For many couples facing infertility, the greatest frustration arises when pregnancy does not occur despite repeated medical interventions and no clear explanation. A new Indian study now shows that advanced genetic technologies can finally provide answers in many such cases.
Largest Genetic Study of Male Infertility in India
Published this month in the Journal of Assisted Reproduction and Genetics, the study analysed 247 Indian men with severe sperm abnormalities between 2021 and 2024. Conducted by the FRIGE Institute of Human Genetics, Ahmedabad, in collaboration with the Indian Council of Medical Research (ICMR), it represents the largest and most systematic genetic investigation of male infertility in India to date. Importantly, it is also among the few global studies to use advanced family-based genetic analysis.
Male Factors Play a Major Role
Although infertility is often perceived as a woman’s condition, researchers emphasized that male factors contribute significantly to infertility. However, identifying the cause in men remains challenging. Many affected men appear healthy and show normal routine blood test results, yet semen analysis reveals either no sperm or extremely low sperm counts. In most cases, clinicians cannot explain the underlying reason.
Limitations of Routine Genetic Testing
Most infertility clinics rely on standard genetic tests, including chromosome analysis and Y-chromosome microdeletion testing. However, these tests detect only large genetic abnormalities. As a result, their diagnostic value remains limited.
According to Dr Deepak Modi, Scientist at the ICMR–National Institute for Research in Reproductive and Child Health, Mumbai, the study detected chromosomal abnormalities in only three men and Y-chromosome microdeletions in eight. Consequently, routine testing could explain infertility in just 11 of the 247 men, leaving the majority without a definitive diagnosis.
Advanced Sequencing Improves Diagnosis
To overcome these limitations, the research team applied newer DNA sequencing technologies that examine infertility-related genes in much greater detail. Specifically, they performed targeted smMIP-based sequencing in 120 men and whole exome sequencing (WES), often involving both parents, in 48 men.
As a result, these approaches increased the diagnostic yield by an additional six to eight per cent. Overall, the researchers confirmed a genetic diagnosis in 19 of the 247 men—approximately one in 13 cases. Based on both known and newly identified genetic causes, the team estimates that as many as one in eight to one in five infertile men may have an underlying genetic reason.
Recessive Inheritance and Its Indian Context
A key insight from the study revealed that most well-established male infertility genes follow a recessive inheritance pattern, meaning a man is affected only when he inherits faulty copies of a gene from both parents.
As reported by The Hindu, this finding holds particular relevance in India, where marriages within communities are more common, explained Jayesh Sheth, Chairman and Co-founder of the FRIGE Institute of Human Genetics and a co-author of the study.
Genetic Diagnosis Shapes Clinical Decisions
Importantly, genetic diagnosis does more than label a condition—it directly influences clinical management. For instance, some men with CFTR gene mutations produce sperm normally, but the ducts that carry sperm are absent or blocked. Without genetic testing, such conditions often go undetected.
When identified early, doctors can plan sperm retrieval and IVF procedures more effectively. In addition, female partners can undergo testing to assess the risk of cystic fibrosis in future children. Ultimately, couples can make informed decisions regarding genetic counselling and pregnancy planning, said Dr Harsh Sheth, Lead Author of the study and Head of the Advanced Genomic Technologies Division at FRIGE.
India-Developed Innovation Reduces Cost and Time
The study also highlights a significant India-developed innovation. The targeted sequencing method used by the team is based on a patented technology designed to detect multiple genetic abnormalities in a single test. According to Dr Harsh Sheth, the inventor of the technology, this approach saves both time and cost while improving diagnostic efficiency.
A Roadmap for Precision Infertility Care
By combining classical genetic testing with modern sequencing technologies, the study offers a clear roadmap for transforming infertility evaluation in India—from exclusion-based testing to precise molecular diagnosis.
For couples struggling with infertility, an accurate genetic diagnosis can shorten years of inconclusive testing, guide realistic decisions around IVF and sperm retrieval, clarify genetic risks for future children and male relatives, and reduce unnecessary emotional and financial stress.
At the same time, the researchers stress balance. “Sequencing should complement, not replace, existing chromosome tests to ensure a comprehensive and cost-effective diagnostic strategy,” Dr Sheth concluded.