Focus on Reproduction ESHRE, ianuarie 2011

Focus onREPRODUCTIONEuropean Society of Human Reproduction and Embryology // JANUARY 2011 // Robert Edwards honoured as Nobel prize winnerl ESHRE newsl Fertility preservation in womenl Charting the progress of IVF in Germany

EXECUTIVE COMMITTEE Chairman Focus on Luca Gianaroli (IT) Chairman Elect Anna Veiga (ES) Members REPRODUCTION Ursula Eichenlaub-Ritter (DE) Jean-François Guerin (FR) l Chairman’s introduction Timur Gürgan (TR) Antonis Makrigiannakis (GR) Carlos Plancha (PT) This new year issue of Focus on Reproduction reflects a Françoise Shenfield (GB) rich vein of events related to ESHRE and assisted Miodrag Stojkovic (RS) reproduction but none more so than the award to Robert Anne-Maria Suikkari (FI) Edwards, the founder of our Society, of the Nobel prize Etienne Van den Abbeel (BE) Heidi Van Ranst (BE) ‘for the development of in vitro fertilization’. This Veljko Vlaisavljevic (SL) prestigious and long-deserved honour, awarded to the man Ex-officio members who inspired our work, takes on even greater significance Joep Geraedts (Past Chairman) as a mark of recognition for reproductive medicine among Søren Ziebe (SIG Sub- the leading disciplines of medicine. committee) ESHRE’s scientific activities, the core of the Society, have FOCUS ON REPRODUCTION now maintained their high standards over many years, and EDITORIAL COMMITTEE it was richly deserved that the European IVF Monitoring consortium celebrated its Paul Devroey tenth anniversary with a commemorative meeting last September in Munich. We Bruno Van den Eede also took part with the ASRM in the third consensus workshop on PCOS, this Hans Evers time on its non-fertility health implications. The report from the first consensus - Joep Geraedts on the diagnosis of PCOS - has become a citation classic. Luca Gianaroli From a social perspective, the European legislative framework for ART is Hanna Hanssen Anna Veiga presently going through something of a turmoil. Legislations in several countries Søren Ziebe (Germany and Malta, for example) are being exposed to the legal test following Simon Brown (Editor) judgements from different national and international courts. I am proud to report that in most of these cases ESHRE has been chosen as an authoritative and Focus on Reproduction is published by privileged interlocutor by the governments dealing with them. The European Society of Human Particularly significant in this same context was the participation of ESHRE in Reproduction and Embryology the European Health Forum held in Gastein, Austria, in October. This meeting was Meerstraat 60 Grimbergen, Belgium a unique opportunity to present our view of the current problems in reproductive info@eshre.eu health to an audience of healthcare managers and European policymakers. It seems www.eshre.eu likely that 2011 will see many changes as far as these issues are concerned, which All rights reserved. hopefully will prompt greater harmonisation in European legislation, a goal that The opinions expressed in this ESHRE has always pursued. magazine are those of the Several opportunities are now opening up for ESHRE outside its traditional authors and/or persons interviewed and do not necessarily reflect the fields of interest. A collaboration between our Task Force on Management of views of ESHRE. Fertility Units and a leading insurance group is behind a workshop planned for Venice in February. This will be the first time that professionals in the fields of JANUARY 2011 ART and insurance have collaborated in such a way, but, as the Task Force reports Cover picture: Nobelprize.org in this issue, there are clear areas in the management of fertility centres where we can improve, both for the sake of ourselves the professionals and our patients. Luca Gianaroli ESHRE Chairman 2009-2011 CONTENTS NEWS FEATURES 4 Rome 2010 reviewed 32 Fertility preservation in women 6 Robert Edwards Nobel laureate Richard Anderson and Claus Yding Andersen review progress 10 New data system for PGD Consortium so far and the realistic options 11 ESHRE’s foray into social media before cancer treatment 12 From Fertility Europe 35 One million cycles recorded Markus Kupka on the 14 Ten year review from the EIM story of IVF in Germany Consortium and how its voluntary 17 Third consensus meeting on PCOS registry has recorded every cycle 18 European Health Forum Gastein 20 From the Special Interest Groups 27 From the Task ForcesFocus on Reproduction January 2011 3

ANNUAL MEETINGS 2010, 2011 Rome retrospective Survey reveals high scientific content scores but some dissatisfaction with logistical arrangements A face-to-face survey of 500 participants during last year’s annual meeting in Rome found an enthusiastic response to Deadline for Stockholm abstract scientific content, but a higher-than-usual level of dissatisfaction about the congress venue and transportation submission is 1st February arrangements. As a result, ESHRE’s Executive Committee Full details of ESHRE’s abstract submission policy are has determined to address these problems specifically and on the ESHRE website (www.eshre.eu), but please ensure they are not encountered again. note: The survey was the fourth to be conducted by ESHRE, l All abstracts must arrive at ESHRE’s Central Office following similar exercises in Lyon (2007), Barcelona no later than 23.59 CET on 1st February 2011. (2008) and Amsterdam (2009). Last year’s questionnaire l Abstracts should be submitted in English only. l Any investigator submitting an abstract can only be covered both organisational and scientific content. the first author for one abstract. As ever, scientific quality - in both the precongress l The material presented should be unpublished and courses and main programme - proved highly rated; on a original material, which has not yet been presented in scale of 1 (minimum rating) to 5 (maximum), scientific any other meeting. content in the invited lectures and oral communication l All abstracts will be refereed ‘blind’. sessions scored 3.9 and 3.7 respectively, ratings consistent l Authors are requested to indicate their preference with those of previous years. Most respondents (75%) for oral and/or poster presentation on the abstract thought the balance of science and clinical medicine ‘just submission form. The decisions of the selection right’, and most (71%) actually took time to view the committee are final. paper posters (a big increase on 2009). It was thus not surprising to find that 51% preferred paper posters, though 22% gave a preference for both paper and electronic which was based on a ten-minute questionnaire interview presentation. This was a big advance in response to poster in Rome, are inevitably the growing pains of a congress viewing opportunities. whose size and shape are so rapidly increasing. ESHRE’s Local chairman Filippo Ubaldi also notes a very Executive Committee now has to plan for a capacity of at favourable response to the congress’s social programme set least 10,000 delegates, and that necessarily limits choice. against the backdrop of one of the world’s most attractive Complaints of those interviewed in Rome were cities. The congress party at the spectacular Villa Miani, concentrated on three organisational aspects: the congress before a panorama of St Peter’s and Rome below, proved a centre itself; transportation; and catering. Many popular and much enjoyed event. respondents were unhappy with the congress venue; the Many of the logistical problems exposed by the survey, congress centre rated a mean satisfaction score of only 3. This rating compared unfavourably with previous venues in Amsterdam (mean rating 3.8) and Barcelona (mean rating 4.3). Venue selection is clearly essential to the success of any annual meeting, and, says the Executive Committee, must be given the highest priority in future. Venue selection - and its location - was also at the heart of transportation complaints, which were mainly a lack ofESHRE CHAIRMAN LUCA buses during off-peak hours. Despite the shuttle service, there were many who complained that access to and from GIANAROLI: ‘THE the congress centre was difficult (and expensive by taxi) SURVEY HAS EXPOSED outside the shuttle time-table, which, says Ubaldi, was PROBLEMS AND WE concentrated on morning and evening peak times. The local MUST LOOK AT THEM.’ organisers and ESHRE’s agents in Rome did their best with 4 Focus on Reproduction January 2011

Scientific content in all parameters measured scored highly among the survey respondents.the shuttle services within a reasonable budget, but clearlyease of travel - preferably by public transport - is apriority for future consideration. Catering in Rome also scored poorly, with a meansatisfaction score of just 2.4. Complaints were mainlyfocused on lunch queues on the opening Monday, whencatering services proved inadequate for such numbers.Food quality was always high, however, and the logisticsof service had improved dramatically by Tuesday. ‘We were not happy with some of these findings,’ saidESHRE’s Chairman Luca Gianaroli, ‘and it’s clear thatmany participants were disappointed in some of theorganisational arrangements. The survey has exposedproblems and we must look at them. I want to reassureour members that we will do our best - even at the earlieststage of venue selection - to ensure we don’t have such A big advance in numbers viewing both paper and electronic posters.complaints again.’ Gianaroli was also confident that many of the logisticalproblems reported in Rome will not be encountered thisyear in Stockholm. The venue, Stockholmsmässan, isfamiliar with large medical congresses and importantly isjust nine minutes away by commuter train fromStockholm Central Station. Trains are frequent andefficient, and the congress station is just a two-minutewalk from the congress centre. The EC and localorganisers will also be paying particular attention tocatering and meeting-room logistics. The invited scientific programme and precongresscourses for Stockholm are already in place, and deadlinefor the submission of abstracts is 1st February. Allabstracts will be scored (blind and weighted) by theScientific Committee. Last year’s event prompted anunprecedented number of abstract submissions, and,despite the shortcomings of Rome, a similar response isexpected this year. Almost 70% of those questioned in The congress party, set against the panorama of St Peter’s and Rome,Rome said they expected to be in Stockholm in 2011.q proved a popular and much enjoyed event.Focus on Reproduction January 2011 5

COVER STORY Bourn Hall days: left, Bob in 2008 at a celebration of 30 years of IVF; below, Lesley Brown with Louise in 1978, and in 2008 at Bourn Hall with Louise and her own baby. Robert Edwards, joint founder of ESHRE, honoured as Nobel laureate am sure that every member of ESHRE was delighted to hear the Klaus Diedrich, Chairman of ESHRE from 1993 to I news that Robert Edwards had been awarded the Nobel Prize for Medicine. Bob, who was born in 1925, has had to wait many years for this richly deserved appreciation of his lifelong and pioneering 1995 and a member of work. The award is also a tribute to the whole sector of reproductive the Society’s original medicine. Bob’s original work was in physiology at the University of temporary committee, Cambridge. As early as the 1950s he was studying the physiology of the congratulates Bob oocyte and the control of maturation, and by the 1960s had achieved the in vitro fertilisation of an oocyte in an animal experiment. Edwards on this much It was in the late 1960s that Bob, who by now was Head of the deserved honour and Department of Physiology in Cambridge, met the gynaecologist Patrick Steptoe. The latter was head of department in Oldham, UK, and one of recalls his distinguished the pioneers of laparoscopy. Before then the retrieval of oocytes was place in ESHRE’s history. performed via laparotomy - unthinkable to Edwards and Steptoe even at that time. They thus developed a concept for detecting the time of optimal oocyte maturation for the retrieval of oocytes by laparoscopy. And, as might be expected with Bob’s experience in animal models, it Pictures: did not take long before the first in vitro fertilisation was achieved. Robert G. Edwards - Photo Gallery. Nobelprize.org Embryo survival, however, proved a challenge, as did the ESHRE archives Klaus Diedrich encouragement of his peers and financial support. But Bob and Patrick6 Focus on Reproduction January 2011

ESHRE days:never gave up, and in 2008 Bob recalled: ‘I in Lübeck in 1983. top, welcoming Patrick Steptoe to ESHRE’s firstwill never forget the day when I first saw a The third World Congress of IVF was held annual meeting in Bonn,human blastotocyst under my microscope. It in Helsinki in 1984 and it was here that Bob 1985, with joint founderwas wonderful.’ This happened in 1972, but it and the French gynaecologist Jean Cohen set Jean Cohen and localwould take six more years before the first IVF about the creation of a European society in congress chairman Klaus Diedrich;baby, Louise Brown, was born. That world- reproductive medicine, which would very soon above left, in 2004 withfamous team of Edwards and Steptoe become ESHRE. From then on ESHRE ESHRE’s chairmen thus farcontinued to work together until Steptoe’s congresses were held every year, and even the (l to r), Pier Giorgiodeath in 1988. first, which I organised in Bonn in 1985, Crosignani, Basil Tarlatzis, Jose Egozcue, Lynn Fraser, * * * * began with 650 participants. Even so, it was Klaus Diedrich, Jean Cohen,I first met Bob in 1978 at a reproduction still possible for Bob and Jean Cohen to greet Bob Edwards, André Vanmeeting in Japan. At the time societies in everyone personally at the door. Steirteghem, (seated) Arnereproductive medicine were springing up all Edwards was the founder and for many Sunde, Hans Evers; above right, acceptingover Europe, and the foundation of our own years the editor of ESHRE’s journals Human honorary membership ofsociety in Germany took place with the close Reproduction, Human Reproduction Update ESHRE in Thessalonikicollaboration of our colleagues in Britain. We and Molecular Human Reproduction. These 1993.had three centres performing IVF: in Erlangen remain among the leading international titlesunder the lead of Siegfried Trotnow, Lübeck in O&G and reproductive biology. Bob alsounder Dieter Krebs, and Kiel under Lieselotte founded Reproductive Biomedicine Online inMettler. Germany’s first IVF baby was born in 2000, following his resignation from theErlangen in 1982 (see page 35) and a second editorship of Human Reproduction. It was aFocus on Reproduction January 2011 7

