About 0.6-1% of all infertile men have microdeletions in the azoospermia factor (AZF) region of the Y chromosome. The prevalence of AZF deletions is 15-20% in non-obstructive azoospermia and about 7-10% in severe oligozoospermia. The DAZ and RBM genes, which are essential for spermatogenesis, are located in the AZF region. Deletions in this area lead to testicular maturation arrest of the spermatogenesis or are associated with the formation of immature, aggregated sperm.
By amplification of a total of six Y chromosome markers from the AZFa, AZFb and AZFc regions, about 90% of the known deletions can be detected. Deletions of the AZFa or AZFb region inevitably lead to azoospermia, so that testicular sperm extraction (TESE) does not seem to be effective for fertility treatment. In contrast, AZFc deletions lead to a very heterogeneous clinical picture, ranging from severe oligozoospermia to azoospermia. In about 50% of men with AZFc deletions, sperm can be found in the testicular biopsy with TESE. Deletions in the AZFc region are passed on to male offspring after artificial insemination by ICSI (intracytoplasmic sperm injection).
Other known causes of azoospermia are pathogenic variants in the AR, NR5A1, DMRT1 and TEX11 genes. In patients without AZF deletions, these genes can be examined within the framework of a multi-gene analysis using NGS.
References
Colaco and Modi 2018, Reprod Biol Endocrinol 16:14 / Schwarzer et al. 2016, Andrologia 48:402 / Krausz et al. 2014, EAA/EMQN best practice guidelines, Andrology 2:5 / Navarro-Costa et al. 2010, J Biomed Biotechnol 2010:936569 / Tüttelmann et al. 2008, Urologe 47:1561 / Simoni et al. 2004, Int J Androl 27:240