Azoospermia, the complete absence of sperm in the ejaculate, affects approximately 1 in 100 men and accounts for up to 20% of male infertility cases. Once considered only a fertility problem, azoospermia is now linked to broader health risks.

Research has shown that men with azoospermia have higher rates of cancer, cardiovascular diseases, and metabolic disorders. These findings suggest that male infertility, particularly azoospermia, could serve as a biomarker for systemic diseases and an entry point for preventive care.

There are two main types of azoospermia: obstructive azoospermia, caused by blockages in the urogenital tract, and nonobstructive azoospermia, in which the testes fail to produce sperm.

Growing evidence indicates an increase in the rates of oncologic, cardiovascular, and metabolic disorders. This paradigm could create an opportunity for crucial healthcare reform, with the infertile phenotype serving as a biomarker for potential pathological conditions.

As men are not subject to routine screening programs comparable to those for women, fertility testing provides a rare opportunity to detect those at elevated risk and initiate timely interventions. This expands the role of urologists beyond fertility treatment to include broader diagnostic and preventive care for men.

Carlos Balmori, MD, urologist and specialist in sexual, reproductive, regenerative medicine and male infertility, Instituto Valenciano de Infertilidad IVI, Spain, noted advances in managing azoospermia, “Just a decade ago, azoospermia meant giving up the possibility of having biological children. However, this paradigm has changed.

There are two types of azoospermia: obstructive, caused by an obstruction or abnormality anywhere along the urogenital tract, and secretory or nonobstructive, which reflects a problem in sperm production in the tests.

The latter, which represents up to 70% of cases, can be congenital or acquired and is often due to hormonal factors, prior infections, aggressive medical treatments, or environmental factors.”

Balmori noted that conventional testicular biopsy (TESE) and microdissection testicular (MicroTESE) sperm extraction now allows sperm retrieval in most obstructive azoospermia cases and in 30%-60% of nonobstructive azoospermia cases. In obstructive azoospermia, sperm can be retrieved in 90%-100% of cases. 

While hormonal therapy may be indicated first in nonobstructive azoospermia with hormonal causes, TESE and microTESE remain options whenever viable sperm are present. 

These procedures are minimally invasive, and even a small number of retrieved gametes can be used in assisted reproduction, such as in vitro fertilization with intracytoplasmic sperm injection.

Recent studies have identified novel PNLDC1 mutations as an underlying cause of nonobstructive azoospermia in humans and mice. 

In a study published in Human Molecular Genetics, researchers used whole-exome sequencing to detect a compound heterozygous mutation (MT1 c.449G > A, p.Trp150* and MT2 c.821A > G, p.His274Ala) in a Chinese patient with nonobstructive azoospermia (P9241) and a homozygous nonsense mutation (MT3 c.1288C > T, p.Arg430*) in a Pakistani patient born to a consanguineous couple.

These findings provide strong functional evidence that PNLDC1 mutations disrupt piRNA biogenesis, impair spermatogenesis, and cause azoospermia in humans and mice.

This story was translated from El Medico Interactivo.