Large-scale mtDNA deletions as genetic biomarkers for susceptibility to male infertility: A systematic review and meta-analysis.

Several complex rearrangements such as deletions in mitochondrial DNA (mtDNA) have been identified in sperm deficiencies. This study aimed to investigate the association of common mtDNA deletions with male infertility using a meta-analysis approach. Standard databases were systematically searched to discover relevant studies. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI) were estimated to analyze the association of mtDNA deletions with male infertility. Our data revealed a significant association between a common 4977-bp deletion and an increased risk of male infertility. A similar association was observed in an Asian population. Stratified analysis by infertility phenotype showed significant associations between the 4977-bp deletion and increased risk of asthenozoospermia, oligoasthenoteratozoospermia, and asthenoteratozoospermia. In addition, significant associations were found in studies with sample sizes >100, age of participants <45 years, subject selection according to WHO criteria, and studies of moderate to high quality. Regarding the other common mtDNA deletions, significant associations were observed between 7436-bp, 7599-bp, and 4866-bp deletions and the risk of male infertility. Our findings suggest that the 4977-bp deletion might be a risk factor for male infertility, especially in an ethnic and infertility phenotype dependent manner.