In 1976, Tiepolo and Zuffardi [2] provided the first evidence that the long arm of the Y chromosome might be required for fertility when they detected large Yq dele­tions in six azoospermic males. Subsequently, the gene cluster postulated to exist on the Y chromosome became known as the azoospermia factor or AZF region. The generation of sequence tagged sites (STSs) map allowed rapid polymerase chain reaction (PCR) detection of small deletions within the AZF region. The analysis of these micro-deletions resulted in the identification of three non overlapping regions on Yq involved in the control of sper­matogenesis, designated as AZFa, AZFb and AZFc [3].

The frequency of Y micro-deletions reported in the literature varies between 1% [4] and 55% [5], mainly due to the selection criteria of the patients. The vast majority of deletions, described in the literature, were found in azoospermic men, less in men with a sperm concentration of <5 x 10⁶/mL, and sporadically in men with sperm con­centrations of >5 x 10⁶/mL [6,7]. Y chromosome micro-deletions represent the etiological factor of 10-15% of idiopathic azoospermia and severe oligozoospermia [8,9]. Micro-deletions most frequently involve the AZFc region (60%), less frequently the AZFb region (16%), and only rarely the AZFa region (5%). Larger micro-deletions involving two or three AZF regions are present in 14% of cases, while in 5% the micro-deletions are located in regions not overlapping AZFa, b or c [7].

The most intriguing data from the studies of Y micro-deletions are related to the genotype/phenotype relation­ship. Although many authors have tried to make a correla­tion between the localization of the deletions (AZFa, b or c) and the clinical phenotype, the published data do not demonstrate a clear relationship between the type of dele­tion(s) and the testicular phenotype or seminal pattern. What seems to be clearly evident is that larger deletions, involving more than one AZF region, are invariably asso­ciated with azoospermia and testicular histology of Sertoly-cell-only syndrome (SCOS), while all the other types of micro-deletions might be associated with both azoospermia and severe oligozoospermia, and testicular histology varying from SCOS to spermatogenic arrest and hypospermatogenesis (HSG) [10].

The determination of Y micro-deletions in infertile men undergoing assisted reproduction techniques, such as intracytoplasmic sperm injection (ICSI), has important clinical and ethical implications, because these micro-deletions, and the related infertility problem, can be trans­mitted to the male offspring [11]. The knowledge about the presence of a Y micro-deletion in an infertile male has an important role for genetic counseling of the infertile couple, and for their decision concerning their therapeutic options. Therefore, in the past few years, PCR screening of Y micro-deletions has become an important step in the characterization of male infertility. The aim of this study was to evaluate the frequency of Y micro-deletions among a randomly selected infertile male population from the Republic of Macedonia.