Universitair Ziekenhuis Brussel

The UZ Brussel, formerly known as AZ VUB, is the university hospital of the Dutch speaking university in Brussels: Vrije Universiteit Brussel (VUB). The UZ Brussel is worldwide pioneer in the introduction of new assisted reproduction techniques (ART) as well as in the follow-up of children born after ART. The renowned ICSI technique was developed in 1991 at the UZ Brussel and was rapidly worldwide implemented for the treatment of male infertility. The Centre for Medical Genetics of the UZ Brussel is an international leader in setting up longitudinal follow-up studies after assisted conception in order to assess the safety of the newly introduced techniques, including Pre- implantation Genetic Testing (PGT) and In vitro Maturation of oocytes (IVM). Indeed, in the clinic, the health of the offspring born after ART is assessed by a thorough physical examination which is rather unique compared to other centres.

Although children born after ART are healthy, an association between ART and epigenetic disorders has been suspected. The general aim of our research is to gain more insight into the influence of assisted reproductive technologies (ART) on the human epigenome. The approach followed so far, focused on DNA methylation analysis in human gametes and preimplantation embryos.  To further address the role of epigenetics in ART, it is essential to separate an inherited (infertility) epigenetic modification from a secondary one caused by ART factors. Families with ART and non-ART siblings are being recruited from the extensive children follow-up database at our centre; these families had an ART treatment for PGT since they were at risk for a genetic disease. Sample collection in these families will allow to carry out genome-wide epigenetic testing using next generation sequencing technologies. The comparison of the ART and non-ART sibling pairs will allow to separate inherited genetic factors from ART-related factors and to reveal if and to which extend ART factors contribute to epigenetic changes in ART children.

Short biography principal investigator

As one of the few centres worldwide, the UZ Brussel can provide data on the long-term health outcomes of young adults born after ART and more precisely is able to deliver biological samples which is unique. Blood and sperm samples from the worldwide eldest ICSI cohort are available. Also, the UZ Brussel can provide data and salivary samples of PGD, ICSI and IVM offspring in order to describe neonatal health outcomes. Furthermore, given the solid database of ART offspring conceived at the UZ Brussel which includes health parameters of mothers and children, the centre will also play an important role in analysing longitudinal data sets.

Maryse Bonduelle (MD, PhD)

Maryse Bonduelle (MD, PhD)

Former Head of department of Medical Genetics of UZ Brussel

Since the introduction of ART at the UZ Brussel, she has been involved in setting-up all longitudinal follow-up studies resulting in a unique database of health parameters at several time points of all offspring conceived at the UZ Brussel. She is besides a paediatrician, head of the Genetics Department (clinical genetics, molecular genetics and cytogenetics) and has therefore the expertise linking for the consequences of ART practice on future generations through genetic and epigenetic analysis.

Key persons involved

Florence Belva (MD, PhD)

Florence Belva (MD, PhD)

She is a paediatrician and has ten-year experience in the set-up of follow-up projects of different ART techniques including vitrification, ICSI, IVM and PGT. Currently, she is focussing on the worldwide eldest ICSI young adult cohort.

Martine De Rycke (PhD)

Martine De Rycke (PhD)


She is a senior scientist  working as a molecular geneticist supervising the  laboratory of preimplantation genetic diagnosis. Her research interests are in the field of epigenetic safety after assisted reproductive technologies.

Key Research Facility and Equipment

The Centre for Medical Genetics of the University Hospital Brussel has the infrastructure (an outpatient clinic) for examining neonates, children and adults. The laboratory of Medical Genetics is accredited according to ISO 15189. The lab hosts a platform with Next Generation Sequencing and microarray equipment allowing (epi)genetic assays together with bioinformatics tools for analysis of large datasets (Brightcore facility at http://www.brightcore.be/). At the university level, the Centre is within the research group REGE (reproduction and genetics) (https://rege.research.vub.be/en/projects/) which is part of the larger research cluster  Reproduction Genetics and Regenerative Medicine.

Current involvement in Research and Training Programmes

IMAGica: an Integrative personalised Medical Approach for Genetic diseases. Inherited Cardiac Arrhythmias as a model. Nowe A, Bonduelle M, Brugada P, Deschepper R, Lenaerts T, Van Dooren S, De Asmundis C, Gidron Y, Bilsen J, De Couck M. IRP –