DFI levels: <10%, 10–20% and >20%. Data are OR (95% CI). CI, confidence interval; DFI, DNA fragmentation index; OR, odds ratio.

Figure 3

OR for outcome of IUI treatment in relation to threshold level for the DFI. Data are OR (95% CI). CI, confidence interval; DFI, DNA fragmentation index; IUI, intrauterine insemination; OR, odds ratio.

Figure 4

Flow chart for a possible use of SCSA in diagnosis and treatment of infertility. SCSA, sperm chromatin structure assay. *if DFI≤25%, DFI, DNA fragmentation index.