Speaker BIO:

Francesca Romana Grati Ph.D. is a Biologist, Medical Geneticist, and European registered Clinical Laboratory Geneticists (ErCLG, European Board of Medical Genetics). She is the R&D Director and Head of the Molecular Cytogenetics Diagnostics Unit at TOMA, Advanced Biomedical Assays S.p.A. laboratory (Busto Arsizio, Varese, Italia). She is also Contract Professor at Graduate School of Medical Genetics (University of Milan).

Dr. Grati's special interests are in prenatal diagnosis and fetal genetics. She has published several articles in peer-reviewed journals including Ultrasound in Obstetrics and Gynecology, Prenatal Diagnosis, Genetics in Medicine and contributed to scientific books. She is an invited speaker at national and international scientific meetings and she also serves as a regular reviewer for numerous international journals, including Prenatal Diagnosis, Journal of Translational Medicine, American Journal of Pathology and American Journal of Medical Genetics. Her research is mainly focused on the genetics and epigenetics of placenta, specifically the characterization of fetoplacental mosaicisms and their impact on prenatal cfDNA testing technologies and the understanding of the epidemiology of chromosome abnormalities in prenatal population; she is also committed in the scientific evaluation of new diagnostic technologies, their setup and their laboratory and clinical validations (eg: preimplantation genetic screenings (PGS), chromosomal microarray (CMA), and cfDNA testing).

In 2000 Dr. FR Grati completed her graduation (summa cum laude) in Medical Genetics at University of Pavia in collaboration with the University of Milan (Dept. Medical Genetics, San Paolo Hospital) with a thesis on genetics and epigenetics of head and neck cancers. Thereafter, she trained as a Ph.D. at University of Pavia and, in 2004, she graduated summa cum laude with a thesis on the genetics and epigenetics of intrauterine growth restriction (IUGR) developed in collaboration with the University of Milan (Dept. Medical Genetics, San Paolo Hospital). In 2011 she collaborated with the European Joint Research Community (JRC) on a project for the European harmonization for NIPT technologies and wrote the 'Applied Genomics in the Clinic' Policy Report by the JRC of the European Commission . She is currently active member of the cytogenetics working group of the Italian Society of Human Genetics (SIGU) contributing to the development of the Italian Guidelines on CMA in prenatal diagnosis and on cytogenetics. She is also ISPD, ACMG and ESHG member.

Speaker BIO:

Francesca Romana Grati Ph.D. is a Biologist, Medical Geneticist, and European registered Clinical Laboratory Geneticists (ErCLG, European Board of Medical Genetics). She is the R&D Director and Head of the Molecular Cytogenetics Diagnostics Unit at TOMA, Advanced Biomedical Assays S.p.A. laboratory (Busto Arsizio, Varese, Italia). She is also Contract Professor at Graduate School of Medical Genetics (University of Milan).

Dr. Grati's special interests are in prenatal diagnosis and fetal genetics. She has published several articles in peer-reviewed journals including Ultrasound in Obstetrics and Gynecology, Prenatal Diagnosis, Genetics in Medicine and contributed to scientific books. She is an invited speaker at national and international scientific meetings and she also serves as a regular reviewer for numerous international journals, including Prenatal Diagnosis, Journal of Translational Medicine, American Journal of Pathology and American Journal of Medical Genetics. Her research is mainly focused on the genetics and epigenetics of placenta, specifically the characterization of fetoplacental mosaicisms and their impact on prenatal cfDNA testing technologies and the understanding of the epidemiology of chromosome abnormalities in prenatal population; she is also committed in the scientific evaluation of new diagnostic technologies, their setup and their laboratory and clinical validations (eg: preimplantation genetic screenings (PGS), chromosomal microarray (CMA), and cfDNA testing).

In 2000 Dr. FR Grati completed her graduation (summa cum laude) in Medical Genetics at University of Pavia in collaboration with the University of Milan (Dept. Medical Genetics, San Paolo Hospital) with a thesis on genetics and epigenetics of head and neck cancers. Thereafter, she trained as a Ph.D. at University of Pavia and, in 2004, she graduated summa cum laude with a thesis on the genetics and epigenetics of intrauterine growth restriction (IUGR) developed in collaboration with the University of Milan (Dept. Medical Genetics, San Paolo Hospital). In 2011 she collaborated with the European Joint Research Community (JRC) on a project for the European harmonization for NIPT technologies and wrote the 'Applied Genomics in the Clinic' Policy Report by the JRC of the European Commission . She is currently active member of the cytogenetics working group of the Italian Society of Human Genetics (SIGU) contributing to the development of the Italian Guidelines on CMA in prenatal diagnosis and on cytogenetics. She is also ISPD, ACMG and ESHG member.