Bob makes the front cover of a 1993 Focus on Reproduction alongside ESHRE’s next four chairmen: Van Steirteghem, Cohen, Crosignani and Diedrich; right, with a note to Klaus Diedrich after the first ESHRE congress in Bonn, 1985. move typical of his character, always searching for new things to discover, realising new visions. Indeed, in reproduction he was the first to cryopreserve surplus embryos and perform time with him, and I am proud to say that Bob was preimplantation diagnosis on animal embryos, awarded honorary membership of the German confident that both techniques would be developed Society of Obstetrics and Gynecology when Dieter for human application. Remarkably, he had Krebs led the society’s congress in Berlin in 1992. experimented with in vitro maturation and The Nobel prize is a fitting tribute to the influence fertilisation in animal models as early as 1965. that Bob’s work has had on infertility throughout Bob and I organised many conferences and the world and for so many years. The members of workshops together, and he was the scientific father ESHRE congratulate Bob and send him their kindest of many German endocrinologists - as well as the regards. driver of infertility treatment in Europe. It was Klaus Diedrich always a special and inspiring experience to spend University of Lübeck, Germany Ruth Edwards accepts the prize on his behalf Too unwell to be in Stockholm for the Nobel prize ceremony in December, Bob was represented by his wife Ruth (who as Ruth Fowler had collaborated with him on several papers on the induction of ovulation in mice in the 1950s). His absence meant that the traditional lecture given by each Nobel laureate was replaced by a symposium in Bobʼs honour. The principal speaker was one of Bobʼs former students in Cambridge, Professor Martin Johnson, who in a detailed and finely illustrated lecture described the many years of research which lay behind the triumph of Louise Brownʼs birth. Professor Johnson closed his lecture with two moving film clips of Bob describing his first association with Patrick Steptoe and forecasting that ʻnext yearʼ (this was shortly after the opening of Bourn Hall in 1981) ʻ1500 IVF babies would be born worldwideʼ. Two follow-up lectures - on the development of IVF and its future directions - were given by Lars Hamberger, whose group achieved Swedenʼs first IVF success in 1982, and Outi Hovatta of the Karolinska Institute. The Nobel Prize in Physiology or Medicine is awarded by the Nobel Assembly at the Karolinska Institute. Martin Johnson delivers the symposium’s first lecture, with Ruth Edwards (inset) also present.8 Focus on Reproduction January 2011

Six handshakes of separation between the‘Bob picture’ and the rest of the worldFormer ESHRE ChairmanHans Evers with his owntribute to Bob EdwardsDid you ever shake hands with Barack Obama?Does Lady Gaga recognise your e-mail address? Doyou know a Nobel laureate on a first-name basis?According to the ‘small world’ hypothesis proposedby Stanley Milgram, each of us is no more than sixhandshakes away from every other human being onthis planet. In 1967 Milgram developed anexperiment to test his hypothesis that members ofa large social network, in this case the entirepopulation of the USA, would be connectedthrough a relatively short chain of in-betweencontacts. He sent a message to 400 randomlyselected people in Wichita, Kansas, and Omaha,Nebraska, (the starting points) and invited them toforward it to a colleague or friend whom theythought more likely to know a given target personin Boston, Massachusetts (the endpoint), whosename was completely unfamiliar to them. Thereason for selecting Wichita and Omaha at one endand Boston at the other was that according toMilgram they represented as long a geographicaland social distance in the USA as possible. His experiment turned out to confirm the theory; Two ‘Bob pictures’ from ESHRE’s first annual meeting in 1985. Bob greets two future chairmen of ESHRE (the first who insists on remainingit took on average six persons to reach the hitherto anonymous, and the second whom we cannot even identify).unknown target person - a phenomenonwhich later became known as the ‘six On hand was a photographer to owner of a ‘Bob picture’ . . . jackpot!degrees of separation’. The most record the moment, and we all still The Nobel prize has been awardedsuccessful chains were composed of treasure our ‘Bob picture’ from that to Bob Edwards. Finally! The Swedesprofessional rather than social links. occasion - as the many resurrected are a brave and independent bunch.Social networks are usually more photos suggest. Against all odds (ie, the Vatican) theyclosely knit, all members know all And Bob was our introduction to honoured Bob, and they honouredother members and the community of the world at large. He went on to win Alfred Nobel, who died childless andfriends does not usually extend far the Lasker award, the King Faisal thus had to find a destination for hisbeyond its original nucleus. award, and the Nobel prize. After accrued capital. What would be moreProfessional networks are less shaking hands with us (handshake 1) appropriate than a Nobel prize forcompact but they reach farther. in Bad Godesberg he received the fighting childlessness? And what ESHRE is a global network of King Faisal award from the hands of would be more appropriate forprofessional links. At its first annual the late King Fahad of Saudi Arabia ESHRE than to have its annualmeeting, in Bonn in 1985, its (handshake 2), who later shook meeting in Stockholm this year?founding father, the 2010 Nobel hands with George Bush senior And finally, what would be morelaureate Professor Robert G. (handshake 3), the father of George appropriate than for our presentEdwards, personally welcomed every W. (handshake/spanking 4), who chairman, Luca Gianaroli, toindividual participant (all 650 of shook hands with Barack Obama personally greet all participants inthem!) at the entrance to the opening (handshake 5) at the latters Stockholm, the city where Alfredreception in the Redoute in Bad inauguration. So, if next time we Nobel was born, with a welcomingGodesberg. meet you shake hands with the proud handshake?q

// PGD CONSORTIUM // An update from the working groups Gary Harton took over from Joyce Harper as Chair of the Steering Committee in June during last years Steering committee members annual meeting in Rome. Shortly after, a ballot was The current Steering Committee comprises: held to ratify the revised Statutes governing the Gary Harton (US, Chair) running of the Consortium. With the Statutes ratified, Joanne Traeger-Synodinos (GR, Deputy Chair) a vote was held to re-elect current members of the Joyce Harper (GB, Past Chair) Steering Committee and elect two new members to Céline Moutou (FR), Katerina Vesela (CZ), begin their term of office immediately. Sioban Sengupta (GB), Georgia Kokkali (GR), Another round of data collection and analysis is Leeanda Wilton (AU), Martine De Rycke (BE), well under way and will be published sometime this Tugce Pehlivan (TR), Pamela Renwick (GB), year. Our Working Group on Guidelines recently Edith Coonen (NL), Francesco Fiorentino (IT) published a set of four documents as a Best Practice Guideline for PGD and PGS. The documents cover clinical PGD analysis and embryo follow-up results, and Organization of a PGD Center, Polar Body and Embryo give a more complete evaluation of the potential rate of Biopsy as it relates to PGD, Amplification-based PGD misdiagnosis. Additionally, it should identify likely and FISH-based PGD and PGS. The guidelines were reasons of discordance (which could include protocol- published online by Human Reproduction in October. related parameters, embryo quality, embryo biology) We have now formed a new working group to highlighting important criteria for optimising clinical consider array-based testing in PGD, which includes PGD results. Data analysis is on-going for both studies, members of the Consortium as well as non-members with completion aimed for Spring 2011 and results interested in array-based technology in single cell and published as multicentre studies. embryo testing. The Array Working Group will be l The Database working group has updated the chaired by Dagan Wells and Leeanda Wilton and will FileMaker Pro database (see box below); the main hold its first meeting in London in March. modification is the use of OMIM numbers for l The Diagnosis Monitoring and Audit group has indications. In addition, the group has contacted progressed with two follow-up studies for the Patrick Haentjens for statistical analysis of the large reanalysis of untransferred and supernumerary amount of data collected since 1997. We are merging embryos. One study is for PCR-based PGD cycles (co- all databases to allow this analysis.The aim of the coordinated by Joanne Traeger-Synodinos, with Jos analysis is to assess reproductive outcome of PGD, and Dreesen as deputy) and the other for FISH-based PGD to evaluate the evolution of this activity with success cycles (co-coordinated by Tugce Pehlivan, with Edith rates in relation to various confounding factors. The Coonen and Gary Harton as deputies). Data analysis group is also working on new ways to collect and assess should identify the rate of discordance between data on frozen embryo cycles, including from groupsa The new method of data collection will be launched The data can be entered in real time so that an later this year. Submission of data via the current accurate and up-to-date record can be logged for FileMaker Pro system has been problematic and each PGD cycle. There will be an option to enter time-consuming, both for centres entering data and referral data for tracking patient history and the the Consortium steering committee trying to analyse database will incorporate options for embryo freezing it. The new on-line system will be an intelligent and at any stage of the process. easy-to-use method of entering, storing, analysing This is an exciting new venture from which we are and submitting PGD data. This new system will now sure many PGD centres will benefit. All Consortium allow PGD centres to easily analyse their own data. members should wait for the e-mail announcing how Once data is entered, it will be simple to produce to register your centre. Anyone who is not already a tables which include your key quality indicators (or member and wishes to join the Consortium, please key performance indicators), such as number of eggs visit the PGD Consortium web page at collected, number of embryos biopsied, and http://www.eshre.eu/ESHRE/English/Specialty- efficiency of the biopsy, diagnosis, pregnancy rates, Groups/SIG/Reproductive-Genetics/PGD-Consortium delivery rates, and so on. Joyce Harper10 Focus on Reproduction January 2011

NEWS// COMMUNICATIONS //ESHRE tweets to a newcommunity of friendsand fans in the onlineworld of social mediaIt’s now more than a year since ESHRE began its forayinto the social media of Facebook, Twitter and YouTube,and first results - as expected - reflect a relatively high andgrowing level of involvement. We now have more than1300 Facebook fans, with the majority of users apparentlyaged between 25 and 34, and female. Facebook posts havebeen used for press releases, workshop announcements,ESHRE statements and ESHRE news. A click on theFacebook icon on the ESHRE website will take visitorsstraight to their Facebook page and links to all ESHREpostings (which so far total almost 50). Similarly, a click on the Twitter icon will take visitors toTwitter where they can follow ESHRE from their ownaccount, or open a new account. Twitter now lists morethan 180 ESHRE followers - with instant reaction andinter-reaction to ESHRE’s own tweets - which includepatient groups, exhibitors, clinics, journalists and Top, clips from a selection of ESHRE videos can be found on YouTube;government bodies. ESHRE itself follows 25 tweeters, such below, the age range of ESHRE’s 1300 Facebook fans.as the BMJ, NatureHealth, New Scientist, and Bionews.Other sites - like Flickr or YouTube - have also been usedby ESHRE to make audio and visual material available, incorporated into one platform for those subscribing toparticularly from last year’s annual meeting in Rome. ESHRE’s RSS feed. Currently, around ten names are signing up each week to A copy of ESHRE’s guidelines on the use of social mediaany of the ESHRE social networks, and all of them can be can be found on the ESHRE website (under ‘ESHRE community’). The guidelines make clear that these new networking technologies are to encourage open dialogue and exchange of ideas. using embryo freezing or vitrification in all IVF cycles. l The main focus of the Molecular Methods group has l The Accreditation working group continues to spread been the primer database, which is available to full the word about improvements in the laboratory Consortium members only. The main aim of the following accreditation and continues to perform a database is to share molecular PGD protocols among yearly survey of the status of accredited centres for full Consortium members. It is hoped that the presentation at the ESHRE annual meeting. The database will benefit PGD groups and allow them to number of centres accredited to ISO 15189 or other save time for optimisation, reduce cost, improve local standards is growing, although at a very slow standardisation, find consensus on specific protocols, pace. It is hoped that an increase will be seen during and be used as a reference. PGD Consortium members this year, as several centres are just in the process of are invited to submit their protocols in order to accreditation. A Campus workshop on Quality populate the database. Any suggestion to Francesco at Management Towards the Accreditation Process is fiorentino@laboratoriogenoma.it . being planned for Athens in the autumn and will be Gary Harton organised in co-operation with Eurogentest. Chair, PGD ConsortiumFocus on Reproduction January 2011 11

