The present study is based on a PubMed search and compares the clinical validity of classical semen parameters (CSP) and the sperm chromatin structure assay (SCSA) in different clinical contexts. The PubMed database was searched using keywords on the sperm diagnostic test for pregnancy in three clinical scenarios: (i) couples attempting to conceive; (ii) couples who had been attempting to conceive for 12months without success; and (iii) couples treated with intrauterine insemination (IUI). There was a considerable heterogeneity among the studies included. For couples attempting to conceive following a SCSA that produced an abnormal result, the likelihood of male factor infertility ranged from a pre-test value of 7.5% to a post-test value of 32.1% [95% confidence interval (CI) 15.7-54.5], while after CSP with an abnormal result, the post-test probability was 17.3% (95% CI 11.8-24.5). For a pre-test prevalence of male factor infertility of 50%, the post-test probability of male factor infertility after an abnormal test is very similar for both SCSA and CSP. In couples treated with IUI, the clinical validity of SCSA is higher than that of sperm morphology alone, but not enough to introduce SCSA as a test in male infertility work-up.