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The Best Possible Start in Life: The Robust and Responsive Embryo
Progress Educational TrustInstitute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
23 November 2011 - 9.30am-5pm
Speakers and chairs include Dr Virginia Bolton, Professor Daniel Brison, Jane Denton, Professor Bobbie Farsides, Dr Simon Fishel, Professor Alan Handyside, Professor Marilyn Monk, Professor Gudrun Moore, Luciano Nardo, Professor Helen Picton, Anthony Rutherford, Professor André Van Steirteghem, Zoe Williams and Dr Maureen Wood. Lunch and refreshments will be provided on the day. Booking details and the conference agenda are included below. The hashtag to use for all conference-related tweets is #earlyembryo Until the 1978 birth of Louise Brown, the first person to be born following IVF, there was considerable scepticism not only about whether fertilisation could occur in vitro, but also about whether a human embryo could successfully be cultured in the laboratory before being transferred to the mother's uterus. That the embryo can survive in a synthetic culture system testifies to a remarkable robustness. But paradoxically, while the embryo is robust it is also responsive. Advances in fields including embryology, genetics and now epigenetics continue to reveal myriad ways in which the circumstances of the embryo's early development influence not only the likelihood of successful pregnancy and birth, but also the development and health of the resulting child. A growing tendency towards delaying conception has increased both the demand for IVF and the difficulty of improving IVF success rates, which remain relatively low. If success rates are to be improved, and the health of children born via IVF is to be maximised, then several challenges need to be met. Eggs (oocytes) must be produced, retrieved and selected in the optimum way; the embryos that result from fertilising these eggs must be cultured and selected in the optimum way; and transfer to the prospective mother's uterus must take place in the optimum way and at the optimum time. Additionally, if the embryos in question have been frozen and stored (cryopreserved), then they must be cooled and thawed in the optimum way and at the optimum time. Precisely what constitutes the 'optimum' in each of these instances is a subject of considerable debate among clinicians and researchers. This conference will explore, for the benefit of the lay public and professionals alike, contrasting views of how best to assure the success of assisted conception and the health of the embryo, in the context of the latter's robustness and responsiveness. In the PET tradition, following introductory presentations, the bulk of each session's running time will be devoted to discussion with input from the audience. Booking for this conference is now closed. The conference agenda is as follows. 9.30am-10am: Registration 10am-10.15am: Session 1 The Best Possible Start in Life: The Robust and Responsive Embryo 10.15am-11.15am: Session 2 Once created by fertilising eggs in the laboratory, embryos are cultured for between two and six days before being transferred to the mother's uterus. During culture, cleavage (division of cells without significant increase in mass) occurs. If the embryo is transferred as late as the fifth or sixth day of development, then it will have achieved a stage known as the blastocyst, where cells in the embryo first begin to be committed to specialised functions. Deciding upon the optimum culture system to use between fertilisation and transfer involves many complex considerations, and these are multiplied if cryopreserved embryos are used. Should the culture system emulate, as closely as possible, the characteristics of the mother's uterus? Or should we embrace the artificiality of the culture system, and seek to optimise it accordingly? Is it best to culture embryos for a shorter duration or a longer duration before transfer? What should be the composition and temperature of the medium and surrounding air in which embryos are cultured? If freezing is involved, should eggs or embryos be frozen in the conventional (slow) way, or using the ultra-fast method of vitrification? And what are the implications of the culture system for the epigenetics of the embryo and resulting child? Culture Shock Coming in from the Cold Dr Virginia Bolton 11.15am-11.45am: Refreshments 11.45am-1.15pm: Session 3 Selecting embryos for transfer to the mother's uterus is a process that involves grading - judging embryos according to established criteria. These criteria can include the form and structure (morphology) of the embryo and the way this changes over time (morphokinetics), the number of cells present in the embryo, the speed and evenness with which cells cleave, evidence of cells having degenerated, aneuploidy (the absence of chromosomes or the presence of extra chromosomes) in the cells, other types of biological data (which fall into the categories of genomics, transcriptomics, proteomics and metabolomics), and the number of cells that have survived the process of thawing (if the embryo was cryopreserved). Methods used to evaluate embryos against these criteria include microscopy, real-time or time-lapse videography, cell biopsy (removal of cells from the embryo for analysis), fluorescence in situ hybridisation (FISH - a means of detecting the chromosomes and genes of a biopsied cell under the microscope), and profiling the depletion and production of metabolites and nutrients (for example, amino acids). The relative merits of these criteria and methods are a subject of ongoing debate, and are complicated by the fact that most of the cells of the blastocyst will go to make up the placenta and membranes rather than the 'embryo proper'. This means that not all (epi)genetic or other defects in early cells impact upon subsequent development. Selecting Embryos: Can We? Should We? Who Will Benefit? From Personal Genomics to Embryomics: How Far Should We