Speaker BIO:

Françoise Shenfield is a Clinical Lecturer in Obstetrics and Gynaecology at UCH London and UCL Medical School and Honorary Lecturer in Medicine (Medical Law and Ethics). She was a Member of the Human Fertilisation and Embryology Authority (1999-2002)

Clinical activities
She has been involved in the care of infertile couples for 30 years at UCLH and has a special interest in the ethical and legal aspects of reproduction -in particular the European comparative dimension of ART.

Academic activities
She has published over 60 articles and 10 chapters in ethics and law in ART in different books, and co edited 5 books on this specific subject. She is a regular speaker at international meetings, workshops and working groups on ethical dilemmas of ART and Cross border reproductive care issues in particular. She takes part in post graduate teaching at UCL and at international meetings (ESHRE, ASRM, FIGO, national fertility societies).

As a member of the European Society for Human Reproduction and Embryology (ESRHE), she set up a special interest group in medical law and ethics for the Society, and is a founder member of the ESHRE Ethics and Law taskforce which reflects on ethical issues on behalf of the Society; the resulting considerations numbering 22, are on ESHRE’s website (www.eshre.eu). She was a member of its executive committee for 6 years till July 2013, coordinator of its Taskforce for Cross Border Reproductive care, which led to the first international publication of data in the field, and is current coordinator of the Special interest group Socio cultural aspects or (in)fertility (SCAIF),studying oocyte cryopreservation for self use with other European colleagues.

She has been also a member of the ethics committee of FIGO (international federation of Obs. and Gynae. societies) for 15 years, and co-chair of the committee for 3 years. All published ethics considerations are on FIGO’s website (www.FIGO.org).

Overview

If “new (genetic) developments are Challenging the Ethical Framework” (Dondorp), what can be said of the ways they affect our socio-cultural long held concepts, challenged at an exponential speed since the first days of IVF. Both legally and socially societies all over the world are struggling to keep pace with technologies, sometimes reinventing old debates (when/ is the embryo a person, and do you define this legally?; what is “eugenics”?), often having difficulties grasping the science.

We have a responsibility as scientist and practitioners to inform the public plainly of the complex new genetic technologies, in order to obtain (informed) consent, a legal and ethical pre requisite.

We also should seek societal compromise. Indeed societal consensus is historically difficult to achieve contrary to what is hopefully the case in science, as many citizens will be afraid of the possibility of testing for a broad range of anomalies, more or less serious or relevant to quality of life. Furthermore this entails the health of our children and future generations, a common responsibility.

Speaker BIO:

September 1971 - June 1975 Clintonville Senior High School, Clintonville, Wisconsin
September 1975 - May 1979 University of Wisconsin - Stevens Point, Stevens Point, Wisconsin, B.S. (Summa cum Laude) Biology
September 1979 - May 1983 University of Wisconsin Medical School, Madison, Wisconsin, M.D.

Overview

The science and application of gene therapy in reproductive medicine has experienced a tumultuous past but promises to move to the bedside for a growing list of applications. This talk will examine the role of gene therapy for the treatment of reproductive cancers, benign gynecologic conditions such as uterine fibroids or endometriosis, treatment of single gene defects, and someday the instant correction of genetic disorders identified at the time of preimplantation genetic diagnosis. The talk will briefly review the recent UK decision to move forward with the use of “3 parent reproduction” to prevent the transmission of mitochondrial DNA defects.

Speaker BIO:

Pierre Ray did his undergraduate studies in biology at the University of Grenoble. After obtaining an MSc at the University of East Anglia, UK he carried out his PhD at the Hammersmith Hospital in London on preimplantation genetic diagnosis (PGD) under Pr Alan Handyside supervision. Between 1999 and 2003 he developed the molecular diagnostics in the first French PGD centre in Paris. In 2003 he became professor in genetics and reproductive biology at Grenoble teaching hospital. He developed a research program focused on the identification and characterization of genes involved in male infertility. In 2007 he could demonstrate that mutations in the AURKC gene were responsible for the production large headed multiflagelled spermatozoa (macrozoospermia). In 2011 he demonstrated that a homozygous deletion of the DPY19L2 gene was found in most men with globozoospermia, a phenotype characterized by the presence of round spermatozoa devoid of acrosome. In 2014 he showed that mutations in the DNAH1 gene lead to the production of sperm with multiple morphological abnormalities of the flagella (MMAF syndrome). He now pursues his quest for the identification of infertility causing mutations by sequencing patients’ whole coding sequence (exome sequencing). This approach has allowed him to identify 12 new genes that are currently being investigated. The next objective of Pierre Ray’s team is now to develop personalised therapies allowing to replace missing or defective gene products and thus to cure some of the gene defects he identified. Different strategies are being tested in the mouse and clinical trials should be carried out in the near future.

