Maastricht UMC+
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About
Carlos Simón is a Professor of Obstetrics and Gynecology at the University of Valencia (Spain), Senior Lecturer PT, BIDMC Harvard University, USA, and Adjunct Clinical Professor at Baylor College of Medicine, USA. His main clinical and scientific interest focuses on understanding human embryonic implantation, a critical process to the survival of the species, by considering the embryo, the maternal endometrium, and their cross-communication as crucial elements.
Read more on prof. Simón's website.
Abstract
Keynote address: Transformative technologies in reproductive medicine
Recent breakthroughs in genome-wide sequencing (GWS) applications in population diagnostics, including the discovery of microbial communities inhabiting the human body, coupled with the rapid development of artificial intelligence (AI) and automation, these advancements are reshaping the landscape of reproductive medicine.
In this presentation, we review current knowledge and potential development of preconception genome medicine to the couple aiming to conceive, and the periconceptional space now and in the future. The extension of reproductive genetic risk assessment to the general population and IVF couples will lead to the identification of carrier couples of recessive mutations, as well as isolated infertility phenotypes such as complete oocyte immaturity or blastocyst development failure.
Taking an embryo's viewpoint, preconception genome medicine in the periconceptional space is driving significant improvements in IVF laboratories. IVF laboratories are currently increasingly complex, biologically unfriendly, and expensive. Every action performed in the IVF laboratory can be considered an automatable process, whereby bioengineering can avoid contamination of any kind and human error. Integrating, standardizing, and simplifying these systems using automation, AI, and non-invasive genetic analysis through embryo cell free DNA analysis (cfDNA) and smart application-like solutions could enable great progress by crystalizing the 'lab in a box’ concept.
The maternal endometrium can be prospectively investigated before pregnancy for a personalized treatment in our patients. The investigation of endometrial bacterial communities has revealed that the endometrial cavity is not sterile. The presence of a Non-Lactobacillus-dominated microbiota (NLD)(<90% Lactobacilli) or pathogens responsible for chronic endometritis (11) in infertile patients are associated with decrease reproductive outcome in terms of implantation, pregnancy and live birth rates. Endometrial receptivity refers to a hormone-limited period in which the endometrial tissue acquires a functional and transient ovarian steroid-dependent status allowing blastocyst adhesion. Functional transcriptomic studies have revealed that the objective detection of the personalized window of implantation (WOI) is possible. We will update the diagnostic and therapeutic efficiency of ERA in patients with implantation failure (IF), through personalization of the day of embryo transfer (pET).
Delivering a healthy baby—the most important battle for prospective parents—should be won before gestation is even initiated. The convergence of reproductive medicine and obstetrics in the periconceptional space has great potential to unravel the pathologies that have been always impacted women´s reproductive health.
With these cutting-edge advancements, we stand at the forefront of a new era in reproductive medicine, offering hope and possibilities to countless families worldwide.
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Lecture: (Pre)conceptional carrier testing in consanguineous couples
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About
Sonja de Munnik (1984) is a clinical geneticist since 2013. She works in the field of reproductive genetics, including prenatal genetics and preimplantation genetic testing. Since 2021, she works two days a week at the MUMC+ where her field of attention is preimplantation genetic testing. She is a member of the Dutch PGT workgroup at the MUMC+, the only center in the Netherlands licensed to offer PGT. Additionally, she is a member of the steering group and advisory board of PGT Netherlands, a partnership of the MUMC+ with the Centres of Reproductive Medicine of the Amsterdam University Medical Centrum, University Medical Centre Groningen and University Medical Centre Utrecht. Furthermore, she contributes to several research projects in the field of PGT and is involved in updating and developing clinical protocols for PGT.