Go? Periconceptual Assessment of Female Reproductive Performance and Individualisation of IVF Treatment Measuring Metabolism: A New Tool for Our Trade? Anthony Rutherford 1.15pm-2.15pm: Lunch 2.15pm-3.30pm: Session 4 The consequences of assisted conception for the embryo's subsequent development, and for the perinatal health of mother and child, are a matter of great concern. Most notably, assisted conception results in a substantially greater chance of multiple birth than natural conception, largely because of the practice of transferring more than one embryo (assisted conception also increases the chance of identical twins resulting from an embryo dividing). Elective single embryo transfer has been promoted as the solution to the risks posed by multiple births, thus raising the challenge of finding ways other than multiple embryo transfer to improve IVF success rates. Then there are the subtler and longer-term consequences of IVF. Fears that IVF babies might go on to have fertility problems have abated, not least because Louise Brown has herself had a naturally conceived and healthy baby. But epigenetics - enduring changes in the pattern of gene activity, during embryo development and beyond, that do not involve alteration of the DNA sequence - may be affected by assisted conception in ways that are as yet poorly understood. For example, genomic imprinting (which, for certain genes, prioritises the activity of the copy from one parent over the activity of the copy from the other parent) is an important epigenetic process whose disruption can lead to congenital disease (including marked learning difficulties). Robust Embryos? Yes - More Than One? No Five Million ART Children Have Been Born – Are They Healthy? Does Assisting Reproduction Disrupt the Imprint? Bobbie Farsides 3.30pm-4pm: Refreshments 4pm-5pm: Session 5 The conference will conclude with a discussion that builds upon the knowledge learned from earlier sessions, and asks whether assisted conception can and should always proceed from a strong evidence base. Is it incumbent upon clinicians to communicate the strength or weakness of the evidence for therapies to patients? What is the difference, if any, between recommending therapies with a weak evidence base and simply making such therapies available? And how do these questions relate to the regulation and cost of fertility treatment? Dr Virginia Bolton Daniel Brison Jane Denton Bobbie Farsides Marilyn Monk Gudrun Moore Anthony Rutherford André Van Steirteghem Dr Maureen Wood Zoe Williams
The 2011 annual conference of the Progress Educational Trust (PET), supported by an unrestricted educational grant from Merck Serono (gold sponsor) and by Ferring Pharmaceuticals (bronze sponsor). Conference sessions include 'Introduction to the Embryo', 'The Embryo's Out-of-Body Experience', 'Making the Grade', 'Growing Concern?' and 'Should Assisted Conception Always Be Evidence-Based?'.Introduction to the Embryo
Marilyn Monk
Emeritus Professor of Molecular Embryology at University College London's Institute of Child HealthThe Embryo's Out-of-Body Experience
Introductions
Daniel Brison
Scientific Director of St Mary's Hospital's Department of Reproductive Medicine, and Honorary Professor of Clinical Embryology and Stem Cell Biology at the University of Manchester's School of Medicine
Dr Maureen Wood
Honorary Research Fellow at the University of Aberdeen's Department of Obstetrics and GynaecologyChair
Cofounder of PET, and Consultant Embryologist at Guy's Hospital's Assisted Conception UnitMaking the Grade
Introductions
Dr Simon Fishel
Managing Director of CARE Fertility, and Founder of the Rachel Foundation
Alan Handyside
Consultant in Preimplantation Genetics and Screening at the London Bridge Fertility, Gynaecology and Genetics Centre, and Visiting Professor of Developmental Biology at the University of Leeds' Faculty of Biological Sciences
Luciano Nardo
Consultant Gynaecologist and Reproductive Surgeon, and Director of GyneHealth, Northwest Fertility and Conceive International
Helen Picton
Professor of Reproduction and Early Development at the University of Leeds' Institute of Genetics, Health and Therapeutics, and Scientific Director of Leeds Teaching Hospitals NHS Trust's Reproductive Medicine UnitChair
Chair of the British Fertility Society, and Consultant in Reproductive Medicine and Gynaecological Surgery at the Leeds Centre for Reproductive MedicineGrowing Concern?
Introductions
Jane Denton
Director of the Multiple Births Foundation
André Van Steirteghem
Emeritus Professor of Embryology and Reproductive Biology at the Free University of Brussels' Centre for Reproductive Medicine, and Editor-in-Chief of Human Reproduction
Gudrun Moore
Professor of Clinical and Molecular Genetics at University College London's Institute of Child HealthChair
Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical SchoolShould Assisted Conception Always Be Evidence-Based?
Speakers
Cofounder of PET, and Consultant Embryologist at Guy's Hospital's Assisted Conception Unit
Scientific Director of St Mary's Hospital's Department of Reproductive Medicine, and Honorary Professor of Clinical Embryology and Stem Cell Biology at the University of Manchester's School of Medicine
Director of the Multiple Births Foundation
Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical School
Emeritus Professor of Molecular Embryology at University College London's Institute of Child Health
Professor of Clinical and Molecular Genetics at University College London's Institute of Child Health
Chair of the British Fertility Society, and Consultant in Reproductive Medicine and Gynaecological Surgery at the Leeds Centre for Reproductive Medicine
Emeritus Professor of Embryology and Reproductive Biology at the Free University of Brussels' Centre for Reproductive Medicine, and Editor-in-Chief of Human Reproduction
Honorary Research Fellow at the University of Aberdeen's Department of Obstetrics and GynaecologyChair
Columnist at the Guardian newspaper
