egg donation Focus on REPRODUCTION The rights and wrongs of l ESHRE news l Sweden: a gold mine of epidemiology l The oncological impact of IVF

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1 A WORK & TURN COVER Focus on REPRODUCTION European Society of Human Reproduction and Embryology // MAY 2011 // The rights and wrongs of egg donation The European Society of Human Reproduction and Embryology Meerstraat 60 Grimbergen, Belgium l ESHRE news l Sweden: a gold mine of epidemiology l The oncological impact of IVF

2 B WORK & TURN EXECUTIVE COMMITTEE Chairman Luca Gianaroli (IT) Chairman Elect Anna Veiga (ES) Members Ursula Eichenlaub-Ritter (DE) Jean-François Guerin (FR) Timur Gürgan (TR) Antonis Makrigiannakis (GR) Carlos Plancha (PT) Françoise Shenfield (GB) Miodrag Stojkovic (RS) Anne-Maria Suikkari (FI) Etienne Van den Abbeel (BE) Jolienke Schoonenberg- Pomper (NL) Veljko Vlaisavljevic (SL) Ex-officio members Joep Geraedts (Past Chairman) Søren Ziebe (SIG Subcommittee) FOCUS ON REPRODUCTION EDITORIAL COMMITTEE Paul Devroey Bruno Van den Eede Hans Evers Joep Geraedts Luca Gianaroli Hanna Hanssen Anna Veiga Søren Ziebe Simon Brown (Editor) Focus on Reproduction is published by The European Society of Human Reproduction and Embryology Meerstraat 60 Grimbergen, Belgium All rights reserved. The opinions expressed in this magazine are those of the authors and/or persons interviewed and do not necessarily reflect the views of ESHRE. MAY 2011 Cover picture: Science Photo Library Focus on REPRODUCTION l Chairman s introduction The last two years have passed in the blink of an eye and now the time has come for me to write my last Chairman s introduction to Focus on Reproduction. In the next issue in September, the picture and words will be those of Anna Veiga; after two years of training as Chairman Elect, she is now poised to take the lead of our Society, and I am sure she will be able to face the challenges which await her and ESHRE in the best possible way. During my term as Chairman several changes have occurred and many interesting projects are still ongoing. The number of members of ESHRE has been steadily increasing and today all continents have a significant representation. Some Task Forces have been disbanded after meeting the objectives for which they were established, while others have been created to deal with new questions related to human reproduction. Scientific studies concerning PGS and reproductive surgery are under way, and collaborations in different fields are being set up to cover emerging areas of interest to our members: training, safety and quality, management... In addition, ESHRE is consolidating its role as privileged interlocutor for governments and EU institutions, and as a collaborating partner in European projects such as in the establishment of effective vigilance and surveillance systems for tissues and cells. Partnerships have been established with other scientific societies, and I am sure they too will lead to the implementation of interesting activities in the near future. These past two years have been extremely intense, sometimes exciting, sometimes tiring, but always requiring concentration and commitment. However, each moment has been important to me and I am honoured to have had the opportunity to represent our Society. I would like to take advantage of this space to thank all those who accompanied me in this journey: members of the Executive Committee, co-ordinators of the SIGs and Task Forces, the editorial boards of our journals, as well as all the many people actively involved in managing our Society. A special thank-you goes to Bruno and all the staff at Central Office, who devote their work and efforts to ensuring the smooth running of ESHRE. What they do every day is extremely precious for all of us. Last but not least, I wish Anna and all members of ESHRE all the very best for the future. Luca Gianaroli ESHRE Chairman CONTENTS NEWS 4 Stockholm preview 6 New Executive Committee members 8 Honorary members Human Reproduction lecture 11 Annual meetings 2013 and ESHRE news 15 Go-ahead for ESHRE PGS trial 16 From Fertility Europe 17 ESHRE certification in embryology 18 The oncological impact of ART 20 From the Special Interest Groups 25 From the Task Forces 30 Chairman s end of term report FEATURES 32 The rights and wrongs of egg donation Guido Pennings considers the controversies from the perspective of a medical ethicist 36 Sweden: a gold mine of epidemiology in reproduction Christina Bergh and Karl Nygren on Sweden s place in ART Focus on Reproduction May

3 ANNUAL MEETING 2011 A four-day smörgåsbord on the menu for Stockholm A packed scientific programme selected from more than 1400 abstracts The final programme for our annual meeting in Stockholm is now confirmed, with 1417 abstracts submitted before the 1st February deadline. And yet again, a wealth of new developments have now been scheduled for free communication, either as oral or poster presentations. The submitted abstracts were arranged in the following categories before review: Category Total Andrology 156 Cross-border reproductive care 10 Developing countries 16 Early pregnancy 74 Embryology (embryo selection) 243 Endometriosis, endometrium, implantation 102 Ethics and law 21 Female (in)fertility 156 Male and female contraception 6 Male and female fertility preservation 58 Paramedical (nursing, laboratory) 30 Psychology and counselling 52 Quality and safety of ART 72 Reproductive endocrinology 232 Reproductive epidemiology 21 Reproductive genetics 84 Reproductive surgery 31 Stem cells 29 Translational research 24 Grand total 1417 All abstracts were reviewed according to our standard procedure of screening and scoring. Screening aims to ensure that abstracts are designated to the correct topic category and to eliminate all submissions of obviously poor quality. Selection for oral and poster presentation was done solely on the basis of scores from three reviewers Venue for ESHRE s 27th annual meeting is the Stockholmsmässan conference centre, no stranger to important medical congresses and just a ten-minute train ride from Stockholm Central station. marking blinded abstracts. The Programme Committee finally selected 254 abstracts for oral presentation from a total of 1004 submitted for oral/poster presentation. As in recent years posters will be presented electronically, but each presenter has also been offered the opportunity of a paper poster. These traditional posters will be presented in the Poster Village, according to special interest subject, as was done last year. Each day, discussion committees will assess the paper posters only, so authors should be prepared for discussion and a brief presentation; the time allocated to each presenting author will be restricted to two minutes only and thereafter three minutes will be available for discussion. Poster discussion schedules will be available in Stockholm. 20 hours of daylight As I look ahead to July it is now the spring equinox in Sweden, with day and night of equal length. When the annual meeting opens on 3rd July there will be no midnight sun in Stockholm (we re too far south!), but the sun does rise at 3:38 and set at So we will have almost 20 hours of daylight. And - as long as the rain keeps away - LOCAL CHAIRMAN KERSTI LUNDIN: A WEALTH OF NEW DEVELOPMENTS SCHEDULED FOR FREE COMMUNICATION. the long Swedish summer evenings are fantastic for sitting out with a drink, and enjoying life go by. Stockholm is indeed a beautiful place to visit in the summer. Hotels are generally of high standard, and a three-star hotel in Sweden is always quite comfortable. Remember that Sweden is not in the euro zone; our currency is the Swedish crown ( kronor ). Now that abstract selection is complete, our programme will provide the usual melting-pot of keynote lectures, debates and oral and poster communication sessions, starting on Sunday with a choice of no fewer than 17 precongress courses arranged by the Special Interest Groups and Task Forces. The Opening Ceremony which follows will formally introduce the meeting and this year s honorary members, Lars Hamberger and Alan Trounson. After the ceremony we will have the chance to mingle in the exhibition area, sustained by refreshment and drinks. The main scientific programme begins on Monday morning (4th July) with two keynote lectures, including the second Human Reproduction journals lecture. The debates are also a recently introduced feature, which this year will once again raise topical and contentious issues: one on the treatment or non-treatment of obese women (starring Mark Hamilton and Wybo Dondorp), and one on payment to gamete donors (starring Herman Tournay and Laura Witjens). Two unique opportunities to rethink your views! We are also looking forward to the historical Total Selected Selected abstracts for oral for poster Spain United Kingdom Italy Japan Netherlands Brazil France Belgium USA South Korea Germany China Sweden Where from? Selected presentations 2011 lecture on Tuesday, another innovation from last year. Also on Tuesday will be the congress party at the stunning Vasa Museum, where on display is the fully intact 17th century warship which sank on her maiden voyage in This is a place to recommend, even if you don t go to the party. Although Stockholm is - by Swedish standards - a big city, it is quite concentrated and easy to navigate. Most of the hotels on ESHRE s booking list are situated near the Central Station, where the train for the congress centre leaves. The station for Stockholmsmässan is at Älvsjö, the third stop (nine minutes) after Central Station. All registered participants will receive a four-day pass (Sunday to Wednesday) for the local transport system. Kersti Lundin Local organising committee Awards on offer in Stockholm Six awards, each with a prize of 2000 euro, will be available in Stockholm, with an additional presentation selected for the Fertility Society of Australia exchange award. Special committees will make the selection for each award. l Basic Science Award for oral presentation, sponsored by Merck-Serono. l Clinical Science Award for oral presentation, sponsored by Schering-Plough. l Basic Science Award for poster presentation l Clinical Science Award for poster presentation l The Fertility Society of Australia Exchange Award, sponsored by Cook l The Exchange Award for Nurses l The ART Laboratory Award technician, sponsored by Labotect GmbH This year s congress party will take place at the Vasa Museum on the Stockholm waterfront. This year marks the 50th anniversary of the Vasa s salvage. The ship sank on her maiden voyage in 1628, and is today the only fully preserved 17th century vessel. 4 Focus on Reproduction May 2011 Focus on Reproduction May

4 ANNUAL MEETING 2011 // GENERAL ASSEMBLY // Selected candidates for new membership of the Executive Committee End of term for five members of ESHRE s Executive Committee General Assembly to ratify seven new nominations With five members of ESHRE s present Executive Committee due to stand down in Stockholm having served two two-year terms, replacements have been nominated for ratification at this year s Annual General Assembly held during the annual meeting. Leaving the ExCo will be Jean Francois Guérin (FR), Timur Gürgan (TR), Carlos Plancha (PT), Françoise Shenfield (GB) and Veljko Vlaisavljevic (SL). Françoise Shenfield will continue in an ex officio capacity as the new Co-ordinator of the Special Interest Group & Task Force Sub-committee following the completion of Søren Ziebe s two-year term of office. Timur Gürgan will become Deputy Co-ordinator. Finnish gynaecologist Juha Tapanainen will become Chairman Elect of ESHRE in Stockholm, and will take over as Chairman in As a clinician, Tapanainen continues the ESHRE tradition of alternating the discipline of its chairmen between clinical medicine and science. Also rejoining the ExCo as Chairman Elect of the Society will be the Finnish gynaecologist Juha Tapanainen, who, as a clinician, will take over as ESHRE Chairman in 2013 from the embryologist Anna Veiga. Anna herself will become Chairman in Stockholm, when Luca Gianaroli concludes his term of office. Juha Tapanainen already has strong experience in ESHRE administration. He was a member of the ExCo from 2001 to 2005, while at the same time a member of the Society s Finance Sub-committee. He was also a Deputy Co-ordinator of the SIG Reproductive Endocrinology from 2007 to He has also had active committee roles with the International Federation of Fertility Societies (IFFS), the ASRM and the Finnish Gynaecology Association. Today, Tapanainen is professor of O&G at Oulu University Hospital, from where his group have reported some of the most influential studies on single embryo transfer in IVF. The nominations for appointment to the ExCo are Carlos Calhaz-Jorge (PT), Jacques De Mouzon (FR), Roy Farquharson (GB), Anis Feki (CH), Niels Lambalk (NL), Milan Macek Jr. (CZ), and Cristina Magli (IT). Their appointments must be ratified by the General Assembly in Stockholm before they take up their positions. The selection of the seven ExCo nominees was completed according to ESHRE s bylaws and Internal Rules. The by-laws (article 11) state that the names of the Chairman, the Chairman-elect, and the members of the Executive Committee will be proposed by the Executive Committee and ratified by the General Assembly of Members. Thus, the power to appoint and dismiss members of the ExCo lies with the General Assembly. The process by which the nominees were selected is also clearly set out in the Internal Rules of ESHRE, whose first draft was approved by the ExCo in These rules, presented as ESHRE s Constitution, provide transparent guidance on the Society s day-to-day operations and on the composition and responsibilities of its many committees and working groups. The rules state that the nominees for new ExCo membership are selected from applications by the ExCo still in office to replace those members whose term will come to an end. The process requires all pre-selected candidates to submit a CV and a statement on how they view their role within the Committee. Candidates are asked to attend an ExCo meeting for presentation of their views and for interview. Each candidacy is discussed by the ExCo in the candidate s absence before a decision is made. The rules additionally state that, while selecting new candidates, the aim should be to maintain a balance within the final composition... between clinicians and basic scientists, male and female. Selection also aims to ensure that those countries comprising ESHRE s greatest membership are represented in the ExCo. The rules, however, add that there cannot be more than one member from the same country in the Executive Committee with the right to vote, unless one of two members from the same country holds the position of Chairman Elect. Carlos Calhaz-Jorge is Head of Gynaecology in the Department of Obstetrics, Gynaecology and Reproductive Medicine of Lisbon University Hospital, Lisbon, Portugal. He is a representative member for Portugal of ESHRE's European IVF Monitoring (EIM) Consortium and a member of the SIG Endometriosis guidelines development group. Jacques De Mouzon is a specialist in the epidemiology of reproduction for INSERM (Institute National de la Santé et de la Recherche Médicale), at the Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris. He is chairman of ESHRE's European IVF Monitoring (EIM) Consortium and a member of the cross-border European study for ESHRE. What we re aiming for in the Executive Committee is quality and fair representation, says current Chairman Luca Gianaroli. We re looking for commitment, experience and ideas, as well as a balance between the disciplines of reproductive science and medicine, the geography of Europe, and the national memberships of ESHRE. We can t always achieve these aims, but they remain our targets. Spanish embryologist Anna Veiga will take over as ESHRE Chairman in Stockholm for a two-year term. Anna has responsibility for research at the Dexeus Institute in Barcelona, and is director of the stem cell bank at the Centre for Regenerative Medicine in Barcelona. Roy Farquharson is Consultant in Obstetrics & Gynaecology at the Liverpool Women's Hospital, Liverpool, UK. With a clinical interest in miscarriage, he was Co-ordinator of ESHRE's SIG Early Pregnancy from 2006 to 2010, and is currently chair of the Association of Early Pregnancy Units UK. He is an associate editor of Human Reproduction Update. Anis Feki is Chef de Clinique in the Reproductive Medicine Unit, and Director of the Stem Cell Research Laboratory, at Geneva University Hospitals, Switzerland. His research interests are in fertility preservation and pluripotent stem cells in reproductive medicine. He is presently Deputy Co-ordinator of ESHRE's SIG Stem Cells. Niels Lambalk is a gynaecologist and fertility specialist at the VU University Medical Center (VUmc), Amsterdam, the Netherlands. He is chair of the Dutch Infertility Registry Foundation, and an associate editor of Human Reproduction. He was a member of the local organising committee for the 2009 ESHRE annual meeting held in Amsterdam. Milan Macek Jr. is Chairman of the Department of Biology and Medical Genetics at Charles University, Prague, Czech Republic, and President of the European Society of Human Genetics. Professor Macek is national coordinator of Orphanet, an advisor to the Czech EU Council Presidency and an advisor to the European Commission on medical genetics. Agenda of the 2011 Annual General Assembly Cristina Magli is Director of Research and Development of SISMeR in Bologna, Italy. She was certified as an ESHRE Senior Clinical Embryologist in 2008, and is now Co-ordinator of ESHRE's SIG Embryology. She was the first in Europe, for SISMeR, to apply the preimplantation genetic diagnosis of aneuploidy by the FISH technique. To be held on Tuesday 5th July 2011, from to 19.00, at Stockholmsmässan, venue of the 27th annual meeting. 1. Minutes of the last meeting (held in Rome and published in Focus on Reproduction, September 2010) 2. Matters arising 3. Membership of the Society 4. Society activities - Annual meetings - Campus meetings - Special Interest Groups and Task Forces 5. Human Reproduction journals 6. Paramedical Group 7. Financial report 8. Ratification of the new Executive Committee - Juha Tapanainen (FI) to become the new Chairman Elect - Jean Francois Guérin (FR), Timur Gürgan (TR), Carlos Plancha (PT), Françoise Shenfield (GB), Veljko Vlaisavljevic (SL) to step down - Ursula Eichenlaub-Ritter (DE), Antonios Makrigiannakis (GR), Miodrag Stojkovic (RS), Anne-Maria Suikkari (FI), Etienne Van den Abbeel (BE) to be re-appointed for a second term of two years - Carlos Calhaz-Jorge (PT), Jacques De Mouzon (FR), Roy Farquharson (GB), Anis Feki (CH), Niels Lambalk (NL), Milan Macek Jr. (CZ), Cristina Magli (IT) to be appointed as new members 9. Retirement of the Chairman, Luca Gianaroli (IT), and installation of the new Chairman, Anna Veiga (ES) 10. Election of the Honorary Members for Any other business 12. Date of the next Annual General Assembly 6 Focus on Reproduction May 2011 Focus on Reproduction May C INNER