Lecture: Challenges in reproductive genetic counseling
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About
Guido de Wert is professor of biomedical ethics at the department of Health, Ethics & Society of Maastricht University, Research Schools GROW (oncology and reproduction) and CAPHRI (public health & primary care). His main research interests regard the ethics of reproductive, genomic and regenerative medicine. He was a Crown-appointed member of the Health Council of the Netherlands for many years, chaired the Task Force Ethics & Law of the European Society of Human Reproduction and Embryology (ESHRE), and is a member of the Policy and Ethics Committee (PEC) of the European Society of Human Genetics (ESHG).
Lecture: Reproductive genomic screening: (how to) steer clear of eugenics?
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About
Olga Tsuiko is a PGT specialist at the Reproductive Genetics Unit (Center of Human Genetics) of University Hospital Leuven and a member of the national Belgian PGT consortium. Her research line has mainly been focused on elucidating the nature, mechanistic origin and consequence of aneuploidy in preimplantation development. Currently her activities revolve around implementation of novel technologies for PGT, clinical evaluation and follow up of comprehensive PGT programs, and ethical aspects of PGT, with specific interest in polygenic embryo screening.
Abstract
Comprehensive PGT: from leveraging clinical care to understanding embryo genetics
Developments in genome-wide technologies leveraged the implementation of universal PGT that combines haplotyping and copy number typing across the whole genome. Universal PGT provides diagnosis for any familial monogenic disorder (PGT-M) or structural rearrangement (PGT-SR), and allows for concurrent aneuploidy screening (PGT-A) in PGT-M/SR cycles, all using the same generic protocol and the same biopsy. For this reason, various universal PGT approaches have been developed in the last 2-3 years and are increasingly making their way to the clinic worldwide. In parallel, these assays allow to characterize a wide range of chromosome aberrations across the genome.
In the current talk, I will provide a comprehensive overview on general trends and outcome of universal PGT practice, using the data recorded at UZ Leuven. I will also discuss the prevalence of different chromosome abnormalities throughout preimplantation development – which are being picked up during PGT - and will highlight the different mechanisms by which whole and segmental aneuploidy arises in human embryos.
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About
Joris R. Vermeesch, Ph.D. Ir, is professor Molecular Cytogenetics and genome research, staff member of the center for human genetics Leuven (Belgium), and scientific director of the genomic core facility of the KU Leuven. He is president elect of PGDIS (International Society of preimplantation genetic Diagnosis) and board member of ISPD (International Society of Prenatal Diagnosis).
The laboratory develops and translates novel genomics methods in preimplantation, prenatal and postnatal diagnosis and more recently, cancer testing. We pioneered array CGH, single cell arrays, massive parallel short and long read sequencing and cell free DNA analysis. Those developments have led to new approaches for PGT and NIPT. The group is partner of the SymbioSys, the systems biology center of excellence in computational biology. Prof. Vermeesch has published over 400 publications with an WOS H-index 64 and GS H-index 81.
Abstract
Next-generation liquid biopsy technologies in reproductive medicine
Noninvasive prenatal screening (NIPS) using cell-free DNA has transformed prenatal and preimplantation care. Most NIPS providers detect fetal aneuploidies by measuring sequencing depth. In addition to information on embryonic and fetal aneuploidies, circulating DNA fragments carry information on the contributing cell’s genome, epigenome, and nuclease content. First, I will show how we have applied copy number screening not only to detect rare autosomal and segmental embryonic and fetal aneuploidies, but also to report clinically relevant maternal CNVs and cancer. Second, we demonstrate cfDNA fragmentome patterns harbor copy neutral information about both maternal and fetal health. I will present how (1) NIPT failures are indicative for both maternal and fetal pathologies, (2) unusual fragmentome patterns can be indicative for autoimmune disorders and allow for stratifying high risk pregnancies requiring specialized prenatal care and (3) fragmentome data can be mined to detect other maternal and fetal pathologies.
