The approach detected multiple types of genetic changes in a single analysis, potentially broadening genetic testing for patients with unexplained POI.
Researchers at the University of Tartu demonstrated that a single genetic analysis can identify causes for premature ovarian insufficiency (POI) in women whose condition was previously unexplained. The condition affects up to 3.5% of women and is a significant cause of female infertility.
POI occurs when normal ovarian function is impaired before age 40. In addition to reduced fertility, it is associated with poorer bone health, an increased risk of cardiovascular disease, reduced quality of life, and a higher risk of premature mortality. While genetic factors contribute to the development of the condition, the underlying cause remains unknown for most patients.
Expanding Beyond Routine Testing
The researchers used exome sequencing, a method that targets the protein-coding regions of the genome, to evaluate 51 Estonian women with POI for whom routine clinical assessments had failed to find a cause. The team searched the exome data for both small-scale single-gene changes and large-scale chromosomal abnormalities.
“POI can be caused by a wide variety of genetic changes. In current clinical practice, established genetic causes are often investigated using separate tests, while broader genomic approaches are not yet routinely implemented. As a result, some disease-causing changes may remain undetected. We therefore wanted to determine whether a single exome-based analysis could identify several different types of genetic changes and provide a more comprehensive assessment of the genetic causes of POI,” says Anu Valkna, junior research fellow in human genetics at the University of Tartu, in a release.
Study Findings and Clinical Impact
The analysis identified a genetic cause in 12% of the women studied, which represents approximately one in eight patients. According to Valkna, this proves that broader genetic analysis can provide a diagnosis for patients whose cause is not identified through currently available routine investigations.
A genetic diagnosis of this nature helps clinicians understand the cause of the condition and provides information regarding whether family members are at risk. It also assists in making informed decisions about family planning and fertility preservation.
The study also suggests that genetic changes in POI are not always limited to ovarian function. Many involved genes are associated with other health conditions, meaning POI may be one feature of a broader clinical condition. Consequently, a genetic diagnosis can reveal other health risks, helping clinicians decide if a patient requires additional evaluation or long-term monitoring.
While causes remain unknown in many cases, researchers say these studies improve the understanding of biological mechanisms underlying infertility. This may eventually lead to more accurate risk assessment, more personalized counseling, and the development of new treatment options.
Photo caption: Researcher Anu Valkna
Photo credit: Lilian Mõttus, University of Tartu
