Male factors account for a significant share of infertility among couples, and advanced genetic technologies can help identify causes that often go undetected by routine tests, according to a new Indian study.
The study, conducted by the FRIGE Institute of Human Genetics, Ahmedabad, in collaboration with the Indian Council of Medical Research (ICMR), is the largest and most systematic genetic study of male infertility in India to date. Published this month in the Journal of Assisted Reproduction and Genetics, it analysed 247 Indian men with severe sperm abnormalities between 2021 and 2024.
Researchers said infertility is commonly perceived as a woman’s health issue, but male factors play a major role. Diagnosing the cause in men is often challenging because many appear healthy and have normal blood tests, yet semen analysis shows no sperm or very low sperm counts. In most such cases, the underlying reason remains unknown.
The study found that standard genetic tests used by most infertility clinics—such as chromosome analysis and Y-chromosome testing—identify only large genetic changes. These tests detected chromosomal abnormalities in three men and Y-chromosome microdeletions in eight, explaining infertility in only 11 of the 247 cases.
To improve diagnosis, researchers used newer DNA sequencing methods to analyse infertility-related genes in greater detail. Targeted sequencing was performed on 120 men, while whole exome sequencing, often involving both parents, was carried out in 48 cases. This increased the diagnostic yield by an additional six to eight per cent, resulting in confirmed genetic diagnoses in 19 men, or about one in 13.
Based on both known and newly identified genetic causes, the researchers estimated that one in eight to one in five infertile men may have an underlying genetic reason. The study also found that most established male infertility genes follow recessive inheritance, meaning a man is affected only if he inherits faulty gene copies from both parents.
