DEMEESTERE Isabelle

Units

Labo repro

Person in charge of the Unit : Oui

Research work in close relation with reproductive science including Assisted Reproductive Technologies: fertility preservation program, genetic of infertility ; and cryobiology of gametes. The laboratory also develops different aspects of Bioethics and Epidemiology in the reproduction field.

Projetcs

Ovarian tissue cryopreservation and transplantation

Thanks to recent progress in diagnosis and treatment of cancer, relapse-free survival rate has greatly improved over the last decades. Quality of life of young cancer survivors including access to motherhood, became a major issues. Long-term adverse effects of adjuvant treatments potentially include infertility and premature ovarian failure in around 40% of premenopausal patients. Fertility preservation procedures prior to chemotherapy became the main research axis of our laboratory, including clinical trials and fundamental research projects. Since several years, de Research Laboratory on Human Reproduction developed different options in order to preserve fertility of young women with premature ovarian failure due to chemotherapy including cryopreservation of ovarian tissue and transplantation. The Laboratory first set up a ovarian tissue bank in Erasme Hospital in 1999 and became the refence centers for around 15 oncological units. In order to restore ovarian function and fertility, the tissue can be thawed and autotransplanted if premature ovarian failure occurs after treatment. Our laboratory early innovated in this field by obtaining one of the first spontaneous pregnancy and live birth after transplantation of cryopreserved ovarian tissue. However, there are still cases where the transplant remains impossible for the moment. Indeed, in some pathologies with a higher risk of dissemination within organs such as leukemias and non-Hodgkin's lymphomas, the risk of tumor development after grafting remains significant. In other pathologies such as neuro- and medulloblastomas, this risk is not well known. The transplantation of cryopreserved ovarian tissue is not indicated in these cases but unfortunately no alternative is currently available to use this ovarian tissue in order to restore fertility. The laboratory has developed, in collaboration with the Department of Genetics (CUB-Erasme), highly sensitive techniques to allow the detection of these residual cells in the ovarian tissue before transplantation and to ensure its safety.

Center of perinatal epidemiology and epidemiological studies

The center of perinatal epidemiology (CePiP) was created by the initiative of the laboratory and allow to register all births in Wallonie and Bruxelles since January 1st, 2008. Thanks to these data, large epidemiological studies have been done in obstetrics and ART fields. These data were recently compared to data collected at the ''Medical College- ART'' in order to analyze the perinatal health of pregnancies obtained after ART.

Study of mechanisms regulating folliculogenesis

Ovarian tissue cryopreservation is usually proposed to preserve fertility of patients at risk of premature ovarian failure after antineoplastic treatment. At present, ovarian tissue transplantation is the only option to restore fertility using cryopreserved ovarian tissue. However, this procedure has several limitations and the present project aims to develop in vitro follicles culture systems in order to produce embryos from stored ovarian tissue without graft. The procedure has been achieved in mice but is still at the beginning in large mammals and in human. In our laboratory, follicular culture system has been largely studied in mice model and we have now developed research program investigating different aspect of human follicular activation in vitro in order to support follicle growth from primordial follicles to maturity. Recently, research projects focus on the role of PI3K/Akt/mTOR and Hippo pathway in the activation of human or animal follicles in vitro.

Gonadotoxicity and pharmacological protection of the ovaries during chemotherapy

The laboratory has also developed an important clinical research activity in collaboration with oncological centers in Belgium and abroad. The objectives are to study the impact of new therapies on ovarian function and to develop innovative pharmaceutical approaches in order to preserve fertility. The laboratory first investigated the protective effect of Gonadotropin-releasing hormone (GnRHa) administrated during chemotherapy in patients with lymphoma (POF trial- NCT01160315). This study gave the opportunity to the lab to develop a large network of international collaborations and to confirm his expertise in the evaluation of the gonadotoxicity of chemotherapies.
The laboratory currently conduct several academic studies at national and international levels as reference laboratory (POSITIVE NCT02308085 ; AHL-2011 NCT01358747) or as promoter (BROVALE NCT02661932 ; CHANCE NCT02595255 ; fAMHOPE). Many retrospective studies have also been carried out in our laboratory and permit somes publications or TFEs.

Recently, the laboratory developed new project to innovate in the pharmacological ovarian protection. As master regulators of genes transcription, microRNAs showed high potential by regulating transcription and post-transcription of targeted genes involved in fundamental cell functions including cell proliferation and apoptosis. Where miRNAs are used as genes modulators to increase the sensitivity of the neoplasic cells to chemotherapy, they might also be useful to reduce toxicity in healthy cells. By studying the role of miRNAs in follicular response to toxic agents, we aim to find a way to keep follicle healthy at the quiescent stage during chemotherapy.

In addition, the lab is studying the impact of new anticancer treatments on the gonads, and more particularly for patients with a genetic mutation predisposing to breast cancer (BRCA) thanks to the transgenic animal model and the use of the ovarian tissue donated for the research.

In vitro maturation and oocytes vitrification in human: efficiency and clinical implications

This project aims to evaluate and developed in vitro maturation technique and oocytes vitrification to improve the survival rate and the developmental competence of the oocytes after thawing. This project allows to develop alternation to the ovarian tissue cryopreservation procedure to preserve fertility. Ongoing study in human and mice also evaluated the safety and the efficiency of adapted ovarian stimulation protocol using letrozole for breast cancer patients in order to collect and vitrify oocytes by avoiding harmful effect of hormones on tumoral progression during treatment.