‘Special Families’ project looks for postcards telling many thousands of stories Fertility Europe’s mission is to bring fertility organisations The idea behind the project is that people send ‘messages together with opportunities for networking and sharing of hope’ - in pictures and words - as an explanation of best practice and information. Well, we certainly did that why a family which had met problems in having a child at our annual meeting in Rome last year. We welcomed 31 now sees itself as ‘special’ in achieving its dreams. The participants representing 19 organisations from 17 pictures and stories, in the native language, are then made countries. into postcards. We unanimously voted in nine organisations as Effective Some of the stories sent in for the pilot were very Members; these were ‘Iskam bebe’ of Bulgaria, ‘Sdruzhenie powerful and show enormous courage and determination - Zachatie’ of Bulgaria, ‘Association Maia’ of France, as well as the multitude of ways for becoming a special ‘Kiveli’ of Greece, ‘Országos Lombikbébi Támogató family. The project has several aims: to raise awareness of Alapitvány’ of Hungary, ‘Nasz Bocian’ of Poland, fertility problems and their impact on those affected; to ‘Associacão Portuguesa de Fertilidade’ of Portugal, ‘SOS show how successful treatment can be and the joy it brings Infertilitatea’ of Romania, and ‘Barnlängtan’ (formerly to people; and to raise awareness of how you can protect IRIS) of Sweden. your fertility. Our aim is for hundreds of thousands of We were delighted to postcards to be presented in Stockholm later this year. welcome Anna Veiga, Chairman Elect of ESHRE, to the Template postcard meeting. Anna spoke for the Special on ‘The latest Families project. challenges in ART’, Fertility Europe which again generated hopes to receive much discussion and many thousands of many questions. We postcards would like to thank Anna for taking time out reflecting theAnna Veiga, impact which theChairman Elect of from what I know was a busy schedule for her in treatment ofESHRE and seen Rome. infertility canhere with sample We also agreed in Rome to form a sub-group have on families.cards from the for developing Fertility Europe policy statements,Special Families which includes Sweden, France, Belgium, Czechproject, spoke at Republic and the UK. The first two policyFertility Europe’s statements will be on reimbursement for fertilityannual meetingabout the treatment and single embryo transfer; the draftschallenges now will be discussed and hopefully ratified byfacing ART. members in Stockholm. We do recognise that Fertility Europe is not there to force any one view on members; however, we hope that this initial work will form a template for future policy statements on, for example, surrogacy and donor anonymity. Special Families project One of our most visible activities is the Special Families project, which was successfully piloted So what are our other plans for 2011? ahead of last year’s annual meeting. At the time of l We will consolidate the results achieved in 2010 from writing, we are waiting news of sponsorship but are very enlarging our network of associations as a ‘reliable voice’ confident that the project will continue successfully. at the lobby level. a 12 Focus on Reproduction January 2011

NEWS// LEGISLATION IN EUROPE //Despite protests, Danish Austria granted right togovernment abandons its appeal after European courtpolicy of state-funded ART finds ART law ‘discriminatory’Denmark has formally abandoned its policy of fully state- In April last year the European Court of Human Rightsfunded ART after the Danish government, supported by in Strasbourg upheld the complaint of two Austrianthe Dansk Folkeparti, approved new legislation in mid- couples that Austria’s legal ban on (heterogeneous)December introducing patient co-payment for ART. oocyte and sperm donation was discriminatory and in The move, which became operative on 1st January, was violation of the couples’ rights under article 14 of thestrongly opposed by professional organisations in European Convention on Human Rights on ‘prohibitionDenmark, including the Danish Fertility Society, which of discrimination’, and article 8 on their ‘right tounanimously but unsuccessfully advised against the respect for family life’.introduction of patient co-payment. Now, in November, a five-judge panel of the Court has Denmark’s former system allowed free-of-charge fertility granted Austria the right to appeal the ruling before thetreatment in public clinics up to a maximum a three Court’s Grand Chamber.completed ART cycles for childless couples. Those who The original case involved two couples seekingdid conceive a first child in a public centre were referred treatment for infertility, one of whom required IVF withto a private clinic for subsequent treatments; however, all donor sperm and the other male and female gametemedication costs were reimbursed for all patients, whether donation.for public or private treatments. In its April judgement the Court said that the ‘wish Now, all patients having fertility treatment must pay for for a child’ is protected by the European Convention,their medication (up to a maximum of DKK 15,000 and that its fulfilment through ART should not be[~2000 euro] per year). In addition, in the public clinics a prevented by ‘unjustified discriminations’. ‘Moralfee of DKK 5000 (~670 euro) is now charged for a fresh considerations’, the Court added, or concerns aboutcycle of IVF or ICSI, DKK 3000 (~400 euro) for a frozen social acceptability, ‘are not in themselves sufficientcycle, and DKK 1271 (~170 euro) for a cycle of IUI. reasons for a complete ban on a specific artificialPatients are also charged for any donor sperm used. The procreation technique such as ova donation’.new regulations thus cover all types of treatments -except The April decision created a storm among pro-life(possibly) PDG, which may be free of charge. organsiations, one warning that ‘If this decision is Rates of access to ART in Denmark have consistently upheld by the Grand Chamber, the flood gates will openbeen among the highest in Europe, with registries for the recognition of a protected right for same sexrecording ART birth rates as high as 8-10% of all babies couples to access artificial procreation with egg orborn. Now, says Søren Ziebe, IVF laboratory director at sperm donors exactly like a couple composed of a manthe Rigshospitalet fertility clinic in Copenhagen, there are and a woman’.fears that the uptake of IVF will decline (as happened in ESHRE itself is seeking advice whether it (and otherGermany when patient co-payment was introduced in interested groups) has the right to submit expert opinion2004), treatments will become more aggressive, and the (‘ad adjuvandum’) to the Grand Chamber court.opportunities for research will shrink.l We will also continue to work closely with ESHRE and continue to collect information about ART andin terms of communications and patient representation. national regulation and reimbursement.l We will continue to actively reach out to increase our Do visit our website at www.fertilityeurope.eu to findmembership so that we can all share our activities with out more. And when you do, if you notice that wemore patient organisations and in turn help them in don’t have a European patient organisation listed fortheir work in their own respective countries your country and you know of one, please get in touchl We will continue to review and add content to our with us.website, increase and diversify our income, develop our Finally, but very importantly, we thank ESHRE forFE policy programme, agree our business and processes their continued support.plan, begin planning for ESHRE 2011 in Stockholm Clare Lewis-Jones, Chair Fertility EuropeFocus on Reproduction January 2011 13

EIM CONSORTIUM // TEN YEARS OF IVF MONITORING REPORTS // More than 600,000 ART and IUI cycles now monitored by ESHRE each year High quality measurement is a prerequisite of confidence The Campus event held in September last year to third most active ART country (behind France and celebrate ten years of ESHRE’s European IVF Germany), can provide registry data on only 60% of Monitoring (EIM) consortium was not just about its activity. Moreover, although amendments to reminiscing, nor even about celebrating. This was Spain’s legislation in 2006 required the countrys 17 also a meeting about the EIM’s future and how administrative regions to collect audited data on a many of the problems faced in building a cycle-by-cycle basis, only one - Catalonia - is fully comprehensive database of ART activity in Europe compliant. As a result, said Jose Antonio Castilla can be resolved. from the University Hospital of Granada, the According to the EIM’s present chairman Jacques responsibility for a registry of nationwide ART de Mouzon, the latest round of data collection - for performance is left to the Spanish Fertility Society 2007 - gathered registry data from 32 European (SEF) and a voluntary system of summary reportsMost of the 32 countries (including Turkey) representing 88% of (clinic-by-clinic, not cycle-by-cycle) which arecountries now clinics in these countries. And, while this is more neither audited nor official. Castilla, who is co-supplying registry than enough to provide a realistic picture of ART ordinator of the SEF registry, said that in 2008 nodata to the EIM life in Europe, there are still major omissions. more than 60% of Spain’s ART cycles were reportedwere represented atthe celebration Spain, for example, which is ranked as Europe’s to the registry - and from only 50% of its clinics.review in Munich. Moreover, the number of centres participating in the scheme in 2008 actually fell by 14% on the previous year. Spain, along with Cyprus, Greece, Switzerland and several countries of eastern Europe, is one of 13 countries to supply only partial information to the EIM. Nevertheless, there was strong representation at this meeting from eastern European registries, including presentations from Russia and Slovenia, and most countries (with the exception of Albania, Croatia, Romania and Slovakia, which did not supply data in 2007) seem keen to be involved. Indeed, Tomaz Tomazevic from the University Clinical Center in Ljubljana, reported that the EIM’s own data reporting system is now the formal mandatory data collection system for the Slovenian Ministry of Health. This official registry, he added, is able to provide ‘optimal endpoint’ data (delivery rate per started cycle) with real demographic impact, for it was on the basis of the annual EIM reports that Slovenia’s public health insurance scheme supported the use of elective single embryo transfer in the first two cycles of treatment by extending coverage from four to six cycles. Such complete systematic reporting - alongside Slovenia’s progressive legislation on ART - is an illustration of how comprehensive data collection can have an effect on national (and Europe-wide)14 Focus on Reproduction January 2011

of such detailed data has allowed benchmarking for EIM data then and now national comparison of efficacy, efficiency, 1997 2007 availability and - to some extent - safety. Certainly, Countries 18 32 with multiple pregnancy the acknowledged major Clinics 482 1016 risk of ART, multiple pregnancy rates and trends as Proportion ? 88% determined by the EIM have reflected ART’s safety Complete reports 10 19 potential as well as its risks. The data, however, have ART cycles 203,893 479,288 not allowed the monitoring of emerging safety IUI cycles None 168,178 parameters, especially in relation to such newly PR per ET IVF 26.1% 32.9% introduced techniques as vitrification or oocyte PR per ET ICSI 26.4% 33.3% cryopreservation. PR per FET 15.2% 22.5% Similarly, the long-term effects of assisted PR egg donation 27.1% 46.3% conception remain beyond the scope of EIM data, SET 11.5% 22.8% and even, in some countries at least, the obstetric DET 35/7% 57.5% outcome of pregnancy. Indeed, the standardisation of Single delivery 70.4% 78.2% all inputs to the database remains a theoretical Twin 25.8% 20.5% objective, said Andersen, although many countries - such as Germany and France - with newly upgraded data systems have the ability to provide detailed cycledemographic initiatives, and this was one of the data with linkage to delivery outcome.EIM’s achievements singled out by its co-founder Taraneh Shojaei reported that responsibility for aAnders Nyboe Andersen. ‘Indeed,’ said Andersen,‘demographic impact is perhaps our finestachievement, and trends identified by our annualreports are now recognised outside the professional Putting the show on the roadcommunity.’ Not only has EIM data confirmed substantialinequalities in access to treatments, but have alsounderlined the ever increasing age of ART patientsand the link between infertility and deferredpregnancy. Such links are now well recognised bythe EU, and the European Parliament’s 2008 reporton ‘the demographic future of Europe’ called on theEuropean Commission to address infertility as ademographic issue; such urging, said Andersen,could not be possible without the strength of theEIM database. The database has also identified a marked butsteady increase in pregnancy rate per transfer ESHREs Executive Committee had already heard one or twothroughout the past decade, which has risen from suggestions for surveillance data collection before Karl Nygren and26% for both IVF and ICSI in 1997 to 33% in Anders Nyboe Andersen, pictured above, submitted a formal proposal2007. Similar increases have been seen in pregnancy in March 1998 for the establishment of a European IVF monitoringrates from frozen embryo transfers (from 15% to (EIM) committee. The two Scandinavians spoke of data monitoring22%) and in oocyte donation (from 27% to 46%). and not data collection, although in their proposal collecting and Andersen further noted that ‘without the EIM auditing data (from national registries) were essential activities.reports no-one would be aware of the positive European monitoring, they said, was needed to prevent IVF activitiestrends’ in the number of embryos transferred. In in any country from derailing as a result of negative publicity.1997 more than one-third of transfers were with The EIM consortium was formally established at the 1999 annualthree embryos, but this rate had more than halved meeting in Tours, and attracted to its first meeting representativesby 2007. Current data suggest that transfer trends from 19 European countries, who each provided an overview ofare now relatively stable; two embryos were national data collection registries.transferred in 57% of cycles in both 2006 and The EIMs first report - on ART activity in 1997 - was published in2007, and one embryo in 22% of cycles. 2000, and its 11th report - on activity in 2007 - presented in Rome However, as Jacques de Mouzon has also insisted, prior to publication. Annual citations of EIM reports now total morethe EIM reports highlight the variability, not the than 100.homogeneity, of European ART, and the collectionFocus on Reproduction January 2011 15

registry data in France has now passed from FIVNAT to the government’s Agence de la Biomedecine (of which she is the evaluation MART safety monitoring department manager), with a legal requirement that project is now ‘making all clinics must participate in the scheme and submit at least summary data, and by 2012 individual cycle real progress’ data. The system, said Shojaei, combines registry, licensing and monitoring requirements in ART with those of the EU’s Tissue and Cell Directives. Similarly, the meeting’s local organiser, Markus Kupka from Munich University Hospital, reported that the German IVF register, whose cumulative data collection is now approaching 1 million cycles since its inception in 1982, allows the submission of individual cycle data through various software packages to a centralised linkage library. A recent analysis performed by the German registry (of almost a half million cycles) suggests that prospective data input is a mark of quality and associated with higher pregnancy rates. ‘Our experience of prospectivity,’ said Kupka, ‘is positive.’ The German data also show that the number of treatment cycles is beginning to rise once again (by around 10% per year) following Following a feasibility report in 2006 and with restrictive changes to reimbursement policy in 2004. funding in place from ESHRE, the University Comprehensive cycle-based systems such as those of Copenhagen and the Danish Agency of in Germany, France or the UK provide what the Science, Technology and Innovation, work on EIM’s other co-founder Karl Nygren called those the MART (Morbidity in ART) project began in ‘high-quality measures which are a pre-requisite for 2008 and has now assembled a provisional building confidence in ART’, and this, he readily database of almost a 100,000 IVF children - acknowledged, was the mission of the EIM’s 21,398 IVF children born between 1984 and foundation more than a decade ago. The challenges, 2007 in Norway, 35,017 in Sweden, 19,065 Nygren added, remain in the definition of ‘key data’ in Finland, and 23,477 in Denmark, all and ‘key outcomes’, but would ideally concentrate matched with around 400,000 controls. on benefit indicators (access, efficacy, safety and The plan now, said Anna-Karina Aaris cost) according to specific interventions. However, Henningsen, pictured above, who is co- there still remains huge variability in definition, ordinating the project from the University tension in the submission of cycle and/or summary Hospital in Copenhagen, is to pool the ART data, and a reliance on extrapolation for data and cross-link with national health system comprehensive coverage. Moreover, said Nygren, registers in the four countries. The sheer size there are still deficiencies in reporting, with many of the cohort, said Henningesen, should reflect pregnancies lost to follow-up and inadequate the prevalence of even rare epigenetic coverage for full risk assessment. disorders or the effects of newly introduced The future, added Nygren, may apply a more techniques. Similarly, the database may well relevant and comprehensive way of reporting over time reflect the perinatal and efficacy (pregnancies, deliveries, singletons, healthy developmental health benefits derived from the singletons . . . ) and a more appropriate definition transfer of fewer embryos. of intervention (started cycles, fresh and frozen, Danish data are ready, and Finnish, Swedish cumulative . . . ), but for the moment he urged and Norwegian data almost available for ongoing surveillance and continuing commitment to pooling. Once completed, the project should the project. There is, he noted, no other comparable not only provide an unequivocal assessment of database in the world, and continuing confidence in the perinatal outcome of 98,957 IVF births in the treatments monitored depends on the these countries, but a clear picture of availability - and transparency - of such data. morbidity trends over time associated with Simon Brown assisted conceptions. Focus on Reproduction16 Focus on Reproduction January 2011

