may11_nwp:Layout 1 26-04-2011 12:16 Page 40 may11_nwp:Layout 1 26-04-2011 12:16 Page 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 [email protected] www.eshre.eu l ESHRE news l Sweden: a gold mine of epidemiology l The oncological impact of IVF may11_nwp:Layout 1 26-04-2011 12:16 Page 2 may11_nwp:Layout 1 26-04-2011 12:16 Page 3 B WORK & TURN

EXECUTIVE COMMITTEE Focus on Chairman Luca Gianaroli (IT) Chairman Elect Anna Veiga (ES) REPRODUCTION Members Ursula Eichenlaub-Ritter (DE) Jean-François Guerin (FR) l Chairman’s introduction Timur Gürgan (TR) Antonis Makrigiannakis (GR) Carlos Plancha (PT) The last two years have passed in the blink of an eye and Françoise Shenfield (GB) now the time has come for me to write my last Chairman’s Miodrag Stojkovic (RS) introduction to Focus on Reproduction. In the next issue in Anne-Maria Suikkari (FI) September, the picture and words will be those of Anna Etienne Van den Abbeel (BE) Jolienke Schoonenberg- Veiga; after two years of ‘training’ as Chairman Elect, she Pomper (NL) is now poised to take the lead of our Society, and I am sure Veljko Vlaisavljevic (SL) she will be able to face the challenges which await her and Ex-officio members ESHRE in the best possible way. Joep Geraedts (Past Chairman) During my term as Chairman several changes have Søren Ziebe (SIG Sub- occurred and many interesting projects are still ongoing. committee) The number of members of ESHRE has been steadily FOCUS ON REPRODUCTION increasing and today all continents have a significant representation. Some Task EDITORIAL COMMITTEE Forces have been disbanded after meeting the objectives for which they were Paul Devroey established, while others have been created to deal with new questions related to Bruno Van den Eede human reproduction. Scientific studies concerning PGS and reproductive surgery Hans Evers are under way, and collaborations in different fields are being set up to cover Joep Geraedts emerging areas of interest to our members: training, safety and quality, Luca Gianaroli Hanna Hanssen management . . . In addition, ESHRE is consolidating its role as privileged Anna Veiga interlocutor for governments and EU institutions, and as a collaborating partner in Søren Ziebe European projects such as in the establishment of effective vigilance and Simon Brown (Editor) surveillance systems for tissues and cells. Partnerships have been established with

Focus on Reproduction other scientific societies, and I am sure they too will lead to the implementation of is published by interesting activities in the near future. The European Society of Human These past two years have been extremely intense, sometimes exciting, sometimes Reproduction and Embryology tiring, but always requiring concentration and commitment. However, each Meerstraat 60 Grimbergen, Belgium moment has been important to me and I am honoured to have had the opportunity [email protected] to represent our Society. I would like to take advantage of this space to thank all www.eshre.eu those who accompanied me in this journey: members of the Executive Committee, All rights reserved. co-ordinators of the SIGs and Task Forces, the editorial boards of our journals, as The opinions expressed in this well as all the many people actively involved in managing our Society. A special magazine are those of the thank-you goes to Bruno and all the staff at Central Office, who devote their work authors and/or persons interviewed and do not necessarily reflect the and efforts to ensuring the smooth running of ESHRE. What they do every day is views of ESHRE. extremely precious for all of us. Last but not least, I wish Anna and all members of ESHRE all the very best for MAY 2011 the future. Cover picture: Science Photo Library Luca Gianaroli ESHRE Chairman 2009-2011

CONTENTS NEWS FEATURES 4 Stockholm preview 32 The rights and wrongs of 6 New Executive Committee members egg donation 8 Honorary members 2012 Guido Pennings considers the controversies from the 9 Human Reproduction lecture perspective of a medical ethicist 11 Annual meetings 2013 and 2014 36 Sweden: a gold mine of 13 ESHRE news epidemiology in reproduction Christina Bergh and 15 Go-ahead for ESHRE PGS trial Karl Nygren on 16 From Fertility Europe Sweden’s place in ART 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 Focus on Reproduction May 2011 3 may11_nwp:Layout 1 26-04-2011 12:16 Page 4 may11_nwp:Layout 1 26-04-2011 12:16 Page 5

ANNUAL MEETING 2011 the long Swedish summer This year’s evenings are fantastic for congress party will take place at sitting out with a drink, and the Vasa A four-day enjoying life go by. Museum on the Stockholm is indeed a Stockholm beautiful place to visit in the waterfront. This smörgåsbord summer. Hotels are generally year marks the 50th anniversary of high standard, and a of the Vasa’s three-star hotel in Sweden is salvage. The ship on the menu always quite comfortable. sank on her Remember that Sweden is maiden voyage in not in the euro zone; our 1628, and is today the only for Stockholm currency is the Swedish fully preserved crown (‘kronor’). 17th century A packed scientific Now that abstract vessel. selection is complete, our programme selected from programme will provide the usual melting-pot of keynote more than 1400 abstracts lectures, debates and oral Venue for ESHRE’s 27th annual meeting is the Stockholmsmässan and poster communication conference centre, no stranger to important medical congresses sessions, starting on Sunday The final programme for our annual meeting in Stockholm and just a ten-minute train ride from Stockholm Central station. with a choice of no fewer is now confirmed, with 1417 abstracts submitted before than 17 precongress courses arranged by the Special lecture on Tuesday, another innovation from last year. the 1st February deadline. And yet again, a wealth of new Interest Groups and Task Forces. The Opening Ceremony Also on Tuesday will be the congress party at the developments have now been scheduled for free marking blinded abstracts. The Programme Committee which follows will formally introduce the meeting and this stunning Vasa Museum, where on display is the fully intact communication, either as oral or poster presentations. finally selected 254 abstracts for oral presentation from a year’s honorary members, Lars Hamberger and Alan 17th century warship which sank on her maiden voyage in The submitted abstracts were arranged in the following total of 1004 submitted for oral/poster presentation. Trounson. After the ceremony we will have the chance to 1628. This is a place to recommend, even if you don’t go categories before review: As in recent years posters will be presented electronically, mingle in the exhibition area, sustained by refreshment to the party. Although Stockholm is - by Swedish standards but each presenter has also been offered the opportunity of and drinks. - a big city, it is quite concentrated and easy to navigate. Category Total a paper poster. These traditional posters will be presented The main scientific programme begins on Monday Most of the hotels on ESHRE’s booking list are situated Andrology 156 in the Poster Village, according to special interest subject, morning (4th July) with two keynote lectures, including near the Central Station, where the train for the congress Cross-border reproductive care 10 as was done last year. Each day, discussion committees will the second Human Reproduction journals lecture. The centre leaves. The station for Stockholmsmässan is at Developing countries 16 assess the paper posters only, so authors should be debates are also a recently introduced feature, which this Älvsjö, the third stop (nine minutes) after Central Station. Early pregnancy 74 prepared for discussion and a brief presentation; the time year will once again raise topical and contentious issues: All registered participants will receive a four-day pass Embryology (embryo selection) 243 allocated to each presenting author will be restricted to two one on the treatment or non-treatment of obese women (Sunday to Wednesday) for the local transport system. Endometriosis, endometrium, implantation 102 minutes only and thereafter three minutes will be available (starring Mark Hamilton and Wybo Dondorp), and one Kersti Lundin Ethics and law 21 for discussion. Poster discussion schedules will be available on payment to gamete donors (starring Herman Tournay Local organising committee Female (in)fertility 156 in Stockholm. and Laura Witjens). Two unique opportunities to rethink Male and female contraception 6 your views! We are also looking forward to the historical Male and female fertility preservation 58 20 hours of daylight Awards on offer in Stockholm Paramedical (nursing, laboratory) 30 As I look ahead to July it is now the spring equinox in Total Selected Selected Six awards, each with a prize of 2000 euro, will be Psychology and counselling 52 Sweden, with day and night of equal length. When the abstracts for oral for poster available in Stockholm, with an additional Quality and safety of ART 72 annual meeting opens on 3rd July there will be no midnight Spain 151 27 69 presentation selected for the Fertility Society of Reproductive endocrinology 232 sun in Stockholm (we’re too far south!), but the sun does United Kingdom 101 29 45 Australia exchange award. Special committees will Reproductive epidemiology 21 rise at 3:38 and set at 22.05. So we will have almost 20 Italy 92 12 49 make the selection for each award. Reproductive genetics 84 hours of daylight. And - as long as the rain keeps away - Japan 89 13 40 l Reproductive surgery 31 Basic Science Award for oral presentation, Netherlands 80 23 39 Stem cells 29 sponsored by Merck-Serono. Brazil 62 8 30 l Translational research 24 Clinical Science Award for oral presentation, France 58 20 19 Grand total 1417 sponsored by Schering-Plough. Belgium 57 14 29 l Basic Science Award for poster presentation LOCAL CHAIRMAN USA 56 17 16 l Clinical Science Award for poster presentation All abstracts were reviewed according to our standard KERSTI LUNDIN: ‘A South Korea 55 2 23 l The Fertility Society of Australia Exchange Award, procedure of screening and scoring. Screening aims to WEALTH OF NEW Germany 46 6 20 sponsored by Cook ensure that abstracts are designated to the correct topic DEVELOPMENTS China 38 5 15 l The Exchange Award for Nurses category and to eliminate all submissions of obviously Sweden 36 9 17 l The ART Laboratory Award technician, sponsored poor quality. Selection for oral and poster presentation SCHEDULED FOR FREE by Labotect GmbH was done solely on the basis of scores from three reviewers COMMUNICATION.’ Where from? Selected presentations 2011

4 Focus on Reproduction May 2011 Focus on Reproduction May 2011 5 may11_nwp:Layout 1 26-04-2011 12:16 Page 6 may11_nwp:Layout 1 26-04-2011 12:16 Page 7

ANNUAL MEETING 2011 // GENERAL ASSEMBLY // Selected candidates for new membership of the Executive Committee 2011-2013 End of term for five members of ESHRE’s Executive Committee

