Genetic and molecular diagnostics of male infertility in the clinical practice

Male infertility represents one of the clearest examples of complex phenotype with substantial genetic basis. It is indeed well established that genetic causes account for 10-15% of infertility cases, including chromosomal abnormalities and single-gene mutations. However, a large proportion of infertile males does not receive a clear diagnosis and thus they are reported as idiopathic or unexplained. Male (in)fertility is commonly based on standard semen analysis, which, however, cannot clearly distinguish fertile from infertile populations and therefore fails to detect any abnormality in many cases. Abnormal sperm function or specific molecular defects can be hypothesized in these cases. This review considers practical genetic and molecular diagnostic tests for male infertility, reporting on the most frequent genetic causes of male infertility and on the pros and cons of most commonly used techniques for genetic, molecular and functional sperm evaluation. Finally, this review will discuss recent advances in pharmacogenetics and new developments on sperm analysis that will form the basis for future research.