Genetic study explains 12 percent of unexplained ovarian failure cases

Estonian researchers identified a genetic cause in about one in eight women whose premature ovarian insufficiency had previously remained unexplained, ERR reported. The analysis also showed that different types of disease-causing genetic changes could be detected from the same data.

Premature ovarian insufficiency, sometimes referred to as premature menopause, occurs when normal ovarian function is disrupted before the age of 40. It affects an estimated 1 to 3.5 percent of women and can cause menstrual problems and make it more difficult to become pregnant. The condition may also increase long-term health risks, including bone loss and cardiovascular disease.

Anu Valkna, a junior researcher in human genetics at the University of Tartu, said genetic factors play an important role in the development of the condition, although its exact cause remains unknown for many women.

“Premature ovarian insufficiency can have many different genetic causes. Current diagnostics examine several well-known causes through separate tests, so a single test does not always provide a complete picture of a patient’s genetic background. We wanted to find out whether a more comprehensive genetic study could provide more information,” Valkna said.

The study included 51 Estonian women who had previously been diagnosed by doctors with premature ovarian insufficiency of unknown cause. Researchers from the University of Tartu, Tartu University Hospital and East Tallinn Central Hospital used exome sequencing, a method that examines the protein-coding regions of the human genome at the same time.

The researchers analysed 288 genes associated with infertility. Using the same exome data, they also looked for the loss or addition of larger sections of DNA, which are usually examined through separate methods.

Larger DNA changes aided diagnosis

The study found a definite genetic cause in 12 percent of the women whose condition had remained unexplained in earlier examinations. Disease-causing changes were identified both in individual genes and as losses of larger DNA sections. Both types of changes contributed to the diagnosis at a comparable rate.

“This was one of the most important results for us. Searching for larger DNA changes in exome data is not yet routinely used in the diagnosis of premature ovarian insufficiency, but in our study these changes produced a diagnosis as often as disease-causing changes found in individual genes. In other words, some of the necessary information is already available. What matters is knowing how to look for it in the data,” Valkna said.

The likelihood of receiving a genetic diagnosis also depended on how the condition manifested. The research team found a genetic cause more often among women whose menstruation had never started, a condition known as primary amenorrhea, than among women whose ovarian function had later become disrupted.