5 ANNUAL MEETING 2011 // OPENING CEREMONY // Two of the real pioneers of IVF chosen for honorary ESHRE membership Awards to Lars Hamberger and Alan Trounson The picture opposite was taken at a Bourn Hall reunion meeting in 1997, and, among the many well respected and well remembered personalities from the IVF Hall of Fame, are both recipients of this year s honorary membership of ESHRE. Standing back right is Alan Trounson from Melbourne, and, centre in the next row, Lars Hamberger from Gothenburg, Sweden. Both they and their distinguished careers need little introduction to ESHRE members. Lars Hamberger The first IVF clinic in the Nordic countries was set up in Gothenburg with Hamberger, and they had responsibility for the region s first IVF birth in Two years later, Hamberger joined ESHRE s formative temporary committee put together by Robert Edwards at the 3rd World Congress of IVF in Helsinki, and it was here too that Hamberger and colleague Matts Wikland described the technique of transvaginal ultrasound scanning for oocyte collection. The technique would revolutionise IVF by finally providing an effective alternative to laparoscopy. Thereafter, the Gothenburg group remained at the sharp end of ART, and were the second in the world (after Brussels) to report term pregnancies with ICSI (in 1993). The group has been similarly influential in the investigation of models for successful implantation (based on uterine epithelial cells) and in the development of culture media consistent with blastocyst formation. This year s honorary ESHRE members: Lars Hamberger, top, and Alan Trounson. Alan Trounson There can be few reproductive biologists more influential than Alan Trounson. He joined the Monash, Melbourne, IVF programme in 1977 and with Carl Wood and colleagues soon thereafter introduced the clomiphene-hmg protocol for ovarian stimulation. Trounson also applied a delay between oocyte collection and insemination to allow the oocytes to complete maturation, which in turn laid the foundations for an ever-improving and repeatable IVF programme in Melbourne. Nine of the world s first ten IVF pregnancies began at Monash. And, as at Bourn Hall, many clinicians and scientists from around the world were trained by the Monash group. The production of multiple oocytes and embryos from the improved procedures developed in Melbourne prompted the development of appropriate freezing techniques, which enabled the preservation of embryos for subsequent use in IVF. It was also from Melbourne that embryo donation was first reported, thereby giving women without ovarian function the chance of parenthood. Trounson s clinical interests progressed to the diagnosis of genetic disease in embryos, and subsequently to the discovery and production of human embryonic stem cells (and their ability to be directed into neurones, prostate and respiratory tissue). In 2008 Trounson became President of the California Institute for Regenerative Medicine in San Francisco, but retains his chair at Monash as Professor of Stem Cell Sciences. // 2011 HUMAN REPRODUCTION JOURNALS LECTURE // Oocyte vitrification set to broaden its scope? Last year s most downloaded paper from HR opens 2011 annual meeting As ever, the scientific programme of this year's annual meeting will open on Monday with two keynote lectures, which, for the second time, include the 'Human Reproduction Journals' lecture. Last year in Rome the inaugural HR lecture attracted one of the biggest audiences of the meeting (and indeed of any ESHRE meeting ever), and this year promises an equally powerful event. Will this be the turning-point at which oocyte cryopreservation begins its journey to the mainstream? The lecture will be presented by Laura Rienzi, laboratory director at the GENERA Centre for Reproductive Medicine in Rome, and based on a randomised non-inferiority trial of fresh versus vitrified MII oocytes performed by her group. 1 The paper had the highest number of full-text downloads during the first six months of publication of all original articles in Human Reproduction between January 2009 and June The study, like so many others on oocyte vitrification, was prompted by Italy's 2004 legislation banning embryo freezing and the insemination of more than three occytes. However, Rienzi makes clear that the implications of this study stretch far beyond Italy: 'This technique is also of paramount importance for fertility preservation, for oocyte donation programmes, and to help overcome ethical issues related to embryo cryopreservation, she said. This was a well designed though not large study - a total of 224 normal MII sibling oocytes randomised to either fresh ICSI or after vitrification and warming. The percentage of good quality embryos was 52% in the fresh group and 52% in the vitrification group; 15 clinical pregnancies were obtained in the vitrification cycles (37.5% per cycle, 38.5% per embryo transfer), with an implantation rate of 20%. Since then, the group has extended the study to a series of 182 ICSI cycles in all of which oocyte vitrification was possible. 2 In those patients who did not become pregnant in the initial fresh cycle, a total of 104 first and 11 second oocyte warming cycles (+ ICSI) were subsequently performed. The ongoing pregnancy rate in the fresh ICSI cycle was 37.4%, in the first vitrification cycle 25%, and in the second vitrification cycle 27%. The overall cumulative ongoing clinical pregnancy rate was found to be 54% per started cycle, with maternal age the only variable found to affect reproductive outcome. Thus, as these cumulative results suggest - as do the authors themselves in their discussion - such progress in the clinical application of oocyte vitrification has implications not just for fertility preservation and oocyte banking for egg donation, but also as a possible alternative to embryo freezing in routine IVF. Despite changes to the law in Italy (which now allow the insemination of more than three oocytes, but with important legal considerations for embryo freezing) Rienzi told Focus on Reproduction that her group continues to limit its supernumerary embryos and to offer oocyte vitrification to all suitable patients - 'with excellent cumulative results'. However, Rienzi would not yet go so far as to see oocyte vitrification as an alternative to embryo freezing in routine IVF. 'The main difference between the two approaches is time to pregnancy,' she said. 'More warming cycles are needed to complete the treatment with vitrified oocytes than with vitrified embryos.' However, Rienzi underlined the value of the technique as a patient insurance against any future cancer treatment. 'The approach is easy, fast, and commercial kits are now available,' she said. 'I cannot imagine how many women affected by malignant diseases or at risk of premature ovarian failure, might benefit. They will be deprived of a child just because the technique has not yet been routinely introduced.' Certainly, as evidenced by the downloads (and s to Rome), interest is considerable - so maybe routine use is not too far away. Other Human Reproduction papers scoring highly as downloads were: l Wennerholm UB, Söderström- Anttila V, Bergh C, et al. Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Hum Reprod 2009; 24: , l Reefhuis J, Honein MA, Schieve LA, et al. Assisted reproductive technology and major structural birth defects in the United States. Hum Reprod 2009; 24: References 1. Rienzi L, Romano S, Albricci L, et al. Embryo development of fresh 'versus' vitrified metaphase II oocytes after ICSI: a prospective randomized sibling-oocyte study. Hum Reprod 2010; 25: Ubaldi F, Anniballo R, Romano S, et al. Cumulative ongoing pregnancy rate achieved with oocyte vitrification and cleavage stage transfer without embryo selection in a standard infertility program. Hum Reprod 2010; 25: Focus on Reproduction May 2011 Focus on Reproduction May C OUTER

6 // PARAMEDICAL GROUP // A paramedic opportunity for hands-on embryo transfer during this year s precongress course The Board of the Paramedical Group is looking to recruit a new English-speaking lab technician to strengthen the team. With a group of four lab technicians, four nurses and one psychologist, we try to give all paramedical members of ESHRE a voice and improve their level of education. Board members are required to attend a board meeting three times a year (once at the annual meeting). It s at these meetings that the paramedical sessions of the annual meeting and Campus courses are planned. The Chair of the paramedical board is a member of the Executive Committee and is therefore well placed to make strong representation for all the paramedical members of ESHRE. Basic training for paramedics Following events in UK (2009) and Spain (2010), in March this year we ran our third two-day basic training course for members and colleagues. Nurses, lab technicians and others new to the field of reproductive health took part. Our enthusiastic speakers provided updates on anatomy and physiology, the causes and diagnosis of infertility, lifestyle factors, counselling and communication, stimulation and treatment techniques. The course took place in the inspiring city of Berlin and was conveniently located near the airport with social events well attended by speakers and delegates. At the end participants could opt for a certificate of attendance or to take part in an exam leading to certification. Learning objectives seemed well achieved, as the vast majority passed their exam and our Berlin delegates are now well equipped for Hands on... Not every moment in Berlin was basic training. Paramedical Board Chair Jolieneke Schoonenberg-Pomper (NL, nurse) Chair Elect Helle Bendsten (DK, lab technician) Past Chair Heidi van Ranst (BE, lab technician) Members Inge Jorgensen (nurse), Eline Dancet (nurse) Helen Kendrew (nurse), Cecilia Westin (lab technician), Patricia Baetens (psychologist) further professional development. Stimulating ideas were exchanged on the inclusion of emotional support in daily clinical care. The next basic training course for paramedicals will be on 24-25th May 2012 in Copenhagen, Denmark. Embryo transfer the theme for Stockholm Our precongress course in Stockholm will focus on embryo transfer. Our embryologist speakers - who include Kersti Lundin and Lynette Scott - will concentrate on the embryo, while others - including Helen Kendrew and Rebecca Goulding - will focus on transfer techniques. Our hands-on session in the afternoon looks very attractive and interesting. All the equipment for an education in the time-lapse assessment of embryos - and for practice in the transfer procedure - will be in place. So we invite you all to enrol for the course and take advantage of these unique practical opportunities. Paramedical Board Annual General Meeting The AGM of the Paramedical Board is also held during the ESHRE annual meeting and the Board encourages all members* to attend in Stockholm. The meeting will take place on Monday 4th July during lunchtime break; we will be pleased to see as many members as possible to discuss our further plans. * You are eligible for ESHRE paramedical membership if you are a nurse, midwife, laboratory technician, ESHRE certified clinical embryologist (BSc level), counsellor or psychologist. Paramedical members currently comprise around 10% of ESHR s full membership. Eline Dancet and Jolieneke Schoonenberg-Pomper ESHRE NEWS // FUTURE MEETINGS // London and Munich selected as venues for 2013 and 2014 annual meetings ESHRE s 29th annual meeting in 2013 will be held in London at the ExCeL convention centre, and the 30th in 2014 at the ICM Munich. These venues have now been confirmed by the Executive Committee. The 2013 event will be the third in the UK, following Cambridge in 1987 and Edinburgh in 1997; 2014 will be a fourth time for Germany, following Bonn in 1985 (ESHRE s first annual meeting), Hamburg in 1995, and Berlin in The ExCeL centre is a modern facility constructed as part of the huge regeneration of London s former docks. Located in the east end of the city, the convention centre is well served by rail and bus links - and the London City airport is only minutes away. This segment of London is also undergoing huge redevelopment for the 2012 Olympics, which are expected to enhance local transport and hotel services even further. The International Congress Centre Munich is one of the most modern and successful congress centres in the world, London and Munich will host ESHRE s 2013 and 2014 annual meetings. with strong experience of international medical meetings. Local organisers and dates for each of the two events have yet to be confirmed by the Executive Committee. ESHRE and ASRM join up for the best of the best ESHRE and the ASRM have agreed to stage a joint annual meeting in which the best of reproductive medicine can be presented in a relaxed scientific environment. The two societies will put their heads and best experience together in a meeting which alternates each year between European and American venues to encourage attendance from both continents. The venues will be selected for their conference facilities and for opportunities to socialise with transatlantic colleagues. The first meeting will be held at the Italian resort of Cortina d Ampezzo on 1-3rd March The three-day meeting will divide its time between scientific lectures and discussion (in the early morning and later afternoon) and recreational activities - hence the emphasis on a socially agreeable venue. The project s mission statement promises that discussion will cover a broad range of reproductive medicine, biology and surgery, with the ultimate goal of enhancing the quality of patient care and improving outcomes, with lectures specifically designed for both practitioners and scientists. Organisation in the first two years will lie in the hands of a scientific committee comprising three ESHRE and three ASRM members - with the second event in 2013 planned for the USA. The ski resort of Cortina d Ampezzo, venue in 2012 for the first best of ESHRE and ASRM spring meeting: an opportunity for learning and recreation. 10 Focus on Reproduction May 2011 Focus on Reproduction May D INNER

