“My objective has always been the same, my patients and their fertility problems, since they are the motivation for my research projects”

The work of Professor Simón Vallés has revealed the relevance of the uterus in the reproductive process, pregnancy and the health of the fetus in the human species.

His research has identified when and how the uterus acquires the state of receptivity that allows embryo implantation, as well as the knowledge of the uterine microbiota in conception and how, on many occasions, the presence of certain germs in the uterus is the cause of a patient not becoming pregnant.

He has discovered and characterized for the first time human endometrial stem cells and introduced their use in clinical practice as cell therapy in Asherman’s Syndrome, a rare pathology that causes infertility.

The clinical translation of his research has allowed him to create new diagnostic tests for endometrial factor that have changed clinical practice internationally.

Madrid, June 14, 2021 – Female infertility hardly holds any secrets for Professor Carlos Simón Vallés, winner of the Lilly Foundation Award for Clinical Biomedical Research 2021, Professor of Pediatrics, Obstetrics and Gynecology at the Faculty of Medicine and Dentistry at the University of Valencia, coordinator of the INCLIVA Reproductive Medicine Research Group and founder of Igenomix. His research in this field has identified a key moment on which the success of conception depends to a great extent and which marks, even, the health of the baby and the baby’s health in adulthood. This is the moment when the embryo implants in the uterine cavity, a moment that Professor Simón Vallés identifies as a dialogue and whose success depends on the endometrium, the tissue that lines the uterine cavity, having very specific molecular and microbiological conditions.

“The research has allowed us to know the characteristics of the uterine microbiota when the embryo reaches the uterus, to understand the dialogue that is established between the embryo and the mother at that moment, just before implantation. We know how the mother’s uterus sends it a series of molecules so that it can implant and how the embryo talks to her to tell her whether it is well or not. We also know how the mother prepares the first layer of the endometrium, which is the epithelium, to indicate to the embryo the most favorable moment for implantation and how, after the initial adhesion, the lower part of the endometrium regulates how deeply it has to invade it”, explains Professor Simón, for whom his patients’ fertility problems are the main motivation for his research projects.

Along these lines, the researcher recognized with the Lilly Foundation Award for Clinical Biomedical Research 2021 declares that assisted reproduction is a “very inefficient” process -only 4 out of every 10 women who undergo one manage to have a baby-, whose success rate improves by 15% when the transfer is planned, that is, when it is carried out at the right time when the endometrial epithelium presents specific molecular conditions which indicate that the mother is receptive. “This is what we have called the transcriptomic signature, the instant at which the 238 genes of the endometrial epithelium are expressed in a certain way,” he explains.

Professor Simón’s work has also revealed the importance of the uterine microbiota in conception and how, on many occasions, the presence of certain germs in it is the cause of a patient’s failure to become pregnant, repeated miscarriages or preterm deliveries. “The genetic revolution allows us to identify existing bacteria. Through a human sample we can distinguish what is human DNA and what is bacterial DNA and, within this, we can know the identity card of all the germs and know if there are bad germs, that is, if we are dealing with dysbiotic microbiota and we must treat them so that a normal pregnancy can take place,” he points out.

Another of the lines of research developed by Professor Carlos Simón Vallés has provided a solution for women affected by Asherman’s syndrome, a rare gynecological pathology that causes adhesions inside the uterine or endometrial cavity, producing a narrowing that leads to embryo implantation problems. The work in the field of cell therapy developed by this scientist has meant an important advance in the approach to this problem. Thanks to his findings, human endometrial stem cells have been characterized for the first time and their use has been introduced into clinical practice as cell therapy to create a new endometrium in those patients who need it.

Studies to evaluate the risk of preeclampsia

On the other hand, Professor Simón has focused his research on preeclampsia, an obstetric condition characterized by high blood pressure in the mother that affects 5% of all pregnancies, with a high impact on the mortality and morbidity of both mother and child. In this regard, these studies have provided evidence that endometrial decidualization resistance is involved in the origin of this disease, offering a new perspective based on the maternal contribution to gestation, with the aim of developing a tool to help patients most susceptible to the disease, to understand the molecular mechanisms of maternal decidualization resistance disorder and its clinical translations, in order to assess the risk and possible treatment of preeclampsia.

“Through a maternal blood test we determine fetal DNA to find out if the fetus is doing well. With our work, what we are trying to do is to develop a test to determine the risk that the mother could have of having preeclampsia. There are several publications on this research, one of them in the scientific journal Proceedings of the National Academy of Sciences (PNAS), which show that when a patient has this disease it is because there is a defect in the maternal endometrium and that by addressing this we could improve obstetric pathologies”, assures Professor Simón Vallés.

Changing international clinical practice

Professor Simón Vallés is a recognized and award-winning national and international expert in Reproductive Medicine. His biomedical research has contributed pioneering work in the study of the human endometrium and its functionality. From the molecular mechanisms that control human endometrial receptivity and its gene regulation, to the discovery of its transcriptomic signature both in whole tissue and at the single cell level. He has identified 6 cell types with specific transcriptomic signatures, as well as the specific functional modifications of the implantation window and the decidualization process. He has also made the first description of the human uterine microbiota, as well as the identification of human endometrial stem cells.

His research has resulted in more than 500 peer-reviewed scientific publications, and his H-index is 113. In addition, he has edited 19 books in English, Spanish and Portuguese, including two recent best sellers. One of these books received the 2018 British Medical Association Medical Book Award in Obstetrics and Gynaecology.

In this regard, the clinical translation of his research has allowed him to create new endometrial factor diagnostic tests, such as Endometrial Receptivity Analysis (ERA) and Endometrial Microbial Metagenomic Analysis (EMMA), which have changed clinical practice internationally. In addition, it has developed cell therapy with autologous endometrial stem cells for the treatment of patients with Asherman’s Syndrome, which has been recognized with the Orphan Drug Designation by the European Medicines Agency (EMA) for this indication.