// PCOS CONSENSUS WORKSHOP // Attention now turns to the health risks of PCOS The report from the first joint Somewhat later in the reproductive ESHRE/ASRM consensus conference lifespan, Felice Petraglia, University on the diagnostic criteria for of Siena, reported that the presence polycystic ovary syndrome has, in of PCOS had been associated with a just seven years since publication, higher incidence of miscarriage and become a citation classic. The an adverse pregnancy outcome. There Rotterdam criteria developed at that was some discussion from the floor meeting recognised that women with about the former, with London PCOS represent a heterogeneous endocrinologist Steve Franks population which cannot be defined doubting the strength of the by strict definitions. Thus, miscarriage data, and Rick Legro Rotterdam concluded that PCOS from Penn State College of Medicine might be confidently diagnosed in noting that in the US randomised women with any two of three trials on the use of metformin there features: polycystic ovaries seen on was no difference found in ultrasound, hyperandrogenism and miscarriage rates among the different oligo/amenorrhoea. The NIH criteria of Bart Fauser, chairman of patient groups. However, Petraglia 1990 which the Rotterdam consensus the writing committee emphasised the adverse effects of PCOS on superseded had required only two for this third PCOS pregnancy outcome through the mediators consensus statement. diagnostic features: hyperandrogenism and of gestational diabetes, pregnancy-induced chronic anovulation. hypertension, pre-eclampsia and fetal As of November last year, the Rotterdam consensus growth retardation. He also noted that this adverse report - published jointly by Human Reproduction effect was not just a matter of obesity, citing data and Fertility & Sterility - was HRs most frequently showing far higher rates of gestational diabetes in cited publication, and F&Ss second. PCOS subjects than in those who were only obese. The second consensus statement, like the first, However, in later life the overriding risks of PCOS considered PCOS from the perspective of infertility, lie with type 2 diabetes and cardiovascular health, and developed consensus on treatment. After lifestyle risks which are amplified anyway in obese women. advice, first-line management was defined as Steve Franks cited the observational Nurses Health ovulation induction (with clomiphene citrate) followed Study to show that the risk of type 2 diabetes was by gonadotrophin therapy or laparoscopic ovarian more than doubled in women with a history of surgery and IVF. irregular cycles. Obesity, he added, would increase Now, a third consensus conference, held in that risk. However, Franks emphasised that PCOS is a Amsterdam in November last year, has shifted the prediabetic state which invariably presents at a focus from infertility to the health implications of younger age; thus, diet and lifestyle advice are the PCOS in early and later reproductive life. So its very most important ways for reducing the diabetes risk in different from the two previous statements, said Bart later life. Fauser, chairman of the writing committee, with the And it is, of course, the presence of type 2 perspective now moving from reproductive disorders diabetes which increases the risk of CVD. The to a population deemed at risk of type 2 diabetes and landmark Interheart case-control study found that other cardiovascular diseases. diabetes was associated with a 4.2 relative risk for In the adolescent, however, even the definition of myocardial infarction. Advice from this meeting, PCOS is confusing, according to Leeds gynaecologist therefore, was to take a multifactorial approach, with Adam Balen, a member of the six-man writing the usual recommendations of weight loss, exercise, committee. Many of the normal features of smoking cessation, and medication. adolescence are similar to those of PCOS, he said, Fauser expects that this broad-scope consensus such as ovarian morphology and cycle regularity. statement will be published later in 2011. Its However, Balen confirmed that oligomenorrhoea development is now in the hands of a writing persisting two years after menarche in the adolescent committee composed of three ESHRE and three is an early sign of PCOS - and a better predictor than ASRM representatives, and publication will once LH or androgen concentrations. again be a joint exercise by both groups’ journals.qFocus on Reproduction January 2011 17

ESHRE NEWS // EUROPEAN HEALTH FORUM // The legislative inconsistency behind cross-border reproductive care ESHRE’s perspective at waiting times for treatment, cost, success rates and availability of donor gametes as the leading reasons for Europe’s leading forum travel. ‘Perhaps it’s because their fertility declines as each for health policymakers month goes by which makes waiting time so sensitive,’ said Clare. Almost all patients (88%) made travel and clinic arrangements themselves, and most were happy with the ESHRE took part in Europe’s leading conference on health outcome. policy in October last year, hosting a workshop on The increasing attraction of clinics in eastern Europe, ‘Individual choice in reproductive health’. The workshop, said Clare, is cost and limited regulation, with prices in which took place at the European Health Forum in Romania, Ukraine and Russia reportedly a quarter that of Gastein, Austria, considered infertility and its treatment private treatment in western Europe. However, her from the perspective of the patient, the drug industry, the underlying theme was the inconsistency of treatment politician and society. regulation throughout Europe. Her recommendations on However, all four presentations ultimately pointed in the behalf of the patient were: one direction of cross-border reproductive care and the l Consistent regulation and recommendations across the multiplicity of regulation and practice now present in whole of Europe, with the same rules applied Europe. It is this very multiplicity - as the panel discussion l Standardised health information (in a range of made clear - which is now driving cross-border movement languages) from health professionals/governments/EU and in European fertility treatment. patient organisations In particular, Clare Lewis-Jones, chair of Fertility Europe l A common minimum standard of care across Europe and speaking on behalf of the patient, described a l Consistent counselling support patchwork of legislation and reimbursement policies which Similarly, from the social perspective ESHRE Chairman made, for example, anonymous donor insemination Luca Gianaroli defined the controversies in ART as allowed in France and Belgium, but outlawed in the surrogacy, anonymous and non-anonymous gamete Netherlands, Germany and UK. donation, embryo freezing and PGD, which were each A survey performed by Infertility Network UK on ‘the reflected in inconsistent national legislation. However, the attraction of overseas clinics’ for UK patients found short legislative anomalies, he said, are increasingly subject to The workshop was chaired by ESHRE’s Past Chairman Joep Geraedts, with presentations by (left to right) Luca Gianaroli, Clare Lewis-Jones, Joan-Carles Arce, and Isabel de la Mata Barranco.18 Focus on Reproduction January 2011

‘Heterogeneous legislation’ also blocks industry’s ‘stagnating’ fertility development pipeline Despite a background of great social and medical need and an ART success story which boasts delivery rates comparable to spontaneous conception, industry research into fertility now commands only a minute proportion of an annual R&D expenditure of $34 billion. Based on data from 22 pharma companies and bundled into the category of GU/sex hormones, fertility (alongside contraception, menopause, BPH and erectile dysfunction) represents no more than 3% of industrys total R&D budget, with little prospect of any advance, according to Joan-Carles Arce, Vice President of Clinical Research & Development at Ferring Pharmaceuticals. He described the development pipeline of the three big players in fertility as stagnating, with only two new entities in phase II, and just one in phase III. Past developments, he added, have not realised aims to improve efficacy or safety, but have improved convenience (in new presentations, delivery routes, and longer action). Dr Arce described biomarkers for diagnostics and treatment, drug delivery technology, and embryo selection processes as new areas with potential for progress. However, he said, any pharma developments in fertility today are constrained by complex targets (notably confined to sub-groups of patients), increasing regulatory requirements (for documenting efficacy and safety), heterogeneous legislations, a necessity to duplicate clinical trials, and cost. There is, he added, a need for joint efforts between industry, governments and organisations to allocate resources and establish structures to ease the burden of infertility, and for realistic drug development objectives and reward to stimulate further development activities in fertility.legal challenge. Gianaroli not only cited the successful concerns and amendments over the outward flow ofchallenges to Italy’s Law 40 requirements (to transfer all patients (and whether prior authorisation is necessary forfertilised oocytes), but a 2010 judgement from the hospital procedures) and over the quality and safety ofEuropean Court of Human Rights that Austria’s Artificial care. Many member states had insisted that priorProcreation Act - which disallows gamete donation - was in authorisation should be necessary, while the Commissionviolation of the Convention because the claimants could itself insisted that any prior authorisation would be annot conceive by any other means than gamete donation. obstacle to the free movement of citizens - which the Court The European overview presented by Gianaroli - as also of Justice would not allow.found on the ESHRE website under ‘Guidelines and Legal’ Now, in its final draft the Council has not only agreed- proved salutary to the audience of health policymakers, that patients are to be reimbursed up to the level theywho appeared astonished at the disparities. ‘There can be would have received in their home country (ie, what wouldno other areas of medicine with such diversity of have been paid for by its own social security system) butlegislation,’ said one bemused guest from the floor. has also added a new provision that member states may decide to cover other related costs, such as accommodationEU cross-border directive and travel expenses (which may still need priorWhile ESHRE’s own Task Force on cross-border authorisation). The latest draft thus lists reasons whyreproductive health is moving ahead with its own member states may refuse authorisation, which seem toguidelines, Isabel de la Mata Barranco, a Principal Adviser involve entitlement to treatment, standards and safety.to the European Commission (DG SANCO) with a special The draft also suggests that each member state mustinterest in public health, reported that the draft directive on ensure, via ‘national contact points’, that patients fromcross-border healthcare (which was approved by the other EU countries can receive information on safety andCouncil of EU ministers in June 2010, backed by the quality standards to make an informed choice.Parliament’s public health committee in October, and is It now seems that the draft proposal has broad supportnow in its second reading in Parliament) will only allow in the EU Parliament and is likely to be accepted at itsreimbursement of costs up to the amount that would have second reading this year. Should that happen, the directivebeen paid had they received that treatment at home. could be adopted as ‘soft’ law by June.Procedures not allowed (or not reimbursible) in the home Speaking to the press in October last year, French MEPcountry will not be reimbursed. Françoise Grossetête, who has been the Parliament’s The directive, said Ms de la Mata, is intended to smooth rapporteur on the directive, said: ‘This directive is designedcross-border healthcare and ensure free citizen movement to allow patient mobility. We already have mobility ofamong member states (in compliance with Article 25 of the workers and students. It’s part of the fundamental rights oforiginal treaty of Europe) while ensuring each country’s European citizens. This does not however encouragerights to run its own health systems. medical tourism. We simply want to allow a wider range of The directive has been bogged down in financial public health for patients.’qFocus on Reproduction January 2011 19