7 ESHRE NEWS // EXECUTIVE COMMITTEE // // FINANCE COMMITTEE // Members of ESHRE committees to disclose conflicts of interest ESHRE s Executive Committee has agreed that, from Stockholm onwards, all its officers must complete a conflict of interest disclosure form. Nominees for the next ExCo have already completed the disclosure such that any potential conflicts of interest have been reviewed before ratification at the General Assembly. The ExCo agreed that the following officers would need to complete the form: l All members of the Executive Committee, including ex officio members l All members of the Paramedical Board l All members of sub-committees l All SIG co-ordinators l All Task Force co-ordinators l All chairmen of ESHRE consortia (PGD and EIM) So far, deputy co-ordinators of the SIGs and Task Forces have not been included, though co-ordinators will be asked if their inclusion is considered necessary. From Stockholm onwards, completion of the conflict of interest form will be a first step in the recruitment of any member to an ESHRE committee. The aim of the move, said Past Chairman Joep Geraedts, is to ensure transparency in ESHRE s activities and to make any potential conflicts of interest public - as now happens, for example, with manuscript submission to the journals. Ad adjuvandum evidence submitted by ESHRE after legal advice to the Grand Chamber of the European Court of Human Rights has been deemed inadmissible. The comment was submitted ahead of an appeal by the Austrian authorities against a European Court ruling that Austria s ban on gamete donation contravened the human rights of two claimants - their rights of respect to family life as set out in article 8 and that the denial of gamete donation was discriminatory. ESHRE s evidence supported the Court s original ruling. Luca Gianaroli, Chairman of ESHRE, said that the rejection of the submission was inexplicable, especially when evidence was allowed from consumer groups and organisations representing the Catholic church. For ESHRE signs up to European alliance for medical research ESHRE has joined a new European alliance of biomedical researchers launched to boost funding and keep Europe competitive against ever-present competition from the USA and increasing competition from Asia. The EU spends just 1 8% of its gross domestic product on all R&D, compared with 2 7% in the USA, and 3 4% in Japan. The Alliance for Biomedical Research in Europe has now been formed to lobby for extra research funding so that Europe is not left behind. Behind the Alliance lie four of Europe s major professional organisations, all with common public health interests: the European Association for the Study of Diabetes (EASD); European Respiratory Society (ERS); European Society of Cardiology (ESC); and European Cancer Organisation (ECCO). Representation from a further 28 societies across Europe - including ESHRE - will give representation to an estimated 400,000 European researchers. Co-ordination of their reseach interests will give a single powerful voice to what has so far been a fragmented exercise. Currently, about 90% of funding for health-related research in EU countries comes from member states' own budgets, with the other 10% coming from the European Parliament. As well as lobbying for more research money, the Alliance will also help the European research community interact with the EU more effectively and provide a single representative voice. ESHRE was represented by Luca Gianaroli and Joep Geraedts at the alliance s inaugural meeting. ESHRE evidence to European court ruled inadmissible example, the Court did grant permission to intervene as a third party to the European Centre for Law and Justice, a self-styled Christian-inspired organisation said to be representing 51 others, many of them openly Catholic. The governments of Germany and Italy were also allowed to comment formally in support of the Austrian government. Among the consumer groups given permission to comment were the Italian organisations Hera Onlus and SOS Infertilità Onlus. A procedural hearing in February confirmed that the Grand Chamber will hear the Austrian government s appeal, but no date was fixed for the hearing or the judgement, which, according to the Court, may yet take several months. Bank balance remains positive despite some declines in revenue The financial report for 2010 presented to the General Assemby in Stockholm will show a favourable balance of income over expenditure. The previous year s activities had resulted in a slight deficit, but 2010 generated a net balance of almost 150,000 euro. Once again, the Society s greatest source of income - and expenditure - was the annual meeting, despite a substantial increase in operating costs and a slight decline in revenue. However, income from the ESHRE journals rose, with expenditure declining a little. Publications accounted for 17% of ESHRE s income, and the annual meeting 65%. Educational activities, with a spend of more than 700,000 euro, accounted for 12% of total expenditure, but with tighter planning requirements costs were somewhat reduced from However, revenues from registrations declined. New members elected to Committee of National Representatives A new Committee of National Representatives will be formed in Stockholm following nominations and elections among local members earlier this year. European countries with more than 15 members are entitled to two Austria Thomas Ebner (basic scientist) Ludwig Wildt (clinician) Belgium Bjorn Heindryckx (bs) Frank Vandekerckhove (c) Bulgaria Tania Milachich (bs) Tania Nikolova Timeva (c) Croatia Patrik Stanic (bs) Hrvoje Vrcic (c) Cyprus Michael Pelekanos (bs) Krinos M. Trokoudes (c) Czech Republic Alice Malenovska (bs) Milan Mrazek (c) Denmark Christina Hnida (bs) Kirsten Tryde Schmidt (c) Finland Sirpa Mäkinen (bs) Laure C. Morin-Papunen (c) France Pierre Boyer (bs) Catherine Rongieres (c) Germany Peter Vogt (bs) Markus S. Kupka (c) Greece Kalliopi Loutradi (bs) Grigoris Grimbizis (c) Hungary Katalin Kanyo (bs) Péter Kovács (c) Ireland Geraldine Emerson (bs) Anthony Walsh (c) Israel Jeremy Don (bs) Zeev Blumenfeld (c) Italy Giovanni Coticchio (bs) Maurizio Guido (c) representatives (one clinical, one basic science), who are elected for a period of three years, with the opportunity to stand for one further term. Those elected after the two rounds of voting are listed below: Macedonia Birol Aydin (bs) Zoranco Petanovski (c) Norway Anette Bergh (bs) Nan Brigitte Oldereid (c) Poland Rafal Kurzawa (bs) Ireneusz Polac (c) Portugal Vasco Almeida (bs) José Domingues Nunes (c) Romania Andreea Sandra Mustata (bs) Bogdan Doroftei (c) Russia Sergey Yakovenko (bs) Anna Smirnova (c) Serbia Nada Tabs (bs) Nebojsa Radunovic (c) Slovenia Borut Kovacic (bs) Eda Vrtacnik-Bokal (c) Spain José Horcajadas Almansa (bs) Alfonso L. De La Fuente (c) Sweden Julius Hreinsson (bs) Pia Saldeen (c) Switzerland Manuel Pensis (bs) Gabriel De Candolle (c) The Netherlands Aafke Van Montfoort (bs) Jesper Smeenk (c) Turkey Basak Balaban (bs) Bulent Urman (c) Ukraine (No basic science candidate) Lyubov Myhailyshyn (c) United Kingdom Julia Paget (bs) Ertan Saridogan (c) 12 Focus on Reproduction May 2011 Focus on Reproduction May D OUTER

8 ESHRE NEWS // EUROPEAN GUIDELINES // Three ESHRE guidelines now under way, all developed according to new manual With ESHRE stepping up development of its European guidelines for clinical management, a manual for their development was produced by the SIG Safety & Quality in ART and published on the ESHRE website in The process was divided into 12 steps, as summarised in the table opposite. In October last year I was appointed as a research specialist to begin or resume the guideline development process on three topics in reproductive medicine and embryology. l The first project is to develop guidelines for the clinical management of endometriosis. A guideline in endometriosis was produced in 2005; thus, the current guideline development group, chaired by Gerard Dunselman, aims to update the text according to the requirements of the manual. Key questions have been written by the group and I am now collecting the evidence for evaluation by the group members before they compose their recommendations on diagnosis and surgical and medical treatment. The aim is to have the document finished as soon as possible. l A second project involving the management of premature ovarian insufficiency was proposed by Adam Balen as Coordinator of the SIG Reproductive Endocrinology. A first meeting has been held with four UK specialists in POI to set the scope of the guideline and discuss composition of the development group. The next step will be the formation of the group (whose chairmanship will be shared by Melanie Davies and Lisa Webber), and production of the key questions. l The third project is for the SIG Psychology & Counselling with its scope defined by the organisation of psychosocial care. The guideline will aim to set minimum standards in the provision of psychosocial care in clinics, with reference to specific groups of patients and the different phases of treatment. For this project, a meeting has already taken place at which Sofia Gameiro was appointed chair of the development group, and where the scope and committee membership were discussed. The scoping of the guideline will be completed through an online forum, which will also help with the next step, composition of the key questions for the guideline. The development of these guidelines is supervised by the Executive Committee, as are other projects requiring the endorsement of existing guidelines. Since guidelines for clinical management are important in many other fields, a request for new project proposals will later be launched. However, to ensure that the existing projects are developed as appropriately and swiftly as possible, this request for new proposals will await completion of the current projects. Nathalie Vermeulen Research Specialist, ESHRE Central Office 12 steps in the guideline process 1 Topic selection 2 Guideline development group 3 Scoping 4 Key questions 5 Evidence search 6 Evidence summary / grading 7 Recommendations formulation 8 Draft version 9 Review and consultation 10 Final version 11 Approval 12 Dissemination and implementation ESHRE consensus on poor ovarian response approved and submitted for publication An ESHRE consensus paper on the definition of poor ovarian response (POR) - and on the use of prognostic tests of ovarian reserve - has been approved by ESHRE s Executive Committee and submitted for publication in Human Reproduction. The consensus was derived from a 2010 workshop in Bologna involving every one of ESHRE s 11 Special Interest Groups. The Bologna criteria defined POR (or expected POR) as the presence of at least two from l advanced maternal age or any other risk factor for POR l a previous poor response to stimulation l an abnormal test of ovarian reserve Age was unanimoulsy defined as the most predictive measure of pregnancy, with four (or fewer) oocytes agreed as a definition of poor response to stimulation. The paper will be published as: Ferraretti AP, La Marca A, Fauser BCJM, et al. Bologna 2010 consensus on the definition and diagnosis of poor response to ovarian stimulation for in vitro fertilization. // ESHRE CLINICAL TRIAL // Green light for polar body microarray CGH trial Following the successful completion of its proof of principle study of polar body biopsy and microarray analysis, ESHRE is now ready for the next step: a randomised controlled trial (RCT). This trial has two primary aims among women with advanced maternal age: first, to estimate the likelihood of having no euploid embryos in future ART cycles; and second, to improve live birth rates. Among women aged 36 to 40 years planning three ICSI cycles, does microarray analysis of all chromosomes in the first and second polar body compared with no intervention increase the likelihood of a live birth within one year? And in women with no euploid embryos what is the likelihood of euploid embryos in a subsequent cycle? The proposed design is a pragmatic, multicentre, randomised double-blind controlled trial with an intention-to-treat analysis. The sample size will be estimated, however, to allow for a secondary analysis limited to patients most likely to be helped by PGS screening. The target population for the trial is women planning IVF or ICSI who are at high risk of having aneuploid embryos because of their age. Inclusion criteria are infertility as an indication for IVF or ICSI, patients between their 36th and 41st birthdays, BMI range kg/m 2, and patients prepared to accept the transfer of two embryos. Exclusion criteria are cycles involving donor gametes, two or more previous failed IVF or ICSI cycles, poor response in any previous cycle and low ovarian reserve as defined by Ferraretti et al (in press, defined by at least two of the following three features: advanced maternal age or any other risk factor for POR; a previous poor ovarian response; and an abnormal ovarian reserve test) and cycles requiring surgical sperm recovery procedures, total astenozoospermia and globozoospermia. The first primary outcome is the accuracy of a first cycle result with all aneuploidy embryos in predicting the same result in the second and third cycle. The second primary outcome is live birth rate within one year after the cycle of treatment, from Joep Geraedts, Chairman of ESHRE s PGS Task Force, which has planned the design of the trial. fresh or frozen embryos. Secondary outcomes include live birth rate in a specific good prognosis group, pathway outcome (implantation rates, ongoing pregnancy rates, abortion rates), genetic outcomes (proportion of aneuploidy, affected chromosomes), diagnostic efficiency, embryo outcomes, and adverse events. The total study will involve 600 couples, allowing for possible losses, with 300 in each arm. The trial will begin soon and the Cambridge company BlueGnome will again be our partner. Blue Gnome will provide training and free arrays and consumables for the study. ESHRE will take care of polar body biopsy training via its pilot study centres in Bonn and Bologna, where the proof of principle study was successfully completed. For the selection of the centres, all European PGD Consortium members (with full membership for the past three years) were invited to apply. The centres had to be experienced in performing embryo biopsy (not specifically polar bodies) and with experience in molecular analysis. No conflict of interest was allowed, meaning that staff members involved in the study should not be a consultant for companies offering a similar technology. Patients should not be charged for PGS and the centres could only take part in other similar studies at the same time if the patient group was not the same. On the basis of these criteria ESHRE's Executive Committee has selected the following five PGD Consortium members (in addition to the training centres in Bonn and Bologna): l Centre for Medical Genetics, University Hospital Brussels, Belgium l Center for Reproductive Medicine, University Women's Hospital, Kiel, Germany l Department of Medical Genetics, Athens University, Greece l Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel l Institut Universitari Dexeus, Barcelona, Spain Joep Geraedts, Chairman Task Force PGS 14 Focus on Reproduction May 2011 Focus on Reproduction May E INNER

9 Fertility Europe has continued its programme of projects and is grateful to ESHRE for sponsorship in Our vision is that fertility organisations from every country in Europe will become a part of Fertility Europe. ESHRE s support will help us expand the network of patient organisations throughout Europe - and employ an office manager (which we have lacked for the last year or so). During that time FE has been run on a purely voluntary basis. Members Spring Meeting Our Members Spring Meeting, also supported by ESHRE, was held in Prague in March. Here, following advertisement, applications and interviews, we appointed as our new office manager Kalina Nedelcheva from the patient organisation Iskam Bebe in Bulgaria. Kalina has all the necessary qualifications for the post as well as a huge knowledge of infertility. A total of 21 representatives from 18 patient organisations joined us in Prague. The meeting had been preceded by a questionnaire sent to all participants on fertility education and infertility prevention in their home countries. The results were summarised by Denisa Priadková, Vice-Chair of FE, and will help form the basis of our session in the Stockholm scientific programme - which is also on the prevention of infertility. The session - Education in fertility awareness, from prevention to action: whose duty? - will take place on Tuesday afternoon and will feature talks on fertility awareness among teenagers in Sweden and infertility prevention campaigns in Belgium. Our policy work has also continued and the first draft of a position statement on Equity of Access to Medically Assisted Reproduction was presented in Prague. After a wide-ranging discussion, we hope to have a final draft ready for Stockholm. Special Families campaign ESHRE s sponsorship also provides financial support for our Special Families project, which was successfully piloted in Rome last summer. The project is based on messages of hope in the form of pictures (photos of family, children, couples, handprints or child illustrations) and words explaining why the family sees itself as special. The pictures and stories in the native language of the country Position paper on access to treatment nears completion; final draft ready for Stockholm Representative members of Fertility Europe at its Spring Meeting in Prague; FE s aim is that patient organisations from every European country will eventually be represented. are then made into postcards. Why the campaign? Sadly, we still have large problems in Europe when it comes to patient access to treatment, with costs still a major barrier. The Special Families project is our way of putting a human face on the impact of infertility - as well as illustrating the numbers affected and the challenges couples face. All over Europe people are struggling to conceive, and Fertility Europe has the deepest respect for couples in this position. However, although difficult for some, they can and do move on, and often create a special family of their own. We hope that they too will join the campaign. If you feel you can help and would like to know more, just contact info@fertilityeurope.eu. And please visit our website at to find out more. And when you do, if you notice that we don t have a European patient organisation listed for your country and you know of one, please get in touch with us via the website. And come and see us at our exhibition stand in Stockholm - we are there to work in partnership with health professionals and all members of ESHRE. Clare Lewis-Jones Chair Fertility Europe // ESHRE EMBRYOLOGY CERTIFICATION // Credits system for continuing embryology certification to be introduced in Stockholm Programme set to include embryologists from outside Europe Demand remains strong for ESHRE s certification in embryology. This year s examinations will take place in Stockholm on Saturday 2nd July at 15:00. There are 65 registered for the senior clinical embryology exam and 136 registered for the clinical embryology exam. Some organisational improvements have been made recently and we invite all embryologists to visit to our improved web page at (under Accreditation & Certification ). The annual meeting in Stockholm will officially introduce two important innovations in the certification programme: l The Continuous Embryology Education Credit System is intended to encourage embryologists to collect education credits, and thereby renew their embryologist certificate. This is a feature for ESHRE members only, and the credits needed for certification renewal should be obtained in threeyear blocks. Specifically, senior clinical embryologists will need ten credits and clinical embryologists six credits, obtained over a three-year period, in order to apply for renewal of their certificate. Attendance at scientific meetings, publications, contributions to meetings and courses will all be taken into consideration for the award of credits. More information on the specific action categories and their corresponding credits is available on the website. Official documents indicating eligibility for credits must be uploaded to the ESHRE website. After having collected six or ten credits, no more documents can be uploaded for that three-year period. Thus, a certified embryologist from 2008 can upload documents collected after 1st January 2009; those from 2009 can upload documents collected after 1st January The first results of Heads down. Certification examinees in Amsterdam There are now more than 700 ESHRE certified embryologists. this programme will be published in January A column with renewed in... will be added to the list of certified embryologists 2008; and in January 2013 the list of certified embryologists from 2009 will be updated. l The second innovation is an extension of the ESHRE certification scheme to outside the borders of Europe. Symbolically, this will begin with the 2012 examination to be held just before our annual meeting in Istanbul. Only senior clinical embryologists will be able to apply at this stage, and there will be a maximum of 60 applicants. All necessary documents (MSc degree and/or PhD, logbook, etc) will need to be translated into English by an official translator and validated, before uploading them through the ESHRE website. More information about this will be placed on the website The ESHRE Embryology Certification Steering Committee 16 Focus on Reproduction May 2011 Focus on Reproduction May E OUTER

10 ESHRE NEWS // CAMPUS WORKSHOP // Data on the oncological impact of ART are reassuring, but the need remains for continuing vigilance Mammographic screening is recommended for nulligravid IVF patients over 35 years Above, US epidemiologist Louise Brinton: biological plausibility of a breast cancer risk. Below, Raphael Ron-el: An important message... Those with long memories (and advancing years) will remember a case-control study from 1993 which found a 2.8 risk of ovarian cancer in women given fertility drugs relative to drug-free controls. The report, by Whittemore and colleagues in Human Reproduction, sent a shiver of concern throughout the world of IVF and prompted a hurriedly convened special session at ESHRE's annual meeting that year in Thessaloniki. Since then, according to Israeli epidemiologist Liat Lerner-Geva, that relative risk - in the association of ovarian cancer with controlled ovarian hyperstimulation - has not been reproduced in any case-control study. Moreover, a 30-year follow-up study performed by her own group in Israel in more than 2000 women given ovulation induction between 1964 and 1974 has found no excess risk of ovarian cancer in the treatment group. A systematic review of the literature was equally reassuring, especially with regard to invasive epithelial and non-epithelial risk. Dr Lerner-Geva was speaking at a well attended Campus meeting organised earlier this year in the Bavarian town of Kempten by ESHRE s SIG Reproductive Endocrinology. The question at the heart of the meeting was, despite a comforting belief that IVF is safe, do we still ignore its oncological impact in the patient and her children. According to US epidemiologist Louise Brinton from the National Cancer Institute, the oncological concern with ART has now shifted from uterine and ovarian cancers to breast cancer, and not without biological plausibility. Breast cancer is associated with nulliparity and an extended exposure to endogenous hormones, and, said Dr Brinton, my personal view is that there s enough reason to be concerned because of biological plausibility. However, the data she reported from cohort and case-control studies are confusing, with some studies finding an increased or decreased risk, or no association. Her own retrospective study of more than 12,000 women investigated for infertility from 1965 to 1999 found no statistically significant associations between treatment and breast or ovarian cancers. Similarly, the French E3N cohort study of 92,000 women found an increased risk of breast cancer only in those women with a family history of the disease. Some studies - including a retrospective cohort study of almost 6000 women in Israel - have found a raised risk of breast cancer associated with ovarian stimulation with clomiphene, but other studies have not confirmed these results. Despite such high numbers in the various cohorts, all these studies, said Dr Brinton, are undermined by interpretive difficulties - small numbers of cases, inconsistent indications, and limited information on the drugs prescribed, their doses, and confounding factors. There are also similar inconsistencies apparent when the study parameter shifts from the broad range of ovarian stimulation to the procedure of IVF itself; Venn et al in 1999 reported an increased risk of breast cancer within 12 months of treatment, while a very recent study from Sweden (of all women having successful IVF between 1982 and 2006) found a significantly lower than expected risk of breast and cervical cancers. However, despite such confusion there was one study and one recommendation which did generate much discussion. The study, described by Raphael Ron-el, again came from Israel and was a follow-up (mean 8.1 years) of 3375 women having IVF, with linkage to the national cancer registry. The bare results found 35 breast cancer cases as compared 18 Focus on Reproduction May 2011 with 24.9 expected, and thus a standardised incidence ratio of 1.4. This was of borderline significance, said Ronel, although highlighting an important message : multivariate analysis of these 35 cases showed that the association was mainly apparent in patients of 40 years or older, in those with hormonal infertility, and in those with more than four treatment cycles. It was because of such results - as well as the biological association between estrogen, its withdrawal and breast cancer risk - that Gunther Emons from the gynaecology clinic at Göttingen, recommended that all nulligravid IVF patients over the age of 35 should be screened (by mammography) for breast cancer. This, said Dr Emons, is already policy in Göttingen - and, apparently, in Israel for patients of 40 years and older. And he added the warning that, because breast tissue only completes its maturation with pregnancy and lactation, and that the immature breast in nulligravids is more susceptible to mutations (because of mitosis), IVF centres should beware of advanced breast cancers at the end of lactation after successful ART. The screening recommendation prompted a heated response from the floor: mammographic screening in all over-35s would be extremely costly, said one, but, added Ricardo Felberbaum, the meeting s organiser, I think it make sense, if only to rule out any risk before treatment. While the oncological risks in patients were the main consideration of this meeting, the children born from ART were not neglected. In 2003 the report of Moll et al in the Lancet describing an elevated incidence of retinoblastoma raised the controversial possibility of induced malignant diseases in IVF children. However, Rotterdam paediatrician Campus organiser Ricardo Felberbaum: Pre-IVF mammography in nulligravid over-35s makes sense. Speakers at the Campus meeting: left to right, Wolfgang Kupker, Gunther Emons, Klaus Diedrich, Raphael Ron-el, Sybille Loibl, Ricardo Felberbaum, Zeev Blumenfeld, Thomas Strowitzki, Louise Brinton, and Irwin Reiss. Irwin Reiss demonstrated very clearly that these findings could not be confirmed by further studies. And so far, he added, there is no clear evidence that IVF treatment itself is associated with any increased risk of cancer in children so conceived. However, he cautioned that ART may well have an epigenetic effect on patterns of DNA methylation and gene expression, but again the evidence - even in such well studied imprinting diseases as Angelman and Beckwith- Wiedemann syndromes - remains conflicting and inconclusive. Overall, as many contributors to this meeting repeated and despite the plethora of studies, hard evidence of any real oncological risk to either patient or baby remains elusive, but that, said Ricardo Felberbaum, is no reason to ignore the possibility. It was just such continuing vigilance, he said, which redefined our understanding of breast cancer risk associated with postmenopausal hormone therapy. Almost everything we heard today was very reassuring, he said. This is good for us and our patients. However, we have to keep our eyes open and encourage further studies. He too agreed that the focus of concern in ART has now moved away from ovarian cancer towards breast cancer - and that pre-ivf mammography in nulligravid over-35s makes sense. I agree totally, he said. The problem is not the initiation of breast cancer but its promotion. It s a small investment to make, and it makes sense given that a first pregnancy after 35 is in itself a risk factor for breast cancer. Simon Brown Focus on Reproduction Focus on Reproduction May F INNER

11 SPECIAL INTEREST GROUPS // REPRODUCTIVE ENDOCRINOLOGY // // EMBRYOLOGY // Ovarian ageing our precongress theme The SIG RE continues to be very active, with meetings recently staged in Madrid and Bavaria. Our Campus event on GnRH agonist triggering of final oocyte maturation - time for a paradigm shift organised by Peter Humaidan (Denmark) and Juan Garcia- Velasco (Madrid) was hosted by IVI-Madrid with around 80 interacting participants. The one-day course focused on the physiological basis of GnRH agonist triggering to induce final oocyte maturation and its clinical applications. In the first session a thorough review of the luteal phase and endometrial receptivity gave way to explore the basic endocrinology. During the second half-day session different alternatives for luteal phase recue were presented with published evidence from different protocols; finally, the possibility of completely avoiding OHSS combined with gamete/embryo freezing was reviewed. At the end of the day, it was concluded that GnRHa triggering is already the protocol of choice in oocyte donation and fertility preservation because it completely eliminates the risk of OHSS and significantly reduces luteal phase estradiol levels; it is a highly attractive option for high risk IVF/ICSI patients, and, after minor fine-tuning of luteal phase support, could successfully be applied to all ART patients. The oncological risks of ART Our first Campus of 2011 was held in Kempten, Bavaria, in February, on ART and the oncological impact, hosted by Ricardo Felberbaum. The meeting, which is reported in more detail on page 18, explored possible relationships between ART and its oncological risks. There is no doubt that sex steroids, especially estrogens, can act as inducers of carcinogenesis. They may act as mitogens as well as mutagens, and can thus be tumor promoters and initiators, as Günther Emons from Göttingen proposed. As a first pregnancy after 35 years of age is in itself a risk factor for breast cancer, careful breast examination (sonography and mammography) before ovarian stimulation seems strongly advisable in this population. There are limitations in cohort studies of breast cancer risk following gonadotrophins or clomiphene citrate. Thus, while Venn et al in 1999 claimed a significantly increased risk (RR 1.96), Dor et al in 2002 found no association, and Kallen in 2011 a reduced risk (RR 0,76). Nevertheless, increased age at the time of first pregnancy remains an important statistical risk factor for breast cancer. The case for large, well designed studies was justificably made by Steering committee Adam Balen (GB), Co-ordinator Richard Anderson (GB), Deputy Co-ordinator Juan Garcia-Velasco (ES), Deputy Co-ordinator Georg Griesinger (DE), Junior Deputy Nick Macklon (GB), Past Co-ordinator Louise Brinton. By the time this issue of Focus on Reproduction is published Nick Macklon will have hosted The embryo as patient in Southampton, UK; we will have a report in the September issue. And in July we look forward to our precongress course in Stockholm on ovarian ageing. The course will cover the formation and loss of oocytes in the ovary, and factors which influence oocyte quality and thereby potential fertility. The causes and management of premature ovarian failure will be described along with ways to preserve fertility by either oocyte or ovarian tissue cryopreservation. We will conclude with a socio-ethical talk on the effect on society of postponing pregnancy with respect to population impact, access to infertility treatment and its financial implications. Future events We shall be holding a further training workshop with our colleagues in the Paramedical Group and SIG Embryology in St Petersburg, Russia, on 7-8th September. The first of these courses in Kiev last May - designed for junior doctors and paramedics - was very popular, so we urge you to register early! Details are on the website. We are also holding a meeting on PCOS in Sofia, Bulgaria, from 8-10th December, where we provide an update on all aspects of PCOS, covering diagnostic workup to management. We will feature the three ESHRE/ASRM consensus statements and the special considerations relating to psychology and quality of life. We are also looking forward to Anti-Mullerian hormone: an update, to be hosted by Didier Dewailly in Lille in May 2012 (10-11th). This Campus workshop aims to provide an evidence-based update on the role of AMH in contemporary reproductive medicine, with discussions on the physiology of AMH and its application in assessing ovarian reserve and predicting fertility. There will also be an appraisal of AMH as a biochemical assay for PCOS. As mentioned in the last issue, I stand down as Coordinator in Stockholm and would like to thank members of the steering committee for their support and efforts in continuing the success of our SIG. I wish George Griesinger, who takes over as Co-ordinator, and his new team (Frank Broekmans, Stratis Kolibianakis and Daniela Romualdi) all the very best for the coming years. Adam Balen Co-ordinator SIG Reproductive Endocrinology A new board, a fresh Atlas, and plans for more innovative courses There is an air of renovation in the SIG Embryology, both in the steering committee and in our activities. At this year s annual meeting Kersti Lundin will take over from Cristina Magli as Coordinator. Deputies will be Maria José de los Santos and Josephine Lemmen, with a new Junior representative whose election is currently ongoing. We also have a new Basic Science Deputy in Carlos Plancha, who already started his collaboration with us a few months ago when taking an active part in our courses in Lisbon and Denver. With his help, we feel that bridging the gap between science and clinical medicine is now much easier. The Atlas of Embryology The original version of the Atlas of Embryology, published in 2000 as a supplement to Human Reproduction, was compiled by the contribution of many embryologists; they provided a collection of images representing the various aspects of oocyte and embryo development. For many years, it was a valuable support for anyone interested in assisted reproduction. The work was encouraged and supported by Bob Edwards, who wrote an extraordinary preface and provided several landmark figures which made history in the story of IVF. Now, things have changed; new techniques and novel approaches have been applied to reproductive biology, and new means of communication are available. These considerations were all behind our preparation of a new atlas, From oocyte to preimplantation embryos, now planned as an official The 2000 Atlas of Embryology, published as a supplement to Human Reproduction, is now to be replaced by a print and online publication titled From oocyte to preimplantation embryos Steering committee Cristina Magli (IT), Co-ordinator Kersti Lundin (SE), Co-ordinator Elect Maria José de los Santos (ES), Deputy Co-ordinator Josephine Lemmen (DK), Junior Deputy Etienne Van den Abbeel (BE), Past Co-ordinator Carlos Plancha (PT), Basic Science journal publication from OUP and as an online ESHRE webbased publication as well. A report on the state of the project will be given during our business meeting in Stockholm. By then, the document from the consensus workshop on embryo assessment prepared in collaboration with Alpha Scientists in Reproduction should also be available as a joint publication in Human Reproduction and Reproductive Biomedicine Online. Future events We have already programmed several courses as a result of suggestions made by SIG Embryology members. Our precongress course in Stockholm, The blastocyst: perpetuating life, has been organised jointly with the SIG Stem Cells. It will be a great opportunity to gain a comprehensive understanding of the physiological processes stretching from gamete union to further development and differentiation. In view of its great success in Kiev last year, the training course The management of infertility - Training workshop for junior, doctors, paramedicals and embryologists will be repeated in St Petersburg on 7-8th September as a joint activity with the SIG Reproductive Endocrinology and Paramedicals. For 2012, we are working with the Task Force Basic Science and the SIG Reproductive Genetics on the seventh course on Mammalian folliculogenesis and oogenesis to be held in Stresa, Italy, on 5-7th April. The course will include an extensive overview of the major processes involved in oocyte and follicle formation and development, with a special emphasis on meiotic maturation and acquisition of developmental competence. We have now agreed that our precongress course in Istanbul in 2012 will be concentrated on the subject of oocyte and embryo nutritional requirements. Because of the several undisclosed formulations of commercially available media which tend to promote vigorous embryo growth, a better knowledge of their eventual effects on later development is now considered necessary. Cristina Magli Co-ordinator SIG Embryology. 20 Focus on Reproduction May 2011 Focus on Reproduction May F OUTER

12 SPECIAL INTEREST GROUPS // ENDOMETRIOSIS & ENDOMETRIUM // Implantation in IVF drives a lively interest; record abstract submissions for Stockholm // PSYCHOLOGY & COUNSELLING // Dealing with third party reproduction our precongress theme for the annual meeting We once again look forward to a very lively interest in the subject of our SIG judging by the number and quality of abstracts submitted for the annual meeting in Stockholm. More than 100 abstracts in the newly defined field of Endometriosis, endometrium, implantation were submitted, and we expect some exciting free communications and posters. The invited programme is also excellent. Speakers include Sudhansu Dey (US) on Peri-implantation communication between embryo and uterus - markers of embryonic competence and uterine receptivity. Session 16 on Tuesday is on fibroids and reproduction and here Jose Horcajadas (ES) will speak on the Impact of fibroids on endometrial function and William Catherino (US) on the Impact of fibroids and fibroid management on reproductive success. The increased interest in the role of the endometrium, reflected in the number of abstracts submitted this year is also a reflection of an increased interest in milder stimulation protocols and in the transfer of embryos in natural cycles. We hope that this trend will continue in the years to come. It is on the endometrium that we focus for this year s precongress course in Stockholm, The impact of the reproductive tract environment on implantation success; the full programme is on the ESHRE website. It s clear that multiple factors have an impact on successful implantation and this course will address its potential systemic (pelvic, metabolic and haematological) and local (uterine and tubal) environmental influences. The content will appeal to basic scientists as well as to all those who manage and focus their research endeavors on patients with endometriosis and fibroids, and in particular those practitioners with an interest in managing patients in early pregnancy and with a problematic early pregnancy. The SIGEE business meeting will be held after the precongress course on Sunday 3rd July (at a time and venue to be advised). World Congress on Endometriosis We remind all SIGEE members that this year is the 25th anniversary of the first world congress on endometriosis, which took place in Clermont-Ferrand in In 2011 Steering committee Hilary Critchley (GB), Co-ordinator Anneli Stavreus-Evers (SE), Deputy Co-ordinator Endometrium Gerard Dunselman (NL), Deputy Co-ordinator Endometriosis Annemiek Nap (NL), Junior Deputy Thomas d Hooghe (BE), Past Co-ordinator the WCE returns to France, to Montpellier, and will take place from 4-7th September. Information can be found at We do hope this meeting will receive strong support from the ESHRE membership. The World Endometriosis Society produces excellent bimonthly e-journals, which they are happy to make freely available to SIGEE members - the latest issue can be downloaded from ejournal.html. WES should also be congratulated on its launch of the very first ever awareness film on endometriosis. This is available from org/news/general/first-ever-awareness-film-onendometriosis-launched-by-world-endometriosis-society/, and is supported by strong (video) statements from WES president Hans Evers and European Parliament Vicepresident Diana Wallis. In April, versions in German, Spanish, French and Italian were introduced. Future SIGEE meetings In October this year we have an ESHRE Campus meeting in Rome on Endometriosis and IVF. The programme, which is now on the ESHRE website, will include a session on the ever controversial subject of surgical intervention before IVF and a presentation on tissue or gamete cryopreservation for fertility preservation in severe endometriosis given by Jacques Donnez. Looking ahead to 2012, the SIGEE has proposed a further Campus course in Leuven, Belgium, on quality control in clinical surgical trials for endometriosis surgery; this has been organised in conjunction with the SIG Reproductive Surgery and the ASRM s SIG Endometriosis for early Finally, I am also pleased to report that the endometriosis guideline development group is now making steady progress with the assistance of ESHRE s research specialist in guideline development. Meanwhile, we look forward to seeing as many of you as possible in Stockholm, Montpellier, and Rome! Hilary Critchley SIGEE Co-ordinator Plans for Stockholm Our precongress course on 3rd July in Stockholm will provide a theory and practice update on third party reproduction. As legislation and professional guidelines have been introduced and modified over the past decades, psychosocial professionals working in their daily practice with donors, recipients and other third parties will gain an understanding of the complex issues involved in dealing with multiples parties. Topics will include openidentity embryo donation, gay men using surrogacy and egg donation, intrafamilial gamete donation, informationsharing with offspring, counselling semen donors for contact with offspring and pre- and post-treatment counselling for egg donors. The course will be chaired by SIG Co-ordinator Petra Thorn and Deputy Chris Verhaak and the full programme can be found online at the ESHRE website. Following the precongress course, our SIG business meeting welcomes members to join in the discussion. Topics this year will include previous and upcoming Campus workshops and an update on the progress of the new Psychology and Counselling Guidelines. In addition, a new board will take over in Stockholm as our current Coordinator, Petra Thorn, will be stepping down after three years of excellent work for our SIG. The results of the election for two new senior deputies and a junior deputy will be revealed and our new Co-ordinator, Chris Verhaak, will be introduced. The annual dinner in collaboration with the International Infertility Counsellors Organisation (IICO) will complete the day s events in the city centre of Stockholm. Those interested in joining the dinner can contact me (uschi.vandenbroeck@uzleuven.be) for more information. Campus workshops: past, present and future Our second Psychology and Counselling Campus workshop held in December last year was a great success despite the difficult snowy weather conditions in Amsterdam. Participants, who arrived from many different countries, included psychosocial professionals as well as doctors, nurses, midwives and administrative personnel. This ensured a multidisciplinary mix which guaranteed an interesting discussion at the various workshops, as well as the opportunity to find common ground and differences in Steerting committee Petra Thorn (DE), Co-ordinator Christianne Verhaak (NL), Deputy Co-ordinator Jan Norré (BE), Deputy Co-ordinator Patricia Baetens (BE) Past Co-ordinator Uschi Van den Broeck (BE), Junior Deputy clinical work around Europe. This year a joint Campus workshop with the SIG Andrology will be organised in Seville, Spain, on 22-23rd September. The objective is to focus on the whole man, with presentations on the care of the man in the clinic, lifestyle factors, diagnosis, treatment, future patients, future health, how to take care of a man s sperm and finally the impact of infertility on the man as a person, not just a sperm producer. This 1.5 day course is targeted at both medical and psychosocial professionals and will introduce participants to issues they may not yet have addressed in their daily practice. It will provide information and an opportunity for discussion on the needs and ways of providing the latest psychological and medical care of the infertile man in our clinics. The full programme can be found on the ESHRE website. In the Spring of 2012 the SIG Psychology and Counselling will step into Eastern Europe with a course in March in Budapest, Hungary. The course will focus on developing competence in psychosocial care and counselling. The course is devised for two groups of Our current Deputy Co-ordinator Chris Verhaak will take over as Co-ordinator in Stockholm when Petra Thorn steps down. professionals: medical and administration staff can improve their understanding for the psychosocial needs of patients and their skills in managing difficult situations such as breaking bad news; psychologists and counsellors can further their professional expertise in the specialist areas of couple counselling or helping clients with issues such as third party reproduction or loss and bereavement. Special attention will be paid to issues relevant for Eastern European professionals and cross-border reproductive care has been a very productive year for the SIG Psychology and Counseling and we hope to see many of you in Stockholm. Uschi Van den Broek Junior Deputy Co-ordinator SIG Psychology and Counselling 22 Focus on Reproduction May 2011 Focus on Reproduction May

13 SPECIAL INTEREST GROUPS // EARLY PREGNANCY // TASK FORCES // DEVELOPING COUNTRIES AND INFERTILITY // New diagnostic tools for EP complications Four SIG-EP events are scheduled over the next 12 months: l Our precongress course in Stockholm, From genes to gestation, is organised in collaboration with the SIG Reproductive Genetics. The programme reflects the very rapid expansion in our knowledge of the human genome and in particular the genes affecting implantation and early embryo development. New genetic diagnostic techniques and therapies will be reviewed. The course is an ideal opportunity to brush up your genetic knowledge in the company of excellent speakers. I should also remind you that invited lectures from two eminent speakers on the first morning of the scientific programme should not be missed: Graham Burton will review interesting new theories on the function of the placenta in very early pregnancy, while Eric Steegers will show how far we have come in imaging the early embryo in utero, an unique technique with very wide perspectives. l If you have always thought that research in immunological factors relating to early pregnancy complications is actually too complicated, think again and take a trip to Copenhagen for 23-26th August. Here, a joint meeting between the SIG-EP and European Society of Reproductive Immunology (ESRI), Early pregnancy // REPRODUCTIVE SURGERY // ESHRE's SIG Reproductive Surgery is now involved in the TROPHY study, a multicentre randomised Trial of Outpatient Hysteroscopy. The study was set up in autumn 2008 in response to the systematic review of Tarek El-Thoukhy, published that year, which reported a positive effect of diagnostic hysteroscopy on IVF outcome. El-Thouky concluded that future robust randomised trials comparing OH (office hysteroscopy) or mini-hysteroscopy with no intervention before IVF treatment would be a useful addition to guide clinical practice. Thus, a randomised trial has now been set up at Guy's and St Thomas hospital in London by El-Thouky, with several centres agreeing to take part (from the UK, Italy, Belgium and Czech Republic). The Karl Storz company has developed a brand new design of Steering committee Ole Christiansen (DK), Co-ordinator Mariette Goddijn (NL), Deputy Co-ordinator Siobhan Quenby (GB), Deputy Co-ordinator Marcin Rajewski (PL), Junior Deputy Roy Farquharson (GB), Past Co-ordinator disorders: integrating clinical, immunological and epidemiological aspects, is an attempt to bring together clinicians and reproductive immunologists with a series of clinically relevant lectures and discussion relating to early pregnancy complications: diagnosis, causes and treatment with a focus on immunology and epidemiology. Even if you have only a modest knowledge about immunology, this is your chance for an update. The full programme is available at and on the ESHRE website; registration is via the former website. l Our precongress course in Istanbul in 2012 is on Gamete quality and ovarian reserve as markers for early pregnancy loss, designed to be of interest to those working in reproductive medicine. Is it possible to identify markers in the gametes of ART patients which can pinpoint those carrying a particularly high risk of miscarriage - and can something be done to prevent it? l For those taking part in this year s ASRM annual meeting in Orlando, Florida, we recommed the ASRM/ESHRE Exchange Early Pregnancy Workshop on 15th October. Ole B. Christiansen Co-ordinator SIG Early Pregnancy Assessing the effect of diagnostic hysteroscopy on IVF outcome instrument (the TROPHYSCOPE- CAMPO compact hysteroscope), with a redesigned tip to reduce trauma and smoothe passage through the cervix. A gliding system provides diagnostic and operative functions in one single instrument. The trial is now an official project of ESHRE s SIG Reproductive Surgery in collaboration with the European Academy of Gynaecologial Surgery. The trial is not yet concluded but all centres are recruiting patients and first data soon will be available. Marco Gergolet Co-ordinator SIG Reproductive Surgery Millennium Development Goal 5: What happened to infertility? The UN s fifth Millennium Development Goal - to improve maternal health, and particularly Goal 5b (to achieve universal access to reproductive health) - is the most offtrack of all the eight MDGs, even though the critical importance of reproductive health to development has been widely acknowledged. Almost all the itemised objectives of Goal 5 deal with reducing maternal mortality, preventing unwanted pregnancies and curbing the spread of sexually transmitted infections, including HIV and AIDS. Nowhere in sight is the treatment (or even prevention) of infertility. Although infertility and childlessness are a global problem in reproductive health, with a silent population of more than 200 million couples according to the WHO, initiatives from the UN are scarce, if any. All organisations working in the field of human reproduction, including scientific organisations, NGOs and foundations, show little or no interest in the field of subfertility in resource-poor countries. Overpopulation and the limited-resources argument are always raised by those opposed to the idea of providing infertility care in developing countries - even if we can make it cheaper and accessible to a much larger part of the world population. Target 5.6 of MDG5 is to achieve, by 2015, universal access to the unmet need for family planning. Most of those at the Millennium Declaration in and at several summit meetings since - must have forgotten that family planning is not just the prevention of unwanted pregnancies but is also the opportunity of pregnancy in involuntary childlessness. We believe it s time for action; it s time to go to the politicians and NGOs and convince them that infertility care must be included in their future action plans. ESHRE training course in Cotonu, Benin During the second GIERAF (Groupe Interafricain d Etude, de Recherche et d Application sur la Fertilité) meeting in 2010 René Frydman and I proposed a multicentre study on the causes and treatment of infertility in Africa. The first results of this study were presented at the third congress of GIERAF held in Cotonou, Benin, in February. As a result of this work, ESHRE agreed to sponsor a one-day workshop in Cotonou on semen analysis and sperm processing, which proved a great success. Instead of the expected 30 persons, 50 took part from ten countries (Benin, Cameroon, Côte d'ivoire, Togo, Mali, Senegal, Madagascar, RD Congo, Congo, and Burkina Faso). Jean François Guerin (coordinator), Martine Albert and Jacqueline Lornage were the trainers on the course, assisted by two Africans (Nicole Akoung from Cameroon and Miriam Kadio Moroko from Ivory Coast) and two French biologists (Ben Khalifa and Benoît Schubert). The training focused on the new WHO standards for semen analysis, sperm preparations for ART (insemination and IVF) and practical demonstrations. GIERAF expressed its hope to continue this fruitful collaboration. ESHRE workshop on semen analysis during the 3rd Congress of GIERAF in Benin, with Jean François Guerin and keen pupils. Social Study Group Our Social Study Group was involved Papreen Nahar speaking at the Social Study in a one-day Group meeting in Durham, UK. colloquium in December 2010 in Durham (UK), which aimed to identify social, cultural and moral issues surrounding infertility and its solutions, particularly focusing on the use of ART in resource-poor countries, Islamic societies and diaspora communities. The workshop, which hoped to make recommendations for policy and practice, turned out to be a very fruitful and interesting meeting. ESHRE message at the ISMAAR congress in India The fourth World Congress of ISMAAR (International Society for Mild Approaches in Assisted Reproduction) was held in Kolkata, India, in January. During the Opening Ceremony two important Indian Ministers (Minister Manata Banerjee and Minister Ghulam Nabi Azad, the current Minister of Health and Family Welfare) each highlighted the importance of access to infertility care in India, a message which was undoubtedly influenced by our Special Task Force. I believe it was the first time in history that such important politicians have expressed their wishes for affordable IVF in resource-poor countries. Willem Ombelet Co-ordinator TF Developing Countries and Infertility 24 Focus on Reproduction May 2011 Focus on Reproduction May

14 TASK FORCES // CROSS-BORDER REPRODUCTIVE CARE // // BASIC SCIENCE // Good practice guide in print; data collection on egg donation in Europe about to begin The ESHRE Good Practice Guide for Cross-border Reproductive Care, which provides advice on dealing with patients seeking treatment outside their home country, has now been published in the ESHRE pages of Human Reproduction. The January edition of Focus on Reproduction explained the guide s gestation and principles, and we here outline how it might be implemented, as well as the Task Force s next plan, which is to collect data on oocyte donors in Europe. We are aware that codes of practice and good practice guides do not have the same pragmatic strength as professional guidelines, which may indeed be recognised in a court of law or for certification, with its corollary of implementation by inspection. Nevertheless, this ESHRE statement on how to ensure quality of care and safety for patients and their future offspring has an important symbolic value in a field which is still making headlines and remains of concern to professional bodies, statutory authorities and patients. Indeed, the first steps in the distribution of the Good Practice Guide show that many such bodies wish to publicise it. As soon as the paper was on the Human Reproduction advance access website, and simultaneously on our Task Force ESHRE website - probably by the time this edition of Focus on Reproduction is distributed - several organisations have agreed to electronically link the Task Force site to their own. We have agreements from ART regulatory authorities, such as the HFEA in Britain, the agency in Portugal, and the Italian Registro Nazionale della Procreazione Medicalmente Assistita. In addition, some national fertility or professional societies have either agreed already to the link (the Danish Fertility Society and Spanish Embryology Society) or are tabling the matter for their next executive meeting (the Collège National des Gynécologues et Obstétritiens Français in France).We are also awaiting feed-back from (not exclusively) our Belgian, Dutch, Czech and German colleagues, and will hopefully enlarge this linkage to a comprehensive array of fertility organisations in Europe. Outside Europe, the board of the Canadian regulatory authority, Assisted Human Reproduction Canada, has agreed to provide a link on their website, and the IFFS plans to discuss the guide with a possible web link at their board meeting preceding our annual meeting in Stockholm. And last but not least, the patients organisation, Fertility Europe, has also agreed to put the guide on its website. This approval of standards, both ethical and practical, will hopefully snowball and encourage more organisations to subscribe to it in time. Data collection on egg donation Our next research endeavor, starting in the Spring of this year, is to gather data on oocyte donors in Europe, another subject of much practical, ethical and political interest in our field. The Task Force, which now comprises founder members Françoise Shenfield, Guido Pennings, Anna Pia Ferraretti and Jacques de Mouzon, has two new members in Amparo Ruiz from Spain and Tonko Mardesic from the Czech Republic. The protocol for the study has now been finalised and approved by ESHRE s Executive Committee. Its main objective is to obtain reliable information on oocyte donors in Europe, whether the donation involves cross-border patients or not. By gaining an insight into the egg donors characteristics, their reasons for donating and the accompanying procedures (information, counselling, reimbursement, etc), we hope to provide a basis of information for all stake holders, including policymakers and patients, and especially promote policy measures which benefit donors and infertile couples in general. We know that some countries are trying to find ways to improve their own egg donation services and discover why others perform more cycles. For instance, the UK s HFEA has launched a public consultation in which some questions ask what is considered appropriate compensation to gamete donors (including benefits in kind). Interest at the international level is confounded by the fact that donor compensation and recruitment vary among European countries, and of course further afield. Still, little evidence is published on such matters. We are thus asking country co-ordinators (many of whom are also EIM co-ordinators) to enrol those centres which perform more than 100 egg donation cycles per year. We expect to collate questionnaires, and begin recruitment between Spring and Autumn this year. We will analyse and write up the results in early 2012, and hope to present them in Istanbul. Hopefully, an informed debate will then help encourage decisions which consider the safety and interests of patients and collaborators. To this end, a good practice guide in egg donation might be the next step, with promotion of a register for egg donors where this does not exist, first at a national and then a European level. Françoise Shenfield Co-ordinator Task Force Cross-border Reproductive Care Oncofertility Consortium expands in the USA and aims now for a global collaboration network l In Stockholm the TFs Basic Science and Fertility Preservation in Severe Disaese will stage a precongress course in collaboration with the US Oncofertility Consortium Survival rates among young cancer patients have steadily increased over the past four decades as a result of more effective cancer treatments. Today, both women and men can look forward to life after cancer, yet many may face the possibility of infertility as a result of the disease itself or its treatments. In January s issue of Focus on Reproduction Richard Anderson and Claus Yding Andersen described recent advances in the techniques of fertility preservation techniques; developing the clinical expertise to treat these patients will provide another avenue of progress. Recognising the need to focus on the fertility threat posed by cancer treatments, a team of oncologists, fertility specialists, bioethicists, legal scholars, advocates and communication scientists formed the Oncofertility Consortium in 2007 to solve this intractable problem. One of the many clinical resources provided by the Consortium is the National Physicians Cooperative (NPC), a US network of fertility sites that serve women, men and children with cancer. The NPC teaches fertility specialists how to work with cancer patients, who have an immediate need for fertility preservation between diagnosis and treatment, who are not as most fertility patients, and who might include adolescents and children. The NPC web portal (www. oncofertility.northwestern.edu) provides information for practitioners about best practices and sets up local oncofertility Number of clinical sites preservation programmes. Member sites, which also advance clinical outcomes by participating in multicentre studies designed to improve fertility preservation care, are an important resource for translational research by providing ovarian tissue to a national repository to improve fertility options for women and girls. While the NPC originally aimed to establish four centres throughout the USA, today patients can be referred to one of over 55 sites. Based on individual site reporting, the NPC provides more than 2700 oncofertility consultations per year, showing the significant need for this growing team nationally and globally. The Oncofertility Consortium also provides a free fertility hotline (FERTLINE, FERT (3378) as a referral resource for oncology professionals and young National Physicians Cooperative sites throughout the USA. In less than five years, the NPC has grown to include more than 55 clinical sites in 31 of 50 states, allowing young cancer patients to receive expert fertility preservation care nearby. cancer patients. Experienced patient navigators can counsel providers and newly diagnosed cancer patients in available fertility options and direct them to NPC sites and fertility preservation programmes. The FERTLINE navigators support patients as they pursue these options and can coordinate services, usually between the oncologist and reproductive endocrinologist, creating a synergistic and interdisciplinary treatment regimen. Calls around the world have been fielded and patients navigated to sites near their cancer treatment centres. If you wish to participate in this programme, please contact oncofertility@northwestern.edu. Johan Smitz Co-ordinator TF Basic Science in Reproductive Medicine Kate Timmerman, Teresa Woodruff Oncofertility Consortium 26 Focus on Reproduction May 2011 Focus on Reproduction May

15 TASK FORCES // MANAGEMENT OF FERTILITY UNITS // With medical claims rising exponentially, how can the IVF clinic insure against the risk of liability? ESHRE s Task Force on the Management of Fertility Units was set up last year to support members in the organisation of their centres and to broaden their management expertise. As a basis for its activities a survey of 250 centres worldwide sought opinions on financial planning, communication, human resources and insurance, and it was the last management responsibility which defined the subject of the Task Force s first workshop, Insurance models for reproductive medicine, which took place in Venice in February. The meeting was another first for ESHRE, because it was organised in close collaboration (through an unrestricted grant) with the Italian insurance giant Generali, three of whose members gave presentations. The meeting was introduced by Mr Giovanni Perissinotto (CEO of Assicurazioni Generali) and Luca Gianaroli (as Chairman of ESHRE and Co-ordinator of the Task Force) who each played a role in the conception and organisation of this meeting. It proved an interesting - and at times salutary - collaboration: for, as medical ethicist Guido Pennings noted, private groups such as insurance companies have no predetermined role in the paradigms of reproductive medicine, which traditionally have focused on patients, doctors and the healthcare systems which provide the funding for treatment. The focus of this meeting - and the insurance model it examined - was liability and the basis on which damages might be sought from patients as a result of malpractice. The legal basis for this, said Flaviano Antenucci from Generali, is slowly changing in many European countries PAUL DEVROEY; THE TECHNOLOGY TO PERFORM SAFE IVF HAS NOW BEEN CLEARLY DEMONSTRATED The vicious circle of escalating claims costs and insurance premiums in the past four years. Three explanations were proposed: l Social change - focus on the individual; patient rights; consumer groups; negative patient-doctor relationships; mass media l Medical progress - from treating the sick to treating the well; improved diagnostics; complex procedures with multidisciplinary approaches (joint liabilities) l Developments in jurisprudence - burden of proof on the physician; less strict definition of causation; from common law to contractual liability; personal injuries (particularly in western Europe) from a common law principle which relies on evidence and expert witness to uphold the right of a claim (as is still the case in the UK and USA) to one based more on an assumed contract between the physician and patient - and thus whether the terms of that contract have been appropriately fulfilled. That decision may be taken by a judge or - as in Spain - by a settlement authority. This major shift from common law to contractual liability has been particularly pronounced in Italy, where since 2000 there has been a ten-fold increase in the number of medical liability cases coming before the courts. Now, said Antenucci, the patient must only prove that the treatment took place and merely claim that the treatment contract has not been fulfilled. The burden of proof lies with the physician to demonstrate that the contract was correctly fulfilled. In IVF, said Antenucci, liability might be claimed as a result of damage during treatment (an abnormal reaction to drugs, infection, or diagnostic failure, for example) or as a result of treatment. The former, he added, might be offset by scrupulous workflow record-keeping and detailed (recorded) communication with the patient (a treatment diary, perhaps); just because a complication is common, however, would not be an adequate defence. There should, he said, be documentary evidence of the clinic s willingness to provide full and understandable information. Remarkably, 70% of medical claims in Italy are related to communication error, not treatment error. Two Italian cases which did lead to substantial insurance pay-outs were connected to the outcome of treatment, both concerning a mix-up of genetic material : the first, the birth of a baby whose race was incompatible with that of the parents ; and the second, the birth of twins affected by a genetic disease not carried by the parents. The compensation sought - and allowed - was substantial, said Antenucci, underlining the necessity of adequate coverage, but also highlighting the difficulty of assessing potential liability and writing (and underwriting) appropriate policies - particularly when the event may take several years to be manifest. Not surprisingly, his colleague, Tommaso Ceccon, described medical malpractice and liability claims as a critical area for insurance companies, noting an ever more litiginous population and a popular press ever more keen to report professional negligence. Indeed, between 1994 and 2008 the annual number of insurance claims in Italy alone rose from 9567 to almost 30,000. And with them, the average amounts in compensation rose ten-fold. As a result, Italian hospitals and physicians are now spending more than 500 million euro each year to provide adequate malpractice coverage. Insurance, of course, as Roberto Gaggero from Generali emphasised, is not the whole story, but only a part of a broader risk management process. Today, he explained, this has become a more proactive function of quality management, concentrating on the systematic identification, reporting, control and analysis of adverse events. Failure mode and effect analysis (FMEA), for example, continually identifies and improves the steps in a process to ensure a safe and clinically desired outcome and thereby prevent problems before they occur. Such a safety culture, he said, has thus shifted the emphasis from an adverse event (whose fault, for what reason, punishment?) to a near miss (what happened, fix the process). Such a shift requires the documentation of any unusual occurrence, even if there is no patient damage. The focus, he said, is on prevention, without fear of litigation. Gaggero listed the risks and potential complications for an IVF clinic as OHSS, bleeding, infection, pregnancy loss, multiple pregnancy, birth defects, prenatal testing, obstetric problems, prematurity and neonatal morbidity, but it was left to a gynaecologist, former ESHRE chairman Paul Devroey, to raise the liability stakes for IVF. Devroey s case was that safe IVF has now been clearly demonstrated, particularly in the prevention of OHSS and multiple pregnancy. A policy of antagonist (and not agonist) cycles, oocyte triggering with an agonist (and not hcg), single (and not double) embryo transfer and the transfer of only frozen (and not fresh) embryos in a non-stimulated cycle would, he said, virtually eliminate these risks. If the technology is available to remove them, he asked, would OHSS or a multiple birth constitute malpractice and the grounds for compensation? However, as Luca Gianaroli observed, risk-free IVF is a hypothesis for the future, and at present OHSS remains a complication of ART, even if its incidence is steadilyly decreasing. Certainly, said Gaggero, a full disclosure of all risks is now a necessary component of informed consent, which, alongside all records of consultations, patient information, tests, treatments and results, forms the core of documentation necessary for risk and quality management. He added that the basic requirements for the insurability of risk are domestic and/or national statistics, risk management models, and documentation (including informed consent). Above all, the risk must be foreseeable and measurable. While the focus of this meeting was insurance against claims for medical malpractice, there were many who thought the real need was in the availability of realistic insurance packages for patients. This need, as evident in the meeting s concluding round-table discussion, is especially complicated by the speed at which ART is moving and the ever-emerging demands for patient treatment - fertility preservation for both medical and social indications, for example, and even fertility insurance packages for teenagers which acknowledge prevention in their reproductive health. The ever increasing demand for fertility treatment was highlighted by ESHRE s own IVF monitoring data, presented by the EIM s chairman elect Anna-Pia Ferraretti, which showed that total IVF and ICSI cycles have more than doubled in the past ten years, and are now running at around 500,000 cycles a year in Europe. ESHRE s own data, as well as those from SART in the USA, indicate that the availability and uptake of treatment remains related to the provision of funding, with overall uptake in Europe steady at around 650 cycles per million inhabitants. In countries without widespread government funding, insurance packages would help increase availability and meet the unmet demand for treatment. q Generali s Roberto Gaggero, pictured at this well attended event in Venice with ESHRE s Chairman Elect Anna Veiga. 28 Focus on Reproduction May 2011 Focus on Reproduction May

16 End of term report With several members of ESHRE s Executive Committee about to stand down from their term of office, outgoing Chairman Luca Gianaroli looks back on ESHRE s achievements of the past two years and ahead to what s still to be done Completed in ESHRE s first textbook Publication of the English version of Reproductive Medicine, a textbook for paramedics, was the first of its kind in Europe - and a first for ESHRE. Free copies of the book were provided to all paramedical members of ESHRE. 7. Consensus on poor ovarian response A consensus on the definition of POR was reached during the first inter-sig campus held in Bologna in March A consensus paper was developed and, following approval by ESHRE s Executive Committee, has been submitted for publication in Human Reproduction. Its publication is expected soon. Consensus - in definition and the use of prognostic tests of ovarian reserve - was steered by an expert group comprising, from left to right, Antonio La Marca, Christina Bergh, Anna Pia Ferraretti, Bart Fauser, Geeta Nargund and Basil Tarlatzis. 2. Agreement with EUROCET EUROCET, the European registry on tissues and cells, aims to collect and publish official and updated figures on donation and transplantation activities throughout Europe. EUROCET is co-ordinated by the Italian National Transplant Centre, but ART activities have been relatively neglected. Now, in collaboration with ESHRE, a specific division of EUROCET is dedicated to ART, and data related to the reproductive cells in ART are collected by EUROCET from national registries. 5. EU Tissue & Cell Directives In order to face the issues raised by the new EUTCD, a dedicated Task Force co-ordinated by Edgar Mocanu was created in Its aims are to ascertain the impact of the EUTCD in Europe, to establish consistently high professional standards in ART, to encourage the best collaboration with the regulators, and to provide ESHRE s national representatives with documentation to help communication with their competent authorities. Among the Task Force s specific objectives was a survey to establish the risk of seroconversion in an IVF population. 8. ESHRE and FIGO A memorandum of understanding between ESHRE and FIGO was signed in The two societies will collaborate in a variety of joint educational activities and provide contributions to each other's scientific events. 3. Fertility and Viral Diseases Co-ordinated by Enrico Semprini, the Task Force aims to provide a platform of collaboration between ESHRE and the Centres for Reproductive Assistance Techniques in HIV in Europe (CREATHE), a nonprofit association for improving the quality and availability of safer conception options for couples affected by HIV and/or other transmissible infections who wish to become parents. 9. EU projects Two ESHRE projects with the EU have been completed. Work with EUSTITE begun in 2007 on proposals for vigilance and adverse event reporting was concluded in 2009 and has now been partly replaced by the EU-funded project Vigilance and Surveillance of Substances of Human Origin (SOHO V&S), which started in March The first phase of a project for the European Commission s DG SANCO (Direction générale de la santé et des consommateurs) was completed with publication in December 2010 of Comparative Analysis of Medically Assisted Reproduction in the EU: Regulation and Technologies (SANCO/2008/C6/051). 4. Task Force PGS The pilot phase of the Task Force s proof of principle study on polar body CGH was favourably completed and a large-scale randomised controlled trial is being set up to verify the results in a clinical setting. 6. Task Force Management of Fertility Units Creation of our Task Force on Management of Fertility Units aims to support ESHRE members in the organisation of IVF units, to broaden their management expertise and to call the attention of politicians to specific management issues. The Task Force has carried out a survey among a selection of ESHRE members on issues related to management and this year organised a workshop in collaboration with Generali Insurance Group to identify potential areas of collaboration between the ART sector and insurance companies. A second workshop will be held in Turkey in October. 10. Eastern Europe In a continuing bid to increase activity in Eastern Europe, an ESHRE Campus workshop on the basics of fertility management was organised in Ukraine in 2010 for junior doctors and paramedics; more workshops will take place in 2011 in Saint Petersburg, Sofia, and Bucharest. Following a new collaboration with the Middle East Fertility Society (MEFS), ESHRE Campus events in Europe will be exported to countries of the Middle East. 30 Focus on Reproduction May 2011 Work in progress 1. EU projects The second phase of our collaboration with DG SANCO began last year with the submission of data on seroconversion in IVF patients from three European IVF units. ESHRE began work as a formal collaborating partner in the SOHO V&S programme in the development of surveillance systems for tissues and cells used in ART. ESHRE will continue as a consultant to EUROCET on data collection in ART. 5. Embryology certification Still on the agenda for ESHRE s embryology certification programme are improvements to the on-line application system, continuous embryology education, and local courses. And still much to do Guidelines Guidelines are central to ESHRE's role as a reference point in European fertility treatment. Several ESHRE guidelines in a variety of fields are currently in development (and a Manual for Guideline Development is in place), but reaching a point of consensus and approval is a long and demanding process, especially when the texts must be applied in countries with different customs and legal requirements. However, it remains the view of ESHRE that guidelines are extremely important tools to guarantee consistency, safety and quality in ART and ESHRE will continue to support this programme. 2. ESHRE and Surgical Science A new collaboration between ESHRE and the Swedish company Surgical Science aims to develop a system of training for embryologists based on the use of virtual simulators. An agreement on training was signed in 2010 in which ESHRE will provide the know-how of its experts, and Surgical Science financial resources and expertise in the production of virtual simulators 2. EU lobbying ESHRE strategies for lobbying the EU have been assessed at several levels, but so far have not been applied or made tangible progress. ESHRE did participate in the European Health Forum in Gastein in October 2010 at which several policy makers were present and useful contacts established. However, there is much left to do as far as this matter is concerned. 3. Grants, awards ESHRE is presently involved in the development of joint research and educational projects with the Chinese Society of Reproductive Medicine with the support of IBSA. ESHRE is also represented on the judging panels of the FRIGGA Award (Ferring Research Infertility and Gynaecology GrAnt) and of the SSIF Award (Serono Symposia International Foundation). 3. Basic science Although a Task Force on Basic Science is in place - to ensure that the knowledge born in the laboratory is effectively communicated to our applied and clinical research programmes - basic research remains less prominent than it should be within ESHRE; this is especially so in view of the important developments now taking place in reproductive medicine which are emerging from the laboratory. 5. Developing countries and low cost IVF 6. Legislation ESHRE is deeply committed to this project, now in the hands of a Task Force. However, because of several factors - not least the difficult practical problems inherent in developing countries - and despite some important initial progress, we are still in the pilot phase of our work, and recognise a continuing need to step forward. 4. TROPHY study The TROPHY study, a Trial of OutPatient Hysteroscopy, is a project of the SIG Reproductive Surgery in collaboration with the European Academy of Gynecologial Surgery and Storz. The aim of this randomised trial is to assess the effectiveness of office hysteroscopy in improving IVF outcome after repeated IVF failures. Eight European centres are involved and data are being collected. 4. Extra-EU activities In an era of globalisation, ESHRE is doing its best to expand horizons outside Europe. To this extent, the 2012 annual meeting in Istanbul will be a huge opportunity to step closer to professionals from other continents. In addition, ESHRE is collaborating with the ASRM in a 'best practice' project designed to report and review just that every year, with an alternating venue in Europe and the USA. ESHRE has already provided consultant advice to several European governments in their discussions on new (or modified) legal regulations in ART. The intervention of ESHRE contributed to revised rulings in Italy (where verdict 151/2009 amended several points of the very restrictive Law 40) and to ongoing discussions in Malta. However, much work lies ahead in several countries: for example, Germany is currently discussing its PGD regulations, while the Polish government is debating new legal proposals for ART which include several of an extremely restrictive nature. Focus on Reproduction May

17 COVER STORY Egg donation has never been more controversial. Stratospheric payments to donors in the USA, anonymity or identity in Europe, altruism or remuneration, a chronic shortage of donors alongside an ever increasing demand, an official consultation on 'compensation' in the UK... Guido Pennings considers the issues from the perspective of a medical ethicist. Egg donation, even more than sperm donation, is frustrated by a wide gap between supply and demand. Those needing donor eggs are mainly older women. The decline in fertility caused by this older maternal age, as well as the high mean age of women at the birth of their first child, has led to an ever increasing demand for eggs. Smaller groups in the hunt for donor eggs are women suffering from premature ovarian failure and those with high genetic risk. Shortage usually drives creativity in its search for solutions; however, in the case of egg donation this has been seen in broad deviations from the standard rules of sperm donation. Systems that were unthinkable for sperm donation - such as known, direct or intrafamilial donation - are now seen as almost normal when it comes to eggs. But even with such broadened flexibility, the shortage in donor eggs has not been resolved. Indeed, quite the reverse. As a result, in such stubbornly resistant circumstances, we have appealed to the ageold universal solution: money. Remuneration Money is considered the most potent motivator of mankind. Despite the strong opposition to payment for body parts in most European countries, remuneration as a solution to the supply of donor eggs keeps popping up in the public debate - as recently seen in comment in the UK media on the HFEA s public consultation on compensation to gamete donors. However, in order to evaluate the role of remuneration, one must be aware of the complexity of gamete donation. The rules of the game are much like those of Mikado pick-up sticks. 1 Peripheral rules (how many children per donor, intrafamilial donation, The rights and wrongs of egg donation and so on.) can be added, removed or altered without too much trouble. But the basic rules, such as payment and anonymity, cannot be shifted without rethinking the whole system. Let s consider anonymity first. There is today an evolving movement towards non-anonymous donation. Several countries now only accept identifiable donors. Parents are following suit, but very slowly. Studies indicate a greater willingness of parents to disclose donor conception to the child. 2 However, in many of these studies the intention to tell and the actual telling to the child are not distinguished, so it s impossible to determine in the findings any effect of social desirability. More importantly, it is only now, long after the removal of donor anonymity, that we realise how many variables (donor and halfsibling contact, social matching of donor and recipients, etc) have still to be organised and investigated. The same tangle can be found in payment. A simple example: the idea of paying high fees to egg donors - as in the USA - is not compatible with the identifiability rule: it would be difficult for any donor to deny that money played a major role in her decision to donate, but this message may not be welcome to recipients or to the donor-conceived children. Payment to the donor will also necessarily raise treatment costs for recipients; they will have to pay the donor s fee as well as the cost of their own cycle. So, while payment to donors may increase their number, it would also make access more difficult for those without the necessary financial resources. The end result would be more eggs for the rich, and that, I assume, was not the original goal in mind. Regardless of the final outcome, we should at least be aware of the potential changes payment may bring about. These persistent attempts to introduce payment are all the more remarkable because so many other systems for donor recruitment have not been tried, or even considered. On this subject, the infertility sector can learn a lot from the field of organ transplantation. Systems such as required request (in which every person who is a possible donor is asked whether she wants to donate) or reciprocity have rarely been seriously considered. The latter, however, also called mirror donation, has been tried with success in ART programmes in Italy and the Netherlands, but still there is very little interest from practitioners. 3 This reciprocal system implies that the partner of the individual needing gametes also donates in exchange (for those gametes of the opposite sex). So the male partner of a woman needing donor eggs donates sperm in exchange for the eggs of a woman who needs donor sperm. This system is based on the basic principle of justice as fairness: a person who agrees to receive donor gametes should, as far as possible, also contribute to the system from which he or she benefits. The most amazing fact about the present discussion on donor recruitment - as clearly illustrated in the HFEA s consultation in the UK - is that preference seems to be for a solution (payment) which violates a fundamental moral principle (noncommodification) to a solution (mirror exchange) which respects a fundamental moral principle (reciprocity). At the same time, the whole question of payment for eggs should be seen in a broader perspective. How to explain, for instance, our inconsistency of attitude between egg donors selling their eggs and clinics selling eggs? Why are clinics allowed to sell what was altruistically given? Consistency requires a system that calculates the real costs of obtaining and storing the gametes, so that a maximum fee can be imposed. Clinics in countries with altruistic donors would then only be allowed to charge recipients the costs they actually incur. Cross-border travel Donor eggs are an important reason for cross-border travel. This is also a major source of concern because anecdotal evidence suggests that some clinics are not overly scrupulous in their dealings with donors. ESHRE s recent good practice guide for crossborder reproductive care sets out a series of rules for the protection of egg donors. At the same time, we still know very little about their general characteristics, motives or circumstances. However, in order to fill this gap, ESHRE s Task Force on 32 Focus on Reproduction May 2011 Focus on Reproduction May