General Assembly to ratify seven new nominations Carlos Calhaz-Jorge Jacques De Mouzon Roy Farquharson is Anis Feki is Chef de Niels Lambalk is a Milan Macek Jr. is Cristina Magli is is Head of is a specialist in the Consultant in Clinique in the gynaecologist and Chairman of the Director of Research Gynaecology in the epidemiology of Obstetrics & Reproductive fertility specialist at Department of and Development of Department of reproduction for Gynaecology at the Medicine Unit, and the VU University Biology and Medical SISMeR in Bologna, With five members of ESHRE’s present Executive Committee due to stand laws and Internal Rules. The by-laws (article Obstetrics, INSERM (Institute Liverpool Women's Director of the Stem Medical Center Genetics at Charles Italy. She was down in Stockholm having served two two-year terms, replacements have Gynaecology and National de la Santé Hospital, Liverpool, Cell Research (VUmc), Amsterdam, University, Prague, certified as an 11) state that ‘the names of the Chairman, Reproductive et de la Recherche UK. With a clinical Laboratory, at the Netherlands. He Czech Republic, and ESHRE Senior been nominated for ratification at this year’s Annual General Assembly the Chairman-elect, and the members of the Medicine of Lisbon Médicale), at the interest in Geneva University is chair of the Dutch President of the Clinical held during the annual meeting. Leaving the ExCo will be Jean Francois Executive Committee will be proposed by University Hospital, Groupe Hospitalier miscarriage, he was Hospitals, Infertility Registry European Society of Embryologist in Guérin (FR), Timur Gürgan (TR), Carlos Plancha (PT), Françoise Lisbon, Portugal. He Cochin-Saint Co-ordinator of Switzerland. His Foundation, and an Human Genetics. 2008, and is now the Executive Committee and ratified by the is a representative Vincent de Paul, ESHRE's SIG Early research interests associate editor of Professor Macek is Co-ordinator of Shenfield (GB) and Veljko Vlaisavljevic (SL). General Assembly of Members’. Thus, the member for Portugal Paris. He is Pregnancy from are in fertility Human national coordinator ESHRE's SIG Françoise Shenfield will continue in an ex officio capacity as the new power to ‘appoint’ and ‘dismiss’ members of of ESHRE's chairman of 2006 to 2010, and is preservation and Reproduction. He of Orphanet, an Embryology. She Co-ordinator of the Special Interest Group & Task Force Sub-committee European IVF ESHRE's European currently chair of the pluripotent stem was a member of the advisor to the Czech was the first in the ExCo lies with the General Assembly. Monitoring (EIM) IVF Monitoring Association of Early cells in reproductive local organising EU Council Europe, for SISMeR, following the completion of Søren Ziebe’s two-year term of office. Timur The process by which the nominees were Consortium and a (EIM) Consortium Pregnancy Units UK. medicine. He is committee for the Presidency and an to apply the Gürgan will become Deputy Co-ordinator. selected is also clearly set out in the Internal member of the SIG and a member of He is an associate presently Deputy 2009 ESHRE annual advisor to the preimplantation Endometriosis the cross-border editor of Co-ordinator of meeting held in European genetic diagnosis of Rules of ESHRE, whose first draft was Human Also rejoining the ExCo as Chairman guidelines European study for Reproduction ESHRE's SIG Stem Amsterdam. Commission on aneuploidy by the Elect of the Society will be the Finnish approved by the ExCo in 2008. These rules, development group. ESHRE. Update. Cells. medical genetics. FISH technique. gynaecologist Juha Tapanainen, who, as a presented as ESHRE’s ‘Constitution’, clinician, will take over as ESHRE provide transparent guidance on the ‘What we’re aiming for in the Chairman in 2013 from the embryologist Society’s day-to-day operations and on the Executive Committee is quality and fair Agenda of the 2011 Annual General Assembly Anna Veiga. Anna herself will become composition and responsibilities of its many representation,’ says current Chairman Chairman in Stockholm, when Luca committees and working groups. Luca Gianaroli. ‘We’re looking for To be held on Tuesday 5th July 2011, from 18.00 to 19.00, at Gianaroli concludes his term of office. The rules state that the nominees for new commitment, experience and ideas, as Stockholmsmässan, venue of the 27th annual meeting. Juha Tapanainen already has strong ExCo membership are selected from well as a balance between the 1. Minutes of the last meeting (held in Rome and published in Focus on Reproduction, September 2010) experience in ESHRE administration. He applications by the ExCo still in office to disciplines of reproductive science and 2. Matters arising was a member of the ExCo from 2001 to replace those members whose term will medicine, the geography of Europe, and 3. Membership of the Society 2005, while at the same time a member of come to an end. The process requires all the national memberships of ESHRE. 4. Society activities Finnish gynaecologist Juha the Society’s Finance Sub-committee. He pre-selected candidates to submit a CV and We can’t always achieve these aims, but - Annual meetings Tapanainen will become was also a Deputy Co-ordinator of the SIG a statement on how they view their role they remain our targets.’ - Campus meetings Chairman Elect of ESHRE in Reproductive Endocrinology from 2007 to within the Committee. Candidates are asked - Special Interest Groups and Task Forces Stockholm, and will take over 2009. He has also had active committee to attend an ExCo meeting for presentation 5. Human Reproduction journals as Chairman in 2013. As a clinician, Tapanainen roles with the International Federation of of their views and for interview. Each 6. Paramedical Group continues the ESHRE Fertility Societies (IFFS), the ASRM and the candidacy is discussed by the ExCo in the 7. Financial report tradition of alternating the Finnish Gynaecology Association. Today, candidate’s absence before a decision is 8. Ratification of the new Executive Committee discipline of its chairmen - Juha Tapanainen (FI) to become the new Chairman Elect Tapanainen is professor of O&G at Oulu made. The rules additionally state that, between clinical medicine - Jean Francois Guérin (FR), Timur Gürgan (TR), Carlos University Hospital, from where his group ‘while selecting new candidates, the aim and science. Plancha (PT), Françoise Shenfield (GB), Veljko have reported some of the most influential should be to maintain a balance within the Vlaisavljevic (SL) to step down studies on single embryo transfer in IVF. final composition . . . between clinicians - Ursula Eichenlaub-Ritter (DE), Antonios Makrigiannakis (GR), The nominations for appointment to the and basic scientists, male and female’. Miodrag Stojkovic (RS), Anne-Maria Suikkari (FI), Etienne Van ExCo are Carlos Calhaz-Jorge (PT), Jacques Selection also aims to ensure that those den Abbeel (BE) to be re-appointed for a second term of two years De Mouzon (FR), Roy Farquharson (GB), countries comprising ESHRE’s greatest - Carlos Calhaz-Jorge (PT), Jacques De Mouzon (FR), Roy Anis Feki (CH), Niels Lambalk (NL), Milan membership are represented in the ExCo. Farquharson (GB), Anis Feki (CH), Niels Lambalk (NL), Milan Macek Jr. (CZ), and Cristina Magli (IT). The rules, however, add that ‘there cannot Macek Jr. (CZ), Cristina Magli (IT) to be appointed as new members Spanish embryologist Anna Veiga will take 9. Retirement of the Chairman, Luca Gianaroli (IT), and installation of the Their appointments must be ratified by the be more than one member from the same over as ESHRE Chairman in Stockholm for a new Chairman, Anna Veiga (ES) General Assembly in Stockholm before they country in the Executive Committee with two-year term. Anna has responsibility for 10. Election of the Honorary Members for 2012 take up their positions. the right to vote’, unless one of two research at the Dexeus Institute in Barcelona, and is director of the stem cell 11. Any other business The selection of the seven ExCo nominees members from the same country holds the bank at the Centre for Regenerative 12. Date of the next Annual General Assembly was completed according to ESHRE’s by- position of Chairman Elect. Medicine in Barcelona.

6 Focus on Reproduction May 2011 Focus on Reproduction May 2011 7

C INNER may11_nwp:Layout 1 26-04-2011 12:16 Page 8 may11_nwp:Layout 1 26-04-2011 12:16 Page 9

ANNUAL MEETING 2011 // 2011 HUMAN REPRODUCTION JOURNALS LECTURE // // OPENING CEREMONY // Oocyte vitrification set to broaden its scope? Two of the real pioneers of IVF chosen Last year’s most downloaded paper from HR opens 2011 annual meeting