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About
Erik Sistermans is full professor of Human Genetics and head of the Genome Diagnostics laboratory of Amsterdam UMC. His main research interest is in improving prenatal diagnostics and screening. He studied chemistry in Leiden and obtained his PhD degree in Nijmegen. He is a registered clinical laboratory geneticist since 1994. Erik Sistermans is project leader of the TRIDENT studies which resulted in the implementation of Non Invasive Prenatal Testing (NIPT) in the Netherlands. He is (co)author of more than 140 papers in peer reviewed journals, of international Best Practice Guidelines, editorials and book chapters. He is chair of the scientific advisory board of GenQA and associate editor of the journal 'Extracellular Vesicles and Circulating Nucleic Acids'.
Genoomdiagnostiek voor professionals Amsterdam UMC
Genome Diagnostics Amsterdam UMCLecture: Genome wide NIPT: pitfalls and future developments
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About
Andres Salumets is the professor of reproductive medicine at the Karolinska Institutet (Stockholm, Sweden) and the University of Tartu (Estonia). Andres Salumets and his team focus on solving the translational challenges of reproductive medicine. In his research, over the past few decades, the central goal has been to get a better understanding of the biological processes of endometrial receptivity. These results have provided better insights into the biology of endometrial receptivity and characterised the interactions between implanting embryo and uterus. In addition, previous studies contributed to an improved understanding of aberrant endometrial receptivity in infertility-associated diseases and conditions, like implantation failure, PCOS and endometriosis. His team has also led the development of the beREADY endometrial receptivity test, which is growingly used by European fertility clinics. Recently, he and his colleagues have also been committed to the implementation of non-invasive tools for endometrial receptivity evaluation, by using proteome analysis of uterine fluid and developing the diagnostics based on extracellular vesicles. Along the aforementioned interests, his research involves human preimplantation embryogenesis, pathogenesis of infertility-causing diseases, and the development of non-invasive prenatal screening methods. Andres Salumets is the current president of the Baltic Fertility Society and was a member of the Executive Committee of ESHRE in 2015-2017. He is the founder of the Competence Centre on Health Technologies, the company in Estonia offering IVD CE marked genomic services for infertility and maternity hospitals.
Lecture: Endometrium biology
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About
Alok Javali is an embryologist with expertise in modelling various developmental processes using stem cells. He co-developed human blastoids, efficient and faithful model of early human embryos derived solely from stem cells. He is currently leveraging blastoids to develop molecular screening platform for discovering clinically relevant pathways and targets to improve IVF outcomes and clinical conditions associated with embryo implantation.
Abstract
Blastoids: faithful and predictive model of blastocyst development and implantation
Preimplantation embryonic development and embryo implantation are the biggest roadblocks to successful pregnancy during natural conception as well as during assisted reproduction techniques such as IVF. Developing novel therapeutic interventions to improve implantation, to improve IVF outcomes or women's reproductive health is strongly limited by the lack of knowledge of mechanisms regulating human pre-implantation development. This is especially challenging because of technical and ethical concerns associated with the research on human embryos. To overcome this challenge, we leveraged the wide development potential of human naive pluripotent stem cells to generate structures that are remarkably similar to human blastocysts, which we termed as blastoids. Blastoid formation is robust, efficient and highly scalable. We show that, blastoid formation recapitulates several aspects of embryonic development. Strikingly, blastoids possess potential to interact with hormonally stimulated endometrial cells in highly specific manner recapitulating the first interactions during embryo implantation. The scalability and amenability to screens of blastoids provide an unprecedented opportunity to discover previously unknown mechanisms of embryonic development and implantation and reveal novel therapeutic targets to improve IVF and other peri-implantation clinical conditions.
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About
Ron van Golde is a gynaecologist and currently leading the unit of Reproductive Medicine of the Maastricht University Medical Center. He obtained his PhD on the genetics of male subfertility in 2002 and was trained as a gynaecologist in Nijmegen, Utrecht and Maastricht. His research is focusing on recurrent Implantation failure and reproductive genetics and preimplantation genetic techniques. In his daily practice he hopes to innovate reproductive health care by combining patient care with basic and translational research to find new diagnostic tools and new treatment modalities.
