Defects in spermatogenesis of men with Y chromosome microdeletions

Abstract

Introduction. Male infertility has multiple etiology, most commonly caused by spermatogenesis disorders, clinically manifested by oligo/azoospermia. Until recently, Y microdeletion had little clinical significance since men with a deletion were considered unable to reproduce. However, by utilizing of Intracytoplasmic sperm injection (ICSI) and Testicular sperm extraction (TESE) it is now possible for oligo/azoospermic men with Y microdeletion to father children. Aim of the study. To analyze the type of defect in spermatogenesis associated with specific Y deletions found in our IVF program, for prevention the transmission of these deletions through ICSI to offspring. Materials and methods. A group of 46 infertile men were investigated during genetic counseling among infertile couples referred for ART treatment. Criteria for including patients were fulfilled if they presented with oligo/azoospermia, raised or normal levels of FSH, LH and testosterone. Genomic DNA was isolated and used to analyze AZF microdeletions by PCR. The regions and sequence-tagged sites of AZFa (SY86, SY84), AZFb (SY127, SY134), and AZFc (SY254, SY255) were sequenced by multiplex PCR. Five non-obstructive azoospermic men had Y chromosomal microdeletions. All five Y-microdeleted men underwent microsurgical observation of testicular architecture and quantitative histology of spermatogenesis in a strip of testicular tissue. The results were compared with the different type of Y microdeletion. Results. Deletions of Y chromosome were seen in the AZFc regions of 2 patients, deleted markers were sY254 and sY255. In both men with AZFc deletions, the histological defects were variable, but no sperm were found. In only one case the defect of Sertoli cell-only syndrome (SCOS) in patient with microdeletions in each region of AZFa-sY84, sY86; AZFbsY127, sY134; AZFc-sY254, sY255 was present. One patient with deletion of AZFb (SY127, SY134) had spermatogenetic maturation arrest. In all men with AZF microdeletions of the Y chromosome, we found severe spermatogenic defects: however, we also did not find, in all of them, mature sperm sufficient for ICSI. The patients were advised to use sperm from the donor for ICSI and IVF. Conclusions. This study highlights for all couples with the diagnosis of male infertility with oligo/azoospermia the need of genetic testing and counseling prior to employment of assisted reproduction techniques. This is important for providing a firm diagnosis and fertility treatment to couples with infertility and for prevention of the transmission of AZFc deletions through ICSI to offspring.