New findings could help offer future treatments for unexplained infertility

A molecule present in elevated levels in the uterine lining could play a key role in a person’s ability to become pregnant, new findings suggest.

The research, led by Professor Eva Dimitriadis from the Department of Obstetrics, Gynaecology and Newborn Health at the University of Melbourne and Royal Women’s Hospital, could unlock new avenues for targeted treatment and future research into unexplained infertility. It is published in the Proceedings of the National Academy of Sciences.

In the paper, the research team identified that the miR-124-3p molecule was elevated in the uterine lining, called the endometrium, in women with unexplained infertility, potentially contributing to making the endometrium inhospitable to embryo attachment. Before an embryo can implant, the endometrium goes through changes to become receptive to an embryo in a short time window in the menstrual cycle.

Professor Dimitriadis explained that targeted therapies to reduce this molecule could help patients undergoing IVF achieve higher rates of success.

“We found that some women with unexplained fertility have high levels of the molecule called miR-124-3p in their uterine lining,” Professor Dimitriadis said.

“We believe this molecule disrupts the normal function of cells and prevents the embryo from attaching. By identifying dysregulated miR-124-3p levels as a potential cause of embryo implantation failure, we can develop targeted interventions to improve the endometrial lining at the time embryos implant and enhance the chances of successful pregnancy for a significant number of people.”

To validate their hypothesis, the team developed a new way to control the molecule in the uterine lining of mice. When artificially elevated specifically and only at the time the embryos were to implant, the embryos failed to firmly attach and implant.

The study was also undertaken in human cells, where lowering the level of the molecule in endometrial cells in people with problems becoming pregnant made it easier for the embryos to attach. This means that targeting miR-124-3p could become a new way to both diagnose and treat uterine related infertility.

“We demonstrated that we can control this molecule only in the uterine lining of mice during the most important time for embryos to attach. This led to failure of embryo implantation,” Professor Dimitriadis said.

“The study highlights the potential of targeting miR-124-3p as a new way to diagnose and treat infertility related to uterine issues, offering a new direction in this area of research. It could serve as a biomarker to identify women with endometrial-driven infertility.”

Academics from Monash IVF, the Hudson Institute of Medical Research, Monash University, University of Cambridge and Jenderal Soedirman University contributed to this research.