Overview

The success rate following IVF-ICSI has now been stagnating for many years demonstrating the limitation of the whole IVF strategy that is proposed to most infertile patients. Alternative treatments will only be possible with an in-depth comprehension of all aspects of spermatogenesis and of the physiopathology of sperm defects. The basis of this comprehension stems from the identification of the genes involved and of their function. It is estimated that over 1000 genes are involved in spermatogenesis indicating that genetic abnormalities must be a frequent cause of male infertility, yet very few genes defects have so far been identified in man. Due to the increasing availability of exome and soon genome sequencing, the number of indentified genes is poised to explode. This will enable the clinician to have a better comprehension of his patient’s infertility and will help him to adopt the best course of treatment for his patient.

We also believe that male infertility might be among the pathologies that are best suited for targeted protein therapy and we are convinced that restoration of a functional spermatogenesis will be possible by reintroducing a deficient or missing protein as: 1) treatment success can be measured easily and objectively by a mere spermogram, 2) in man spermatogenesis lasts approximately 70 days. This corresponds to the necessary treatment duration to obtain functional gametes which can then be cryopreserved and used at a later date to initiate any number of pregnancies. This relatively short treatment is in sharp contrast with life-long supplementation needed for most other genetic diseases.

I will describe our work which has allowed us to identify over 12 candidate genes for various phenotype of male infertility. I will then describe our first attempts to develop some targeted therapies to compensate for missing of defective gene products.

Speaker BIO:

Early research focussed on preimplantation development of the mouse embryo and involvement in the first attempts to isolate embryonic stem cells directly from mouse blastocysts with Prof Matt Kaufman and Prof Sir Martin Evans. Developed the first transgenic mouse knockout of the HPRT gene using embryonic stem cells as a model of the human X‐linked inherited disease, Lesch‐Nyhan Syndrome. Subsequently joined Prof Lord Robert Winston at Hammersmith Hospital, London and in 1990 achieved the first pregnancies worldwide following in vitro fertilisation (IVF) and preimplantation genetic diagnosis (PGD) of inherited disease. First chairman of the European Society for Human Reproduction and Embryology (ESHRE) Special Interest Group in Reproductive Genetics and co‐founder and first chairman of the ESHRE PGD Consortium. Currently a consultant in preimplantation genetics at the Bridge Centre, London and Embryogenesis, Athens, Principal Scientist, Illumina, Cambridge, Visiting Professor in the Faculty of Biological Sciences, University of Leeds, Leeds and Honorary Professor at the School of Biosciences, University of Kent in Canterbury, UK

Overview

With improvements in blastocyst culture and the development of a minimally invasive method for laser assisted excision of small numbers of trophectoderm cells, blastocyst biopsy is being used increasingly for both preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) for aneuploidy. Nevertheless, polar body biopsy is also minimally invasive and has the advantage that female meiotic errors, a major cause of aneuploidy in later pregnancy, can be identified specifically. The various methods for detecting aneuploidy and the possible applications of polar body testing will be reviewed.

Speaker BIO:

Professor in Reproductive Medicine
Medical school and University-hospital of Montpellier, France

Chair: Reproductive Biology department
Chair: ART/PGD Division at Arnaud de Villeneuve hospital, Montpellier
Head: INSERM U 1203 ' Early embryo development and pluripotency’
Member of national council of AIDS

Research Field:
Gene expression profiles of human cumulus–oocyte complexes, early embryo and endometrial cells, RNA profiles on the genomic scale, and identifying specific transcripts using DNA chips, and Embryo stem cells and hiPS.

Publications in refereed journals: more 150
Books chapters: 50
Books: 10
(Male Gametes: Production and Quality; Epididymis: its Role and Importance in Male Infertility, Male Infertility for Motility Disorders: etiological factors and treatment, Ovocyte et Embryon: de la Physiologie à la Pathologie, Médecine et Biologie de la Reproduction, Médecine et Biologie du Développement).
Invited speaker to national and international scientific meetings: 300

Overview

An enormous amount of knowledge about the human oocyte and CCs have been generated over the last years, due in part to the recent advances in gene expression technologies using microarray, CGH array and high-fidelity RNA amplification.
Numerous small endogenous non-coding transcripts, termed microRNAs (miRNAs), have been found to execute key functions in silencing expression of specific target genes in plant, animal and human systems.

