A big step in understanding a major cause of infertility in women has been made by a team of scientists led by Professor Evdokia Dimitriadis, from the Department of Obstetrics, Gynaecology and Newborn Health at the University of Melbourne and Royal Women’s Hospital.

Their findings, published in the peer-reviewed journal of the National Academy of Sciences (PNAS), suggest that a tiny molecule present in elevated levels in the uterine lining could play a key role in a person’s ability to fall pregnant.

“This is a very small signalling molecule (miR-124-3p), and what it does, it prevents proteins from being produced,” Prof. Dimitriadis told Neos Kosmos in an interview about this recent breakthrough.

Normally the levels of this molecule are up throughout the menstrual cycle, Prof Dimitriadis continues. But during that very small window of implantation (three to four days in the second half of the menstrual cycle), if it doesn’t get reduced as it is supposed to, the proteins needed are kept low, preventing embryos from attaching and then implanting in the womb successfully.

“We have been able to demonstrate this in pre-clinical models in Melbourne but also in human models, in vitro.

“Up until recently, most of the research has focused on the whole endometrial tissue, but we’ve been able to really focus on the endometrial lining, the site where embryos would attach. We’ve been able to look specifically at those cells, which most of the studies haven’t been able to do, because the technology hasn’t been there.”

The breakthrough comes as the team has been able to develop a new genetic method in the laboratory which closely mirrors what happens in women.

The development of targeted therapies could be a game changer for women undergoing IVF

The Greek Australian researcher is excited to put their findings to the test across several infertility and IVF clinics they collaborate with. The development of targeted therapies to reduce this molecule could be a game changer for women undergoing IVF.

“We want to screen large cohorts of infertile women.”

“By setting up multi-centred trials -which I’m in the process of doing at the moment- we’ll be able to look at other molecules as well, because it could be that this might not be applicable to all women who are infertile. We could identify other factors by using really new technologies that work, as the current technologies have not been proven to work.”

One of the key advantages of this small signalling molecule is that it is released by cells and can be detected in uterine fluid. Hence collecting uterine fluid samples from women at specific times would measure the molecule’s levels when an embryo is meant to implant.

Often, during IVF, even when a high-quality embryo is transferred, implantation fails for unknown reasons. The professor believes their findings could provide insight into what’s wrong with the endometrial lining, allowing for targeted interventions.

“At the time of embryo transfer, we could potentially infuse the uterine cavity with specific proteins, and that would allow embryos to adhere correctly.”

The research, a collaboration with Monash IVF and Monash University, began when Prof. Dimitriadis was at the Hudson Institute of Medical Research.

It’s been a long time coming, she adds.

Prof. Dimitriadis points out that historically, there has been limited investment in women’s health.

“Now governments in Australia and across the world are investing more in this field. It’s in everyone’s interest to focus on women’s health.”

People with endometriosis, for example, often experience infertility, however why remains a mystery, with some theories pointing to ovarian issues, while others suggest problems with the endometrium— which is the focus of her research. These findings could therefore lead to new treatments for endometriosis too, as some of the women with infertility screened also had this condition.

“Taking an individualised approach -which is being done in many diseases- is something we need to be doing in the infertility field. It’s not a one size fits all.

“We want to understand too, what happens in utero, why some babies are born small for example, as it may impact their health later on in life. So, there are huge benefits, to continuing this work.”

As they prepare for trials, the team is also engaging with women who have experienced infertility and undergone IVF, in order to develop a test they would be happy to do, to establish whether they present with high levels of this molecule during the critical window of implantation.

“There are no tests like this available. There’s no other proven method to identify whether the womb can accept a fertilised egg. So, it is very exciting.”