for honorary ESHRE membership 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 Awards to Lars Hamberger and Alan Trounson 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 picture opposite was taken at a Bourn Hall The lecture will be presented by Laura Rienzi, laboratory director at the GENERA reunion meeting in 1997, and, among the many Centre for Reproductive Medicine in Rome, and based on a randomised non-inferiority well respected and well remembered personalities trial of fresh versus vitrified MII oocytes performed by her group.1 The paper had the from the IVF Hall of Fame, are both recipients of highest number of full-text downloads during the first six months of publication of all this year’s honorary membership of ESHRE. original articles in Human Reproduction between January 2009 and June 2010. Standing back right is Alan Trounson from The study, like so many others on Melbourne, and, centre in the next row, Lars oocyte vitrification, was prompted by overall cumulative ongoing clinical fast, and commercial kits are now Hamberger from Gothenburg, Sweden. Both they Italy's 2004 legislation banning pregnancy rate was found to be 54% available,' she said. 'I cannot imagine and their distinguished careers need little embryo freezing and the insemination per started cycle, with maternal age how many women affected by introduction to ESHRE members. of more than three occytes. However, the only variable found to affect malignant diseases or at risk of Rienzi makes clear that the reproductive outcome. Thus, as these premature ovarian failure, might Lars Hamberger implications of this study stretch far cumulative results suggest - as do benefit. They will be deprived of a The first IVF clinic in the Nordic countries was set beyond Italy: 'This technique is also the authors themselves in their child just because the technique has up in Gothenburg with Hamberger, and they had of paramount importance for fertility discussion - such progress in the not yet been routinely introduced.' responsibility for the region’s first IVF birth in preservation, for oocyte donation clinical application of oocyte Certainly, as evidenced by the 1982. Two years later, Hamberger programmes, and to help overcome vitrification has implications not just downloads (and e-mails to Rome), joined ESHRE’s formative ethical issues related to embryo for fertility preservation and oocyte interest is considerable - so maybe ‘temporary committee’ put together cryopreservation,’ she said. banking for egg donation, but also as routine use is not too far away. by Robert Edwards at the 3rd World This was a well designed though a possible alternative to embryo Other Human Reproduction papers Congress of IVF in Helsinki, and it not large study - a total of 224 freezing in routine IVF. scoring highly as downloads were: was here too that Hamberger and colleague Matts turn laid the foundations for an ever-improving and normal MII sibling oocytes Despite changes to the law in Italy l Wennerholm UB, Söderström- Wikland described the technique of transvaginal repeatable IVF programme in Melbourne. Nine of randomised to either fresh ICSI or (which now allow the insemination of Anttila V, Bergh C, et al. Children ultrasound scanning for oocyte collection. The the world’s first ten IVF pregnancies began at after vitrification and warming. The more than three oocytes, but with born after cryopreservation of technique would revolutionise IVF by finally Monash. And, as at Bourn Hall, many clinicians and percentage of good quality embryos important legal considerations for embryos or oocytes: a systematic providing an effective alternative to laparoscopy. scientists from around the world were trained by the was 52% in the fresh group and embryo freezing) Rienzi told Focus review of outcome data. Hum Reprod Thereafter, the Gothenburg group remained at Monash group. 52% in the vitrification group; 15 on Reproduction that her group 2009; 24: 2158-2172, the sharp end of ART, and were the second in the The production of multiple oocytes and embryos clinical pregnancies were obtained in continues to limit its supernumerary l Reefhuis J, Honein MA, Schieve world (after Brussels) to report term pregnancies from the improved procedures developed in the vitrification cycles (37.5% per embryos and to offer oocyte LA, et al. Assisted reproductive with ICSI (in 1993). The group has been similarly Melbourne prompted the development of cycle, 38.5% per embryo transfer), vitrification to all suitable patients - technology and major structural birth influential in the investigation of models for appropriate freezing techniques, which enabled the with an implantation rate of 20%. 'with excellent cumulative results'. defects in the United States. Hum successful implantation (based on uterine epithelial preservation of embryos for subsequent use in IVF. Since then, the group has However, Rienzi would not yet go Reprod 2009; 24: 360-366. cells) and in the development of culture media It was also from Melbourne that embryo donation extended the study to a series of 182 so far as to see oocyte vitrification as consistent with blastocyst formation. was first reported, thereby giving women without ICSI cycles in all of which oocyte an alternative to embryo freezing in References ovarian function the chance of parenthood. vitrification was possible.2 In those routine IVF. 'The main difference 1. Rienzi L, Romano S, Albricci L, et al. Alan Trounson Trounson’s clinical interests progressed to the patients who did not become between the two approaches is time Embryo development of fresh 'versus' There can be few reproductive biologists more diagnosis of genetic disease in embryos, and pregnant in the initial fresh cycle, a to pregnancy,' she said. 'More vitrified metaphase II oocytes after ICSI: a influential than Alan Trounson. He joined the subsequently to the discovery and production of total of 104 first and 11 second warming cycles are needed to prospective randomized sibling-oocyte Monash, Melbourne, IVF programme in 1977 and human embryonic stem cells (and their ability to be study. Hum Reprod 2010; 25: 66-73. oocyte warming cycles (+ ICSI) were complete the treatment with vitrified with Carl Wood and colleagues soon thereafter directed into neurones, prostate and respiratory 2. Ubaldi F, Anniballo R, Romano S, et subsequently performed. The ongoing oocytes than with vitrified embryos.' introduced the clomiphene-hMG protocol for tissue). In 2008 Trounson became President of the al. Cumulative ongoing pregnancy rate This year’s honorary pregnancy rate in the fresh ICSI However, Rienzi underlined the ovarian stimulation. Trounson also applied a delay California Institute for Regenerative Medicine in achieved with oocyte vitrification and ESHRE members: Lars cycle was 37.4%, in the first value of the technique as a patient Hamberger, top, and between oocyte collection and insemination to San Francisco, but retains his chair at Monash as cleavage stage transfer without embryo vitrification cycle 25%, and in the insurance against any future cancer Alan Trounson. allow the oocytes to complete maturation, which in Professor of Stem Cell Sciences. selection in a standard infertility program. second vitrification cycle 27%. The treatment. 'The approach is easy, Hum Reprod 2010; 25: 1199-1205.

8 Focus on Reproduction May 2011 Focus on Reproduction May 2011 9

C OUTER may11_nwp:Layout 1 26-04-2011 12:16 Page 10 may11_nwp:Layout 1 26-04-2011 12:16 Page 11

ESHRE NEWS // PARAMEDICAL GROUP // // FUTURE MEETINGS // A paramedic opportunity for hands-on embryo London and Munich transfer during this year’s precongress course selected as venues The Board of the Paramedical Group is looking to recruit a new English-speaking lab technician to Paramedical Board for 2013 and 2014 strengthen the team. With a group of four lab Chair Jolieneke Schoonenberg-Pomper technicians, four nurses and one psychologist, we try (NL, nurse) to give all paramedical members of ESHRE a voice annual meetings Chair Elect Helle Bendsten and improve their level of education. Board members (DK, lab technician) are required to attend a board meeting three times a Past Chair Heidi van Ranst (BE, lab technician) ESHRE’s 29th annual meeting in 2013 will be held in year (once at the annual meeting). It’s at these Members London at the ExCeL convention centre, and the 30th in meetings that the paramedical sessions of the annual Inge Jorgensen (nurse), Eline Dancet (nurse) 2014 at the ICM Munich. These venues have now been meeting and Campus courses are planned. The Chair Helen Kendrew (nurse), Cecilia Westin (lab confirmed by the Executive Committee. of the paramedical board is a member of the Executive technician), Patricia Baetens (psychologist) The 2013 event will be the third in the UK, following Committee and is therefore well placed to make strong Cambridge in 1987 and Edinburgh in 1997; 2014 will be a representation for all the paramedical members of fourth time for Germany, following Bonn in 1985 ESHRE. (ESHRE’s first annual meeting), Hamburg in 1995, and further professional development. Stimulating ideas Berlin in 2004. Basic training for paramedics were exchanged on the inclusion of emotional support The ExCeL centre is a modern facility constructed as Following events in UK (2009) and Spain (2010), in in daily clinical care. part of the huge regeneration of London’s former docks. March this year we ran our third two-day basic training The next basic training course for paramedicals will Located in the ‘east end’ of the city, the convention centre course for members and colleagues. Nurses, lab be on 24-25th May 2012 in Copenhagen, Denmark. is well served by rail and bus links - and the London City technicians and others new to the field of reproductive airport is only minutes away. This segment of London is London and Munich will host ESHRE’s 2013 and 2014 health took part. Our enthusiastic speakers provided Embryo transfer the theme for Stockholm also undergoing huge redevelopment for the 2012 annual meetings. updates on anatomy and physiology, the causes and Our precongress course in Stockholm will focus on Olympics, which are expected to enhance local transport diagnosis of infertility, lifestyle factors, counselling embryo transfer. Our embryologist speakers - who and hotel services even further. with strong experience of international medical meetings. and communication, stimulation and treatment include Kersti Lundin and Lynette Scott - will The International Congress Centre Munich is one of the Local organisers and dates for each of the two events techniques. The course took place in the inspiring city concentrate on the embryo, while others - most modern and successful congress centres in the world, have yet to be confirmed by the Executive Committee. of Berlin and was conveniently located near the airport including Helen Kendrew and Rebecca Goulding - will with social events well attended by speakers and focus on transfer techniques. Our hands-on session in delegates. At the end participants could opt for a the afternoon looks very attractive and interesting. All certificate of attendance or to take part in an exam the equipment for an education in the time-lapse ESHRE and ASRM join up for the best of the best leading to certification. Learning objectives seemed assessment of embryos - and for practice in the well achieved, as the vast majority passed their exam transfer procedure - will be in place. So we invite you ESHRE and the ASRM have agreed to stage a joint annual lectures specifically designed for both practitioners and and our Berlin delegates are now well equipped for all to enrol for the course and take advantage of these meeting in which the ‘best of’ reproductive medicine can scientists. Organisation in the first two years will lie in the unique practical opportunities. be presented in a relaxed scientific environment. The two hands of a scientific committee comprising three ESHRE societies will put their heads and best experience together and three ASRM members - with the second event in 2013 Paramedical Board Annual General Meeting in a meeting which alternates each year between European planned for the USA. The AGM of the Paramedical Board is also held during and American venues to encourage attendance from both the ESHRE annual meeting and the Board encourages continents. The venues will be selected for their conference The ski resort all members* to attend in Stockholm. The meeting will facilities and for opportunities to socialise with of Cortina take place on Monday 4th July during lunchtime break; d’Ampezzo, transatlantic colleagues. The first meeting will be held at venue in we will be pleased to see as many members as possible the Italian resort of Cortina d’Ampezzo on 1-3rd March 2012 for the to discuss our further plans. 2012. The three-day meeting will divide its time between first ‘best of’ * You are eligible for ESHRE paramedical membership if you scientific lectures and discussion (in the early morning and ESHRE and are a nurse, midwife, laboratory technician, ESHRE certified ASRM spring later afternoon) and recreational activities - hence the clinical embryologist (BSc level), counsellor or psychologist. meeting: an Paramedical members currently comprise around 10% of emphasis on a socially agreeable venue. opportunity for learning ESHR’s full membership. The project’s mission statement promises that discussion will cover a broad range of reproductive medicine, biology and Hands on . . . Not every moment in Berlin was basic training. Eline Dancet and Jolieneke Schoonenberg-Pomper recreation. and surgery, ‘with the ultimate goal of enhancing the quality of patient care and improving outcomes’, with

10 Focus on Reproduction May 2011 Focus on Reproduction May 2011 11

D INNER may11_nwp:Layout 1 26-04-2011 12:16 Page 12 may11_nwp:Layout 1 27-04-2011 11:05 Page 13

ESHRE NEWS // EXECUTIVE COMMITTEE // // FINANCE COMMITTEE //

Members of ESHRE Bank balance remains committees to disclose ESHRE signs up to European positive despite some alliance for medical research conflicts of interest declines in revenue ESHRE has joined a new European alliance of biomedical ESHRE’s Executive Committee has agreed that, researchers launched to boost funding and keep Europe The financial report for 2010 presented to the from Stockholm onwards, all its officers must competitive against ever-present competition from the USA General Assemby in Stockholm will show a complete a conflict of interest disclosure form. and increasing competition from Asia. The EU spends just favourable balance of income over expenditure. The Nominees for the next ExCo have already 1·8% of its gross domestic product on all R&D, compared previous year’s activities had resulted in a slight completed the disclosure such that any potential with 2·7% in the USA, and 3·4% in Japan. The Alliance for deficit, but 2010 generated a net balance of almost conflicts of interest have been reviewed before Biomedical Research in Europe has now been formed to 150,000 euro. ratification at the General Assembly. The ExCo lobby for extra research funding so that Europe is not left Once again, the Society’s greatest source of agreed that the following officers would need to behind. income - and expenditure - was the annual meeting, complete the form: Behind the Alliance lie four of Europe’s major professional despite a substantial increase in operating costs and l All members of the Executive Committee, organisations, all with common public health interests: the a slight decline in revenue. However, income from including ex officio members European Association for the Study of Diabetes (EASD); the ESHRE journals rose, with expenditure declining l All members of the Paramedical Board European Respiratory Society (ERS); European Society of a little. Publications accounted for 17% of ESHRE’s l All members of sub-committees Cardiology (ESC); and European Cancer Organisation income, and the annual meeting 65%. l All SIG co-ordinators (ECCO). Representation from a further 28 societies across Educational activities, with a spend of more than l All Task Force co-ordinators Europe - including ESHRE - will give representation to an 700,000 euro, accounted for 12% of total l All chairmen of ESHRE consortia (PGD and EIM) estimated 400,000 European researchers. expenditure, but with tighter planning requirements So far, deputy co-ordinators of the SIGs and Task Co-ordination of their reseach interests will give a single costs were somewhat reduced from 2009. However, Forces have not been included, though co-ordinators ‘powerful’ voice to what has so far been a fragmented revenues from registrations declined. will be asked if their inclusion is considered exercise. Currently, about 90% of funding for health-related necessary. From Stockholm onwards, completion of research in EU countries comes from member states' own the conflict of interest form will be a first step in the budgets, with the other 10% coming from the European New members elected to Committee of National Representatives recruitment of any member to an ESHRE Parliament. As well as lobbying for more research money, committee. the Alliance will also help the European research community A new Committee of National Representatives will be representatives (one clinical, one basic science), who are The aim of the move, said Past Chairman Joep interact with the EU more effectively and provide a single formed in Stockholm following nominations and elections elected for a period of three years, with the opportunity to Geraedts, is to ensure transparency in ESHRE’s representative voice. among local members earlier this year. European countries stand for one further term. Those elected after the two activities and to make any potential conflicts of ESHRE was represented by Luca Gianaroli and Joep with more than 15 members are entitled to two rounds of voting are listed below: interest public - as now happens, for example, with Geraedts at the alliance’s inaugural meeting. manuscript submission to the journals. Austria Laure C. Morin-Papunen (c) Macedonia Eda Vrtacnik-Bokal (c) Thomas Ebner (basic scientist) France Birol Aydin (bs) Spain Ludwig Wildt (clinician) Pierre Boyer (bs) Zoranco Petanovski (c) José Horcajadas Almansa (bs) Belgium Catherine Rongieres (c) Norway Alfonso L. De La Fuente (c) ESHRE evidence to European court ruled inadmissible Bjorn Heindryckx (bs) Germany Anette Bergh (bs) Sweden Frank Vandekerckhove (c) Peter Vogt (bs) Nan Brigitte Oldereid (c) Julius Hreinsson (bs) Bulgaria Markus S. Kupka (c) Poland Pia Saldeen (c) ‘Ad adjuvandum’ evidence submitted by ESHRE after legal example, the Court did grant permission to intervene as a Tania Milachich (bs) Greece Rafal Kurzawa (bs) Switzerland advice to the Grand Chamber of the European Court of third party to the ‘European Centre for Law and Justice’, a Tania Nikolova Timeva (c) Kalliopi Loutradi (bs) Ireneusz Polac (c) Manuel Pensis (bs) Human Rights has been deemed inadmissible. The self-styled ‘Christian-inspired’ organisation said to be Croatia Grigoris Grimbizis (c) Portugal Gabriel De Candolle (c) comment was submitted ahead of an appeal by the representing 51 others, many of them openly Catholic. The Patrik Stanic (bs) Hungary Vasco Almeida (bs) The Netherlands Austrian authorities against a European Court ruling that governments of Germany and Italy were also allowed to Hrvoje Vrcic (c) Katalin Kanyo (bs) José Domingues Nunes (c) Aafke Van Montfoort (bs) Cyprus Péter Kovács (c) Romania Jesper Smeenk (c) Austria’s ban on gamete donation contravened the human comment formally in support of the Austrian government. Michael Pelekanos (bs) Ireland Andreea Sandra Mustata (bs) Turkey rights of two claimants - their rights of respect to family Among the consumer groups given permission to comment Krinos M. Trokoudes (c) Geraldine Emerson (bs) Bogdan Doroftei (c) Basak Balaban (bs) life as set out in article 8 and that the denial of gamete were the Italian organisations Hera Onlus and SOS Czech Republic Anthony Walsh (c) Russia Bulent Urman (c) donation was discriminatory. ESHRE’s evidence supported Infertilità Onlus. Alice Malenovska (bs) Israel Sergey Yakovenko (bs) Ukraine the Court’s original ruling. A procedural hearing in February confirmed that the Milan Mrazek (c) Jeremy Don (bs) Anna Smirnova (c) (No basic science candidate) Denmark Zeev Blumenfeld (c) Serbia Lyubov Myhailyshyn (c) Luca Gianaroli, Chairman of ESHRE, said that the Grand Chamber will hear the Austrian government’s Christina Hnida (bs) Italy Nada Tabs (bs) United Kingdom rejection of the submission was inexplicable, especially appeal, but no date was fixed for the hearing or the Kirsten Tryde Schmidt (c) Giovanni Coticchio (bs) Nebojsa Radunovic (c) Julia Paget (bs) when evidence was allowed from consumer groups and judgement, which, according to the Court, may yet take Finland Maurizio Guido (c) Slovenia Ertan Saridogan (c) organisations representing the Catholic church. For several months. Sirpa Mäkinen (bs) Borut Kovacic (bs)

12 Focus on Reproduction May 2011 Focus on Reproduction May 2011 13

D OUTER may11_nwp:Layout 1 26-04-2011 12:16 Page 14 may11_nwp:Layout 1 26-04-2011 12:16 Page 15

ESHRE NEWS // EUROPEAN GUIDELINES // // ESHRE CLINICAL TRIAL // Three ESHRE guidelines now under way, Green light for polar body microarray CGH trial Following the successful completion fresh or frozen embryos. Secondary all developed according to new manual of its proof of principle study of polar outcomes include live birth rate in a body biopsy and microarray analysis, specific good prognosis group, ESHRE is now ready for the next pathway outcome (implantation With ESHRE stepping up development of its European guidelines step: a randomised controlled trial rates, ongoing pregnancy rates, for clinical management, a manual for their development was 12 steps in the guideline process (RCT). This trial has two primary abortion rates), genetic outcomes produced by the SIG Safety & Quality in ART and published on 1 Topic selection aims among women with advanced (proportion of aneuploidy, affected the ESHRE website in 2009. The process was divided into 12 2 Guideline development group maternal age: first, to estimate the chromosomes), diagnostic efficiency, steps, as summarised in the table opposite. 3 Scoping likelihood of having no euploid embryo outcomes, and adverse In October last year I was appointed as a research specialist to 4 Key questions embryos in future ART cycles; and events. begin or resume the guideline development process on three topics 5 Evidence search second, to improve live birth rates. The total study will involve 600 in reproductive medicine and embryology. 6 Evidence summary / grading Among women aged 36 to 40 couples, allowing for possible losses, l The first project is to develop guidelines for the clinical 7 Recommendations formulation years planning three ICSI cycles, with 300 in each arm. management of endometriosis. A guideline in endometriosis was 8 Draft version does microarray analysis of all chromosomes in the The trial will begin soon and the Cambridge produced in 2005; thus, the current guideline development group, 9 Review and consultation first and second polar body compared with no company BlueGnome will again be our partner. chaired by Gerard Dunselman, aims to update the text according 10 Final version intervention increase the likelihood of a live birth Blue Gnome will provide training and free arrays to the requirements of the manual. Key questions have been 11 Approval within one year? And in women with no and consumables for the study. written by the group and I am now collecting the evidence for 12 Dissemination and implementation euploid embryos what is the likelihood of ESHRE will take care of polar body evaluation by the group members before they compose their euploid embryos in a subsequent cycle? biopsy training via its pilot study centres in recommendations on diagnosis and surgical and medical The proposed design is a pragmatic, Bonn and Bologna, where the proof of treatment. The aim is to have the document finished as soon as multicentre, randomised double-blind principle study was successfully possible. controlled trial with an intention-to-treat completed. l ESHRE consensus on ‘poor A second project involving the management of premature analysis. The sample size will be For the selection of the centres, all ovarian insufficiency was proposed by Adam Balen as Co- ovarian response’ approved estimated, however, to allow for a European PGD Consortium members (with ordinator of the SIG Reproductive Endocrinology. A first meeting and submitted for publication secondary analysis limited to patients full membership for the past three years) has been held with four UK specialists in POI to set the scope of most likely to be helped by PGS screening. were invited to apply. The centres had to the guideline and discuss composition of the development group. An ESHRE consensus paper on the definition The target population for the trial is be experienced in performing embryo The next step will be the formation of the group (whose of poor ovarian response (POR) - and on the women planning IVF or ICSI who are at Joep Geraedts, Chairman biopsy (not specifically polar bodies) and chairmanship will be shared by Melanie Davies and Lisa Webber), use of prognostic tests of ovarian reserve - has high risk of having aneuploid embryos of ESHRE’s PGS Task with experience in molecular analysis. No and production of the key questions. been approved by ESHRE’s Executive because of their age. Force, which has conflict of interest was allowed, meaning l planned the design of The third project is for the SIG Psychology & Counselling with Committee and submitted for publication in Inclusion criteria are infertility as an that staff members involved in the study the trial. its scope defined by the organisation of psychosocial care. The Human Reproduction. The consensus was indication for IVF or ICSI, patients should not be a consultant for companies guideline will aim to set minimum standards in the provision of derived from a 2010 workshop in Bologna between their 36th and 41st birthdays, BMI range offering a similar technology. Patients should not psychosocial care in clinics, with reference to specific groups of involving every one of ESHRE’s 11 Special 20-30 kg/m2, and patients prepared to accept the be charged for PGS and the centres could only take patients and the different phases of treatment. For this project, a Interest Groups. The ‘Bologna criteria’ defined transfer of two embryos. Exclusion criteria are part in other similar studies at the same time if the meeting has already taken place at which Sofia Gameiro was POR (or expected POR) as the presence of at cycles involving donor gametes, two or more patient group was not the same. appointed chair of the development group, and where the scope least two from previous failed IVF or ICSI cycles, poor response in On the basis of these criteria ESHRE's Executive and committee membership were discussed. The scoping of the l advanced maternal age or any other risk any previous cycle and low ovarian reserve as Committee has selected the following five PGD guideline will be completed through an online forum, which will factor for POR defined by Ferraretti et al (in press, defined by at Consortium members (in addition to the training also help with the next step, composition of the key questions for l a previous poor response to stimulation least two of the following three features: advanced centres in Bonn and Bologna): the guideline. l an abnormal test of ovarian reserve maternal age or any other risk factor for POR; a l Centre for Medical Genetics, University Hospital The development of these guidelines is supervised by the Age was unanimoulsy defined as the most previous poor ovarian response; and an abnormal Brussels, Belgium Executive Committee, as are other projects requiring the predictive measure of pregnancy, with four (or ovarian reserve test) and cycles requiring surgical l Center for Reproductive Medicine, University endorsement of existing guidelines. Since guidelines for clinical fewer) oocytes agreed as a definition of poor sperm recovery procedures, total astenozoospermia Women's Hospital, Kiel, Germany management are important in many other fields, a request for new response to stimulation. and globozoospermia. l Department of Medical Genetics, Athens project proposals will later be launched. However, to ensure that The paper will be published as: The first primary outcome is the accuracy of a University, Greece the existing projects are developed as appropriately and swiftly as Ferraretti AP, La Marca A, Fauser BCJM, et al. first cycle result with all aneuploidy embryos in l Medical Genetics Institute, Shaare Zedek possible, this request for new proposals will await completion of Bologna 2010 consensus on the definition and predicting the same result in the second and third Medical Center, Jerusalem, Israel the current projects. diagnosis of ‘poor response’ to ovarian cycle. The second primary outcome is live birth rate l Institut Universitari Dexeus, Barcelona, Spain Nathalie Vermeulen stimulation for in vitro fertilization. within one year after the cycle of treatment, from Joep Geraedts, Chairman Task Force PGS Research Specialist, ESHRE Central Office

