The genetic causes of male and female infertility

When we meet a couple with infertility problems, it is essential to study the possible underlying causes. In some cases, the causes remain unknown and are thus referred to as "infertility sine causa". Among the identifiable causes, genetic factors account for up to 50% of the causes of infertility in couples. These factors can be detected through specific tests, some of which are routinely performed in the diagnostic pathway of infertile couples. The genetic causes of infertility can be classified according to the type of genetic alteration and the mechanism by which these alterations affect fertility. It is important to distinguish between male and female causes. In the case of male infertility, chromosomal abnormalities are particularly relevant. These abnormalities can be identified by karyotype testing, which analyzes the number and shape of chromosomes. Normally, humans have 46 chromosomes: variations in number or shape can be associated with infertility problems.

Klinefelter syndrome, characterized by the presence of an extra sex chromosome (XXY instead of XY), is the most common male chromosomal abnormality and causes abnormal sperm maturation and often there is an absence of sperm at all. Other abnormalities include balanced translocations, where parts of the chromosome are swapped between different chromosomes, affecting sperm maturation. In addition, abnormalities in specific genes, such as those associated with cystic fibrosis, can interfere with the development of the vas deferens, leading to the absence of sperm in the seminal fluid. In some cases, sperm are retrieved via testicular biopsy and used for IVF. Women can also have genetic causes of infertility, although they are less frequent than men. An example is the alteration of the FNR1 gene, which causes fragile X syndrome, known to cause intellectual disability in males and early menopause in women.

Identifying the causes of infertility is a crucial step not only to try to solve the problem, but also to provide information on reproductive risk to the couple and their relatives, especially if hereditary diseases are present in one of the two partners.