SPECIAL INTEREST GROUPS // REPRODUCTIVE ENDOCRINOLOGY // New elected officers in place after Stockholm The SIG RE ended 2010 with period. Examples of how continuing activity in joint Officers nutrition, environmental factors meetings, the latest in September Adam Balen (GB), Co-ordinator and fertility interventions may in Dubrovnic, Croatia, on ‘A Richard Anderson (GB), Deputy Co-ordinator affect developmental healthy start - The determinants of Juan Garcia-Velasco (ES), Deputy Co-ordinator endocrinology, long-term health a successful pregnancy’. This was a Georg Griesinger (DE), Junior Deputy and fertility in the offspring will joint Campus event with the SIGs Nick Macklon (NL), Past Co-ordinator be reviewed, and intervention Early Pregnancy and Reproductive strategies discussed. Surgery but unfortunately there were fewer delegates than We agreed at our AGM in Stockholm that this year’s speakers - a great shame, as the quality of the precongress course will be titled Ovarian ageing and will presentations and the high level of discussion were very cover the formation of oocytes in the ovary and stimulating. We do need to ensure that our meetings are determinants of their rate of loss. The causes and well attended, especially as they are now held in varied management of premature ovarian failure will also be locations and our speakers take a lot of time out of busy described, as will ways to preserve fertility by oocyte or schedules to share their knowledge and participate in our ovarian tissue cryopreservation. The day will conclude academic sessions. with a socio-ethical talk on the effect on society of The third joint ESHRE/ASRM PCOS consensus meeting postponing pregnancy. on medical problems associated with PCOS took place in We shall be holding a further training workshop with November hosted by Bart Fauser and Basil Tarlatsis, both our colleagues in the Paramedical Group and SIG former co-ordinators of the SIG RE. The programme Embryology in St Petersburg, Russia, from 7-8th started with a one-day open meeting and continued with a September. The first of these courses in Kiev last May was two-day, closed consensus workshop along the lines of the very popular and so we encourgae you to register early! earlier Rotterdam and Thessaloniki meetings. As our short We are also considering a meeting on PCOS for Bulgaria report on page 17 indicates, the aim was to develop a later in the year. consensus on the impact of PCOS on early and later reproductive life, and those aspects not necessarily seen . . . and into 2012 from a fertility perspective (as in the two previous reports). The precongress course in Istanbul in 2012 will be Thus, on the agenda were quality of life, obesity, hyper- Optimising the IVF protocol and the use of adjunctive androgenism, pregnancy and, in later reproductive life, therapies, covering such controversial issues as aspirin, type 2 diabetes, the menopause and cardiovascular health. DHEA, growth hormone, steroids, heparin, acupuncture, homeopathy etc, etc... Training programme in 2011 Also in 2012 we plan an update on the use and role of For 2011 we encourage you to register for the first GnRH antagonists to be hosted by Georg Griesinger in Campus in Kempten, Bavaria, on 4th February on ART Luebeck, Germany. And in the Spring in Lille, hosted by and the oncological impact, hosted by Ricardo Dideir Dewailly, an update on AMH. We also have a Felberbaum. The programme includes presentations on: proposal for a meeting in Montenegro to be hosted by Sexual steroids and their oncogenic potency; Estrogens, Tatjana Motrenko Simic, the programme for which is still endometriosis and ovarian cancer: is there a missing link; to be finalised. Cancer incidence in infertile women after COH; Incidence I stand down as Co-ordinator of the SIG RE in 2011 of malignancies in children born after IVF - results of and would like to thank the committee for their hard epidemiological studies; Ovarian protection during work, help and suggestions. Georg Griesinger takes over as chemotherapy by GnRH agonists. Co-ordinator at Stockholm. We have just held our first Nick Macklon will be hosting The embryo as patient on fully open election to the committee and we are pleased to 13-14th May in Winchester, UK. It is now clear that the announce that joining as Deputy Co-ordinators are Frank periconceptional period determines not only perinatal Broekmans and Stratis Kolibianakis, with Daniela outcomes but has an impact on the long-term health of Romualdias the new Junior Deputy. I wish Georg and his mother and child. This one-day course will cover the new team all the very best for the coming years. evidence base supporting the developmental origins of Adam Balen health and disease (formerly referred to as the ‘Barker Co-ordinator SIG Reproductive Endocrinology hypothesis’), and how this relates to the periconceptional adam.balen@leedsth.nhs.uk.20 Focus on Reproduction January 2011

// SAFETY & QUALITY IN ART //Central Office research support for guidelinesIt is now three years since an design, preparation, review,invitational meeting was convened Officers dissemination and evaluation ofby the SIG Safety & Quality in Petra De Sutter (BE), Co-ordinator guidelines. And it was according toART (SQUART) - represented by Karl Nygren (SE), Deputy Co-ordinator these internationally acceptedPast Co-ordinators Christina Bergh Willianne Nelen (NL) , Deputy Co-ordinator criteria that the SIG SQUARTand Jan Kremer - in Nijmegen to Jan Kremer (NL), Past Co-ordinator developed an ESHRE manual forconsider the future of ESHRE’s guideline development; theclinical guidelines. After two days of discussion, guideline programme has now become one of the corerepresentatives of ESHRE’s SIGs, journals and Executive activities of the SIG SQUART, with Willianne Nelen asCommittee (as well as the Cochrane Collaboration) programme co-ordinator.concluded that ESHRE, as an authority in reproductive Publication of the ESHRE manual for guidelinescience and medicine in Europe, does have a responsibility development has in the meantime also sharpened the rulesto set guideline standards for high-quality clinical practice. for publication of other ESHRE documents. Thus, anyThus, at the end of this meeting the ESHRE guideline ESHRE document (eg, position statements, specialityprogramme was born - at least in name - and the rules of reviews, notice of intention and clinical guidelines) mustthe game determined. now either be commissioned by the Executive Committee The overall aim of the guideline programme is to itself or its subject approved in advance. In addition,decrease practice inconsistency and increase the overall manuscripts must be posted on the ESHRE website forquality of patient care in reproductive medicine in Europe. review by members (fixed as one month) before theirThus, it was agreed that the guidelines emerging from the publication. The rules, said past ESHRE Chairman JoepESHRE programme would be authoritative, based on the Geraedts, were introduced to bring some consistency - asbest available evidence (most relevant and highest level), well as authority - to the increasing output of ESHREreliable and consistent in style and approach. It was clear documents, and an accepted and uniform methodology forthat such guidelines would be aimed at professionals composition and approval will inevitably raise the value of(doctors, scientists, paramedics, etc), with patients the documents.involved as stakeholders in a consultation process. However, the principal aim of the manual is to provide aProduction would be according to up-to-date process and stepwise practice tool for members of ESHRE’s guidelinequality indicators. development groups and is available for consultation on The development of clinical guidelines has generally the ESHRE website. Each chapter of the manualbecome a formalised process in recent years. Instruments corresponds with one of the interdependent activities ofsuch as that of the Appraisal of Guidelines for Research guideline development (eg, scoping, search and selectionand Evaluation in Europe (AGREE) collaboration (see of evidence, dissemination) and consists of a description,www.agreecollaboration.org) provide structures for the an overview in flow chart form and some practical a ESHRE’s new research specialist for guideline development The missing link in full-speed ESHRE guideline development has been the absence of a research specialist, but now, with the addition of a full-time researcher in Central Office from October last year, that gap has ben filled. Nathalie Vermeulen, 27, has been appointed as a research specialist on behalf of the ESHRE guideline programme. She graduated in biochemistry from Leuven in 2005 and obtained her PhD on serological markers in inflammatory bowel disease in January 2010. Before starting at ESHRE, she was employed as a pharmaceutical company product manager. As a research specialist Nathalie will assist the SIGs in the development of guidelines, and in that capacity will document existing guidelines, conduct stepwise literature search and summarise evidence, formulate and classify recommendations, record evidence gaps and update the literature search every two years for every guideline. Nathalie can be contacted at nathalie@eshre.euFocus on Reproduction January 2011 21

SPECIAL INTEREST GROUPS // STEM CELLS // SIG Stem Cells agrees endorsement of ISSCR research and clinical guidelines The SIG Stem Cells organised its first University of Geneva and Jose two ESHRE Campus meetings in Officers Inzunza at the Karolinska Institute 2010, in February in Barcelona and in Carlos Simon (ES), Co-ordinator in Stockholm joining the initiative. November in Valencia; both combined Karen Sermon (BE), Deputy Co-ordinator a basic update course on pluripotent Anis Feki (CH), Deputy Co-ordinator Stockholm 2011 stem cells and a hands-on workshop. Rita Vassena (ES), Junior Deputy We are pleased to announce that the The meetings were organised with the Anna Veiga (ES), Past Co-ordinator precongress course in Stockholm, Spanish Stem Cell Bank (Instituto de The blastocyst: perpetuating life, is Salud Carlos III) and involved a number of speakers from already prepared and announced. The course is a different areas of stem cell biology, from academia to collaboration between our SIG and the SIG Embryology commercial companies, and covered biological, technical and will be chaired by Karen Sermon and Cristina Magli. and ethical aspects of stem cell research. The basic course The course will cover the common ground between was followed by a four-day intensive workshop on the embryology (embryo polarity, pluripotency) and stem cells derivation and culture of pluripotent stem cells. Both (epigenetic regulation, micro RNAs and pluripotency). Full workshops were fully booked, and were attended by details can be found on the ESHRE website. We will be students coming from Europe (Bulgaria, UK, Latvia, Italy, delighted to receive any suggestions or contributions for Germany), Asia (Russia, Turkey, India), Africa (Gambia), the preparation of future events. and Latin America (Brazil). Participants had the chance to learn how to derive mouse Research guidelines embryonic stem cell lines, to culture, expand and freeze The field of regenerative medicine is rapidly expanding human embryonic stem cells, to test pluripotency of human thanks to the discovery of human embryonic and induced ES cells by making embryoid bodies and teratomas, to pluripotent stem cells.1,2,3 In addition, current preliminary, reprogramme human fibroblasts, and to manipulate proof-of-principle studies in model systems indicate a real embryos during their preimplantation development. The therapeutic value of pluripotent or progenitors cells.4,5,6 students were followed by tutors on almost a one-to-one Regenerative medicine through pluripotent cells promises basis with a highly personalised teaching system that to tackle some of the most devastating and life altering covered most of the techniques actually in use in hES cells diseases, such as Parkinsons disease, diabetes, spinal cord and induced pluripotent stem cell research. injury derived paralysis, and many more. We now plan to continue this teaching initiative every six In the last few years, basic research into the derivation months at the labs of SIG members, with Anis Feki at the and the biology of human embryonic stem (hES) cells has SIG Safety & Quality continued suggestions. The manual also recommends that all ESHRE about the new guideline development methodology, and guidelines are kept to a reasonable size to ensure their this will be repeated for all future development groups to development within an 18-24 month period. And now, to help them follow the manual help in meeting tighter deadlines, each guideline and to guarantee a consistent development group will be supported by the ESHRE level of methodological quality. research specialist to provide technical support and facilitate evidence search and selection. Several SIGs, including Endometriosis & Endometrium, Willianne Nelen Early Pregnancy and Psychology & Counselling, have Deputy Co-ordinator SIG already announced that their (updated) guidelines will be SQUART developed in accordance with the new manual. In April and co-ordinator of the ESHRE 2009 a training course was organised to inform all SIGs guideline programme22 Focus on Reproduction January 2011

Participants in the fully booked 2010 update and hands-on courses in Valencia (left) and Barcelona.increased considerably. There are now hundreds of hES cell mobilised and injected percutaneously in the kidney region;lines banked across the world, and more are being derived. the patient developed angioproliferative tumors neverThis situation naturally leads to transnational research, and described before, and likely of stem cell origin.8the need of a sound scientific and ethical framework is In the wake of these events, the SIG Stem Cells hasstrongly felt. It is for this reason that the SIG Stem Cells agreed to take a clear stance on the issue of cell therapies,endorses the Guidelines for the Conduct of Human in order to protect the interests of patients and familiesEmbryonic Stem Cell Research, prepared by the seeking a cure for highly invalidating diseases. The SIGInternational Society for Stem Cell Research Stem Cells has therefore also endorsed the Guidelines for(http://www.isscr.org/guidelines/ISSCRhESCguidelines- the Clinical Translation of Stem Cells, again prepared by2006.pdf). The ISSCR is the leading international scientific the ISSCR (http://www.isscr.org/clinical_trans/pdfs/-association for pluripotent cell scientists and clinicians, and ISSCRGLClinicalTrans.pdf). The document details, forits guidelines set the standard of practice and the ethical instance, the conduct to be taken when faced with issuesframework for the use of hES cells in research. The such as patient information, disclosure of source of cells,guidelines also offer guidance to researchers and clinicians disclosure of safety and efficacy trials, and advice tocollaborating across national (and often legislative) patients on unproven procedures. We warmly invite allborders, address important ethical issues (such as ESHRE members to adopt these two sets of guidelinesprocurement of embryonic material for hES cell derivation), when planning hES-based research activities and discussingand help in defining the scope of acceptable research the potential of cell therapy approaches with their patients.projects (for instance, by taking a clear stance against Carlos Simonreproductive cloning). Co-ordinator SIG Stem CellsA stand against unproven treatments 1. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. EmbryonicThe great promise of regenerative therapies, although so far stem cell lines derived from human blastocysts. Science 1998; 282:unproved in clinical trials, has prompted a keen interest 1145-1147.among professionals and patients alike. As research into 2. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by definedthe clinical potential of pluripotent and progenitor cells factors. Cell 2006; 126: 663-676.advances, so does the hope of patients and families in their 3. Takahashi K, Tanabe K, Ohnuki M, et al. Induction ofsearch for solutions to severe health problems. Sadly, in pluripotent stem cells from adult human fibroblasts by definedparallel to the rigorous testing and initial clinical trials now factors. Cell 2007; 131: 861-872.under way with pluripotent cells, there also flourishes a 4. Raya A, Rodriguez-Piza I, Guenechea G, et al. Disease-correctedmarket of unproven, and often dangerous, treatments. haematopoietic progenitors from Fanconi anaemia inducedNumerous clinics, mostly in countries with lax legislative pluripotent stem cells. Nature 2009; 460: 53-59.frameworks, market their ‘treatments’ directly to the 5. Hanna J, Wernig M, Markoulaki S, et al. Treatment of sicklepatients, often without disclosing the source of the cells cell anemia mouse model with iPS cells generated from autologousinfused (among them embryo and fetal derived skin. Science 2007; 318: 1920-1923.preparations), the details of the protocol, and, most 6. Wernig M, Zhao JP, Pruszak J, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brainimportantly, without rigorous efficacy and safety data. and improve symptoms of rats with Parkinson’s disease. Proc Nat Two dramatic cases stand out from the recent literature, Acad Sci USA 2008; 105: 5856-5861.one involving the development of a donor cell-derived 7. Amariglio N, Hirshberg A, Scheithauer B, et al. Donor-derivedbrain tumor in a 13-year-old boy undergoing fetal neural brain tumor following neural stem cell transplantation in an ataxiastem cell treatment to treat ataxia teleangiectasia,7 and one telangiectasia patient. PLoS Med 2009; 6(2): e1000029.involving a 46-year-old woman with systemic lupus 8. Thirabanjasak D, Tantiwongse K, Thorner PS.erythematosus who had her own hematopoietic stem cells Angiomyeloproliferative lesions following autologous stem cell therapy. J Am Soc Nephrol 2010; 21: 1218-1222.Focus on Reproduction January 2011 23

SPECIAL INTEREST GROUPS // ANDROLOGY // Defining the broad boundaries of andrology In earlier issues of Focus on down as committee member and Reproduction I have noted that Officers I will take over as Past Co- that SIG-A - and indeed the whole Roelof Menkveld (ZA), Co-ordinator ordinator from Lars Björndahl. field of andrology - is not just Jose Antonio Castilla (ES), Deputy Co-ordinator As mentioned in the last edition about the laboratory and semen Sheena Lewis (GB), Deputy Co-ordinator of Focus on Reproduction analyses. Andrology is the study Jessica Tu (SE), Junior Deputy Sheena Lewis will take over as of all facets of reproductive health Co-ordinator at the next SIG-A in the man, and therefore includes clinical andrology, members business meeting scheduled to take place after laboratory andrology and basic andrology. our precongress course in Stockholm. We will also have to l Clinical andrology will mainly include those subjects elect a new Junior Deputy in the place of Jessica Tu, related to male (in)fertility - its diagnosis and treatment, whose term also ends in Stockholm. Candidates for the HIV, immunological aspects, environmental influences, age, junior position must be clinicians or scientists younger ejaculation (spinal injuries), contraception, surgery, sperm than 35 years of age. The newly elected members will retrieval (MESA, TESA, TESE), varicocelectomy and sperm serve a term of two years. After one year, one of the two donation. new committee members will be appointed by the Co- l Laboratory andrology will include such topics as basic ordinator and Past Co-ordinator as the Co-ordinator elect semen analysis, diagnostic tests, sperm functional tests, to take over from Sheena at the annual meeting in 2013. semen preparation, semen preservation and sperm DNA All SIG-A members, clinical and scientists, can nominate tests. new members. l Basic andrology will include spermatogenesis, an understanding of the entire process of ejaculation, sperm Training activities function and roles of spermatozoa and sperm DNA up to Recent activities have included a combined meeting with and including the whole process of fertilisation and embryo the SIG Reproductive Surgery, which took place in development. Treviso, Italy, in October last year. Although we presented With these definitions in mind it is clear that clinicians and a very interesting and well balanced programme of female scientists working in andrology are equal partners in the and male surgery, the meeting was very poorly attended, field - and thus in all aspects and functions of SIG which was of course a big disappointment. Andrology. Future activities will include the presentation of our precongress course in Stockholm (on 3rd July), which this New committee members year will be on a more basic science theme of Lifestyle and A little later in this year we will need to elect two new male reproduction. We also plan a SIG-A Campus meeting members for the SIG-A committee; Jose Castilla will step in Seville, Spain, on 22-23rd September titled The whole man. This will focus on the impact of infertility on men’s well-being, sexuality and social relationships, as well as our care of the man and his sperm in the clinic. SIG-A members are invited to send in suggestions for topic for campus meetings with possible venues and dates and any other suggestions regarding SIG-A matters to me at the address below. Roelof Menkveld Co-ordinator SIG-Andrology rme@sun.ac.za Despite an attractive programme, our combined meeting with the SIG Reproductive Surgery in Treviso was poorly attended.24 Focus on Reproduction January 2011

// EARLY PREGNANCY //Enjoying the benefits of joint meetingsA mantra for the SIG Early immunologists and be of benefit toPregnancy is joint meetings with Officers the work of both.other SIGs or non-ESHRE societies. Ole Christiansen (DK), Co-ordinator In October, as a precongress eventFor a relatively small SIG like ours it Mariette Goddijn (NL), Deputy Co-ordinator before the ASRM meeting inis advantageous that joint meetings Siobhan Quenby (GB), Deputy Co-ordinator Orlando, there will be an ASRM-can attract speakers and participants Marcin Rajewski (PL), Junior Deputy ESHRE postgraduate exchangefrom both societies; this improves Roy Farquharson (GB), Past Co-ordinator course on early pregnancy. Coursethe scientific quality of the meetings organisers are Mary D. Stephensonand results in a better economic balance. for the ASRM and Ole B. Christiansen for the SIG EP.We have good experience from organising joint meetings in Our annual winter symposium, to be held this year inthe past and we hope 2011 continues the trend. Birmingham, UK, on 17-18th November is titled Our precongress course (3rd July) in Stockholm will be a Comparing management of pregnancy loss in differentjoint meeting with SIG Reproductive Genetics titled From settings and will give participants the opportunity togenes to gestation. We think that we have produced a very exchange best practice. The symposium has been organisedexciting programme with up-to-date overviews of the most as a joint meeting with the British Association of Earlyimportant discoveries relating to the genes of importance in Pregnancy Units by Siobhan Quenby. The presentationsimplantation and early pregnancy. given by both physicians and nurses at this meeting are From 24-26th August we have organised a joint meeting informative for doctors, psychologists and paramedicalwith the European Society for Reproductive Immunology in staff (nurses, midwives, etc) working with couples withCopenhagen. The aim of the meeting is mainly to present early pregnancy disorders.research which integrates the clinical, immunological and Ole B. Christiansenepidemiological aspects of early pregnancy disorders. We Co-ordinator SIG Early Pregnancyhope the meeting will attract both clinicians and olbc@rn.dk // ENDOMETRIOSIS & ENDOMETRIUM // Call for abstracts for Stockholm . . . and Montpellier Let me first remind all March. All abstracts SIG members about the Officers submitted will be peer abstract deadline (1st Hilary Critchley (GB), Co-ordinator reviewed, and the five February) for this year’s Anneli Stavreus-Evers (SE), Deputy Co-ordinator Endometrium top submissions in each annual meeting in Gerard Dunselman (NL), Deputy Co-ordinator Endometriosis category will be selected Stockholm. We hope to Annemiek Nap (NL), Junior Deputy for plenary presentation. build on last years The remainder will be impressive number of abstracts in the areas of judged for the free communications and posters. endometriosis, endometrium, implantation and fallopian l Our precongress course this year in Stockholm tube, and that the programme once again reflects the focuses on the female tract environment. The growing interest in these areas of womens health and programme is now on the ESHRE website and we look female reproductive tract biology. forward to another full-house attendance. On that note I should add that abstract submission is l A Campus event planned for Rome on 28-29th now open for the 11th World Congress on Endometriosis October aims to highlight the impact of endometriosis to be held in Montpellier, France, on 4-7th September. on fertility status. Importantly, the meeting will address This is an abstract-driven congress, with very few our current knowledge of the interface between IVF and invited speakers; clinicians and scientists have the endometriosis and provide an opportunity for discussion opportunity to present their work in a plenary session about current views on management. covering one of 19 topics. You can submit your Hilary Critchley abstracts at www.wce2011.com – deadline is 31st Co-ordinator SIG Endometriosis & EndometriumFocus on Reproduction January 2011 25

SPECIAL INTEREST GROUPS // EMBRYOLOGY // First draft of the new Atlas of Embryology planned for presentation in Stockholm The second half of 2010 proved of how important the selection very active, with two courses Officers of culture medium is for their and the kick-off for the Atlas of Cristina Magli (IT), Co-ordinator laboratories. Embryology. Maria José de los Santos (ES), Deputy Co-ordinator The first course took place in Kersti Lundin (SE), Co-ordinator Elect Events in 2011 Lisbon in October on Forgotten Josephine Lemmen (DK), Junior Deputy Our next course Practical knowledge about gamete Etienne Van den Abbeel (BE), Past Co-ordinator aspects of non invasive selection physiology and its impact on of gametes, embryos and embryo quality with 136 participants. The course was blastocysts in a modern IVF laboratory will be in Salzburg organised in collaboration with the Portuguese Society of on 1-2nd April. The programme is very attractive and can Reproductive Medicine and refreshed our be found on our web page. The course will provide clinical basic knowledge of biology, including embryologists with the latest information on the rather gametogenesis, fertilisation and new technologies for gamete, embryo and blastocyst embryogenesis. It was a great opportunity selection. The course is organised in collaboration with the to review those basic mechanisms Austrian Reproductive Medicine Society. regulating cell growth. Evaluation forms filled in by participants indicated a very The Atlas of Embryology high degree of satisfaction. Our host, The working groups involved in the revised Atlas of Carlos Plancha, delighted participants Embryology are now very active. Many images have been with his warm hospitality, which collected for allocation to four main chapters: oocytes, included a small exhibition of artefacts pronuclear stage, embryos and blastocysts, all of which from Africa related to the promotion of include cryopreservation. Our idea is to prepare an fertility and campaigns against electronic document where many images are presented, infertility. including those which also focus on those deviating from Our second course was a full-day what is commonly considered the gold standard. These postgraduate course held at this year’s deviations from the norm will be characterised in terms of ASRM meeting in Denver on The frequency and implantation potential. It is planned to have enrichment of culture media: towards an initial sample of the final document ready for the best environment for IVF presentation at the annual meeting in Stockholm. embryos? All speakers gave excellent Our Octobermeeting in Lisbon presentations illustrating how, in many Elections for Junior Deputy on ‘forgotten aspects, culture conditions are set up without The present steering committee of the SIG Embryology will knowledge’ of full knowledge of human requirements (for change in Stockholm. The new committee will consist of agamete physiology example, osmolarity). There was concern in Kersti Lundin as Co-ordinator, Cristina Magli as Past included an exhibtion of many discussions that, in order to promote Cordinator, and Maria José de los Santos and Josephine African artefacts embryo growth in vitro, media are now Lemmen as the two Deputies. There is vacancy for therelated to fertility. supplemented with growth factors, anti- Junior Deputy for which we ask nominations before 15th oxidants, cytokines and vitamins at February. To be eligible, the candidates must be under the concentrations which are often far from age of 35 and be member of ESHRE with embryology as physiological. Several formulations are now commercially their primary field of interest. Nominations will be available, but their composition is usually not disclosed. It evaluated by the steering committee and candidates was quite clear from our discussions in Denver that there is meeting the requirements will be proposed to stand for now an urgent need to know whether promoting embryo election - for which all SIG Embryology members will be growth so intensively might have an effect on later asked by e-mail to cast their vote. Please see more development. A very lively debate co-ordinated by Luca information on the ESHRE website. Gianaroli followed the presentations, and there is no doubt Cristina Magli that participants left the room with a renewed awareness Co-ordinator SIG Embryology26 Focus on Reproduction January 2011

TASK FORCES// MANAGEMENT OF FERTILITY UNITS //Fertility centres list‘human resources’ astop management priorityA survey of 207 fertility centres performed by theTask Force has found that ‘human resources’ rankshighest among their business priorities. The survey,which was conducted last year, sought informationon human resources, data management and In terms of external communications, theplanning, financial planning, communication, website is now the favoured means ofinsurance cover, and business management. The communication for nearly all fertility clinics.clinics surveyed were mainly from Europe (146),but North America (24 units), Africa (eight units),Asia (24 units) and Australia (eight units) were alsorepresented. With respect to human resources, only aroundone-third of centres had established trainingsystems in place for medical staff, nurses andlaboratory staff (though most said they wouldwelcome some active involvement by ESHRE). Themajority of centres (147/207) have a fullydedicated manager on site. The level of data management in clinics wasfound to be varied, with around one-fifth reportinga fully implemented system of document Among six areas of management identified by the Task Force, human resourcesmanagement (treatment information, informed proved the number one priority among the clinics surveyed.consents, cycle details), but a similarproportion had no such system in (111/200), or used an external cryostorage of gametes andplace. The same proportions were agent, but their favoured embryos, or for the reimbursementevident with respect to data communications tool was by far of costs to the patient.management for monitoring the website. Internally, almost all As a follow-up to the survey theoutcome and treatment statitsics. communication was conducted by Task Force is organising a meeting There were similar levels of intranet and e-mail. The phone and in February at the Fondazione Cinivariability found in financial letter are rapidly becoming in Venice on Insurance models formanagement, with only a relatively redundant. reproductive medicine. The two-small number of clinics (37/207) On the question of insurance, day meeting, which has beennegotiating an annual budget with 164 of 207 centres responding did facilitated by an unrestricted grantrespect to personnel, investments, have liability cover - but 43 did from the insurance companyIT and operations. However, most not. The majority of those with Generali, will consider insuranceclinics (92/207) periodically cover (82) had a limit to their for medical malpractice, the legalevaluate financial performance and indemnity of 1 million euros or implications of ART, and lossare interested in developing models less. Only 30 centres had coverage prevention - within a context offor the evaluation of financial above 5 million euros. Coverage demographic dynamics, cross-performance. was also concentrated on the border care, outcome and cryo- Less variable is the favoured clinicians, with embryologists and preservation. Full details are on themeans of external communication - paramedics only rarely covered. ESHRE website under ‘Calendar’.the website. Indeed, many centres Very few centres had Luca Gianaroliemployed an in-house supplementary cover (over and Co-ordinator Task Forcecommunications manager above legal requirements) for the Management of Fertility UnitsFocus on Reproduction January 2011 27

TASK FORCES // CROSS-BORDER REPRODUCTIVE CARE // ESHRE ‘guidance’ on cross-border reproductive care now approved by Executive Committee While cross-border reproductive care continues to make international headlines, the Task Force’s Good Practice Guidance to Cross Border Reproductive Care has now been approved by ESHRE’s Executive Committee. The guide is applicable to centres and individual practitioners, and will shortly be published in full. Members of the Task Force are aware that this is only a first step, and aware too that ‘guidance’ is not a top-heavy system of certification or accreditation. So this must be seen as a first step on a European scene which more and more demands control of standards to ensure the safety of patients, gamete donors and surrogates, as well as the children born. Our guidance also provides an inter-professional communication We already know the facts: patients, and we hope that patient support groups like l Cross border reproductive care refers to a widespread Fertility Europe will continue to lobby in this direction phenomenon in which infertile patients or collaborators and at all levels.2 Meanwhile, back in the real world many (such as egg donors or potential surrogates) cross national patients continue to travel, and, economic crisis or not, boundaries in order to obtain or provide reproductive this trend will continue; indeed, many ART treatments treatment outside their home country. overseas are now cheaper abroad than in London, even l The reasons for travelling vary between countries, but when the cost of travel is included. the most common is to circumvent a law which forbids a This first paper from the Task Force sets out guidance particular technique or a particular group from treatment. for fertility clinics and physicians treating foreign patients, There may be other access limitations, such as long but may also help regulators and policymakers create a waiting-lists at home, or a perceived better quality of care framework by which centres can follow the rules. abroad, or cheaper treatment.1,2 Although in principle the care of foreign and local patients Our guidance report reiterates the fact that the ideal should be the same and meet the best possible standards, scenario is fair access at home to all treatments for all there is evidence that this is not always the case. We focus on several principles - equity, safety, efficiency, effectiveness (including evidence-based care), timeliness TASK FORCE and patient centeredness - as applied to patients, gametes CO-ORDINATOR donors, surrogates and professionals. In our view, these FRANÇOISE SHENFIELD: principles are all of equal importance and have no fixed ‘THE FIRST STEP ON A order of priority. EUROPEAN SCENE The messages of this guidance WHICH MORE AND MORE 1. Patients DEMANDS CONTROL OF l Any differences between local and foreign patients STANDARDS.’ should be justified, as, for instance, the extra cost for28 Focus on Reproduction January 2011

interpreters. appropriate legal advisors. There have been headlines from l Patients should receive clear information about some cases of surrogacy from the Ukraine for UK-intended investigations and their cost, waiting-lists and the expected parents, or from India for Japanese-intended parents, and time they will have to spend outside their home country. possible conflicts with the law in the home country should l The provision of accurate success rate of the centre is be explained to the patients. important to help patients agree on a treatment plan. We also discuss the degree of collaboration and l Communication and collaboration between the home responsibility between doctors of different countries. and foreign teams is an essential aspect of patient safety. Indeed, this may be a legal concern for our German l Understanding is the key to proper consent, and it may colleagues, who are technically forbidden to even mention be difficult to ensure that patients understand enough to ‘illegal’ treatments abroad - although the picture in give appropriate consent when there is no common Germany seems rapidly changing following a failed language. Counselling and psychological support should be prosecution brought under the 1990 embryo protection available in a language understood by the patients. laws. We are also seeing some German patients travelling l There should always be the possibility of redress for the to neighbouring Czech Republic for PGD, where German patients, including the name of the foreign clinic’s practitioners are said to be looking after them. ombudsman or the person to whom complaints should be addressed. Where to in 2011? Our first aim will be to enroll as many signatures as 2. Gamete donation possible to the guidance, from regulatory bodies to l The requirements of the EU Tissue & Cells Directives national fertility societies. We already have a principled should always be followed, with special regard to screening agreement from the IFFS on this matter. processes and non-commercialisation. Second, our research will consider the unknown aspects l Donors should receive the same degree of care as of gamete donation, and especially oocyte donation across patients. borders. This will not only mean donors in those countries l The question of donor safety has been less investigated where our patients choose to go, but also ‘travelling’ than patient safety, and will be the focus of our efforts this oocytes from the banks which are beginning to proliferate year. This indeed forms the core of the Task Force plans since introduction of vitrification. for new research, with the collaboration already engaged As usual, Focus on Reproduction readers will be the first of Belgian, Spanish, Czech and Dutch colleagues. The facts to be informed. are that reliable data regarding risks are scarce, especially Françoise Shenfield, in the case of repeated donation. We thus feel it is Co-ordinator Task Force Cross-border Reproductive Care essential to establish national registers of gametes donors, and for centres to participate in the collection of national 1. Shenfield F, de Mouzon J, Pennings G, et al. Cross border or international data. We plan to introduce such a reproductive care in six European countries. Hum Reprod 2010; database via ESHRE, with the help of our colleagues in the 25: 1361-1368. EIM consortium. 2. ESHRE Task Force on Ethics and Law 14. Equity of access to ART. Hum Reprod 2008: 23; 772-774. We recommend that all treatments should comply with 3. Good Clinical Treatment in Assisted Reproduction, the rules of ESHRE’s ‘good clinical treatment in ART’, www.eshre.eu. which stress the avoidance of multiple pregnancy.3 Legal problems What about the well publicised legal problems which have happened in some cases of cross-border reproductive care, albeit rarely? We stress that the provision of legal advice about local rules is essential. There is already one law firm in the UK specialising in such advice, but such advice should also be provided by the local practitioner, or, if not possible, through referral toFocus on Reproduction January 2011 29

FEATURE It is now six years since the worlds first baby was born following the cryopreservation of ovarian tissue. Yet this and other techniques of fertility preservation remain in their infancy. Richard Anderson and Claus Yding Andersen review progress so far and the realistic fertility options for women facing cancer treatment. T Fertility he preservation of female fertility in the face of significant disease and its treatment is a rapidly growing preservation clinical field. It is the subject of a dedicated ESHRE Task Force as well as an international society yet it remains in many in women ways a subject in its infancy, with no more than 14 babies born worldwide through the replacement of frozen/thawed ovarian tissue over the six years since the first report of success.1 This surge in activity is based largely on the improved survival of women and girls from malignant disease. This has been particularly so in paediatric oncology, with a transformation from very low success rates for many conditions to the current situation where 80-90% of children with cancer can expect to survive long term. The loss of fertility is a common consequence of the use of many therapeutic agents for non-malignant as well as malignant conditions, including systemic lupus erythematosis and other rheumatological diseases. Bone marrow stem cell transplantation with chemotherapy conditioning is now being used in sickle cell disease and tried in other conditions. There is also the remarkable series of ovarian transplants in monozygotic twins discordant for premature ovarian failure, with several successful pregnancies now reported from both fresh and frozen ovarian tissue.2 Moreover, the growing public awareness of the age-related decline in female fertility may well bring many more requests for fertility preservation for social reasons in the years to come. Effects of chemotherapy and radiotherapy The adverse affects of chemotherapy and radiotherapy on female reproductive30 Focus on Reproduction January 2011

RICHARD ANDERSON (left) and CLAUS YDING ANDERSEN: ‘PATIENT SELECTION REMAINS A CHALLENGE, TO BE CONFIDENT IN OFFERING TREATMENT TO THOSE WHO NEED IT, AND REASSURING TO THOSE WHO DO NOT.’function have been extensively reviewed, although there are understanding is based on a premise that women have afew data on the precise effects of chemotherapy on the finite population of oocytes. This axiom, of course, hasovary. It is clear that alkylating agents have high been the subject of vigorous debate in recent years and,gonadotoxicity compared with other drugs but many while many of us will have seen pregnancies in womenregimes use combinations, thereby complicating assessment. with established post-cancer ovarian failure, clinicalIn addition, oncology is a rapidly advancing speciality and evidence for recovery of the follicle population is stillgood quality data on, for example, the prevalence of acute lacking.ovarian failure with modern regimes are lacking. There arealso international variations, so the need for fertility Options for fertility preservationpreservation for a given diagnosis will also differ between As illustrated below, there is a range of clinical scenarios incountries. which different fertility preservation techniques are Women who have had radiotherapy to the uterus are at appropriate. These can be discussed with the patient or, inan increased risk of miscarriage and premature labour, the case of a child, with the patient and her parents. Thealthough there are no data on whether current tests to most established technique is of embryo cryopreservation,assess uterine function - such as uterine artery blood flow which is available in all IVF units. IVF protocols are wellanalysis - are predictive of pregnancy outcome in these defined, although it may be helpful under somecircumstances. There are therefore substantial opportunities circumstances to induce luteolysis with a GnRH antagonistto improve our data on the effects of cancer therapies on to allow FSH injections to start sooner.3 GnRHreproductive function in women, and thus our advice to antagonists also allow for a shorter duration of treatment.patients. One area of recent development here is the more While it is well recognised that some women with widespread use of embryo vitrification, which - as withapparent acute ovarian failure during and immediately after oocyte vitrification - is becoming much more common. Itchemotherapy do show some recovery, our current is unclear, however, whether the embryos obtained from Pathways for fertility preservation in women. Adapted from Lobo RA. Potential Options for Preservation of Fertility in Women. N Engl J Med 2005; 353: 64-73.Focus on Reproduction January 2011 31

women having emergency IVF under these circumstances are of normal quality. The women involved are of course unwell and this may have an adverse impact on oocyte/embryo quality, just as semen quality can be markedly impaired in men with cancer. There are no published data on this but our own limited experience in Edinburgh and Copenhagen suggests that the pregnancies following embryo replacement in cancer patients are fewer than expected. Clearly, this is an important question to be addressed as it will affect the efficacy of fertility preservation and potentially the technique that a woman may choose to have. The provision of IVF varies hugely between Histomicrograph of plentiful primordial follicles in a prepubertal girl. countries and in these times of economic Courtesy of Dr M McLaughlin, University of Edinburgh. austerity state funding may well become more restricted. Women with a newly diagnosed cancer cannot go on a waiting-list but, if resources are situation. The efficacy of this approach also needs finite, treating one woman may delay the treatment of thorough evaluation. another. One could argue that treatment of a couple whose aetiology is, for example, of unexplained infertility is a Ovarian tissue better use of resources than treatment of a couple where An alternative option therefore is to store ovarian tissue, the woman has a serious disease associated with significant which may contain many more oocytes. In contrast to short and long-term morbidity and mortality. On the other many fertility-related treatments, ovarian tissue storage hand, many patients find that the mere fact of receiving has been introduced into clinical practice following fertility preservation is of substantial psychological benefit. development in a large mammalian species, the sheep.5 There are also theoretical concerns over the high Advantages include the fact that no other treatment is concentrations of estradiol generated during IVF cycles, required and it can be carried out at short notice. It particularly in such estrogen-responsive conditions as some requires no male involvement, but does require a surgical breast cancers. Ovarian stimulation regimes which procedure both to recover the tissue and replace it at a minimise this effect with aromatase inhibitors have been later date. Replacement provides the option of described.4 However, it remains unclear how much of a spontaneous rather than assisted conception as well as the real risk an IVF cycle is to a woman with breast cancer chance of more than one pregnancy; this has now been given that the tumour would have been growing for many demonstrated.6,7 Importantly, ovarian tissue months before becoming clinically apparent; there are also cryopreservation also offers a potential option for children no data on the pregnancy outcome from embryos and adolescents for whom ovarian stimulation is generated from these protocols. However, many women inappropriate. This, however, may be better described as a and their physicians will choose not to expose an estrogen- theoretical option; as yet no adolescent girl has gone on to responsive cancer to more estrogenic stimulation than is have a child following this procedure. strictly necessary. One important consideration is that a significant amount of ovarian tissue must be removed from the Avoiding the need for fertilisation patient and will not therefore be available for spontaneous Embryo cryopreservation also requires a male involvement. fertility should she not be sterilised by her cancer The woman’s male partner may find himself in a position treatment. of significant emotional pressure to take part in an embryo At present there is debate over whether unilateral cryopreservation procedure. There have been well oophorectomy or ovarian biopsy is the more appropriate publicised cases where the man has subsequently surgical technique - and there are both clinical and withdrawn his consent for the transfer of embryos, so organisational considerations here. It is clear that requiring them to be destroyed. This difficult situation can following cryopreservation and reimplantation some 70% be avoided by the use of oocyte cryopreservation, which is of follicles are lost. This needs to be balanced against the now being more widely used. Success rates are improving number likely to be lost as a result of the cancer treatment and approaching those of fresh IVF. Both embryo and itself. And accurate data on how to assess this are lacking. oocyte cryopreservation will, however, leave a woman with Our practice in Edinburgh is generally to carry out a limited number of chances to become pregnant, with ovarian biopsy, taking strips of ovarian cortex from one only one cycle of stimulation likely in this time-limited ovary and leaving the contralateral ovary intact. The32 Focus on Reproduction January 2011

