Around one in seven couples face challenges when trying to conceive naturally, with male infertility being a key factor in half of these cases. Male infertility is often linked to either a complete absence or a low number of mature sperm. Despite advances in medical practice, over half of these infertility cases remain unexplained, making effective counseling, treatment, and prevention difficult. While known genetic factors account for about 10% of male infertility, many cases of unexplained sperm production failure are likely caused by genetic defects that aren’t currently analyzed in routine clinical tests.
A team led by Prof. Maris Laan from the University of Tartu and Prof. Margus Punab from Tartu University Hospital’s Andrology Clinic aimed to identify the genetic causes of male infertility. They analyzed the genetic variations of 638 genes linked to male infertility in 521 men with unexplained sperm production failure and 323 fertile men as part of the ESTonian ANDrology (ESTAND) cohort.
The study revealed that approximately 12% of the patients had genetic defects that could be linked to infertility. The researchers discovered disease-causing variants in 39 genes related to sperm production, genital development, and reproductive health. Interestingly, some of these genetic variants were found in multiple patients within the ESTAND cohort or had been previously reported in other populations. Some men also carried more than one genetic defect contributing to their infertility.
These findings highlight an important issue: since many of the identified genes serve multiple functions, the genetic defects causing infertility may also affect a man’s overall health. In this study, men with genetic infertility were found to have a fourfold higher risk of developing early-onset cancer compared to the general Estonian male population. This suggests that a precise molecular diagnosis is crucial not only for managing infertility but also for addressing other health risks linked to these genetic defects.
This study is one of the largest investigations into the genetic causes of male infertility. The results have already been integrated into clinical practice at Tartu University Hospital’s Andrology Clinic since the fall of 2022. A new molecular diagnostic test, based on a male infertility gene panel, is now offered to patients with relevant medical indications. This test helps quickly identify DNA defects in hundreds of genes associated with sperm production failure and improves personalized treatment for infertile couples. According to Laan, gene panel-based tests for male infertility are still rare outside of private practices, making this a unique opportunity for patients in Estonia.
The Andrology Clinic of Tartu University Hospital treats over 95% of infertile men in Estonia. Given the diverse forms of severe infertility among the study cohort, the findings have the potential to be applied in andrology clinics globally.
Related topics:
