25-26 October Dubai, UAE

Transcription

1 FINAL PROGRAMME AND ABSTRACT BOOK Advanced workshop in embryology October Dubai, UAE

2

3 General information Venue The live educational workshop takes place at the: Towers Rotana Dubai Sheikh Zayed Road PO Box Dubai, U.A.E. Language The official language of the live educational workshop is English. Scientific secretariat Serono Symposia International Foundation Salita di San Nicola da Tolentino, 1/b Rome, Italy Associate Project Manager: Simona Pantaleoni Tel.: +39 (0) Fax: +39 (0) Mobile info@seronosymposia.org Specialist Medical Advisor: Irene Zerbetto Specialist Medical Advisor: Angelo Marino Serono Symposia International Foundation is a Swiss Foundation with headquarters in 14, Rue du Rhône, 1204 Geneva, Switzerland Organising secretariat JLM Consultants Block B, 2nd Floor, 225 Al Attar Centre, Karama Trade Centre Road Dubai, United Arab Emirates P O Box Tel: , Fax: Contact: Rosetta Lobo reservations@jlm-consultants.ae Register to Serono Symposia International Foundation website: follow us on SSIF_RM 1

4 Advanced workshop in embryology Serono Symposia International Foundation live educational workshop on: Advanced workshop in embryology October Dubai, UAE Aim of the live educational workshop Advances in technology require continuous re evaluation of IVF laboratory practice, revision of old techniques and implementation of new methodologies and practices. This live educational workshop aims to provide the attendees with concise and authoritative reviews of new technologies and laboratory practice guidelines. It will also provide an interactive forum for discussion of topics that have been the subject of controversy, including how to provide the optimal laboratory and culture environments for human embryos. The live educational workshop offers an interactive programme with many lectures followed by video sessions and debate on hot topics. The aim is to give participants both the latest knowledge and the opportunity to share their experiences with renowned biologists and embryologists. Learning objectives By attending this live educational workshop the learners will be able to: Recognise new markers of gamete quality Identify new objective criteria for selecting the embryos with the highest implantation potential Assess the best standards for improving quality management in IVF laboratory Target audience This live educational workshop is aimed at scientists and biologists with experience in this field who seek to enhance their knowledge of new technologies. Accreditation Serono Symposia International Foundation ( is accredited by the European Accreditation Council for Continuing Medical Education (EACCME ) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), The CME workshop on: Advanced workshop in embryology held on October 2013 in Dubai, UAE, is designated for a maximum of 7 (seven) hours of European CME credits (ECMEC). Each medical specialist should claim only those credits that he/she actually spent in the educational activity. EACCME credits are recognized by the American Medical Association (AMA) towards the Physician's Recognition Award (PRA). To convert EACCME credit to AMA PRA category 1 credit, please contact the AMA. Serono Symposia International Foundation (SSIF) adheres to the principles of the Good CME Practice Group (gcmep) 2

5 Scientific organiser Robert Fischer Fertility Center Hamburg Hamburg, Germany Scientific co-organisers Alan R. Thornhill Assisted Conception Unit, Guy's Hospital, London, UK Chair, ALPHA, Scientists in Reproductive Medicine Zsolt Peter Nagy Reproductive Biology Associates, Atlanta, Georgia, USA Secretary, ALPHA, Scientists in Reproductive Medicine Serono Symposia International Foundation developed this programme in collaboration with: ALPHA, Scientists in Reproductive Medicine. List of faculty members Thomas Ebner IVF Unit Women s General Hospital Linz, Austria Robert Fischer Fertility Center Hamburg Hamburg, Germany Marcos Meseguer Infertility Institute of Valencia (IVI) Valencia, Spain Karen Turner Oxford Fertility Unit Institute of Reproductive Sciences Oxford Business Park North Oxford, UK Serono Symposia International Foundation developed this programme in collaboration with: ALPHA, Scientists in Reproductive Medicine. We value your opinion! We are continually trying to develop and improve our educational initiatives to provide you with cutting-edge learning activities. Prior and after this live educational event you will be asked to answer an online survey to help us to better tailor our future educational initiatives. We thank you for participating! All Serono Symposia International Foundation programmes are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotional activities are permitted. This programme is made possible thanks to an educational grant received from Merck Serono Middle East. 3

6 Scientific programme October 2013 Friday, 25 October Registration Serono Symposia International Foundation (SSIF) welcome and introduction R. Fischer (Germany) Session I Gamete and embryo evaluation Session II Laboratory technologies: cryopreservation and PGS Chairs: R. Fischer (Germany) - K. Turner (UK) L1: Oocyte quality and stimulation protocols M. Meseguer (Spain) L2: Sperm evaluation: high magnification sperm morphology T. Ebner (Austria) L3: Embryo classification: time-lapse technique M. Meseguer (Spain) Coffee break WG1: Video sessions M. Meseguer (Spain) T. Ebner (Austria) Questions time Lunch Chairs: R. Fischer (Germany) - M. Meseguer (Spain) L4: How to identify embryos with highest implantation potential T. Ebner (Austria) L5: Update on cryopreservation technique T. Ebner (Austria) Coffee break L6: PGS and micro-array CGH technique for embryo biopsy M. Meseguer (Spain) WG2: Case studies M. Meseguer (Spain) T. Ebner (Austria) Questions time End of the first day Legend L : Lecture; : Questions time; WG : Working Group; 4

7 Saturday, 26 October Session III Laboratory setup in IVF centre Chairs: R. Fischer (Germany) - T. Ebner (Austria) L7: Laboratory organization: materials and techniques K. Turner (UK) L8: How to implement QMS in ART K. Turner (UK) Video session on Laboratory organization: materials and techniques K. Turner (UK) Questions time Coffee break Discussion on laboratory Concluding remarks End of the live educational workshop and closing lunch 5

8 Disclosure of faculty relationships Serono Symposia International Foundation adheres to guidelines of the European Accreditation Council for Continuing Medical Education (EACCME ) and all other professional organizations, as applicable, which state that programmes awarding continuing education credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses for pharmaceutical agents, medical devices, and other products (other than those uses indicated in approved product labeling/package insert for the product) may be presented in the programme (which may reflect clinical experience, the professional literature or other clinical sources known to the presenter). We ask all presenters to provide participants with information about relationships with pharmaceutical or medical equipment companies that may have relevance to their lectures. This policy is not intended to exclude faculty who have relationships with such companies; it is only intended to inform participants of any potential conflicts so that participants may form their own judgements, based on full disclosure of the facts. Further, all opinions and recommendations presented during the programme and all programme-related materials neither imply an endorsement nor a recommendation on the part of Serono Symposia International Foundation. All presentations represent solely the independent views of the presenters/authors. The following faculty provided information regarding significant commercial relationships and/or discussions of investigational or non-emea/fda approved (off-label) uses of drugs: Robert Fischer Declared no potential conflict of interest. Marcos Meseguer Declared benefit from a relationship as speaker at Merk Serono Symposia. Karen Turner Declared no potential conflict of interest. The following faculty have provided no information regarding significant relationship with commercial supporters and/or discussion of investigational or non-emea/fda approved (off-label) uses of drugs as of 15 October Thomas Ebner 6

9 Biosketch

10 Biosketch Thomas Ebner IVF Unit Women s General Hospital Linz, Austria Assoc. Prof. Dr. Thomas Ebner graduated with honours from the University of Salzburg, Austria in After his doctorate and postdoctoral thesis, he became a university lecturer in Salzburg and Graz. He has published more than 100 papers and book chapters as first or co-author. His research interests include non-invasive IVF selection processes, andrology, vitrification and culture media. He was certified as a senior clinical embryologist by ESHRE in 2008 and re-certified in Currently, he is Executive Board Member (Treasurer) of ALPHA - Scientists in Reproductive Medicine, head of the Embryological Forum Austria (EFA) and National Representative of Austria in the Advisory Committee of ESHRE. Robert Fischer Fertility Center Hamburg Hamburg, Germany Robert Fischer is Founder and Medical Director of the IVF unit at the Hamburg Fertility Center, one of the largest and leading German IVF centres. In July 1998 the Fertility Center of Hamburg was one of the first centres in Germany and worldwide to introduce certified quality management according to the ISO In 2002 the IVF laboratory was ISO certified. Prior to this he was Medical Director of the first outpatient IVF unit in Hamburg. Author of numerous publications in national and international scientific journals and books, as well as lectures at conferences worldwide, Dr Fischer is an active member of the American Society of Reproductive Medicine, founding member of the European Society of Human Reproduction and member of its advisory committee as well as founding member of the AG Gynäkologische Endokrinologie und Fortpflanzungsmedizin and Berufsverband Reproduktionsmedizinischer Zentren, both in Germany. 8

11 Marcos Meseguer Infertility Institute of Valencia (IVI) Valencia, Spain Marcos Meseguer received his PhD (Obstetrics and Gynaecology) and MD from the University of Valencia, Spain, and a masters degree in Research Methods, Design and Statistics from Universidad Autónoma de Barcelona, Spain. From 2000 to 2004, Dr Meseguer served as Co-Director of the Andrology Laboratory at the Instituto Valenciano de Infertilidad (IVI) and is currently a Senior Embryologist in the IVF unit of IVI Valencia. Dr Meseguer is a member of various scientific societies and has received the prize paper of the Society of Reproduction and Infertility (American Society of Reproductive Medicine), three times the Lalor Foundation International Award from the American Society of Andrology, and twice the research award from the Spanish Society of Fertility. The primary areas of his research are embryology, male infertility and assisted reproduction in HIV/VHC serodiscordant couples. As Principal Investigator, his work has been funded through 10 projects sponsored by the Spanish Government and the Valencian Government, including two EUREKA projects (granted to high-quality technological projects) supported by the European Community. He is currently Statistics Assessor and Scientific Updater of IVI Valencia, and Associate Professor of the Master in Biotechnology from the University of Valencia. Dr Meseguer has published over 85 articles and 40 reviews or book chapters, and made more than 250 presentations at national and international congresses. Karen Turner Oxford Fertility Unit Institute of Reproductive Sciences Oxford Business Park North Oxford, UK As an experienced embryologist, Karen joined Oxford Fertility Unit to lead the laboratory team in The Unit now performs over 2000 cycles per annum. Previously, Karen has lead laboratory teams at both Sheffield Fertility Centre and Burton Centre for Reproductive Medicine. Karen is a State Registered Clinical Scientist. She was Chair of the Association of Clinical Embryologists (ACE), the UK professional body for Embryologists, from 2000 to 2003 and was an External assessor on the Training Committee for a number of years. Karen was the first embryologist to sit on the British Fertility Society committee and has previously been an external advisor for the HFEA. She has recently become the first President of the ACE. 9

12 Abstracts

13 L1. Oocyte quality and stimulation protocols Marcos Meseguer Infertility Institute of Valencia (IVI), Valencia, Spain Evaluation of gametes and embryos in vitro has improved greatly over the past 20 years. Classical assessment has been supplemented by evaluation of several additional morphological characteristics that allow prediction of the developmental potential of an oocyte or an embryo and the probability of achieving pregnancy for an infertile couple. Time-lapse observation presents an opportunity for optimising this embryo selection based on morphological grading as well as providing novel kinetic parameters, which may further improve accurate selection of viable embryos. The technological advances in hi-tech research have enabled also non-invasive determination of proteomic and metabolic status of the embryo. Oxygen consumption measurements from oocytes and embryos could be applied routinely in the clinical embryology laboratory in order to assess quality, complementing the classical microscope-based methods to select embryos. In this lecture, we present a unique clinical study which combines oxygen consumption measurements with time-lapse imaging of embryo development for human embryos. The study presents - to our knowledge - the largest set of transferred embryos after timelapse analysis and thus a novel opportunity to correlate morphokinetic parameters to implantation and ongoing pregnancy. We have generated and evaluated a tool for the selection of viable embryos based on the exact timing of embryo development events together with morphological patterns by using an automatic time-lapse system to monitor embryo development. The parameters studied have been postulated as new markers of oocyte quality and embryo implantation but also we have observed variations in these markers depending on stimulation protocols and procedures: 1. Oocyte oxygen consumption is being affected by stimulation protocols. 2. The type of protocol used for controlled ovarian stimulation influences embryonic developmental kinetics, but these differences are not reflected in embryo quality, assessed on the basis of cleavage timings. 3. No significant differences in embryo developmental kinetics for any of the gonadotropin regimens evaluated have been observed. An optimal range of gonadotropin dosage and steroid concentrations within embryos can be described, showing relevant differences in developmental dynamics. Time-lapse video system allows us to establish kinetic variations depending on the type and total doses of gonadotropins used for controlled ovarian stimulation. The choice and the total dose of gonadotropin impact serum levels of estradiol and progesterone which influence embryo kinetics. 11

14 L2. Sperm evaluation: high magnification sperm morphology Thomas Ebner IVF Unit, Women s General Hospital, Linz, Austria It has been suggested that an oocyte/embryo s ability to survive to the blastocyst stage and its potential to implant can be improved by selection of a normal spermatozoon with a vacuole-free head. Intracytoplasmic morphologically selected sperm injection (IMSI), for example, allows the observation of live human spermatozoa at high magnification (at least x6300) particularly identifying sperm head vacuoles that are not necessarily seen at lower magnifications. The only prospectively randomised study on sibling oocytes did not show a difference in oocyte fertilisation rate, nor in embryo development between high-magnification IMSI and conventional ICSI. This does not automatically exclude that there are particular subgroup of patients that might benefit from IMSI, but it questions the routine application of IMSI in unselected artificial reproductive technology cases. Furthermore, recent evidence indicates that large as well as smaller vacuoles are not cavities within the sperm head. Instead vacuoles appear to be superficial thumbprint-like structures that are not related to linked DNA damage but to failure of chromatin condensation. To summarize, IMSI may not be required for patients who produce high-quality semen. 12

15 L3. Embryo classification: time-lapse technique Marcos Meseguer Infertility Institute of Valencia (IVI), Valencia, Spain The efforts aimed at improving pregnancy rates have focused on the search for additional markers of viability to supplement current criteria for embryo selection. Time-lapse technology represents a powerful tool in assisted reproduction techniques evaluating embryos from a dynamic point of view. Standard methods of embryo assessment are based on subjective morphology evaluation at discrete time points, limiting the information for selecting embryos. Time-lapse is based on especially designed instruments which take images of the embryos every min automatically, without removing the embryos from the incubator to minimise manipulation. This also provides additional information to the embryologist, who is able to evaluate embryos from a dynamic point of view and study the exact timings of some important parameters of embryo development. We are presenting the largest set of transferred embryos after time-lapse analysis and thus a novel opportunity to correlate morphokinetic parameters to implantation and ongoing pregnancy. We have been able to analyse how chromosomal abnormalities may condition embryo morphokinetics too. Nowadays, a hypothesis has been developed in an attempt to elucidate whether time-lapse monitoring system together with embryo selection by morphokinetics is able to improve reproductive outcome. This presentation details what is known about time-lapse imaging, providing an overview of the advantages and applications of this technology as well as reviewing some of the most important studies published by our group in this field. 13

16 L4. How to identify embryos with highest implantation potential Thomas Ebner IVF Unit, Women s General Hospital, Linz, Austria High frequencies of embryo demise prior to the blastocyst stage indicate that the current embryo selection procedures are ineffective. Time-lapse assessment introducing morphokinesis would certainly provide a more powerful tool. Applying solely morphological criteria, however, might be helpful if used properly. In detail, assessment of syngamy and time of first cleavage provides first predictive power. The following days of preimplantation development symmetry of blastomeres, degree of fragmentation, presence of bi- and multinucleation and beginning of compaction not only allow for prediction of blastulation but also of implantation. Two rare phenomena were shown to negatively influence developmental speed and outcome of treatment: planar clover-like shapes and ovoid embryos In general. It has been hypothesised that later stages of embryo development had higher sensitivity and specificity in the prediction of implantation. These observations suggest that there is an additional value in assessing blastocyst development for the prediction of embryo potential. It is very likely that in the near future time-lapse imaging will more or less replace static morphological observation. 14

17 L5. Update on cryopreservation technique Thomas Ebner IVF Unit, Women s General Hospital, Linz, Austria Hundreds of thousands of healthy human babies have been born from oocytes/embryos/blastocysts that have been cryopreserved by either slow freezing or vitrification techniques. One theoretical limitation of vitrification is that human cells are immersed directly into liquid nitrogen which may expose them to potential contamination by viruses or microbes. Nevertheless a growing number of publications demonstrated that vitrification is as good as, and usually better than, standard slow freezing. Little is known about the effects of these technologies on oocyte and embryo gene expression. Both cryopreservation procedures negatively affected the gene expression profile of human MII oocytes in comparison with controls but vitrification performs significantly better compared with slow freezing. Furthermore, vitrified embryos develop better overnight than slowly frozen embryos, regardless of the number of cells lost. Analysis of metabolism revealed that vitrification had less impact on the metabolic rate of the embryo than freezing, which is reflected in higher survival rate and subsequent development. Successful cryopreservation of blastocysts from the early up to expanded blastocyst stages is also possible using a closed HS device. It has been shown that survival rates in cryopreserved expanded blastocysts could be improved by reducing the fluid content. Vitrification is comparable to slow freezing in terms of preserving follicles in human ovarian tissue. Ovarian stroma had significantly better morphological integrity after vitrification than after controlled-rate freezing. 15

18 L6. PGS and micro-array CGH technique for embryo biopsy Marcos Meseguer Infertility Institute of Valencia (IVI), Valencia, Spain Preimplantation genetic diagnosis (PGD) is offered in many IVF centres to improve the reproductive outcome of specific groups of patients. PGD is used to discard affected embryos in carriers of monogenic diseases and structural chromosome anomalies. Preimplantation genetic screening (PGS) is a variant of PGD applied to the screening of numerical chromosome anomalies in couples with normal karyotype, but with infertility problems. Current indications for PGS are: advanced maternal age (AMA), recurrent miscarriage (RM), repetitive implantation failure (RIF), and severe male factor infertility (SMF). In PGS programmes, the technique most widely employed for the cytogenetic analysis of blastomeres has been fluorescence in situ hybridisation (FISH) for a selected panel of chromosomes. The chromosomes most commonly tested are: 13, 15, 16, 17, 18, 21, 22, X and Y, allowing the detection of 85% of embryo aneuploidies. Using FISH protocols, an improvement in implantation and pregnancy rates has been described in retrospective studies in AMA, SMF and RM patients, whereas their benefit in RIF couples has been more controversial. In recent years, prospective randomised trials (RCT) concluded that PGS should not be recommended in AMA patients. Other authors have argued that there are some important methodological pitfalls in the published RCTs, such us patient inclusion criteria, the embryo biopsy procedure, embryo culture conditions as well as the type of genetic analysis performed. It has been proposed that greater benefits would be achieved if the whole set of chromosomes could be tested. Comparative Genomic Hybridization (CGH) is the option closer to karyotyping, and although it has been applied to clinical practice, the time required for the analysis must be reduced. The best approximation seems to be array-cgh, which would offer the most complete analysis of the embryo, giving information about all 24 chromosomes and extra information that can be customised. At present, aneuploidy screening in trophectoderm biopsies using array analysis for 24-chromosome analysis is offering high pregnancy and implantation rates and the usefulness of PGS is being revisited. In this lecture, we will present current data with a CGH analysis for different indications. 16

19 L7. Laboratory organization: materials and techniques Karen Turner Oxford Fertility Unit, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, UK The planning process of a new laboratory within an IVF unit is crucial to the subsequent successful running and organisation of not just the laboratory but the IVF unit itself due to its central role within the clinical process of IVF. It must meet with local planning and government licensing regulations and must conform to IVF specific certification/accreditation and health and safety requirements. In addition to this, the work flow and personnel flow within the laboratory must be considered so that sub-optimal conditions for gametes and embryos (eg temperature, ph changes etc) are kept to a minimum. Staffing levels and skill mix within the laboratory need to be appropriate for the volume and the type of work performed. On a basic level the laboratory may perform IVF procedures from egg collection through to embryo transfer and perhaps freezing. At a more advanced level, laboratories may perform more complex procedures like embryo biopsy, IVM, IMSI etc. Equipment therefore needs to be fit for purpose eg microscope magnification, type etc and take account of the need to work within a contamination free environment. The equipment within the laboratory will depend on the techniques and procedures performed and it should be appropriately sited within. The materials and equipment used both in the design of the laboratory and the IVF process itself can have a major influence on the subsequent performance of the laboratory. Since the primary objective of an embryologist is to provide a controlled, stress-free environment for gametes and embryos, these factors need to be taken into consideration. These factors may be environmental eg air quality and temperature; physical eg type of incubator or chemical eg culture media. Finally patients need to be fully informed about the processes and procedures that both they and their gametes and embryos will be subjected to. Thus it is important that patients have access to Patient Information sheets that adequately describe the procedures they will be going through, with any associated risks explained. In addition, they should give written consent to these procedures taking place. Both the information and consenting process should take place so that couples have a minimum of 24 hrs to consider the procedures involved and have the opportunity to ask questions. 17

20 L8. How to implement QMS in ART Karen Turner Oxford Fertility Unit, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, UK The introduction of the EU Directive on human tissues and cells in 2006 had a major impact on the functioning of IVF laboratories in the UK as this specifies that a Quality Management System should be in place in all centres offering IVF. The world s largest developer of standards is ISO (International Organisation for Standardisation). Oxford Fertility Unit first obtained its ISO Quality Management certification (ISO 9001:2008) in 2004 and we have been running the Quality Management System ever since with annual ISO inspections. A Quality Management System aims to ensure that an organisation can consistently deliver a product that meets the customer s requirements and enhances their satisfaction. In the case of an IVF Unit this will not only be the care and treatment outcome that patients receive but the service provided to referring GPs and to its own staff. Quality Management covers everything that an organisation does from its management structure, training and standard operating procedures (SOPs) to its reference manuals, reporting forms and the measurement and monitoring of equipment and performance by audit. This talk will give our experience in implementing and running the ISO Quality Management System and the impact it has had on our working practice. It will also explain how we have addressed the specific ISO standards and how we have maintained them. Whilst it was initially a long, hard process for us to go through, we are feeling the benefits and our unit has undergone a dramatic transformation. Documents and forms are now controlled and easily accessible. Staff responsibilities are clearer. Communication has been vastly improved and we now have regular and minuted meetings at all levels. Our existing training standards have been formalised for all areas and we have developed a mechanism for setting, monitoring and achieving specific goals. Finally it has enabled us to constantly monitor our performance through audit and respond to sub-optimal outcomes in our key performance areas. Quality Management is a relatively new concept in IVF but it can be an extremely effective tool in helping to run and improve an organisation. By its very nature, it involves and affects all staff at all levels and therefore understanding Quality Management is relevant to everyone working within an IVF Unit. 18

21 Video session on Laboratory organization: materials and techniques Karen Turner Oxford Fertility Unit, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, UK This session will consist of a series of photographs to support the earlier lecture on this subject in more depth. Laboratory layout and flow of both personnel and gametes/embryos will be demonstrated. The location and use of equipment, both for fundamental IVF procedures as well as more advanced ones will be discussed. Finally, the materials used, both in design and in the IVF process itself, will be shown so that participants can appreciate the importance of the quality of the materials used in order to try to achieve the best results for their patients. 19

22 NOTES

23

24 Improving the patient's life through medical education Serono Symposia International Foundation Headquarters 14, Rue du Rhône Geneva, Switzerland Representative Office Salita di San Nicola da Tolentino 1/b Rome, Italy T +39.(0) F +39.(0) Copyright Serono Symposia International Foundation, All rights reserved.