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

High resolution array analysis has been introduced in the field of prenatal diagnosis, especially for pregnancies with fetuses at risk for a chromosomal aberration based on ultrasound findings. Results obtained with array analysis can range from normal to clearly pathogenic and explaining the ultrasound anomalies. This presentation, however, will focus on results of which the clinical significance is unclear or uncertain.

Speaker BIO:

Dr. Francesco Fiorentino, is founder and CEO of GENOMA, a private molecular genetics laboratory which is now one of the world's largest, fully integrated, specialized provider of genetics services. Dr. Fiorentino is a molecular biologist, internationally recognized in the fields of reproductive genetics, for its leadership in Preimplantation Genetic Diagnosis (PGD) and for its pioneering work in infertility and genetics. He is also well known as one of the pioneers in the creation of the specialties of reproductive and prenatal genetics and was the impetus behind development of many important concepts and techniques that have become standard in these important fields.

Dr. Fiorentino began his career at the the Italian Police Department- Forensic Science Service (FSS), Rome - Italy, where he spent 3 years performing research and investigation on forensic genetics, coordinating the DNA analysis unit.

Dr. Fiorentino later established GENOMA Laboratory, where he initiated a highly successful preimplantation genetic diagnosis (PGD) program, which has grown exponentially since its inception becoming one of the worldwide leaders in both in quality and volume.

Dr. Fiorentino is actively involved in PGD and the study of human oocytes and embryos, since almost two decades. His laboratory has a strong translational emphasis and is actively involved in the development of new techniques for improving the success rates of in vitro fertilization (IVF) treatment. Dr. Fiorentino’s research also aims to create novel PGD methods that are more comprehensive and more reliable than those in current use.

During his PGD activity, Dr. Fiorentino conceived and implemented the innovation of using Minisequencing technique for mutation detection on single cells, a procedure that is now widely used by most of the PGD centers.

Dr. Fiorentino and his group began clinical trials of array-comparative genomic hybridization (arrayCGH), a comprehensive chromosome screening method, aimed at revealing which of the embryos produced during an in vitro fertilisation (IVF) treatment cycle has the greatest potential for producing a child. The clinical application of this approach has been associated with some of the highest IVF pregnancy rates ever recorded and is now widely practiced worldwide.

Recently, he was responsible for the development and the first clinical application of Next Generation Sequencing (NGS) technology in Preimplantation Genetic Screening (PGS), for reliably screening the entire chromosome complement in embryos.

Dr. Fiorentino research work has been noted for its novelty and has frequently produced advances that have been translated from the research lab into clinical practice. His research has led to the publication of more than 40 peer-review papers and book chapters and has generated a great deal of media interest.

Overview

A significant number of important and large prospective clinical trials on chromosome microarray analysis(CMA) for prenatal testing that have been published recently. The combined data from these studies clearly indicate that, compared with conventional karyotyping, the use of CMA in prenatal diagnosis improves substantially the detection rate of pathogenic chromosomal abnormalities. The higher detection rate by CMA is not confined to cases with abnormal ultrasound findings. The results of the above studies demonstrate the improved diagnostic ability of CMA to detect clinically relevant abnormalities and the utility of bringing CMA into routine prenatal practice as a primary diagnostic tool for a number of other indications.
Findings to date provide substantial evidence for the introduction of CMA as a first-line test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors, with the ultimate goal of improved prenatal diagnosis and a lower risk of giving birth to a chromosomal abnormal neonate.

Speaker BIO:

Vincenzo Cirigliano is based in Barcelona where he heads the Molecular Genetics dept of General Lab-Labco the largest network of clinical laboratories in Spain. Graduated at the University of Naples, he was trained in Genetics at the National Research Council before moving to the Obs&Gyn dept. of University College London. He obtained his PhD cum laude in molecular and cell Biology at the “Universitat Autonoma of Barcelona” where he is now actively involved in Master and PhD programs as well as research projects of basic and clinical cytogenetics.
His main focus is reproductive genetics- prenatal diagnosis, including non invasive prenatal diagnosis using free fetal nucleic acids in maternal plasma and fetal cells from the endorcervical canal. He pioneered development and large scale clinical application of rapid prenatal detection of aneuploidies by QF-PCR and he is experienced in the development and clinical implementation of new molecular diagnostic assays.