14 Focus on Reproduction May 2011 Focus on Reproduction May 2011 15

E INNER may11_nwp:Layout 1 26-04-2011 12:16 Page 16 may11_nwp:Layout 1 26-04-2011 12:16 Page 17

// ESHRE EMBRYOLOGY CERTIFICATION // Position paper on access to treatment nears completion; Credits system for continuing embryology final draft ready for Stockholm certification to be introduced in Stockholm

Fertility Europe has continued its programme of projects Programme set to include embryologists from outside Europe and is grateful to ESHRE for sponsorship in 2011. Our vision is that fertility organisations from every country in Europe will become a part of Fertility Europe. ESHRE’s Demand remains strong for ESHRE’s certification in support will help us expand the network of patient embryology. This year’s examinations will take organisations throughout Europe - and employ an office place in Stockholm on Saturday 2nd July at 15:00. manager (which we have lacked for the last year or so). There are 65 registered for the senior clinical During that time FE has been run on a purely voluntary embryology exam and 136 registered for the clinical basis. embryology exam. Some organisational improvements have been Members Spring Meeting made recently and we invite all embryologists to Our Members Spring Meeting, also supported by ESHRE, visit to our improved web page at www.eshre.eu was held in Prague in March. Here, following (under ‘Accreditation & Certification’). advertisement, applications and interviews, we appointed The annual meeting in Stockholm will officially as our new office manager Kalina Nedelcheva from the introduce two important innovations in the patient organisation Iskam Bebe in Bulgaria. Kalina has all certification programme: the necessary qualifications for the post as well as a huge l The Continuous Embryology Education Credit knowledge of infertility. Representative members of Fertility Europe at its Spring Meeting in System is intended to encourage embryologists to A total of 21 representatives from 18 patient Prague; FE’s aim is that patient organisations from every European collect education credits, and thereby renew their organisations joined us in Prague. The meeting had been country will eventually be represented. embryologist certificate. This is a feature for Heads down. Certification examinees in Amsterdam 2009. preceded by a questionnaire sent to all participants on ESHRE members only, and the credits needed for There are now more than 700 ESHRE certified embryologists. fertility education and infertility prevention in their home are then made into postcards. certification renewal should be obtained in three- countries. The results were summarised by Denisa Why the campaign? Sadly, we still have large problems year blocks. Specifically, senior clinical this programme will be published in January 2012. Priadková, Vice-Chair of FE, and will help form the basis in Europe when it comes to patient access to treatment, embryologists will need ten credits and clinical A column with ‘renewed in . . .’ will be added to the of our session in the Stockholm scientific programme - with costs still a major barrier. The Special Families project embryologists six credits, obtained over a three-year list of certified embryologists 2008; and in January which is also on the prevention of infertility. The session - is our way of putting a human face on the impact of period, in order to apply for renewal of their 2013 the list of certified embryologists from 2009 Education in fertility awareness, from prevention to action: infertility - as well as illustrating the numbers affected and certificate. will be updated. l whose duty? - will take place on Tuesday afternoon and the challenges couples face. All over Europe people are Attendance at scientific meetings, publications, The second innovation is an extension of the will feature talks on fertility awareness among teenagers in struggling to conceive, and Fertility Europe has the deepest contributions to meetings and courses will all be ESHRE certification scheme to outside the borders of Sweden and infertility prevention campaigns in Belgium. respect for couples in this position. However, although taken into consideration for the award of credits. Europe. Symbolically, this will begin with the 2012 Our policy work has also continued and the first draft of difficult for some, they can and do move on, and often More information on the specific action categories examination to be held just before our annual a position statement on Equity of Access to Medically create a special family of their own. We hope that they too and their corresponding credits is available on the meeting in Istanbul. Only senior clinical Assisted Reproduction was presented in Prague. After a will join the campaign. website. embryologists will be able to apply at this stage, and wide-ranging discussion, we hope to have a final draft If you feel you can help and would like to know more, Official documents indicating eligibility for credits there will be a maximum of 60 applicants. All ready for Stockholm. just contact [email protected]. must be uploaded to the ESHRE website. After necessary documents (MSc degree and/or PhD, And please visit our website at www.fertilityeurope.eu to having collected six or ten credits, no more logbook, etc) will need to be translated into English Special Families campaign find out more. And when you do, if you notice that we documents can be uploaded for that three-year by an official translator and validated, before ESHRE’s sponsorship also provides financial support for don’t have a European patient organisation listed for your period. Thus, a certified embryologist from 2008 uploading them through the ESHRE website. More our Special Families project, which was successfully piloted country and you know of one, please get in touch with us can upload documents collected after 1st January information about this will be placed on the website in Rome last summer. The project is based on ‘messages of via the website. And come and see us at our exhibition 2009; those from 2009 can upload documents The ESHRE Embryology Certification hope’ in the form of pictures (photos of family, children, stand in Stockholm - we are there to work in partnership collected after 1st January 2010. The first results of Steering Committee couples, handprints or child illustrations) and words with health professionals and all members of ESHRE. explaining why the family sees itself as ‘special’. The Clare Lewis-Jones pictures and stories in the native language of the country Chair Fertility Europe

16 Focus on Reproduction May 2011 Focus on Reproduction May 2011 17

E OUTER may11_nwp:Layout 1 26-04-2011 12:16 Page 18 may11_nwp:Layout 1 26-04-2011 12:16 Page 19

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

18 Focus on Reproduction May 2011 Focus on Reproduction May 2011 19

F INNER may11_nwp:Layout 1 26-04-2011 12:16 Page 20 may11_nwp:Layout 1 26-04-2011 12:16 Page 21

SPECIAL INTEREST GROUPS // REPRODUCTIVE ENDOCRINOLOGY // // EMBRYOLOGY //

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

20 Focus on Reproduction May 2011 Focus on Reproduction May 2011 21

F OUTER may11_nwp:Layout 1 26-04-2011 12:16 Page 22 may11_nwp:Layout 1 26-04-2011 12:16 Page 23

SPECIAL INTEREST GROUPS // ENDOMETRIOSIS & ENDOMETRIUM // // PSYCHOLOGY & COUNSELLING //

Implantation in IVF drives a ‘lively’ interest; Dealing with ‘third party’ reproduction our record abstract submissions for Stockholm precongress theme for the annual meeting

