Diagnostic tools and technologies are rapidly evolving across the world, changing and challenging the way reproductive genetic diagnosis and screening are performed, leading scientists to examine the impact of a variety of DNA and RNA on embryo competence.
Cambridge Healthtech Institute’s Inaugural Reproductive Genetic Diagnostics conference aims to examine the latest advances in next-generation sequencing (NGS) and other technologies, their applications in carrier screening,
preimplantation genetic diagnosis (PGD) and screening (PGS), and product of conception (POC) testing, as well as how other types of DNA are being examined and validated for clinical use. Furthermore, as each country’s laws differ, we must continue
to examine and debate the ethics, efficacy, and implications of preimplantation genetic diagnosis and screening across the world.
WEDNESDAY, 6 APRIL
12:00 – 13:00 Registration
13:00 Chairperson’s Opening Remarks
Bert Smeets, Ph.D., Professor, Clinical Genomics, Mitochondrial Diseases, Maastricht University Medical Center, The Netherlands
» 13:05 KEYNOTE PRESENTATION: 25 YEARS OF CHROMOSOMAL PGD AND COUNTING
Darren K. Griffin, Ph.D., DSc, FIBiol, FRCPath, FRSA, Professor, Genetics,
School of Biosciences, University of Kent, United Kingdom
The talk will chronicle the chromosomal aspects of PGS and its early beginnings, to clinical applications in the last 25+ years. The rise, fall, and rise again of PGS will be covered from a scientific perspective with many a cautionary tale along
the way, and the presentation with conclude with the implementation of novel technologies (such as Karyomapping) for universal PGD.
13:35 Shallow Whole Genome Sequencing is Well Suited for the Detection of Chromosomal Aberrations in Human Blastocysts
Björn Menten, Ph.D., Center for Medical Genetics, Ghent University, Ghent University Hospital,
Recent advances in in vitro fertilization techniques such as vitrification and trophoblast biopsy, as well as the advent of massive parallel sequencing, open up new possibilities for better preimplantation genetic diagnosis and screening. I will discuss
the benefits of day 5 biopsy combined with next-generation sequencing for the detection of aneuploidy and smaller copy number aberrations in human embryos.
14:05 Evaluating PGS in the Laboratory
Sebastiaan Mastenbroek, Center for Reproductive Medicine, Academic
Medical Center, University of Amsterdam, The Netherlands
Rating quality of evidence and grading strength of recommendations are cornerstones of evidence-based medicine. Careful analysis of currently available trials on PGS shows that there is not enough evidence to justify the current use of PGS in routine
14:35 Refreshment Break in the Exhibit Hall with Poster Viewing
15:15 Genetic Counselling Challenges in a Rapidly Evolving Diagnostic Arena: Spotlight on Preimplantation Genetic Screening (PGS)
Karen A. Sage, MSc, GC, Genetic Service Manager, CARE Fertility; The Bridge Centre; The London Women’s
Clinic, United Kingdom
The transitions to Next-Generation Sequencing (NGS) and whole genome amplification (WGA) are leading to increased challenges for clinicians at the front line. How do we discuss these unknowns with the patient/couples undergoing this treatment? How
do we counsel patients prior to embryo transfer and what are we offering patients post transfer? What is the consensus for PGS embryo transfer and follow up? What are the current guidelines and are they appropriate and current? This talk will
illustrate some of the challenges faced by clinicians today offering PGS and PGD in practice.
15:45 Haplarithmis Enables Both Copy Number Profiling and Haplotyping of Single Cells and Improves Preimplantation Genetic Diagnosis
Joris Vermeesch, Ph.D.Ir, Professor, Molecular Cytogenetics and Genome Research, KU
We developed a novel method, enabling concurrent copy number profiling and haplotyping, which improves preimplantation diagnosis. The approach and analysis pipeline, the validation and results from its clinical implementation will be presented.
16:15 Molecular Diagnostic and Reproductive Challenges in mtDNA Disease
Smeets, Ph.D., Professor, Clinical Genomics, Mitochondrial Diseases, Maastricht University Medical Center, The Netherlands
The mitochondrial DNA (mtDNA) is a circular, maternally transmitted multicopy genome, located within the mitochondria Mutations in the mtDNA are a frequent cause of severe metabolic disorders. This presentation will focus on NGS protocols to identify
mtDNA mutations, bioinformatics tools to classify the pathogenicity, and reproductive options, like PGD, to prevent the transmission of mtDNA diseases to future generations.
16:45 Close of Day One
THURSDAY, 7 APRIL
8:30 Registration and Morning Coffee
9:00 Chairperson’s Remarks
Darren K. Griffin, Ph.D., D.Sc., FIBiol, FRCPath, FRSA, Professor, Genetics, School of Biosciences, University of Kent, United Kingdom
9:05 Preimplantation Genetic Diagnosis and Screening: Now and the Future
Simone Palini, Ph.D., Senior Clinical Embryologist, Lab Director, IVF Unit, “Cervesi”
Hospital Cattolica, Italy
Recent works describe the possibility of a non-invasive diagnosis on the blastocoele fluid and culture media, but its use has yet to be demonstrated in the clinic. This talk will discuss the use of PGS for the detection of aneuploid embryos,
due to the presence of mosaicism in the embryo, and to discuss the limits that label an embryo as healthy. The future goal is to complement PGD and PGS with the analysis of other non-invasive matrices.
9:35 The Potential of Extracellular Embryo DNA for Preimplantation Genetic Testing
Luca Galluzzi, Ph.D., Research Fellow, Biomolecular Sciences, School of Biotechnology,
University of Urbino, Italy
Preimplantation genetic diagnosis and screening currently rely on biopsy of one or few embryo cells. To avoid or limit this invasive procedure, the presence of embryo genomic DNA has been evaluated in extracellular matrices such as blastocoele
fluid and embryo culture medium. The potential use of this extracellular DNA in genotyping applications has been then investigated.
10:05 Novel Correlates of Embryo Viability
Gabor L. Kovacs, M.D., Ph.D., DSc, Professor, Laboratory Medicine, Szentágothai
Research Centre of the University of Pécs, Hungary
A novel polpeptide marker was found to differentiate between viable and nonviable embryos during in vitro fertilization. This molecule was identified with MS as the α-1 fragment of human haptoglobin. Further questions are if there is
any correlation between the amount of the haptoglobin fragment in spent embryo culture medium with embryo morphology and cell free nucleic acid release into the medium.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 FEATURED POSTER PRESENTATION: Molecular Analysis of Fetoplacental Discrepancies in Products of Conception (POCS) Obtained by Hysteroembryoscopy
Sandra García-Herrero, Senior Biologist, PGD Molecular
Cytogenetics, Preimplantation Genetic Diagnosis Unit, IGENOMIX, Assistant Professor, Biotechnology of Assisted Human Reproduction Techniques, Valencia University
The analysis of the chromosomal status of POCs (Products of conception) is crucial to determine the cause of sporadic or recurrent pregnancy loss and allows the estimation of the of recurrence risk for future pregnancies. In some cases, chromosomal
abnormalities are confined to the placenta, in rare instances, the placental karyotype can be normal, while fetal cells show an abnormal karyotype. To infer the real incidence of fetoplacental discrepancies, we retrospectively analyzed
results from miscarriages where tissues from both, embryo and trophectoderm were obtained by hystroembryoscopy and analyzed by molecular genetic techniques.
11:45 How the in vitro Environment Shapes Human Preimplantation Embryo Development
Sjoerd Repping, Head, Center for Reproductive Medicine, Academic Medical Center,
University of Amsterdam, The Netherlands
During medically assisted reproduction, preimplantation embryos are exposed to an in vitro environment. This talk will shed light on how this environment affects the competence and development of human embryos, how these effects are mediated
and what the potential consequences of these effects are for MAR success rates and health of offspring.
12:15 Enjoy Lunch on Your Own
14:15 Dessert Break in the Exhibit Hall with Poster Viewing
14:55 Chairperson’s Remarks
Simone Palini, Ph.D., Senior Clinical Embryologist, Lab Director, IVF Unit, “Cervesi” Hospital Cattolica, Italy
15:00 Embryo Development with Regard to Its Chromosomal Status
Olga Chaplia, Embryologist, Cytogeneticist, IVF Laboratory, Medical Centre Reproductive
Genetics Clinic Victoria, Ukraine
As genetic component of embryo significantly affects its implantation capacity, certain developmental patterns may reflect the chromosome status of embryo. The use of proper morphologic criteria indirectly advances selection of euploid embryos
for transfer if genetic testing is not feasible.
15:30 Time-Lapse and PGS: Better Together?
Belén Ramos, Ph.D., Clinical Embryologist, IVF Spain – Alicante, Spain
Some groups suggest markers such as mitochondrial DNA levels in order to select the most viable embryo among the euploid ones. In our PGS program, we hypothesized that time-lapse could be as an additional viability marker to the euploidy in
order to increase implantation. This talk will discuss our findings in a study focused on morphokinetic parameters, including P2 and P3, and how they correlate to blastocyst formation, euploidy, and implantation rates.
16:00 How Has Vitrification Changed Our Practice?
Amelia Rodríguez, MD, Obstetrics and Gynecologist specialized
in ART, Medical Director, Eugin Clinic, Spain
Vitrification of oocytes and embryo has opened up new possibilities for assisted reproduction technology. Increased safety in ovarian stimulation, social and medical fertility preservation, improvement in oocyte donation efficiency, and
the possibility of effectively perform preimplantation diagnosis at the blastocyst stage are some of its main consequences, which will be discussed in detail in this talk.
16:30 Reproductive Genetic Testing: Dynamics and Ethics
Guido de Wert, Ph.D., Professor, Biomedical Ethics, Faculty of Health, Medicine
and Life Sciences, Department of Health, Ethics & Society, Maastricht University, The Netherlands
Reproductive genetic testing, including both screening and diagnosis, and applied in the context of preconception care, medically assisted reproduction and during pregnancy, may help to avoid serious harms and contribute to human welfare.
At the same time, such testing raises substantive and procedural normative questions. What are the proper aims of such testing in these different contexts? Which ethical principles and ethical frameworks should be guiding? And how
to handle possible conflicts between different stakeholders?
17:00 Refreshment Break
17:15 Panel Discussion: The Future of Preimplantation Genetic Diagnostics and Screening: Ethical Implications and Future Prospects
Kosztolányi, Ph.D., President, Human Reproduction Committee of Scientific Health Council, Professor Emeritus, University of Pécs, Hungary
Sjoerd Repping, Head, Center for Reproductive Medicine,
Academic Medical Center, University of Amsterdam, The Netherlands
Juliet Tizzard, Director, Strategy and Corporate Affairs, Human Fertilisation
& Embryology Authority, United Kingdom
Amelia Rodríguez, MD, Obstetrics and Gynecologist specialized
in ART, Medical Director, Eugin Clinic, Spain
Diagnostic tools and technologies are rapidly evolving across the world, changing and challenging the way reproductive genetic diagnosis and screening are performed. We must continue to examine and debate the ethics, efficacy, and implications
of preimplantation genetic diagnosis and screening across the world, as well as keep an eye toward regulatory challenges across Europe and the world.
18:15 Close of Conference