Testing for genetic contributions to infertility: potential clinical impact

Area of Science:

• Reproductive Medicine and Genetics
• Human Genetics and Genomics

Background:

• Male infertility impacts approximately 7% of the global male population.
• It is a complex condition with multifactorial and polygenic origins.
• Known genetic factors contribute to 20-25% of male infertility cases across various etiological categories.

Purpose of the Study:

• To review routinely available genetic tests for male infertility.
• To discuss indications for genetic testing based on sperm count and specific phenotypes.
• To highlight the role of genetic testing in managing idiopathic male infertility and informing clinical decisions.

Main Methods:

• Description of genetic tests for chromosomal anomalies and Y chromosome microdeletions.
• Explanation of mutation screening in candidate genes for specific semen/testis phenotypes.
• Mention of whole exome sequencing for identifying novel genetic causes in idiopathic cases.

Main Results:

• Genetic testing indications are primarily based on sperm count (severe oligozoospermia/azoospermia) and specific clinical phenotypes.
• Whole exome sequencing is a valuable tool for uncovering genetic causes in approximately 40% of idiopathic infertility cases.
• The highest prevalence of genetic anomalies is observed in cases of severe spermatogenic impairment.

Conclusions:

• Genetic testing is essential for clinical decision-making in male infertility, guiding treatment and predicting outcomes like testicular sperm retrieval.
• Diagnosis of genetic factors is critical for couples undergoing in vitro fertilization (IVF) due to the risk of transmitting disorders.
• Identifying known and novel genetic factors in idiopathic infertility is of paramount clinical importance for effective management and reproductive planning.