Speaker BIO:

Lyn Chitty is in the unique position of being the only UK Professor of Genetics and Fetal Medicine, and was appointed to this chair at the UCL Institute of Child Health in 2009.  She is also Consultant in Fetal Medicine at UCLH NHS Foundation Trust.  She has published extensively on prenatal diagnosis and ultrasound screening of fetal abnormalities, specifically skeletal abnormalities, and was responsible for creating the fetal size standards now in use throughout the UK and beyond.   Her main current research interest is in NIPD and she leads a 5‐year NIHR programme grant (‘Rapid Accurate Prenatal non‐Invasive Diagnosis (RAPID) – an integrated project to refine and implement safer antenatal testing’) which is designed to develop standards for routine implementation of this exciting new technology.  A member of the National Screening Committee on Routine Fetal Anomaly Scanning for some years, she is also an editor of the journal  Prenatal Diagnosis, and on the Board of Directors of the ISPD.  She has recently been appointed Clinical Director of the NIHR Clinical Research Network: North Thames.

Speaker BIO:

Lyn Chitty is in the unique position of being the only UK Professor of Genetics and Fetal Medicine, and was appointed to this chair at the UCL Institute of Child Health in 2009.  She is also Consultant in Fetal Medicine at UCLH NHS Foundation Trust.  She has published extensively on prenatal diagnosis and ultrasound screening of fetal abnormalities, specifically skeletal abnormalities, and was responsible for creating the fetal size standards now in use throughout the UK and beyond.   Her main current research interest is in NIPD and she leads a 5‐year NIHR programme grant (‘Rapid Accurate Prenatal non‐Invasive Diagnosis (RAPID) – an integrated project to refine and implement safer antenatal testing’) which is designed to develop standards for routine implementation of this exciting new technology.  A member of the National Screening Committee on Routine Fetal Anomaly Scanning for some years, she is also an editor of the journal  Prenatal Diagnosis, and on the Board of Directors of the ISPD.  She has recently been appointed Clinical Director of the NIHR Clinical Research Network: North Thames.

Overview

Newly developed non-invasive prenatal diagnosis (NIPD) tests based on analysis of cell free fetal DNA are allowing couples at risk of some single gene disorders to have prenatal diagnosis using a maternal blood test from nine weeks in pregnancy.

In the United Kingdom (UK), NIPD for autosomal dominant conditions such as achondroplasia, thanatophoric dysplasia, and Apert syndrome are now in routine clinical service, as is NIPD for paternal exclusion of cystic fibrosis. NIPD for recessively inherited single gene disorders is more complex as high background level of maternal mutant alleles must be taken into account. Currently the majority of these tests are done using next generation sequencing which is now lending itself to NIPD for recessive disorders such as congenital adrenal hyperplasia. The process by which we have developed these tests and gained approval for use in the UK National Health Service will be described, data relating to patients experience of NIPD will be presented and issues relating to implementation of a prenatal diagnostic service based on NIPD will be discussed.

Speakers BIO:

Howard Stephen Cuckle
UNIVERSITY EDUCATION:
1968-72 Leeds; 1972-76 Oxford, Balliol College and Wolfson College (Graduate Scholar)

DEGREES:
BA (Class 1) Mathematics & Philosophy, Leeds, 1972; MSc Applied Statistics, Oxford, 1976; DPhil Mathematical Logic, Oxford, 1975

THESES:
Models for intuitionistic logic, Oxford, 1975; Maternal serum AFP in pregnancy, Oxford, 1976

PRESENT APPOINTMENTS:
Visiting Associate Professor, Obstetrics and Gynecology, Faculty of Medicine, Tel Aviv University, Israel; 2013-. Adjunct Professor of Obstetrics and Gynecology, Columbia University Medical Center, New York, USA; 2006- Emeritus Professor, University of Leeds, UK; 2006-

Thomas J. Musci, MD
Dr. Musci is board certified in Maternal‐fetal Medicine and Clinical Genetics.   He is a former tenured faculty at the University of California, San Francisco School of Medicine.   He has authored numerous publications in basic science, prenatal diagnosis and clinical genetics.  Currently, Dr. Musci is the Chief Medical Officer of Ariosa Diagnostics, a company specializing in the development of new technologies for prenatal testing.  He has served as chair of the Genetics Committee for the American Congress of Obstetricians and Gynecologists (ACOG), and as a member of the Professional Practice Guidelines Committee for the American College of Medical Genetics (ACMG). He was co‐ founder of San Francisco Perinatal Associates, Inc., and retains an appointment as associate clinical professor with the Department of Obstetrics and Gynecology at University of California, San Francisco (UCSF).

