Major genetic defect linked to female infertility identified

Up to 15% of all couples suffer from infertility at some point in their lives. Lack of knowledge about the causes of fertility problems can lead to prolonged clinical testing and extended treatment periods.

A study led by the University of Helsinki used the FinnGen Study cohort to uncover the genetic basis of female infertility. The study is published in The American Journal of Human Genetics.

By comparing over 22,000 women who had received infertility treatments with nearly 200,000 women who had given birth, the research team identified five genetic regions associated with the risk of infertility.

About one in 100 Finns carry the TBPL2 gene defect

The strongest association was found with a genetic defect in a gene called TBPL2. This mutation is more than 40 times more common in Finland than elsewhere in the world. About one in 100 Finns carry this genetic defect.

The TBPL2 gene defect was found to cause infertility only in women who have inherited the non-functional form of the gene from both parents. The genetic defect does not affect male fertility.

“Our results showed that the association of the TBPL2 mutation and the average number of children in women is very clear,” says Sanni Ruotsalainen, lead author of the study, from the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki.

“We can estimate that there are about 400–500 women in Finland with two copies of this gene defect.”

Knowledge of the gene defect could guide infertility treatments

The study also identified other genetic variants associated with infertility in women. These genetic regions have previously been linked either to infertility or to conditions causing it, such as endometriosis and polycystic ovary syndrome, and their impact on infertility risk is smaller than that of the TBPL2 gene defect.

The TBPL2 gene is known to act as a regulator of other genes in the ovaries. It appears that the absence of the correct gene product prevents normal maturation of oocytes.

“Next, we aim to determine if there is a specific characteristic in women who have inherited two copies of the genetic defect that could help identify them during a doctor’s visit. A diagnostic genetic test could be one way to utilize our findings, but first we need more information about prognosis and the most effective treatments,” says FIMM Group Leader Elisabeth Widén who led the study.

“More medical research is needed to better understand the genetic factors associated with infertility and to better assist couples affected by it.”