Chromosome defects and male factor infertility

Although a routine semen analysis and an endocrine evaluation (usually of the gonadotropins and androgen levels) are the cornerstone of clinical diagnostic evaluation of the male seeking evaluation and treatment of the couple with infertility, in recent years, the American Urological Association/American Society for Reproductive Medicine Practice Guidelines for Male Infertility stressed the importance of assessing chromosomal anomalies, such as numerical and structural anomalies in men with spermatogenic failure. This narrative review of chromosomal anomalies as a cause of male factor infertility will provide an understanding of the technical approaches to defining the defects, as well as the clinical consequences of these abnormalities for a wider group of men with infertility. Karyotype anomalies are a significant cause of male factor infertility and are present in approximately 6% of men with infertility. These cytogenetic anomalies include numerical defects that underlie conditions such as Klinefelter syndrome, which is among the most overlooked diagnosis in reproductive medicine, and other sex chromosome aneuploidies. Structural chromosomal defects are more varied and complex and include chromosomal translocations, inversions, insertions, and copy number variations, some of which result in spermatogenic failure, oligozoospermia, asthenozoospermia, or even normozoospermia. Other structural defects affect pregnancy outcomes or health of the offspring conceived or cause birth defects. The criteria needed for a chromosomal assessment for the diagnosis male factor infertility should probably be expanded beyond the existing American Urological Association/American Society for Reproductive Medicine Practice Guidelines. Their recommendation that a karyotype be performed for the evaluation of men with nonobstructive azoospermia and men with severe oligozoospermia (<5 million sperm/mL) is solid; however, the prevalence of cytogenetic anomalies in men with sperm counts below 20 million sperm/mL is also increased compared with fertile men who would not be likely to be tested. Karyotypic anomalies are even present in a subset of men with infertility with normozoospermia. A karyotype can also detect structural chromosomal anomalies, such as translocations that impact male reproductive function and the health of the offspring. Advanced technologies to identify microdeletions and microduplications can also guide patient care. Knowledge of the etiology of the male's infertility may impact the couple's treatment options and improve their reproductive outcomes.