Chromosomal microarray analysis of infertile men with azoospermia factor microdeletions.

Area of Science:

• Genetics
• Reproductive Biology
• Human Molecular Genetics

Background:

• Azoospermia factors (AZF) on the Y chromosome are crucial for spermatogenesis.
• Microdeletions in AZF regions are associated with male infertility.
• Partial AZFc deletions can present with diverse clinical phenotypes.

Purpose of the Study:

• To investigate the relevance of Y chromosome deletions and Y-linked copy number variations (CNVs) in infertile men.
• To clarify the relationship between phenotypic heterogeneity and Y chromosome deletions.
• To utilize chromosomal microarray analysis (CMA) for detailed CNV analysis.

Main Methods:

• Reviewed Y chromosome screening results in 554 infertile patients.
• Compared CMA results with routine screening in 29 patients with Y chromosomal microdeletions.
• Identified Y-linked CNVs associated with oligoasthenospermia using CMA and ACMG guidelines.

Main Results:

• Prevalence of Yq microdeletions was 5.23% (29/554), with 93% in the AZFc region.
• CMA provided more detailed information on deletion location, size, and involved genes compared to multiplex-PCR.
• Nine pathogenic and 20 VUS CNVs were detected; most deletions were in the AZFc region.

Conclusions:

• CNV size and the involvement of critical spermatogenesis genes are key factors determining the clinical relevance of AZFc deletions.
• CMA is a valuable tool for detailed characterization of Y-linked CNVs in male infertility.
• Understanding Y-linked CNVs aids in explaining phenotypic heterogeneity in infertile men.