Premature ovarian insufficiency affects up to 3.5% of women and is an important cause of female infertility. However, in most cases, the underlying cause remains unknown. A recent study by researchers at the University of Tartu showed that a single comprehensive genetic analysis can identify genetic causes in some women whose condition had previously remained unexplained.
Premature ovarian insufficiency (POI) occurs when normal ovarian function becomes impaired before the age of 40. In addition to reduced fertility, POI is associated with poorer bone health, an increased risk of cardiovascular disease, reduced quality of life and a higher risk of premature mortality. Although genetic factors are known to play an important role in the development of POI, the underlying cause remains unknown in most patients, explained Anu Valkna, Junior Research Fellow in Human Genetics at the University of Tartu.
“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,” said Valkna.
To achieve this, the researchers used exome sequencing, a genetic analysis method that sequences the protein-coding regions of the genome. The study included 51 Estonian women with POI for whom routine clinical assessment had not identified an underlying cause. The researchers analysed their exome data to search for both small-scale (single-gene) and large-scale (parts of chromosomes) abnormalities.
The analysis identified a genetic cause in 12% of the women studied, corresponding to approximately one in eight patients whose condition had remained unexplained after previous clinical evaluation. According to Valkna, this demonstrates that broader genetic analysis can provide a diagnosis for some patients whose underlying cause remains unidentified using currently available routine investigations.
“A genetic diagnosis of this kind helps us better understand the cause of the condition and can provide important information about whether other family members may also be at risk. It can also support more informed decisions about fertility preservation and family planning,” Valkna emphasised.
These genetic changes are not necessarily limited to ovarian function. Many of the genes involved have also been associated with other health conditions, meaning that POI may, in some cases, represent one feature of a broader clinical condition. A genetic diagnosis may therefore provide information not only about the cause of POI but also about other potential health risks, helping clinicians determine whether additional evaluation or long-term monitoring is needed.
Although the genetic cause of the condition still remains unknown in many cases, studies like this help better understand the biological mechanisms underlying infertility, and enable more accurate risk assessment, more personalised counselling and the development of new treatment options in the future.
Human Reproduction Open
Observational study
Not applicable
All-in-one exome sequencing approach for genetic testing of unexplained premature ovarian insufficiency
17-Jun-2026
The authors declare no conflicts of interest.