18 The rules of the game are much like those of Mikado 'pick-up ' sticks. Peripheral rules (how many children per donor, intrafamilial donation, and so on) can be added, removed or altered without too much trouble. But the basic rules, such as payment and anonymity, cannot be shifted without rethinking the whole system. Cross-border Reproductive Care will this year begin a Europe-wide study on egg donation, focusing specifically on the donors. As with payment, the cross-border quest for eggs is highly complex, with both push and pull factors interacting in unpredictable ways. Most of the time, the trigger of the process is a push factor, that is, the shortage of donor eggs and the ensuing waitinglists. The pull factor is clearly the immediate availability of egg donors in foreign countries such as Spain and, depending on the country, the possibility of selecting the donor from a catalogue, as in the USA. The present reaction from the public (law makers and professionals included) in countries from which people travel is envy; clinics or authorities may criticise the patients for travelling and the host countries for accepting these patients, but they do very little to solve the problem at home. Just as for other scarce resources such as organs, selfsufficiency should be the goal. But generally, neither the clinics nor the governments are making much of an effort. Awareness and recruitment campaigns usually amount to little more than distributing a leaflet. But in reality most countries just do nothing. Several factors may explain this lack of enthusiasm but one important reason, according to me, is a fundamental ambiguity towards gamete donation. Unlike organ and blood donation, gamete donation challenges our traditional views on the family and is always seen as a second-best solution. As a result, it is much more difficult to convince governmental organisations to take a heartfelt initiative in egg donation. European developments In the very near future the European framework for cross-border medical care is set to change. The European Parliament and the Council of the European Union are completing a directive to facilitate the use of healthcare in another member state through clearer rules on reimbursement, procedural guarantees and information for patients. The directive establishes a specific framework for cross-border healthcare in the EU. The implications of this directive are difficult to predict. The impact for the field of assisted reproduction will probably be limited, since there are conditions attached to reimbursement. The most important condition is that countries will not have to reimburse treatments that are illegal in the home country. 4 Moreover, the directive does not prejudice the right of each member state to decide what type of healthcare treatment is appropriate. 5 For example, a German woman leaving her home country for egg donation treatment in the Czech Republic cannot claim reimbursement because egg donation is legally prohibited in Germany. The same rule may apply when more specific rules are violated by patients who go abroad; if the law of the home country states that no payment should be provided for a certain service or body part, reimbursement could be refused when that rule is not respected abroad. While the European Parliament clearly confirms the right of individual member states to decide on the ethical acceptability of certain types of treatment, the European Court of Human Rights recently struck down provisions in Austria s law on medically assisted reproduction in the case of SH and others vs Austria. The court first acknowledged the wide margin of appreciation of the member state, which means that the state is free to regulate assisted reproduction the way it wants to. But it then decided, on the basis of the proportionality principle, that the total ban on egg donation could not be justified according to the reasons given by the Austrian state. Although many observers seem to (want to) believe that this may be a first step towards a European harmonisation in the field of assisted reproduction, it is far from clear what the implications are (assuming the decision stands following Austria s appeal). It certainly does not imply that Austria has to allow egg donation. In fact, Austria could remain within the limits of the margin of appreciation by outlawing all medically assisted reproduction, or all types of gamete donation as in Italy. Time will tell which direction will be taken. The future One important obstacle in egg donation is the burden of treatment for the donor. This burden has two main components: the sickness and inconveniences resulting from ovarian stimulation; and the risk of ovarian hyperstimulation syndrome. Yet there is a technical solution to both these complications. Inconveniences and sickness can be avoided by opting for mild stimulation. Even if a clinic is reluctant to apply this protocol in its routine IVF, there is at least one very good reason to do so in egg donation: the doctor s moral obligation to minimise risks when the patients has no personal benefit from the treatment. The other main risk, OHSS, can also be reduced considerably by using GnRH antagonists and triggering oocyte maturation with an agonist. 6 If this modified protocol were applied, clinics would be in a much stronger position to recruit donors. The objections raised by feminist and prolife groups would lose much of their strength if a procedure were applied that was both safe and easy to bear. Finally, the vitrification of oocytes Egg donation in Europe Egg donation cycles as reported to ESHRE s EIM Consortium: , , ,028 l The EIM report for 2006 noted: The number of ED cycles increased in the same proportion, reaching 12,685 (+10.5%), reported by 22 countries, the main contributor being Spain (6547 cycles). may well have far-reaching consequences for the practice of egg donation. Not only will vitrification increase opportunities for egg donation (egg banking, for example, will facilitate the whole enterprise), it will also make possible social freezing (a misnomer only meant to prevent tarnishing its application in cancer patients). Once more women freeze their eggs in good time (that is, before they turn 35), there will be less need (and demand) for donor eggs. Nevertheless, this development will most likely make only a small dent in the increasing demand for donor eggs, which will surely continue to rise with the postponement of pregnancy in the developed world. The main challenge for fertility centres is to construct an ethically and psychologically coherent and acceptable set of rules for gamete donation. In order to do that, we need a broad societal debate about the framework in which to position the procedure. Only with a sustained effort to diminish the ambiguity towards gamete donation still current in most societies will it be possible to recruit a sufficient number of donors. Guido Pennings is Professor of Ethics and Bioethics at the at the Bioethics Institute Ghent (BIG) at Ghent University, Belgium, and Past Co-ordinator of ESHRE s SIG Ethics & Law. GUIDO PENNINGS: UNLIKE ORGAN AND BLOOD DONATION, GAMETE DONATION CHALLENGES OUR TRADITIONAL VIEWS ON THE FAMILY AND IS ALWAYS SEEN AS A SECOND-BEST SOLUTION. References 1. Pennings G. The rough guide to insemination: cross-border travelling for donor semen due to different regulations. Facts, Views and Vision in Obstetrics and Gynaecology, monograph 'Artificial insemination: an update' 2010: Söderström-Anttila V, Sälevaara M, Suikkari AM. (2010) Increasing openness in oocyte donation families regarding disclosure over 15 years. Hum Reprod 2010; 25: Pennings G. Gamete donation in a system of need-adjusted reciprocity. Hum Reprod 2005; 20 : Council of the European Union. Position of the Council at first reading with a view to the adoption of a directive of the European Parliament and of the Council on the application of patients' rights in cross-border healthcare. Adopted by the Council on 13 September European Parliament. Draft European Parliament Legislative Resolution on the proposal for a directive of the European Parliament and of the Council on the application of patients' rights in crossborder healthcare (COM(2008) C6-0257/ /0142(COD)). 6. Devroey P, Aboulghar M, Garcia- Velasco J, et al. Improving the patient's experience of IVF/ICSI: a proposal for an ovarian stimulation protocol with GnRH antagonist co-treatment. Hum Reprod 2009; 24: Focus on Reproduction May 2011 Focus on Reproduction May

19 CHRISTINA BERGH AND KARL NYGREN: 70% OF ALL ART CYCLES IN SWEDEN HAVE BEEN SINGLE EMBRYO TRANSFER SINCE Sweden A gold mine of epidemiology in reproduction With this year s annual meeting in Stockholm, last year s Nobel prize for medicine awarded to Bob Edwards (and the Nobel committee resident at the Karolinska Institute), Sweden is once again in the ART spotlight. Two of the country s stalwarts, Christina Bergh and Karl-Gösta Nygren, take a look at its past, present and future place in assisted reproduction. IVF in Sweden started early, in the country s second city of Gothenburg. It was there that Lars Hamberger and his group, at what was the original IVF clinic in the Nordic countries, had their first IVF baby in However, more than 20 years before then Carl Gemzell and colleagues at Uppsala University had achieved pregnancies in infertile hypogonadotropic women with the administration of gonadotrophins as ovarian stimulation. In the mid-1980s another Nordic group led by gynaecologist Matts Wikland, again in Gothenburg and with Danish colleagues, described and introduced the technique of transvaginal ultrasound for the puncture and aspiration of follicles, a development which would revolutionise IVF around the world and transform egg collection into a simple day-care procedure. Still in good shape today Thereafter, enthusiasm for IVF in Sweden spread quickly and today access to treatment is high. Around 13,000 cycles are performed each year, one-third as fresh IVF, onethird fresh ICSI and one-third frozen/thawed cycles. From these treatments around 3500 IVF babies are born annually, representing 3% of all babies born in Sweden each year. Reimbursement policies are generous, with most regions offering three publicly funded fresh IVF cycles - but with limitations according to age and previous children. There is a functional mix of public and private clinics. Law and regulations are relatively accommodating, and increasingly so over time; both egg and sperm donation are allowed, but not embryo donation or surrogacy. The gold mine of epidemiology One feature quite unique to the Nordic countries, and to Sweden in particular, is their databases. Sweden is a virtual gold mine for IVF outcome research. For around 50 years we have had several national population-based health registers for births, in-patient hospital diagnosis, out-patient diagnosis, birth defects, prescribed drugs, cancer, and cause of death. All events for all citizens are collected and stored in these registers, according to a personal ID number. From the very beginning of IVF in Sweden there has been an IVF register of information, which included the ID number of every woman who delivered and her children. This IVF register has been cross-linked at regular intervals to all the health registers. Thus, IVF births have been monitored and reported since its introduction in a way which is not possible in most countries. Comparisons can be (and have been) made between all children born and their mothers, and with children from the general population and their mothers. These cross-linkages have provided much important information, not only on obstetric outcomes such as birth weight, gestational age/preterm rate and malformations, but also on child morbidity in general and cancer. Sweden's first important challenge: the trade-off between efficacy and safety In the early days of IVF, clinics in Sweden - as everywhere else - were inclined to transfer large numbers of embryos to boost efficacy. At its peak in 1991, the proportion of multiple deliveries reached 35%. However, our outcome monitoring system eventually showed that the price paid for this greater efficacy, by both mother and child, was high, with increased multiple rates leading to more preterm birth and low birth weight, both of which were associated with child morbidity. Clinicians, patients and regulating authorities all agreed that the trade-off between efficacy and safety was clearly out of balance and should not be tolerated. Clinical research on single embryo transfer (SET) and its efficacy versus multiple delivery convincingly demonstrated that SET as the norm would be beneficial and clinically feasible. However, while numerous observational studies showed similar live birth rates after transfer of one and two embryos, randomised controlled trials clearly demonstrated higher delivery rates after two embryo transfers. Studies from the Nordic countries, however, showed that this discrepancy could be overcome by transferring one fresh and one subsequent thawed embryo when there was no pregnancy in the fresh cycle. Thus, in the light of this information, there was a nationwide shift in the uptake of SET in Sweden from 10% to 70% within just a few years. This resulted in no loss of efficacy as assessed by delivery rate, and most importantly a dramatic reduction in multiple birth rates, from 25% to around 5%. Similar patterns and results have been found in our cryocycles, in which embryos are now frozen and thawed for transfer one by one. The decrease in multiple birth rates has resulted in a huge drop in our preterm delivery rate, from 40% to less than 10%, and also in the rate of severe child morbidity (such as cerebral palsy). Adverse maternal outcomes, such as pre-eclampsia, have also decreased. The balance between efficacy and safety has thus been dramatically improved by SET in both fresh and frozen cycles. Although SET was first widely introduced in Finland, Sweden is now at its forefront worldwide. 36 Focus on Reproduction May 2011 Focus on Reproduction May

20 Delivery rate per embryo transfer, multiple birth rate, and single embryo transfer rate (%) in Sweden Delivery rate per embryo transfer (%) in relation to standard IVF, microinjection/icsi, and frozen/thawed cycles Data presented in Rome last year from ESHRE s IVF monitoring consortium showed that 70% of all ART cycles in Sweden have been SET since 2004; no other country has had such high rates, although this important transition is now happening in many countries, with the other Nordic countries, Belgium and the Netherlands close behind. Future challenges for safety To maintain confidence in IVF in Sweden, we are committed to monitoring future developments. The transition to SET and our one-at-a-time policy has unequivocally been shown to decrease the risks of IVF, but not every risk. Singletons born after IVF (even singletons born after SET) are still associated with a higher rate of preterm birth and lower birth weight when compared to singletons in the general population. The risk of birth defects is increased by about 25% for both multiples and singletons born after ART. And one study has indicated a small increased risk of childhood cancer. These additional risks, even for singletons, can at least in part be explained by certain patient characteristics, such as age, parity and the subfertility of the parents. Other suggested risk factors have included ovarian stimulation or lab technologies (such as culture media or time in culture), or combinations of these factors. Epigenetic mechanisms might be involved. Future research will need to discover the relative importance of these factors, to see if our stimulation strategies or lab procedures can be modified to decrease the risks further. National registries will be important tools in this endeavour, to allow continuous monitoring and long-term follow-up of both children and mothers. Future monitoring strategies Our ART monitoring system is now being further developed with a recently installed IVF quality register, which collects cycle-by-cycle data. This register, with full patient identification, will cover every patient having assisted reproduction treatment, whether the cycle results in a baby or not. The new system thus replaces both our earlier anonymous register (in which all IVF clinics reported aggregated annual data to the National Board of Health and Welfare), and the identified IVF Register (for those women delivering an IVF baby). The new register includes all Swedish IVF clinics and collects around 50 treatment and outcome variables; cross-links to the national health registers will continue and will now be much more complete. Confidence and functionality don't come easy IVF and its monitoring in Sweden may both seem robust. But public confidence, that our registers are well kept and protected, must now and again be defended. Even if Sweden is a country with an abundance of quality registers (more than 70), and with big governmental support, new rules and regulations are always cropping up, making it ever more difficult and time-consuming to collect the data and maintain the registries. Similarly, reimbursement policies are not written in stone; Denmark recently abandoned its generous reimbursement without much warning and to the detriment of infertile patients. Opinions may shift. But so far, here in Sweden we are optimistic - and believe we have good reasons to be. Christina Bergh is Professor of Obstetrics & Gynaecology at the Sahlgrenska University Hospital, Gothenburg, Sweden, Past Co-ordinator of ESHRE s SIG Safety and Quality in ART, and head of the Swedish Quality Registry on Assisted Reproduction. Karl-Gösta Nygren is Associate Professor of O&G, Sophiahemmet, Stockholm, Sweden, and Chairman of the International Committee Monitoring Assisted Reproductive Technologies (ICMART). 38 Focus on Reproduction May 2011