Molecular Analysis of Y Chromosome Microdeletions in Infertile Men

Idiopathic infertility is a condition of couples unable to conceive for more than two years, with no abnormalities seen on repeated investigations of tubes or as regard with ovulation, luteal phase, cervical mucus, semen, sperm-oocyte interaction or intercourse. Among the major causes of infertility, chromosomal abnormalities, microdeletions, cystic fibrosis transmembrane conductance regulator (CFTR) mutations and other genetic factors (Follicle stimulating hormone (FSH) receptor mutation) are important. Genetic factors cause about 10% of male infertility. Among these, genes in AZF regions including AZFa, AZFb, AZFc and AZFd on the long arm of Y chromosome are considered to be the most important for spermatogenesis. Deletions in these regions are thought to be pathogenetically involved in some cases of male infertility associated with azoospermia or oligozoospermia. The aim of this study was to determine the incidence of AZF deletions among male infertile patients. We analyzed a total of 215 azoospermic infertile men for the presence of 12 sequence tagged site (STS) markers, 3 markers for each AZF region including AZFa, AZFb and AZFc, on the Y chromosome using multiplex PCR. Among the patient group the observed frequency of deletions was about 11.1%, among them the azoospermic men showed more significant deletions (7.4%) than the severe oligospermic men (3.7%) selected for the study. The deletion in AZFa region was 20.83% of the total deletions. The relative frequency of deletions in AZF a, b and c regions in infertile men in this study is AZFa in 1/24 (4.16%); AZFb in 5/24 (20.8%); AZFc in 11/24 (45.83%); AZF a+c in 2/24 (8.3%); AZF b+c in 3/24 (12.5%); AZF a+b+c in 2/24 (8.3%). No microdeletions were found in the control group. According to relatively high incidence of Y chromosome microdeletions among azoospermic patients, molecular screening for detection of these microdeletions seems to be very informative, since different types of these deletions have prognostic value in predicting the outcome of testicular sperm retrieval for assisted reproduction.