Y chromosome microdeletions are the most frequent genetic cause of severe oligozoospermia (<5 million spermatozoa/ml) and azoospermia (absence of spermatozoa in the ejaculate).¹ Microdeletions associated with infertility occur in specific regions of the long arm of the Y chromosome, called azoospermia factor (AZF) regions.^2,3 In 1996, three types of AZF deletion (AZFa, AZFb, and AZFc) were described by Vogt et al; however, after the complete physical map and sequence of the AZFb and AZFc regions was produced,⁴ it became evident that the AZFb and AZFc intervals partially overlap.⁵ The Y chromosome is extremely rich in repetitive sequences, organised in amplicons.⁶ Ampliconic sequences are characterised by sequence pairs showing nearly complete (>99.9%) nucleotide identity, organised in massive palindromes. These repeated sequences may undergo genetic exchange through gene conversion—that is, non-reciprocal transfer of sequence information occurring between duplicated sequences within the chromosome, a process that could account for the >99.9% nucleotide identity between the arms of a palindrome. Although this mechanism may serve to preserve Y chromosome genes from the gradual accumulation of deleterious mutations and thus prolong their genetic fitness,⁶ this peculiar organisation also provides the structural basis for deletions and rearrangements.

The classical AZFc deletion, which removes 3.5 Mb between the b2/b4 amplicons, is the most frequent type of deletion. Taking into consideration the Y chromosome structure and the suggested deletion mechanism, a number of other possible partial deletions have been proposed in both the AZFb and AZFc regions.^7,8 The frequency and the pathological significance of these partial deletions is not yet clear, although recently a partial deletion termed gr/gr has been described specifically in infertile men with varying degrees of spermatogenic failure.^9,10 This deletion removes half the AZFc gene content, including two copies of the major AZFc …