Genetics of azoospermia: current knowledge, clinical implications, and future directions. Part II: Y chromosome...

We reviewed the most recent advances in the genetics of male infertility focusing on Y chromosome microdeletions.

We searched the literature using the PubMed and skimmed articles published from January 1998 to October 2007. The keywords were the Y chromosome, microdeletions, male infertility, and azoospermia factor (AZF). The full texts of the relevant articles and their bibliographic information were reviewed and a total of 78 articles were used.

Three regions in the long arm of the Y chromosome, known as AZFa, AZFb, and AZFc, are involved in the most frequent patterns of Y chromosome microdeletions. These regions contain a high density of genes that are thought to be responsible for impaired spermatogenesis. In 2003, the Y chromosome sequence was mapped and microdeletions are now classified according to the palindromic structure of the euchromatin that is composed of a series of repeat units called amplicons. Although it has been shown that the AZFb and AZFc are overlapping regions, the classical AZF regions are still used to describe the deletions in clinical practice.

Y chromosome microdeletions are the most common genetic cause of male infertility and screening for these microdeletions in azoospermic or severely oligospermic men should be standard. Detection of various subtypes of these deletions has a prognostic value in predicting potential success of testicular sperm retrieval for assisted reproduction. Men with azoospermia and AZFc deletions may have retrievable sperm in their testes. However, they will transmit the deletions to their male offspring by intracytoplasmic sperm injection.