We once again look forward the WCE returns to France, Plans for Stockholm clinical work around Europe. Steering committee Steerting committee to a very lively interest in to Montpellier, and will Our precongress course on 3rd This year a joint Campus Hilary Critchley (GB), Co-ordinator Petra Thorn (DE), Co-ordinator the subject of our SIG take place from 4-7th July in Stockholm will provide a workshop with the SIG Andrology Anneli Stavreus-Evers (SE), Deputy Co-ordinator Endometrium Christianne Verhaak (NL), Deputy Co-ordinator judging by the number and September. Information can theory and practice update on will be organised in Seville, Spain, Gerard Dunselman (NL), Deputy Co-ordinator Endometriosis Jan Norré (BE), Deputy Co-ordinator quality of abstracts be found at ‘third party reproduction’. As on 22-23rd September. The Annemiek Nap (NL), Junior Deputy Patricia Baetens (BE) Past Co-ordinator submitted for the annual http://www.wce2011.com/. legislation and professional objective is to focus on ‘the whole Thomas d’Hooghe (BE), Past Co-ordinator Uschi Van den Broeck (BE), Junior Deputy meeting in Stockholm. More We do hope this meeting guidelines have been introduced man’, with presentations on the than 100 abstracts in the will receive strong support and modified over the past care of the man in the clinic, newly defined field of ‘Endometriosis, endometrium, from the ESHRE membership. decades, psychosocial professionals working in their daily lifestyle factors, diagnosis, treatment, future patients, future implantation’ were submitted, and we expect some exciting The World Endometriosis Society produces excellent bi- practice with donors, recipients and other third parties will health, how to take care of a man’s sperm and finally the free communications and posters. monthly e-journals, which they are happy to make freely gain an understanding of the complex issues involved in impact of infertility on the man as a person, not just a The invited programme is also excellent. Speakers include available to SIGEE members - the latest issue can be dealing with multiples parties. Topics will include open- sperm producer. This 1.5 day course is targeted at both Sudhansu Dey (US) on Peri-implantation communication downloaded from http://www.endometriosis.ca/ identity embryo donation, gay men using surrogacy and medical and psychosocial professionals and will introduce between embryo and uterus - markers of embryonic ejournal.html. WES should also be congratulated on its egg donation, intrafamilial gamete donation, information- participants to issues they may not yet have addressed in competence and uterine receptivity. Session 16 on Tuesday launch of the very first ever awareness film on sharing with offspring, counselling semen donors for their daily practice. It will is on fibroids and reproduction and here Jose Horcajadas endometriosis. This is available from http://endometriosis. contact with offspring and pre- and post-treatment provide information and an (ES) will speak on the Impact of fibroids on endometrial org/news/general/first-ever-awareness-film-on- counselling for egg donors. The course will be chaired by opportunity for discussion on function and William Catherino (US) on the Impact of endometriosis-launched-by-world-endometriosis-society/, SIG Co-ordinator Petra Thorn and Deputy Chris Verhaak the needs and ways of fibroids and fibroid management on reproductive success. and is supported by strong (video) statements from WES and the full programme can be found online at the ESHRE providing the latest The increased interest in the role of the endometrium, president Hans Evers and European Parliament Vice- website. psychological and medical care reflected in the number of abstracts submitted this year is president Diana Wallis. In April, versions in German, Following the precongress course, our SIG business of the infertile man in our also a reflection of an increased interest in milder Spanish, French and Italian were introduced. meeting welcomes members to join in the discussion. clinics. The full programme stimulation protocols and in the transfer of embryos in Topics this year will include previous and upcoming can be found on the ESHRE natural cycles. We hope that this trend will continue in the Future SIGEE meetings Campus workshops and an update on the progress of the website. years to come. In October this year we have an ESHRE Campus meeting new Psychology and Counselling Guidelines. In addition, a In the Spring of 2012 the It is on the endometrium that we focus for this year’s in Rome on Endometriosis and IVF. The programme, new board will take over in Stockholm as our current Co- SIG Psychology and ordinator, Petra Thorn, will be stepping down after three precongress course in Stockholm, The impact of the which is now on the ESHRE website, will include a Counselling will step into Our current Deputy reproductive tract environment on implantation success; the session on the ever controversial subject of surgical years of excellent work for our SIG. The results of the Eastern Europe with a course in March Co-ordinator Chris full programme is on the ESHRE website. It’s clear that intervention before IVF and a presentation on tissue or election for two new senior deputies and a junior deputy in Budapest, Hungary. The course will Verhaak will take over multiple factors have an impact on successful implantation gamete cryopreservation for fertility preservation in severe will be revealed and our new Co-ordinator, Chris Verhaak, focus on developing competence in as Co-ordinator in will be introduced. Stockholm when Petra and this course will address its potential systemic (pelvic, endometriosis given by Jacques Donnez. psychosocial care and counselling. The Thorn steps down. metabolic and haematological) and local (uterine and tubal) Looking ahead to 2012, the SIGEE has proposed a The annual dinner in collaboration with the International course is devised for two groups of environmental influences. The content will appeal to basic further Campus course in Leuven, Belgium, on quality Infertility Counsellors Organisation (IICO) will complete professionals: medical and administration staff can improve scientists as well as to all those who manage and focus their control in clinical surgical trials for endometriosis surgery; the day’s events in the city centre of Stockholm. Those their understanding for the psychosocial needs of patients research endeavors on patients with endometriosis and this has been organised in conjunction with the SIG interested in joining the dinner can contact me and their skills in managing difficult situations such as fibroids, and in particular those practitioners with an Reproductive Surgery and the ASRM’s SIG Endometriosis ([email protected]) for more information. breaking bad news; psychologists and counsellors can interest in managing patients in early pregnancy and with a for early 2012. further their professional expertise in the specialist areas of problematic early pregnancy. Finally, I am also pleased to report that the Campus workshops: past, present and future couple counselling or helping clients with issues such as The SIGEE business meeting will be held after the endometriosis guideline development group is now making Our second Psychology and Counselling Campus workshop third party reproduction or loss and bereavement. Special precongress course on Sunday 3rd July (at a time and venue steady progress with the assistance of ESHRE’s research held in December last year was a great success despite the attention will be paid to issues relevant for Eastern to be advised). specialist in guideline development. difficult snowy weather conditions in Amsterdam. European professionals and cross-border reproductive care. Meanwhile, we look forward to seeing as many of you Participants, who arrived from many different countries, 2010 has been a very productive year for the SIG World Congress on Endometriosis as possible in Stockholm, Montpellier, and Rome! included psychosocial professionals as well as doctors, Psychology and Counseling and we hope to see many of We remind all SIGEE members that this year is the 25th Hilary Critchley nurses, midwives and administrative personnel. This you in Stockholm. anniversary of the first world congress on endometriosis, SIGEE Co-ordinator ensured a multidisciplinary mix which guaranteed an Uschi Van den Broek which took place in Clermont-Ferrand in 1986. In 2011 interesting discussion at the various workshops, as well as Junior Deputy Co-ordinator the opportunity to find common ground and differences in SIG Psychology and Counselling

22 Focus on Reproduction May 2011 Focus on Reproduction May 2011 23 may11_nwp:Layout 1 26-04-2011 12:16 Page 24 may11_nwp:Layout 1 26-04-2011 19:41 Page 25

SPECIAL INTEREST GROUPS TASK FORCES // EARLY PREGNANCY // // DEVELOPING COUNTRIES AND INFERTILITY //

New diagnostic tools for EP complications Millennium Development Goal 5:

Four SIG-EP events are scheduled disorders: integrating clinical, What happened to infertility? over the next 12 months: Steering committee immunological and epidemiological l Ole Christiansen (DK), Co-ordinator Our precongress course in aspects, is an attempt to bring The UN’s fifth Millennium Development Goal - to improve Akoung from Mariette Goddijn (NL), Deputy Co-ordinator Stockholm, From genes to gestation, together clinicians and reproductive maternal health, and particularly Goal 5b (to achieve Cameroon and Siobhan Quenby (GB), Deputy Co-ordinator is organised in collaboration with immunologists with a series of universal access to reproductive health) - is the most off- Miriam Kadio Marcin Rajewski (PL), Junior Deputy the SIG Reproductive Genetics. The clinically relevant lectures and track of all the eight MDGs, even though the critical Moroko from Ivory Roy Farquharson (GB), Past Co-ordinator programme reflects the very rapid discussion relating to early importance of reproductive health to development has been Coast) and two expansion in our knowledge of the pregnancy complications: diagnosis, widely acknowledged. Almost all the itemised objectives of French biologists (Ben human genome and in particular the genes affecting causes and treatment with a focus on immunology and Goal 5 deal with reducing maternal mortality, preventing Khalifa and Benoît implantation and early embryo development. New genetic epidemiology. Even if you have only a modest knowledge unwanted pregnancies and curbing the spread of sexually Schubert). The diagnostic techniques and therapies will be reviewed. The about immunology, this is your chance for an update. The transmitted infections, including HIV and AIDS. Nowhere training focused on course is an ideal opportunity to brush up your genetic full programme is available at www.jem2011.com and on in sight is the treatment (or even prevention) of infertility. the new WHO ESHRE workshop on semen analysis during the 3rd Congress of GIERAF in Benin, with knowledge in the company of excellent speakers. the ESHRE website; registration is via the former website. Although infertility and childlessness are a global standards for semen l Jean François Guerin and keen pupils. I should also remind you that invited lectures from two Our precongress course in Istanbul in 2012 is on Gamete problem in reproductive health, with a silent population of analysis, sperm eminent speakers on the first morning of the scientific quality and ovarian reserve as markers for early pregnancy more than 200 million couples according to the WHO, preparations for ART programme should not be missed: Graham Burton will loss, designed to be of interest to those working in initiatives from the UN are scarce, if any. All organisations (insemination and review interesting new theories on the function of the reproductive medicine. Is it possible to identify markers in working in the field of human reproduction, including IVF) and practical placenta in very early pregnancy, while Eric Steegers will the gametes of ART patients which can pinpoint those scientific organisations, NGOs and foundations, show little demonstrations. show how far we have come in imaging the early embryo carrying a particularly high risk of miscarriage - and can or no interest in the field of subfertility in resource-poor GIERAF expressed its in utero, an unique technique with very wide perspectives. something be done to prevent it? countries. Overpopulation and the limited-resources hope to continue this l l If you have always thought that research in For those taking part in this year’s ASRM annual argument are always raised by those opposed to the idea of fruitful collaboration. immunological factors relating to early pregnancy meeting in Orlando, Florida, we recommed the providing infertility care in developing countries - even if complications is actually too complicated, think again and ASRM/ESHRE Exchange Early Pregnancy Workshop on we can make it cheaper and accessible to a much larger Social Study Group take a trip to Copenhagen for 23-26th August. Here, a 15th October. part of the world population. Target 5.6 of MDG5 is to Our Social Study joint meeting between the SIG-EP and European Society of Ole B. Christiansen achieve, by 2015, universal access to ‘the unmet need for Group was involved Papreen Nahar speaking at the Social Study Reproductive Immunology (ESRI), Early pregnancy Co-ordinator SIG Early Pregnancy family planning’. Most of those at the Millennium in a one-day Group meeting in Durham, UK. Declaration in 2000 - and at several summit meetings since colloquium in - must have forgotten that family planning is not just the December 2010 in Durham (UK), which aimed to identify // REPRODUCTIVE SURGERY // prevention of unwanted pregnancies but is also the social, cultural and moral issues surrounding infertility opportunity of pregnancy in involuntary childlessness. We and its solutions, particularly focusing on the use of ART Assessing the effect of diagnostic hysteroscopy on IVF outcome believe it’s time for action; it’s time to go to the politicians in resource-poor countries, Islamic societies and diaspora and NGOs and convince them that infertility care must be communities. The workshop, which hoped to make ESHRE's SIG Reproductive Surgery is now involved in instrument (the TROPHYSCOPE- included in their future action plans. recommendations for policy and practice, turned out to be the TROPHY study, a multicentre randomised ‘Trial of CAMPO compact hysteroscope), a very fruitful and interesting meeting. Outpatient Hysteroscopy’. The study was set up in with a redesigned tip to reduce ESHRE training course in Cotonu, Benin autumn 2008 in response to the systematic review of trauma and smoothe passage During the second GIERAF (Groupe Interafricain d’Etude, ESHRE message at the ISMAAR congress in India Tarek El-Thoukhy, published that year, which reported a through the cervix. A gliding de Recherche et d’Application sur la Fertilité) meeting in The fourth World Congress of ISMAAR (International positive effect of diagnostic hysteroscopy on IVF system provides diagnostic and 2010 René Frydman and I proposed a multicentre study on Society for Mild Approaches in Assisted Reproduction) outcome. El-Thouky concluded that ‘future robust operative functions in one single the causes and treatment of infertility in Africa. The first was held in Kolkata, India, in January. During the randomised trials comparing OH (office hysteroscopy) or instrument. results of this study were presented at the third congress of Opening Ceremony two important Indian Ministers mini-hysteroscopy with no intervention before IVF The trial is now an official GIERAF held in Cotonou, Benin, in February. As a result of (Minister Manata Banerjee and Minister Ghulam Nabi treatment would be a useful addition to guide clinical project of ESHRE’s SIG Reproductive Surgery in this work, ESHRE agreed to sponsor a one-day workshop Azad, the current Minister of Health and Family Welfare) practice’. collaboration with the European Academy of in Cotonou on semen analysis and sperm processing, which each highlighted the importance of access to infertility care Thus, a randomised trial has now been set up at Gynaecologial Surgery. proved a great success. Instead of the expected 30 persons, in India, a message which was undoubtedly influenced by Guy's and St Thomas hospital in London by El-Thouky, The trial is not yet concluded but all centres are 50 took part from ten countries (Benin, Cameroon, Côte our Special Task Force. I believe it was the first time in with several centres agreeing to take part (from the UK, recruiting patients and first data soon will be available. d'Ivoire, Togo, Mali, Senegal, Madagascar, RD Congo, history that such important politicians have expressed Italy, Belgium and Czech Republic). The Karl Storz Marco Gergolet Congo, and Burkina Faso). Jean François Guerin (co- their wishes for affordable IVF in resource-poor countries. company has developed a brand new design of Co-ordinator SIG Reproductive Surgery ordinator), Martine Albert and Jacqueline Lornage were the Willem Ombelet trainers on the course, assisted by two Africans (Nicole Co-ordinator TF Developing Countries and Infertility