Changes in miRNA expression profiles have been linked to pathologies such as cancer and infertility: female mice with global miRNA deficiency are sterile from several causes, including defects in oocyte function. In addition, the messenger RNA (mRNA) expression in mice and bovine during oogenesis shows that a large proportion of maternal genes are under the control of miRNAs. Thus, miRNA profiling offers an effective means of acquiring novel and valuable information regarding the regulation of transcripts involved in human reproduction.

The miRNAs study of oocyte-cumulus complex offers a promising opportunity, by a non-invasive method, to evaluate ovarian failure and pregnancy outcome

Speaker BIO:

2013- Fellow of the Royal Society for the encouragement of Arts, Manufactures and Commerce (FRSA)
2011- President - International Chromosome and Genome Society (VP from 2008)
2008- Doctor of Science (DSc), University of Manchester
2007- Fellow of the Royal College of Pathologists (FRCPath)
2002- Postgraduate Certificate in Teaching and Learning in Higher Education, Brunel University (PGCertHE)
2001- Editorial Board “Prenatal Diagnosis”
2000- Fellow of the Society of Biology (CBiol, FSB)
1992- Doctor of Philosophy (PhD), Human Genetics, University College London
1988- Bachelor of Science (BSc), Genetics and Cell Biology, University of Manchester

Overview

Counting chromosomes is, in effect, the original PGD in that Bob Edwards detected the Barr body (inactive sex chromosome in females) to sex rabbit preimplantation embryos in 1968. When applied clinically in the early 1990s, following the realization that the oft-lauded Y chromosomePCR based sexing approach would inevitably prove unreliable, attention turned to FISH as a means of selecting female only embryos in families at risk of transmitting sex linked disorders. A highly successful method of FISH sexing using X and Y probes lasted for nearly 20 years. An obvious next step was to target carriers translocation carriers and the subsequent FISH-based approach was only superseded when array-based approaches became commonplace. FISH also persisted from the late 1990s to the mid 2000s and the screening for aneuploidy became the most widespread means of performing PGD. Following the results of randomised trials “PGS” became a buzzword for all that is bad about PGD and, with it, the much-used multicolour FISH (mFISH) based approach fell into disrepute. Array CGH ultimately came to the rescue and the newly badged “PGD-A” now analyses products of polar body or trophectoderm biopsy to great effect. Array CGH is also helping us to understand the fundamentals of early human development and why cleavage stage PGS was such a disaster. An emerging picture of a “fluid” karyotype from cell to cell in early cleavage divisions is emerging, stabilising by blastulation. High-density SNP genotyping takes chromosome counting a step further by detecting phase and parent of origin of the error. Karyomapping uses the outputs of SNP array interrogation, traces parental haplotypes and identifies the independent segregation patterns of parental chromosomes as well as patterns of recombination. This allows simultaneous detection of aneuploidy, uniparental disomy, unbalanced structural rearrangements and, by linkage, the presence of any inherited disease-related monogenic trait. Clinical validation of Karyomapping has been successful and has recently resulted in unaffected live births. The principles of Karyomapping also contain inherent future proofing in that the algorithm is as applicable to next generation sequencing data.

Speaker BIO:

Professor Mark Hughes graduated in Biology and Chemistry from St. Johns University followed by a Masters in Biophysics at Stanford University and a Ph.D. in Molecular Biochemistry at the University of Arizona Medical Center. He continued his training at the Baylor College of Medicine in Houston as a postdoctoral fellow with Bert O’Malley, where his pivotal work was published in Science and Nature and involved the cloning of the vitamin D and progesterone receptors and characterization of the first mutations found in human gene transcription factors. Mutations in the “tips” of zinc fingers of the vitamin D receptor were identified in the DNA of patients with rickets. These were the first mutations identified in any human gene transcription factor. Following this training Hughes completed his M.D. at Baylor, followed by house staff training in Internal Medicine and clinical subspecialty training at Duke University. He then returned as junior faculty to Baylor’s newly formed Genetics Institute led by Thomas Caskey and Arthur Beaudet. Among his accomplishments was the realization that single cells could be molecularly data mined for diagnostic advantage: This led to a multi-year collaboration with reproductive endocrinologists and embryologists at the Hammersmith and UCLondon; the field of Preimplantation Genetic Diagnosis was born. In 1993 Hughes' research was recognized by Science magazine as being one of the "ten most significant advances" in all of science that year; spanning all the physical, biological and mathematical sciences for that year.

It was then that Professor Hughes was recruited to be one of the first 11 members of the Human Genome Institute at NIH. The Genome Project was getting underway and Hughes was recruited to lead the section on Translational Genomic Diagnostics. He also was named chair of Human Genetics at Georgetown University. Doctor Hughes then moved to Michigan to take a position as Professor and Director of Molecular Medicine and Genetics, Professor of OB-Gyn, and Professor of Pathology at Wayne State. He was named as the Director of the State of Michigan’s ‘Life Sciences Genomics Hub’, a joint state-wide project with the University of Michigan and Michigan State University.

Hughes’ work has centered on understanding gene expression in the early human embryo. His work on embryonic stem cells was acknowledged in 2001 when, along with Ian Wilmut (of Dolly the sheep fame) Hughes was awarded the “Pioneer in Stem Cell Biology” award. Professor Hughes, along with Professor Lord Robert Winston and Dr. Alan Handyside developed and performed the world’s first cases of has PGD. As we know, this field is now practiced world wide – today’s speaker continues to push the frontiers of this technology and guide it in all its ethical ramifications, while he has expanded this work to systems-wide molecular understanding of early embryo development. In January he co-authored the first proven somatic cell nuclear transfer involving human somatic cells and oocytes (in other words, these scientists actually did what the South Korean group lied about). His clinical/scientific goal has been to better understand, and hopefully prevent, many inherited birth defects of children. You may have seen him on the two hour BBC special last month. He has appeared on “Good Morning America”, the “Today show”, “CBS Evening News”, and the subject of television newsmagazine segments for 60 Minutes and 20/20, and full hour programs on the Discovery Channel. His PGD work to assist couples avoid serious disease in their children and, at the same time, obtain a stem cell cure for a sick child already in the family, has gained world-wide attention. Most recently, his group has begun a program for patients with inherited neoplasia. Patients (250) undergo fertility preservation with oocyte/embryo genetic analysis prior to cancer treatment. Because of federal funding limitations on embryonic stem cell science, he moved the clinical PGD aspects of his work into the Genesis Genetics Institute where this technology is provided in concert with some 470 human reproductive centres in North and South America, Europe, Africa and Asia.

Speaker BIO:

1987 - 1993
Catholic University Nijmegen, The Netherlands
Student: biology, specialism: medical biology
November 1993 – August 1997
PhD thesis: “Rhesus blood group antigens: from postnatal phenotyping to prenatal genotyping”. (defense: January 9, 1998).
Carried out at the Department of Experimental Immunohematology, CLB (now: Sanguin), Amsterdam, The Netherlands (funded by a grand from Praeventiefonds). Supervisor: prof dr CE van der Schoot.
September 1997 - September 1998:
Postdoc at the department of Experimental Immunohematology, CLB, Amsterdam, The Netherlands.
Supervisor: prof dr CE van der Schoot.
September 1998 – June 2000:
Trainee Laboratory Specialist Clinical Genetics at the department of Cytogenetics, Division of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
June 2000 – October 2002:
Laboratory Specialist Clinical Genetics trainee at the department of Human Genetics, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
October 2002 – present:
Laboratory Specialist Clinical Genetics, registered according to the Dutch rules for laboratory specialists. Mainly specialized in prenatal diagnosis, but also sufficiently experienced in postnatal diagnostics. Expertise in all different molecular and cytogenetic laboratory techniques, such as karyotyping, MLPA, QFPCR, array analysis and NIPT.

Overview

The field of prenatal diagnosis has changed tremendously over the past few years. After karyotyping invasively for many years, Rapid Aneuploidy Detection was introduced , followed by whole genome high resolution array analysis and NonInvasive Prenatal Testing, the latter being carried out on noninvasively obtained material. Moreover, technologies are rapidly advancing and more technological changes are expected in the near future. This presentation will give an overview of the recently introduced molecular tests, with basic principles, advantages and disadvantages.