Abstract
Fertility preservation in breast cancer patients
In women, breast cancer is the most commonly diagnosed malignancy. Worldwide, 180,000 women younger than 40 years of age, are annually diagnosed with early-stage breast cancer. Since young age is a poor prognostic factor, (neo)adjuvant chemotherapy is frequently recommended to these women. However, chemotherapy may induce premature ovarian insufficiency and hereby impair fertility. Therefore, it is recommended to counsel women to opt for fertility preservation before undergoing chemotherapy due to these gonadotoxic effects. In this presentation aspects of counseling, safety and genetics will be addressed.
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About
Pauliina Damdimopoulou is senior lecturer in reproductive and perinatal toxicology at the Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, in Stockholm, Sweden. She defended her PhD thesis on dietary polyphenols and estrogen signaling in 2008 at the University of Turku, Finland, and has thereafter carried out postdoctoral studies on androgen signaling within biotech industry in Paris, France, and on early embryo development and ovarian biology at Karolinska Institutet in Stockholm Sweden. She started her independent laboratory, that focuses on the impact of chemicals on ovaries and fertility in women, in 2015. She is the co-coordinator of Sveafertil, the national fertility preservation study for girls and young women in Sweden, and an academic co-leader of the WISE women in science and education network at Karolinska Institutet. She has authored over 60 research papers.
Abstract
Human ovaries at single-cell resolution
Ovaries play a pivotal role in both endocrine health and fertility for women. The fundamental functional units of the ovaries, primordial follicles, form during fetal development and constitute the ovarian reserve. Follicles of the reserve activate to grow continuously, and after puberty, typically, one mature follicle is ovulated each month. However, most follicles die through atresia, and ovaries age prematurely in comparison to other organs. The entire reserve becomes depleted on average around the age of 50, with the quality of ovulated oocytes declining long before that.
Globally, fertility rates are on the decline, while the utilization of assisted reproduction is steadily increasing. Therefore, understanding ovarian function at a cellular and molecular level is becoming increasingly critical. By gaining insights into the effects of factors such as age, medications, diagnoses, and lifestyle on ovarian function, we can design strategies to safeguard fertility, develop more effective infertility treatments, and advance innovations like vitro gametogenesis.
In this talk, I will provide an overview of the current state of single-cell research within the context of human ovaries and its implications.
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About
Susana M. Chuva de Sousa Lopes is Full Professor Human Developmental Biology at the Dept. Anatomy and Embryology, Leiden University Medical Center, the Netherlands and appointed Guest Professor at the Dept. Reproductive Medicine, University Ghent, Belgium. Her lab studies the urogenital system, in particular male and female gametogenesis, but is interested in all the processes that take place during human development. She uses human pluripotent stem cells as model to study aspects of human development. She was awarded the de De Snoo-van’t Hoogerhuijs prize and Aspasia award, is funded by ERC and VICI grants and is the past coordinator of the Special Interest Group “Stem Cells” of the European Society of Human Reproduction and Embryology (ESHRE).
Abstract
Artificial gametes: how far are we from making (mature) human oocytes and sperm cells?
Human gametogenesis is a complex process that we are still far from understanding and even further from mimicking in the laboratory. Oogenesis starts with the specification of primordial germ cells and culminates with the production of mature (metaphase II) oocytes, ready to be fertilized and finally resume meiosis. I will discuss our ongoing efforts to characterize the different stages of human oogenesis at the single-cell (transcriptomics) level and how this framework together with bioengineering technologies, such as the use of microfluids and biomaterials, is contributing to optimize protocols to develop and mature human oocytes from the (fetal and adult) ovary. I will also discuss the progress in male gametogenesis. Moreover, I will present our advances regarding in vitro gametogenesis starting from pluripotent stem cells. Learning how to develop and mature gametes in the laboratory may lead to more effective personalized-therapy for fertility preservation and contribute to the development of an in vitro mini-gonad organoid model to use in human reproductive toxicology and disease modelling.