A genetic study revealed the causes behind the side effects of infertility treatment

The results of a study conducted with the participation of researchers from the University of Tartu will enable couples struggling with infertility to be treated more effectively in the future. The researchers found that the progesterone supplements used to promote pregnancy in infertility treatment cause different reactions than expected in patients with polycystic ovary syndrome, including inflammatory effects in uterine mucosal cells.

Infertility affects one in six couples, and the most common problem in women is hormonal abnormalities, which lead to metabolic disorders and irregular menstrual cycles. Abnormalities are in most cases diagnosed as polycystic ovary syndrome (PCOS), in which the release of oocytes from the ovary is severely impaired. PCOS affects 5-13% of all women of childbearing age and accounts for 10-20% of female-related cases that reach an infertility clinic.

The research was published in the journal Scientific Reports of the Nature group, and researchers from the University of Tartu, the Competence Centre on Health Technologies (CCHT), and the University of Oulu participated in the collaboration.

The study found that the lining of the uterus of patients with PCOS, where the embryo attaches, responds differently to the progesterone supplement used to treat infertility than it does compared to a healthy patient’s uterine lining. “Our result shows that the treatment method used currently does not achieve the normal function of uterine mucosal cells at the molecular level. The latter is an important prerequisite for successful embryo attachment and for the pregnancy to be carried to term. This is also supported by the fact that women with PCOS are three times more likely to have an early miscarriage,” explained Marina Loid, a doctoral student of medical sciences at the University of Tartu and a researcher at CCHT.

Alvin Meltsov, a data analyst at CCHT, pointed out that an important discovery was that the progesterone supplement significantly affected inflammatory processes in women with PCOS, as well as other signaling pathways important for cell growth and interaction. “We were surprised to see that cells in women with PCOS behaved differently from cells in healthy women as a result of hormonal treatment. This is a very important result that needs further research to reach its full medical value,” said Meltsov.

For the study, uterine mucosal tissue samples were taken from six patients with PCOS and six healthy women at the University of Oulu Hospital. In the laboratory, cells isolated from samples were treated with three sex hormones that are important for embryo attachment and endometrial maturation. After this exposure, tissue samples were examined for gene expression by sequencing technology, and the results were confirmed by additional laboratory experiments.

“For example, depending on the progesterone supplement used, and the health status of the cell donor, there were changes in the expression of genes responsible for cell mobility and metabolism during mucosal maturation,” added Darja Lavõgina, one of the authors of the study, co-professor of bioorganic chemistry at the University of Tartu.

There is still much potential to help patients with PCOS, both in infertility treatment and in personal medicine in general. “On the one hand, it is clear that the progesterone supplements currently used in infertility treatment or its route of administration are not ideal for patients with PCOS. On the other hand, we urgently need to improve the testing capacity of personal medicine for infertility treatment so that patients with PCOS are also better helped,” one of the leading authors of the study, Professor of Reproductive Medicine at the University of Tartu and Head of CCHT Andres Salumets commented about the next steps.

Additional information: Andres Salumets, Professor of Reproductive Medicine, University of Tartu, 5620 4004, andres.salumets@ut.ee