Dick Oepkes
I. Positions and employment
Obstetrician, Head of Fetal Medicine section, Professor, Leiden University Medical Centre, Dept. of Obstetrics

II. Other relevant experience and professional memberships
Prof. Oepkes has been working in the field of prenatal medicine since 1988. He works and conducts research in prenatal screening, prenatal diagnostics, and fetal therapy. Since 2002 he heads the section of prenatal diagnosis in the LUMC. He is the scientific secretary of the Dutch Working group of Prenatal Diagnosis and Therapy, he has occupied the chair of the Regional Center of Prenatal Screening North-South Netherlands, and has been a member of the Dutch Centraal Orgaan of Prenatal Screening, and member of several RIVM committees on prenatal screening. Active member of the International Society for Prenatal Diagnosis (Chairman of Fetal Surgery Special Interest Group), International Fetal Medicine and Surgery Society, Fetoscopy Group. Associate Editor of Prenatal Diagnosis and Fetal Diagnosis & Therapy. Board member of the Dutch Fetal Medicine Foundation. He is co-founder, chairman and an active driving force in the Dutch NIPT consortium.

III. Honors and awards
NIHCD Fellowship Award to join the Perinatal Research Society Banff, Alberta, Canada, September 15-17, 2000
Award for Best Clinical Presentation: ‘Evaluation of simulator-based teaching for invasive perinatal procedures’, 24th Annual Eastern Canada Perinatal Investigators Meeting, Kingston, Ontario November 9-11, 2000
Award for Best Poster Presentation: ‘ Teaching Invasive Perinatal Procedures: Assessment of a High Fidelity Simulator-based Curriculum’. Annual General Meeting of the Association of Professors in Obstetrics and Gynecology. Toronto, Canada December 2, 2000.
Award for Best Fellow Research 2001, Dept. of Obstetrics and Gynaecology, University of Toronto: ‘Teaching Invasive Perinatal Procedures: Assessment of a High Fidelity Simulator-based Curriculum’. 19th Annual Research Day, Toronto, Canada, 11 May 2001
Award of Research Excellence, Society for Maternal Fetal Medicine, for oral presentation of "Minimally Invasive Management of Rh-alloimmunization in Pregnancy: Can Amniotic Fluid

Overview

As primary screening to all patients:
The introduction of non-invasive prenatal testing (NIPT) via cell-free DNA analysis has led to marked increases in the accuracy of screening for Down syndrome and other chromosome conditions compared to standard serum-based screening protocols. Studies have demonstrated sensitivity of >99% and an extremely low FPR (0.1%) for trisomy 21. While early clinical validation studies were focused on enriched patient groups with high risk of aneuploidy, recent studies have demonstrated this same performance in the general screening population. As such, careful consideration is appropriately being given to implementation of this technology both on an individual provider level and as part of a nationwide or public prenatal screening program. Rationale for the offering of NIPT as a first line screening to any woman opting for aneuploidy risk assessment will be discussed.

As contingent screening in very high and intermediate risk patients:
The conventional Combined test has model predicted 85% Down syndrome detection rate for a 5% false-positive rate whilst maternal plasma cell-free (cf)DNA testing has rates of 99.3% and less than 0.14% respectively. However, current costs preclude replacing conventional screening by routine cfDNA screening in public health programs. Contingent cfDNA screening is an affordable compromise protocol restricting cfDNA to those with very high and/or intermediate Combined test risks with or without additional markers. The protocol also helps overcome the relatively high cfDNA test failure rate and retains detection of other disorders (eg NT and cardiac abnormalities) or pregnancy conditions (eg PAPP-A and pre-eclampsia).

Speaker BIO:

Lee P. Shulman MD is the Anna Ross Lapham Professor in Obstetrics and Gynecology and Chief of the Division of Clinical Genetics at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois. He also serves as the Co-Director of the Cancer Genetics Program of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, the Director of the Northwestern Ovarian Cancer Early Detection and Prevention Program and the Medical Director of Reproductive Genetics Innovations and Insight Medical Genetics. Dr. Shulman is also an Adjunct Professor in the Department of Medicinal Chemistry and Pharmacognosy at the University of Illinois at Chicago College of Pharmacy. He is a Fellow of the American College of Obstetricians and Gynecologists and a Founding Fellow of the American College of Medical Genetics.

