Comprehensive 5-year study of cytogenetic aberrations in 668 infertile men

Abstract

Purpose: The causes of male infertility are heterogeneous but more than 50% of cases have a genetic basis. Specific genetic defects have been identified in less than 20% of infertile males and, thus, most causes remain to be elucidated. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions. To refine the incidence and nature of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 668 infertile men with oligozoospermia and azoospermia.

Materials and methods: High resolution Giemsa banding chromosome analysis and/or fluorescence in situ hybridization were done in 668 infertile males referred for routine cytogenetic analysis between January 2004 and March 2009.

Results: The overall incidence of chromosomal abnormalities was about 8.2%. Of the 55 patients with abnormal cytogenetic findings sex chromosome aneuploidies were observed in 29 (53%), including Klinefelter syndrome in 27 (49%). Structural chromosome abnormalities involving autosomes (29%) and sex chromosomes (18%) were detected in 26 infertile men. Abnormal cytogenetic findings were observed in 35 of 264 patients (13.3%) with azoospermia and 19 of 365 (5.2%) with oligozoospermia.

Conclusions: Structural chromosomal defects and low level sex chromosome mosaicism are common in oligozoospermia cases. Extensive cytogenetic assessment and fluorescence in situ hybridization may improve the detection rate in males with oligozoospermia. These findings highlight the need for efficient genetic testing in infertile men so that couples may make informed decisions on assisted reproductive technologies to achieve parenthood.

Figure 1

Different rearrangements in male infertile cohort. A, proportion of each category detected in 55 men with chromosomal defects. B, X and Y chromosome aneuploidy in 29 men with numerical chromosome defects. C, sex and autosomal chromosome aberrations in 26 men with structural rearrangements.

Figure 2

FISH using X (green dye) and Y (red dye) specific probes. A, normal hybridization pattern using X chromosome centromere and SRY specific probes in male patient. B, isodicentric Y chromosome in patient 8. C, infertile patient 3 with 46,XX karyotype and derivative chromosome X resulting from translocation between X and Y chromosomes. Yp11.2 region containing SRY gene was detected at long arm of chromosome X.

Figure 3

Cytogenetic findings in semen categories of tested infertile men. A, chromosome abnormalities. B, cytogenetic abnormalities. Black bars represent numerical sex chromosome abnormalities. Open bars represent structural sex chromosome abnormalities. Hatched bars represent structural autosomal aberrations.