24 Focus on Reproduction May 2011 Focus on Reproduction May 2011 25 may11_nwp:Layout 1 26-04-2011 12:16 Page 26 may11_nwp:Layout 1 26-04-2011 12:16 Page 27

TASK FORCES // CROSS-BORDER REPRODUCTIVE CARE // // BASIC SCIENCE //

Good practice guide in print; data collection Oncofertility Consortium on egg donation in Europe about to begin expands in the USA and aims now for a global The ESHRE Good Practice Guide for Cross-border hopefully snowball and encourage more organisations to Reproductive Care, which provides advice on dealing with subscribe to it in time. collaboration network patients seeking treatment outside their home country, has now been published in the ESHRE pages of Human Data collection on egg donation Reproduction. The January edition of Focus on Our next research endeavor, starting in the Spring of this l In Stockholm the TFs Basic Science and Reproduction explained the guide’s gestation and year, is to gather data on oocyte donors in Europe, another Fertility Preservation in Severe Disaese will principles, and we here outline how it might be subject of much practical, ethical and political interest in stage a precongress course in collaboration implemented, as well as the Task Force’s next plan, which our field. The Task Force, which now comprises founder 60 is to collect data on oocyte donors in Europe. members Françoise Shenfield, Guido Pennings, Anna Pia with the US Oncofertility Consortium We are aware that ‘codes of practice’ and ‘good practice’ Ferraretti and Jacques de Mouzon, has two new members 50 guides do not have the same pragmatic strength as in Amparo Ruiz from Spain and Tonko Mardesic from the Survival rates among young cancer patients have steadily 40 increased over the past four decades as a result of more professional guidelines, which may indeed be recognised in Czech Republic. 30 a court of law or for certification, with its corollary of The protocol for the study has now been finalised and effective cancer treatments. Today, both women and men implementation by inspection. Nevertheless, this ESHRE approved by ESHRE’s Executive Committee. Its main can look forward to life after cancer, yet many may face the 20 statement on how to ensure quality of care and safety for possibility of infertility as a result of the disease itself or its 10

objective is to obtain reliable information on oocyte donors Number of clinical sites patients and their future offspring has an important in Europe, whether the donation involves cross-border treatments. In January’s issue of Focus on Reproduction Richard Anderson and Claus Yding Andersen described symbolic value in a field which is still making headlines patients or not. By gaining an insight into the egg donors’ 2007 2008 2009 2010 and remains of concern to professional bodies, statutory characteristics, their reasons for donating and the recent advances in the techniques of fertility preservation authorities and patients. accompanying procedures (information, counselling, techniques; developing the clinical expertise to treat these National Physicians Cooperative sites throughout the USA. In less than five years, the NPC has grown to include more than 55 clinical sites in Indeed, the first steps in the distribution of the Good reimbursement, etc), we hope to provide a basis of patients will provide another avenue of progress. 31 of 50 states, allowing young cancer patients to receive expert fertility Practice Guide show that many such bodies wish to information for all stake holders, including policymakers Recognising the need to focus on the fertility threat posed by preservation care nearby. publicise it. As soon as the paper was on the Human and patients, and especially promote policy measures which cancer treatments, a team of Reproduction advance access website, and simultaneously benefit donors and infertile couples in general. oncologists, fertility specialists, preservation programmes. Member cancer patients. Experienced on our Task Force ESHRE website - probably by the time We know that some countries are trying to find ways to bioethicists, legal scholars, sites, which also advance clinical patient navigators can counsel this edition of Focus on Reproduction is distributed - improve their own egg donation services and discover why advocates and communication outcomes by participating in providers and newly diagnosed several organisations have agreed to electronically link the others perform more cycles. For instance, the UK’s HFEA scientists formed the Oncofertility multicentre studies designed to cancer patients in available fertility Task Force site to their own. We have agreements from has launched a public consultation in which some Consortium in 2007 to solve this improve fertility preservation care, options and direct them to NPC ART regulatory authorities, such as the HFEA in Britain, questions ask what is considered appropriate compensation intractable problem. are an important resource for sites and fertility preservation the agency in Portugal, and the Italian Registro Nazionale to gamete donors (including benefits in kind). Interest at One of the many clinical translational research by providing programmes. The FERTLINE della Procreazione Medicalmente Assistita. In addition, the international level is confounded by the fact that donor resources provided by the ovarian tissue to a national navigators support patients as they some national fertility or professional societies have either compensation and recruitment vary among European Consortium is the National repository to improve fertility pursue these options and can co- agreed already to the link (the Danish Fertility Society and countries, and of course further afield. Still, little evidence Physicians Cooperative (NPC), a options for women and girls. While ordinate services, usually between Spanish Embryology Society) or are tabling the matter for is published on such matters. We are thus asking country US network of fertility sites that the NPC originally aimed to the oncologist and reproductive their next executive meeting (the Collège National des co-ordinators (many of whom are also EIM co-ordinators) serve women, men and children establish four centres throughout endocrinologist, creating a Gynécologues et Obstétritiens Français in France).We are to enrol those centres which perform more than 100 egg with cancer. The NPC teaches the USA, today patients synergistic and interdisciplinary also awaiting feed-back from (not exclusively) our Belgian, donation cycles per year. We expect to collate 1000-1500 fertility specialists how to work can be referred to one of over 55 treatment regimen. Calls around Dutch, Czech and German colleagues, and will hopefully questionnaires, and begin recruitment between Spring and with cancer patients, who have an sites. Based on individual site the world have been fielded and enlarge this linkage to a comprehensive array of fertility Autumn this year. We will analyse and write up the results immediate need for fertility reporting, the NPC provides more patients navigated to sites near organisations in Europe. in early 2012, and hope to present them in Istanbul. preservation between diagnosis and than 2700 oncofertility their cancer treatment centres. If Outside Europe, the board of the Canadian regulatory Hopefully, an informed debate will then help encourage treatment, who are not as most consultations per year, showing the you wish to participate in this authority, Assisted Human Reproduction Canada, has decisions which consider the safety and interests of patients fertility patients, and who might significant need for this growing programme, please contact agreed to provide a link on their website, and the IFFS and collaborators. To this end, a ‘good practice guide’ in include adolescents and children. team nationally and globally. [email protected]. plans to discuss the guide with a possible web link at their egg donation might be the next step, with promotion of a The NPC web portal (www. The Oncofertility Consortium Johan Smitz board meeting preceding our annual meeting in Stockholm. register for egg donors where this does not exist, first at a oncofertility.northwestern.edu) also provides a free fertility hotline Co-ordinator TF Basic Science in And last but not least, the patients organisation, Fertility national and then a European level. provides information for (FERTLINE, 866-708-FERT Reproductive Medicine Europe, has also agreed to put the guide on its website. Françoise Shenfield practitioners about best practices (3378) as a referral resource for Kate Timmerman, Teresa Woodruff This approval of standards, both ethical and practical, will Co-ordinator Task Force Cross-border Reproductive Care and sets up local oncofertility oncology professionals and young Oncofertility Consortium

26 Focus on Reproduction May 2011 Focus on Reproduction May 2011 27 may11_nwp:Layout 1 26-04-2011 12:16 Page 28 may11_nwp:Layout 1 26-04-2011 19:41 Page 29

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

28 Focus on Reproduction May 2011 Focus on Reproduction May 2011 29 may11_nwp:Layout 1 26-04-2011 12:16 Page 30 may11_nwp:Layout 1 26-04-2011 12:16 Page 31

Work in progress

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

30 Focus on Reproduction May 2011 Focus on Reproduction May 2011 31 may11_nwp:Layout 1 26-04-2011 12:16 Page 32 may11_nwp:Layout 1 26-04-2011 12:16 Page 33

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

32 Focus on Reproduction May 2011 Focus on Reproduction May 2011 33 may11_nwp:Layout 1 26-04-2011 12:16 Page 34 may11_nwp:Layout 1 26-04-2011 12:16 Page 35

