Male infertility affects about one in seven couples trying to conceive, with half of these cases linked to male factors. The main causes are a lack of sperm or a low sperm count. Despite this, more than half of male infertility cases remain unexplained. This makes it difficult to provide effective treatment and predict associated health issues. Known genetic factors are responsible for roughly 10% of male infertility, but many unexplained cases may be caused by genetic defects that are not currently tested for.
A research team led by Prof. Maris Laan from the University of Tartu and Prof. Margus Punab from Tartu University Hospital set out to investigate whether a single defective gene is responsible for a significant portion of male infertility cases. They analyzed genetic variations in 638 candidate genes associated with various forms of male infertility. The study involved 521 men with unexplained spermatogenic failure and 323 fertile men, all part of the ESTonian ANDrology (ESTAND) cohort.
The team identified genetic causes in about 12% of the patients studied. They found disease-causing mutations in 39 genes that affect sperm production, genital development, and reproductive hormones. Some of these mutations were recurrent, meaning they were found in more than one patient, while others involved multiple genetic defects contributing to infertility in a single individual.
Many of the genes involved in infertility also play roles in other areas of health. In this study, men with genetic infertility were found to have a fourfold higher risk of early-onset cancer compared to the general male population in Estonia. This highlights the importance of a precise molecular diagnosis to address not only infertility but also other potential health risks linked to these genetic defects.
This study is one of the largest to explore the genetic causes of male infertility. The findings have already been integrated into clinical practice at Tartu University Hospital’s Andrology Clinic, where a molecular diagnostic test based on a male infertility gene panel is available. This test can quickly detect genetic defects in hundreds of genes associated with sperm production, helping to provide more personalized treatment for infertile couples. According to Prof. Laan, this gene panel is currently a unique tool for male infertility diagnosis in public healthcare.
The Andrology Clinic at Tartu University Hospital treats over 95% of infertile men in Estonia. Given the diverse range of infertility cases included in the study, the results are likely to be applicable to andrology clinics worldwide.
Related topics:
