About one in seven couples struggle to conceive naturally. In half of these cases, the problem lies with the man—either because of no sperm or too few mature sperm cells. However, more than half of male infertility cases remain unexplained in today’s medical practice. This makes it hard for doctors to provide the best advice, treatment, and to prevent related health problems.
Known genetic causes explain only about 10% of male infertility. Researchers believe many cases without clear reasons are due to genetic defects that current tests do not detect.
A research team from the University of Tartu, led by Prof. Maris Laan and Prof. Margus Punab, studied this issue in depth. They analyzed genetic variations in 638 candidate genes linked to male infertility. The study included 521 men with unexplained sperm production problems and 323 fertile men from the ESTonian ANDrology (ESTAND) cohort.
The team discovered that about 12% of the men with infertility had a single faulty gene causing their condition. They found harmful variants in 39 genes involved in sperm production, development of reproductive organs before birth, and hormone regulation. Some of these genetic problems were found repeatedly in different patients or reported in other populations. Interestingly, some men had more than one genetic defect that contributed to their infertility.
Because many of these genes also affect other body functions, the genetic defects causing infertility may influence overall health. The study found that men with genetic infertility had four times higher rates of early-onset cancer compared to the general male population in Estonia. This highlights the importance of precise genetic diagnosis—not only to guide infertility treatment but also to identify other health risks.
This research is one of the largest studies on single-gene causes of male infertility. Its findings have already been put into clinical use at the Andrology Clinic of Tartu University Hospital since autumn 2022. The clinic now offers a molecular diagnostic test based on a panel of male infertility genes to all patients who qualify. This test quickly detects DNA defects in hundreds of genes linked to sperm production failure, allowing doctors to provide more personalized care.
Prof. Laan notes that offering this gene panel test within public healthcare, not just private clinics, is a unique advantage in male infertility care.
The Andrology Clinic at Tartu University Hospital treats over 95% of infertile men in Estonia. Because the study included patients with different types of severe infertility, its results could benefit andrology clinics around the world.
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