Male infertility and its ties to next generation sequencing as a new forward path to definite diagnoses

Based on the WHO infertility definition, couples who failed to conceive a baby after one year of unprotected sexual intercourse are infertile. About 50 million couples suffer infertility around the word and men are equally involved. Male infertility is a heterogeneous and multi-factorial complex disorder. Like most diseases, genetic factors play a role in this issue too. Genetic defects such as Klinefelter syndrome (XXY), Y Chromosome Microdeletions (YCMDs), and monogenic mutations contribute to male infertility. Currently, 4% of infertile males have a genetic reason, while 60-70% remain unexplained. Attempting to identify the new causal genes/variants in male fertility and following it by improving diagnostic panels are the aims of recent studies in this field. It is estimated that around 2000 genes contribute to germ cell preservation and successful meiosis whereas over 100 genes are identified in male infertility. Although karyotype, Y chromosome screening, and microarray remain effective techniques for diagnosing male infertility, Next-Generation Sequencing (NGS) is becoming a more widely used technique. NGS has accelerated the introduction of male infertility genes and introduced more genes to the infertility panels in the past decade. It hopes to decrease cases of unexplained male infertility and shed more light on them.