‘The rules of the healthcare in the EU. The implications of appreciation by outlawing all GUIDO PENNINGS: ‘UNLIKE ORGAN game are much of this directive are difficult to medically assisted reproduction, or all like those of AND BLOOD DONATION, GAMETE Mikado 'pick-up’' predict. types of gamete donation as in Italy. DONATION CHALLENGES OUR sticks. Peripheral The impact for the field of assisted Time will tell which direction will be TRADITIONAL VIEWS ON THE rules (how many reproduction will probably be limited, taken. FAMILY AND IS ALWAYS SEEN AS A children per donor, since there are conditions attached to intrafamilial SECOND-BEST SOLUTION.’ donation, and so reimbursement. The most important The future on) can be added, condition is that countries will not One important obstacle in egg removed or altered have to reimburse treatments that are donation is the burden of treatment without too much illegal in the home country.4 for the donor. This burden has two trouble. But the basic rules, such Moreover, the directive does not main components: the sickness and as payment and prejudice the right of each member inconveniences resulting from ovarian anonymity, cannot state to decide what type of healthcare stimulation; and the risk of ovarian be shifted without treatment is appropriate.5 For hyperstimulation syndrome. Yet there rethinking the whole system.’ example, a German woman leaving is a technical solution to both these her home country for egg donation complications. Inconveniences and may well have far-reaching References treatment in the Czech Republic sickness can be avoided by opting for consequences for the practice of egg 1. Pennings G. The rough guide to cannot claim reimbursement because mild stimulation. Even if a clinic is donation. Not only will vitrification insemination: cross-border travelling for egg donation is legally prohibited in reluctant to apply this protocol in its increase opportunities for egg donor semen due to different regulations. Germany. The same rule may apply routine IVF, there is at least one very donation (egg banking, for example, Facts, Views and Vision in Obstetrics and Gynaecology, monograph 'Artificial when more specific rules are violated good reason to do so in egg donation: will facilitate the whole enterprise), it insemination: an update' 2010: 55-60. by patients who go abroad; if the law the doctor’s moral obligation to will also make possible ‘social 2. Söderström-Anttila V, Sälevaara M, of the home country states that no minimise risks when the patients has freezing’ (a misnomer only meant to Suikkari AM. (2010) Increasing openness payment should be provided for a no personal benefit from the prevent tarnishing its application in in oocyte donation families regarding certain service or body part, treatment. The other main risk, cancer patients). Once more women disclosure over 15 years. Hum Reprod reimbursement could be refused when OHSS, can also be reduced freeze their eggs in good time (that is, 2010; 25: 2535-2542. that rule is not respected abroad. considerably by using GnRH before they turn 35), there will be less 3. Pennings G. Gamete donation in a Cross-border Reproductive Care will effort. Awareness and recruitment While the European Parliament antagonists and triggering oocyte need (and demand) for donor eggs. system of need-adjusted reciprocity. Hum this year begin a Europe-wide study campaigns usually amount to little clearly confirms the right of individual maturation with an agonist.6 If this Nevertheless, this development will Reprod 2005; 20 : 2990-2993. on egg donation, focusing specifically more than distributing a leaflet. But in member states to decide on the ethical modified protocol were applied, most likely make only a small dent in 4. Council of the European Union. Position on the donors. reality most countries just do nothing. acceptability of certain types of clinics would be in a much stronger the increasing demand for donor eggs, of the Council at first reading with a view to the adoption of a directive of the As with payment, the cross-border Several factors may explain this treatment, the European Court of position to recruit donors. The which will surely continue to rise with European Parliament and of the Council quest for eggs is highly complex, with lack of enthusiasm but one important Human Rights recently struck down objections raised by feminist and pro- the postponement of pregnancy in the on the application of patients' rights in both push and pull factors interacting reason, according to me, is a provisions in Austria’s law on life groups would lose much of their developed world. cross-border healthcare. Adopted by the in unpredictable ways. Most of the fundamental ambiguity towards medically assisted reproduction in the strength if a procedure were applied The main challenge for fertility Council on 13 September 2010. time, the trigger of the process is a gamete donation. Unlike organ and case of SH and others vs Austria. The that was both safe and easy to bear. centres is to construct an ethically and 5. European Parliament. Draft European push factor, that is, the shortage of blood donation, gamete donation court first acknowledged the wide Finally, the vitrification of oocytes psychologically coherent and Parliament Legislative Resolution on the donor eggs and the ensuing waiting- challenges our traditional views on margin of appreciation of the member acceptable set of rules for gamete proposal for a directive of the European lists. The pull factor is clearly the the family and is always seen as a state, which means that the state is Egg donation in Europe donation. In order to do that, we Parliament and of the Council on the immediate availability of egg donors second-best solution. As a result, it is free to regulate assisted reproduction need a broad societal debate about application of patients' rights in cross- in foreign countries such as Spain much more difficult to convince the way it wants to. But it then Egg donation cycles as reported to the framework in which to position border healthcare (COM(2008)0414 - C6- and, depending on the country, the governmental organisations to take a decided, on the basis of the ESHRE’s EIM Consortium: the procedure. Only with a sustained 0257/2008 - 2008/0142(COD)). 6. Devroey P, Aboulghar M, Garcia- possibility of selecting the donor from heartfelt initiative in egg donation. proportionality principle, that the 1998 4411 effort to diminish the ambiguity Velasco J, et al. Improving the patient's a catalogue, as in the USA. total ban on egg donation could not 1999 3867 towards gamete donation still current The present reaction from the European developments be justified according to the reasons experience of IVF/ICSI: a proposal for an 2000 6530 in most societies will it be possible to ovarian stimulation protocol with GnRH public (law makers and professionals In the very near future the European given by the Austrian state. 2002 7677 recruit a sufficient number of donors. antagonist co-treatment. Hum Reprod included) in countries from which framework for cross-border medical Although many observers seem to 2003 7548 2009; 24: 764-774. people travel is envy; clinics or care is set to change. The European (want to) believe that this may be a 2004 10,334 Guido Pennings is Professor of Ethics and authorities may criticise the patients Parliament and the Council of the first step towards a European 2006 12,685 Bioethics at the at the Bioethics Institute for travelling and the host countries European Union are completing a harmonisation in the field of assisted 2007 15,028 Ghent (BIG) at Ghent University, Belgium, for accepting these patients, but they directive to facilitate the use of reproduction, it is far from clear what l The EIM report for 2006 noted: and Past Co-ordinator of ESHRE’s SIG do very little to solve the problem at healthcare in another member state the implications are (assuming the ‘The number of ED cycles increased Ethics & Law. home. Just as for other scarce through clearer rules on decision stands following Austria’s in the same proportion, reaching resources such as organs, self- reimbursement, procedural guarantees appeal). It certainly does not imply 12,685 (+10.5%), reported by 22 sufficiency should be the goal. But and information for patients. The that Austria has to allow egg countries, the main contributor generally, neither the clinics nor the directive establishes a specific donation. In fact, Austria could being Spain (6547 cycles).’ governments are making much of an framework for cross-border remain within the limits of the margin

34 Focus on Reproduction May 2011 Focus on Reproduction May 2011 35 may11_nwp:Layout 1 26-04-2011 12:16 Page 36 may11_nwp:Layout 1 26-04-2011 12:16 Page 37

CHRISTINA BERGH AND KARL NYGREN: ‘70% OF ALL ART CYCLES IN SWEDEN HAVE BEEN SINGLE EMBRYO TRANSFER SINCE 2004.’

annually, representing 3% of all babies born in numbers of embryos to boost efficacy. At its peak in Sweden each year. Reimbursement policies are 1991, the proportion of multiple deliveries reached generous, with most regions offering three publicly 35%. However, our outcome monitoring system funded fresh IVF cycles - but with limitations eventually showed that the price paid for this according to age and previous children. There is a greater efficacy, by both mother and child, was functional 50-50 mix of public and private clinics. high, with increased multiple rates leading to more Law and regulations are relatively preterm birth and low birth weight, both of which accommodating, and increasingly so over time; were associated with child morbidity. Clinicians, both egg and sperm donation are allowed, but not patients and regulating authorities all agreed that embryo donation or surrogacy. the trade-off between efficacy and safety was clearly Sweden out of balance and should not be tolerated. The gold mine of epidemiology Clinical research on single embryo transfer (SET) One feature quite unique to the Nordic countries, and its efficacy versus multiple delivery convincingly and to Sweden in particular, is their databases. demonstrated that SET as the norm would be Sweden is a virtual gold mine for IVF outcome beneficial and clinically feasible. However, while research. For around 50 years we have had several numerous observational studies showed similar live national population-based health registers for birth rates after transfer of one and two embryos, AA goldgold minemine ofof epidemiologyepidemiology inin reproductionreproduction births, in-patient hospital diagnosis, out-patient randomised controlled trials clearly demonstrated diagnosis, birth defects, prescribed drugs, cancer, higher delivery rates after two embryo transfers. and cause of death. All events for all citizens are Studies from the Nordic countries, however, collected and stored in these registers, according to showed that this discrepancy could be overcome by a personal ID number. transferring one fresh and one subsequent thawed With this year’s annual meeting in Stockholm, last year’s Nobel prize for From the very beginning of IVF in Sweden there embryo when there was no pregnancy in the fresh has been an IVF register of information, which cycle. Thus, in the light of this information, there medicine awarded to Bob Edwards (and the Nobel committee resident at the included the ID number of every woman who was a nationwide shift in the uptake of SET in Karolinska Institute), Sweden is once again in the ART spotlight. Two of the delivered and her children. This IVF register has Sweden from 10% to 70% within just a few years. country’s stalwarts, Christina Bergh and Karl-Gösta Nygren, take a look at its been cross-linked at regular intervals to all the This resulted in no loss of efficacy as assessed by health registers. Thus, IVF births have been delivery rate, and most importantly a dramatic past, present and future place in assisted reproduction. monitored and reported since its introduction in a reduction in multiple birth rates, from 25% to way which is not possible in most countries. around 5%. Comparisons can be (and have been) made between Similar patterns and results have been found in all children born and their mothers, and with our cryocycles, in which embryos are now frozen VF in Sweden started early, in the country’s second city technique of transvaginal ultrasound for the puncture and children from the general population and their and thawed for transfer one by one. The decrease in of Gothenburg. It was there that Lars Hamberger and aspiration of follicles, a development which would mothers. These cross-linkages have provided much multiple birth rates has resulted in a huge drop in his group, at what was the original IVF clinic in the revolutionise IVF around the world and transform egg important information, not only on obstetric our preterm delivery rate, from 40% to less than I Nordic countries, had their first IVF baby in 1982. collection into a simple day-care procedure. outcomes such as birth weight, gestational 10%, and also in the rate of severe child morbidity However, more than 20 years before then Carl Gemzell age/preterm rate and malformations, but also on (such as cerebral palsy). Adverse maternal and colleagues at Uppsala University had achieved Still in good shape today child morbidity in general and cancer. outcomes, such as pre-eclampsia, have also pregnancies in infertile hypogonadotropic women with the Thereafter, enthusiasm for IVF in Sweden spread quickly decreased. The balance between efficacy and safety administration of gonadotrophins as ovarian stimulation. and today access to treatment is high. Around 13,000 Sweden's first important challenge: the trade-off has thus been dramatically improved by SET in In the mid-1980s another Nordic group led by cycles are performed each year, one-third as fresh IVF, one- between efficacy and safety both fresh and frozen cycles. gynaecologist Matts Wikland, again in Gothenburg and third fresh ICSI and one-third frozen/thawed cycles. From In the early days of IVF, clinics in Sweden - as Although SET was first widely introduced in with Danish colleagues, described and introduced the these treatments around 3500 IVF babies are born everywhere else - were inclined to transfer large Finland, Sweden is now at its forefront worldwide.

36 Focus on Reproduction May 2011 Focus on Reproduction May 2011 37 may11_nwp:Layout 1 26-04-2011 12:16 Page 38

Delivery rate per embryo transfer (%) in relation to standard IVF, Delivery rate per embryo transfer, multiple birth rate, and single microinjection/ICSI, and frozen/thawed cycles 1991-2008 embryo transfer rate (%) in Sweden 2000-2008.

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

38 Focus on Reproduction May 2011