The Prevalence of Y-chromosome Microdeletions in Oligozoospermic Men: A Systematic Review and Meta-analysis of European and North American Studies

Abstract

Context: European and North American guidelines recommend Y-chromosome microdeletion (YCM) screening in azoospermic and oligozoospermic men with sperm concentrations of <5 million sperm/ml; however, numerous studies have suggested that YCMs are rare when sperm concentrations are >1 million sperm/ml.

Objective: We systematically reviewed and meta-analyzed European and North American studies to determine the prevalence of a complete YCM in oligozoospermic men with sperm concentrations of >0-1, >1-5, and >5-20 million sperm/ml, and to determine whether 1 or 5 million sperm/ml is the most appropriate sperm concentration threshold for YCM screening.

Evidence acquisition: A systematic review of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov was performed for studies assessing the prevalence of a complete YCM in oligozoospermic men in European and North American studies.

Evidence synthesis: Thirty-seven studies were identified during a systematic review (n = 12 492 oligozoospermic men). All complete YCMs in oligozoospermic men were AZFc microdeletions. Eighteen studies contained data conducive to meta-analysis (n = 10 866 men). Comparing the pooled estimated prevalence by sperm concentration, complete YCMs were significantly more common in men with sperm concentrations of >0-1 million sperm/ml (5.0% [95% confidence interval {CI}: 3.6-6.8%]) versus >1-5 million sperm/ml (0.8% [95% CI: 0.5-1.3%], p < 0.001). YCMs were similar in men with sperm concentrations of >1-5 and >5-20 million sperm/ml (0.8% [95% CI: 0.5-1.3%] vs 0.5% [95% CI: 0.2-0.9%], p = 0.14).

Conclusions: In Europe and North America, the majority of YCMs occur in men with sperm concentrations of ≤1 million sperm/ml, with <1% identified in men with >1 million sperm/ml. Male infertility guidelines for North America and Europe should reconsider the sperm concentration screening thresholds to recommend testing for YCMs only for men with sperm concentrations of <1 million sperm/ml.

Patient summary: Complete Y-chromosome microdeletions (YCMs) are rare in men with >1 million sperm/ml. Routine screening for YCMs should occur only if sperm concentration is ≤1 million sperm/ml.

Keywords: Gene deletion; Genetics; Infertility; Meta-analysis; Semen analysis; Y chromosome.