Currently, since most genetic diseases lack effective treatments, it is particularly important to adopt corresponding strategies at different stages before an individual is born to diagnose early and maximize the prevention of the birth of children with severe genetic diseases, thereby reducing the harm caused by genetic diseases. Genetic counseling is established based on this principle. The main consulting targets are patients or carriers who are found to have a genetic disease in either or both partners before or during pregnancy, individuals at increased risk of chromosomal or neural tube defects discovered during Down syndrome screening in early to mid-pregnancy, and pregnant women found to have certain abnormalities in the fetus during ultrasound examination. Reproductive genetic counseling primarily addresses hereditary diseases related to infertility or habitual miscarriage. With the widespread application of assisted reproductive technology, this genetic counseling also involves the screening of genetic diseases in sperm (egg) donors and genetic testing of pre-implantation embryos.

In male infertility caused by genetic factors, the probability of sperm chromosomal aneuploidy, structural abnormalities, and DNA damage increases, posing a risk of transmission to the next generation.

1. Chromosomal Abnormalities
The incidence of chromosomal abnormalities in male infertility patients is 5.7%, with sex chromosome abnormalities accounting for 4.2% and autosomal abnormalities for 1.5%. For patients with severe spermatogenic dysfunction, the incidence of autosomal abnormalities increases significantly, especially in patients with non-obstructive azoospermia, who have the highest prevalence.

Klinefelter’s syndrome is the most common sex chromosome abnormality disease, accounting for about 10% of azoospermia patients. The karyotype is 47,XXY or 46,XY/47,XXY mosaic. Clinical features include hypergonadotropic hypogonadism. Patients usually have tall stature, long limbs, sparse body hair, poor secondary sexual development, and small testes, with pathological manifestations of seminiferous tubule sclerosis. Testosterone replacement therapy can improve the patient’s quality of life but does not significantly enhance fertility. Microsurgical testicular sperm extraction can effectively increase the sperm extraction rate in Klinefelter’s syndrome patients. However, due to the significantly increased incidence of sex chromosome and autosomal abnormalities in the embryos of Klinefelter’s syndrome patients, pre-implantation genetic diagnosis (PGD) should be performed before ART.

In patients with poor semen quality, translocations and deletions between autosomes or between autosomes and sex chromosomes can often be found. These chromosomal abnormalities can be inherited by the next generation and can also lead to habitual miscarriage and congenital malformations in offspring.

2. Gene Mutations
Deletions on either the short arm or long arm of the Y chromosome can cause male infertility. The SRY gene located at the end of the short arm of the Y chromosome determines testicular development and affects sperm production. The production of normal sperm is directly influenced by other genes on the short arm of the Y chromosome besides SRY, mainly the azoospermia factor (AZF) located on Yq11.23 at the proximal end of the long arm of the Y chromosome. AZF is divided into three regions: a, b, and c. Deletion or mutation of AZF mainly leads to spermatogenic failure, causing oligospermia or azoospermia, also known as Y chromosome microdeletion syndrome, which follows a Y-linked inheritance pattern.

For patients diagnosed with congenital absence of the vas deferens, both partners need to be tested for mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene, in addition to causing cystic fibrosis, is also associated with congenital bilateral absence of the vas deferens. If both partners carry mutations in this gene, there is a 25% chance that their offspring will have cystic fibrosis or congenital absence of the vas deferens.