Dr. Shulman was graduated from Cornell University in 1979 with a BA degree in the College Scholar program. He then attended Cornell University Medical College where he received his Doctor of Medicine degree in 1983. Dr. Shulman completed an internship and residency in Obstetrics and Gynecology at North Shore University Hospital -- Cornell University Medical College in 1987 and served as Chief Resident during his final year. From there he completed a fellowship in Reproductive Genetics at the University of Tennessee, Memphis and then joined the Ob/Gyn faculty of the University of Tennessee, Memphis, becoming the Director of Reproductive Genetics in 1994. In 1999 he relocated to the University of Illinois at Chicago where he was Professor of Obstetrics and Gynecology and Molecular Genetics and Deputy Head of the Department of Obstetrics and Gynecology, Director of the Divisions of Reproductive Genetics and Ambulatory Care Services and medical director of the Center of Excellence in Women’s Health.

Dr. Shulman is a member of numerous regional, national and international organizations that pertain to the health and care of women. His work has been recognized regionally and nationally; most recently, he was again included in the list of ‘‘Top Doctors’’ in Chicago (2007-14) and the United States (2005-14). He is the Editor-inChief of the Yearbook of Obstetrics and Gynecology and Reproductive Medicine, an Editor of the European Journal of Contraception and Reproductive Health, is a Contributing Editor for The Journal of Reproductive Medicine and the Executive Editor of the Journal of Gynecologic Surgery. He also serves on the editorial boards of Prenatal Diagnosis, Contraception, Menopause, Journal of Pregnancy, Climacteric and as a peer-reviewer for 37 other journals. Dr. Shulman served as Chair of the Board of Trustees of the Association of Reproductive Health Professionals from 2006-2008 and has been an examiner for the American Board of Obstetrics and Gynecology since 1999. A frequent contributor to the peer-reviewed and informational literature with over 200 peer-reviewed articles and over 60 book chapters, Dr. Shulman’s major research interests are in reproductive and cancer genetics, contraception, menopause, women’s healthcare advocacy and botanical interventions in women’s health.

Speaker BIO:

I. Positions and employment
Obstetrician, Head of Fetal Medicine section, Professor, Leiden University Medical Centre, Dept. of Obstetrics

II. Other relevant experience and professional memberships
Prof. Oepkes has been working in the field of prenatal medicine since 1988. He works and conducts research in prenatal screening, prenatal diagnostics, and fetal therapy. Since 2002 he heads the section of prenatal diagnosis in the LUMC. He is the scientific secretary of the Dutch Working group of Prenatal Diagnosis and Therapy, he has occupied the chair of the Regional Center of Prenatal Screening North-South Netherlands, and has been a member of the Dutch Centraal Orgaan of Prenatal Screening, and member of several RIVM committees on prenatal screening. Active member of the International Society for Prenatal Diagnosis (Chairman of Fetal Surgery Special Interest Group), International Fetal Medicine and Surgery Society, Fetoscopy Group. Associate Editor of Prenatal Diagnosis and Fetal Diagnosis & Therapy. Board member of the Dutch Fetal Medicine Foundation. He is co-founder, chairman and an active driving force in the Dutch NIPT consortium.

III. Honors and awards
NIHCD Fellowship Award to join the Perinatal Research Society Banff, Alberta, Canada, September 15-17, 2000
Award for Best Clinical Presentation: ‘Evaluation of simulator-based teaching for invasive perinatal procedures’, 24th Annual Eastern Canada Perinatal Investigators Meeting, Kingston, Ontario November 9-11, 2000
Award for Best Poster Presentation: ‘ Teaching Invasive Perinatal Procedures: Assessment of a High Fidelity Simulator-based Curriculum’. Annual General Meeting of the Association of Professors in Obstetrics and Gynecology. Toronto, Canada December 2, 2000.
Award for Best Fellow Research 2001, Dept. of Obstetrics and Gynaecology, University of Toronto: ‘Teaching Invasive Perinatal Procedures: Assessment of a High Fidelity Simulator-based Curriculum’. 19th Annual Research Day, Toronto, Canada, 11 May 2001
Award of Research Excellence, Society for Maternal Fetal Medicine, for oral presentation of "Minimally Invasive Management of Rh-alloimmunization in Pregnancy: Can Amniotic Fluid

Overview

In many countries, non-invasive prenatal testing (NIPT) became available to pregnant women in 2012 or 2013. At first, since only a few laboratories in the USA, China and Germany were able to provide this service, obstetricians after counseling took blood samples and shipped them to these labs. Patients paid the, at first, high costs themselves. In 2014, non-commercial (university) laboratories were able to perform NIPT themselves. National screening programs emerged incorporating NITP, and prices dropped conside