Role of genetics in azoospermia

Objective: To review established genetic causes of azoospermia, the most severe form of male infertility, and help clinicians, scientists, and infertile couples considering assisted reproductive technologies (ART) to understand the complexity of the disorder and to maximize the chances of having a healthy infant through proper counseling and treatment.

Method: An initial literature search was performed on PubMed using the key words "azoospermia" "oligospermia," and "genetics." The results were limited to the studies on humans and written in English, which were written within last 10 years. Although preliminary query results showed more than 900 articles, further queries using key words, such as "Y chromosome," "monogenics," "aneuploidy," "mitochondrial DNA," and "epigenetics," along with "azoospermia," narrowed the results to 30 papers, which were included in the present study.

Results: Genetic defects causing azoospermia were categorized into two large categories: chromosomal and nonchromosomal. Chromosomal defects were further categorized into (1) structural abnormalities, such as Y chromosome micro/macrodeletions, chromosomal inversions, and translocations; and (2) numerical abnormalities, also known as aneuploidy. Nonchromosomal defects included sperm mitochondrial genome defects and epigenetic alterations of genome.

Conclusions: As a result of advancements in ART, understanding the potential implications of genetic disorders for infertile couples is critical. Analysis of a potential genetic role in azoospermia holds promise to expand our knowledge to evaluate male infertility and to guide treatments.