rationale behind this is to do the minimum amount of do, however, offer the opportunity for our improvedharm and it’s been our experience that a surprisingly large understanding of the extra-ovarian requirements for normalproportion of patients referred for fertility preservation go follicular and oocyte development.on to retain spontaneous fertility.8 And this is despite a The malignant contamination of the ovarian tissue mustclear statement required from the treating oncologist that also be considered. So far, a total of some 30 women havethe patient faces a greater than 50% risk of ovarian failure received transplantation of ovarian tissue without anyfollowing the anticipated treatment. This may well reflect reports of relapse caused by the transplantation. Two largebiological variability and age of the patient, plus a lack of series of ovarian biopsies in breast cancer patients haveprecise knowledge of the gonadotoxic effect. recently revealed no evidence of malignant cell The alternative approach is taken in Denmark, where contamination,10,11 but the availability of specificmost patients will have a unilateral oophorectomy. This molecular tumour markers in some conditions has revealedallows the surgery to be performed at a hospital the potential for contamination. This is a particular issueconvenient for the patient, with the ovary subsequently for haematological malignancies;12 importantly,transported to the central lab for preparation and chemotherapy prior to ovarian cryopreservation did notcryopreservation. Although only a small fraction of the preclude contamination.follicles may survive the procedure, they will be usedsequentially and only after the endogenous store has been In vitro follicle growthexhausted. This hub and spoke model has advantages but One option in cases where the ovary might beis not possible in the UK because of the tight regulatory contaminated is in vitro follicle maturation. Theenvironment imposed by the Human Tissue Authority and development of IVM has been a challenge, even in smallHFEA. laboratory animals, and it remains in its infancy in humans. At present a total of 14 children have been born to Significant developments in culture techniques have,women who have had ovarian tissue cryopreserved and however, been reported using a multi-step process. Clearly,reimplanted. Both spontaneous and assisted conceptions there’s a long way to go to show that this technique is bothhave been demonstrated, but interestingly no successful effective and safe.pregnancies have yet been described following heterotopictransplantation of the ovary.9 Sites where follicular growth Protection strategieshas been observed include the anterior abdominal wall and Alternatively, an agent which protects the oocyte in situthe arm, although successful non-human primate would be attractive. Prominent among these approaches ispregnancies have been reported following fresh the use of GnRH analogues. Their use has been promotedtransplantation to a subcutaneous site. These approaches for many years but remains a heated topic for discussion. Preparation of ovarian tissue for cryopreservation.Focus on Reproduction January 2011 33

References 1. Donnez J, Dolmans MM, Demylle D, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 2004; 364: 1405-1410. 2. Silber SJ, Lenahan KM, Levine DJ, et al. Ovarian transplantation between monozygotic twins discordant for premature ovarian failure. N Engl J Med 2005; 353: 58-63. 3. Anderson RA, Kinniburgh D, Baird DT. Preliminary evidence of the use of a gonadotrophin releasing-hormone antagonist in superovulation/IVF prior to cancer treatment. Hum Reprod 1999; 14: 2665-2668. 4. Oktay K, Hourvitz A, Sahin G, et al. Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy. J Clin Endocrinol Metab 2006; 91: 3885-3890. 5. Gosden RG, Baird DT, Wade JC, Webb R. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at Isolated human preantral follicles for in vitro growth. -196oC. Hum Reprod 1994; 9: 597-603. 6. Ernst E, Bergholdt S, Jorgensen JS, Andersen CY. The first At present, the data are unconvincing, with most findings woman to give birth to two children following transplantation of derived from non-randomly controlled studies. There are, frozen/thawed ovarian tissue. Hum Reprod 2010; 25: 1280-1281. however, large studies under way which may yield 7. Demeestere I, Simon P, Moffa F, et al. Birth of a second healthy definitive answers. girl more than 3 years after cryopreserved ovarian graft. Hum Reprod 2010; 25: 1590-1591. So it’s fair to say that there have been substantial advances 8. Anderson RA, Wallace WH, Baird DT. Ovarian in fertility preservation in the last decade, but there still cryopreservation for fertility preservation: indications and outcomes. Reproduction 2008; 136: 681-689. remain very significant gaps in our knowledge as to how 9. Rosendahl M, Loft A, Byskov AG, et al. Biochemical pregnancy best to proceed. Patient selection remains a challenge, to be after fertilization of an oocyte aspirated from a heterotopic confident in offering treatment to those who need it and autotransplant of cryopreserved ovarian tissue: case report. Hum reassuring to those who do not. In this respect we have Reprod 2006; 21: 2006-2009. recently shown that serum AMH predicts long-term 10. Sanchez-Serrano M, Novella-Maestre E, Rosello-Sastre E, et ovarian function following chemotherapy in women with al. Malignant cells are not found in ovarian cortex from breast breast cancer. Indeed, in a multivariate analysis only AMH cancer patients undergoing ovarian cortex cryopreservation. Hum - but not age or FSH - remained a significant predictor.13 Reprod 2009; 24: 2238-2243. This result, if confirmed, may allow a more individualised 11. Rosendahl M, Timmermans V, Nedergaard L, et al. risk assessment based on the proposed treatment regime Cryopreservation of ovarian tissue for fertility preservation: no and a measure of the patients ovarian reserve. evidence of malignant cell contamination in ovarian tissue from patients with breast cancer. Fertil Steril 2010; in press. 12. Dolmans MM, Marinescu C, Saussoy P, et al. Reimplantation Richard A Anderson is Professor of Clinical Reproductive Science of cryopreserved ovarian tissue from patients with acute at the Centre for Reproductive Biology, University of Edinburgh, lymphoblastic leukemia is potentially unsafe. Blood 2010; 116: Scotland, and Deputy Co-ordinator of ESHREs SIG Reproductive 2908-2914. Endocrinology. 13. Anderson RA, Cameron DA. Prediction of ovarian function Claus Yding Andersen is Professor of Human Reproductive after chemotherapy for breast cancer. Hum Reprod 2010; 25 Physiology, Laboratory of Reproductive Biology, University of (suppl 1): O-100. Copenhagen, Denmark34 Focus on Reproduction January 2011

FEATURE// IVF IN GERMANY // Germany’s first IVF baby was born on 16th April 1982 in the care of the late Professor Siegfried Trotnow (pictured below, right, in 1983) and Safaa Al-Hasani at the University Hospital of Erlangen, still one of Germany’s leading centres in reproductive medicine. One million cycles and still counting Markus Kupka tells the story of IVF in Germany and how its successful history has been recorded cycle by cycle in a non-governmental registry system. The German IVF IVF, with 585 follicles punctured and collection requirements. By 2009, Registry (Deutsches 404 egg cells obtained; embryo when the registry adopted a new legal IVF Register, D.I.R) transfer was achieved in 95 patients, form and created articles of was founded in and pregnancy in 14 cases. Since then, incorporation, 120 IVF centres were 1982, the year that and reflecting the remarkable advance providing data, reporting a total (West) Germany’s of ART in Germany, data submitted performance of 49,602 IVF and ICSIfirst IVF birth was announced, a baby to the D.I.R for 2010 are likely to cycles that year.boy born in April at the University reach a cumulative total of 1 million The registry itself remains anHospital of Erlangen. Two years later cycles reported. initiative based on the involvement ofthe Lübeck group reported that And just as Germany’s IVF all physicians engaged in the field ofbetween July 1982 and March 1983 programmes moved so rapidly reproductive medicine in the Germanthey had treated 130 patients with forward, so did the country’s data healthcare system - that is, it is notFocus on Reproduction January 2011 35

Table 1. The number of IVF and ICSI cycles performed in Germany between 1982 and 2009 1982 1986 1990 1994 1996 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 IVF 742 3806 7343 16175 14344 14024 21880 28945 28506 23936 28058 11848 11410 11062 11362 11048 11715 ICSI 5856 16108 22420 21244 15752 24897 37692 51389 25339 26370 28015 31452 33591 37006 Total* 742 3806 7343 22031 30452 37933 44086 45487 54098 62306 80434 37633 38382 39769 43612 45461 49602 * The value of combined IVF/ICSI cycles is included in the total - eg, 881 cycles in 2009 supported by the government. So, decrease in cycle numbers, which is the babies born. financial support is provided by the only now creeping back towards However, the German healthcare IVF units themselves and is not part former levels. system, unlike that of Denmark or the of any government funding scheme. D.I.R participates in data collection UK, has no social security number or As can be seen in Table 1 above, for the European IVF Monitoring other unique registration system for the percentage of ICSI cycles consortium (EIM) of ESHRE, and each individual. Thus, D.I.R is now increased rapidly in Germany from also sends data to the International preparing a dedicated ID based on the 1993 onwards - as it did throughout Committee Monitoring Assisted so-called ‘DDR code’, which creates a Europe - and today ICSI accounts for Reproductive Technologies unique case number out of the family almost three times the ART activity of (ICMART), which operates on a name, first name, date of birth and IVF. The other major trend, clearly worldwide scale. Germany now ranks sex. This code can only be read in one evident in the table, is that until 2004 as Europe’s second most active ART direction, which means that government reimbursement covered country (after France) according to individual identity cannot be decoded 100% of the cost of four treatment data submitted to the EIM. from the eight-digit number, but case, cycles. But that year the reimburse- In comparison to other treatment and outcome can be ment system was changed to provide international and European registries, tracked, as well as couples changing only 50% payment for three cycles. D.I.R employs a large dataset which their treatment centre. This change prompted a dramatic also collects follow-up information on Unfortunately, the code is not sufficient to analyse cross-border activities, which appear to play an important role throughout Germany but especially in the southern regions, where overseas clinics with more liberal laws are highly promoted. Legal restrictions in Germany - the MARKUS KUPKA: ‘THE principal reason for cross-borderFRAMEWORK FOR ART IN treatment - are currently among the most restrictive in Europe. The GERMANY IS MUCH Embryo Protection Law, passed 20 DIFFERENT FROM THAT years ago in 1991, allows the freezing OF MOST OTHER of fertilised oocytes only at the EUROPEAN COUNTRIES.’ pronuclear stage, outlaws embryo36 Focus on Reproduction January 2011

Table 2. Clinical pregnancy and miscarriage rates by age group from IVF treatments in 2009. The right- hand column below provides estimated results for ‘ideal’ patients.selection, and requires that no more of 18.2%. A twin rate of 20.8% (and options. The second section is athan three embryos can be higher multiple births of 0.8%) was uniform analysis of all reportedtransferred. The legislation is documented from pregnancies. cycles and contains detailed chartsunequivocal: ‘Anyone will be Since 1996, the annual report has and tables. The third section focusespunished with up to three years been published as a single booklet on those special statistics which varyimprisonment or fine who attempts, (www.deutsches-ivf-register.de/ from year to year and considerwithin one treatment cycle, to Jahresberichte). But now, starting in lifestyle aspects or regionaltransfer more than three embryos 2010, the report is also published in differences. An epilogue, a commentinto an woman and attempts to English in the Journal of Reproduct- on aspects related to the statistics andfertilise more egg cells from a woman ive Medicine and Endocrinology data processing together with a list ofthan may be transferred to her within (www.kup.at/journals/reproduktions- all participating centres, is alsoone treatment cycle.’ Egg donation medizin). included.and research on embryos or PGD are Nearly all German IVF units are Since 1997, more than 80% of allalso illegal. currently using a standard, computer- ART cycles reported to the system The framework for ART in based dataset description, but employ have been entered prospectivelyGermany, therefore, is much different different software tools to submit (within seven days of the start offrom that of most other European their data to the registry. These tools ovarian stimulation). This is intendedcountries. Nevertheless, over the have undergone numerous to prevent cycle selection, and is oneyears our success rates have been developments, but, from its inception, of the most powerful quality tools incomparable, as demonstrated in the the registry has been collecting data the system. A dynamic link libraryannual reports of D.I.R, which were on a cycle-by-cycle basis. The report (DLL) maintained by the registryfirst made available in 1991. Average thus represents a summary of all allows data plausibility to bepregnancy rate for IVF cycles reported cycles, but, because of monitored either online or shortlyreported for 2009 was 30%, and German legal requirements and after data input. Participation in the28.9% for ICSI. As explained in internal procedural rules, no data registry became mandatory in 1999.Table 1, a single cycle combination of related to specific centres can be In 2009, a total of 75,662 cyclesIVF and ICSI was performed in 881 released. were reported, 84% prospectively. Ininstances in 2009, while frozen The report is broken down into contrast to the IVF registries of othertransfers (embryos derived from three sections. The first is a patient- countries, the D.I.R containsoocytes cryopreserved at the 2PN based section comprising responses to information about reproductivestage) were performed in 17,646 common questions or offering history and pre-existing conditionscases and achieved a pregnancy rate comments on different therapeutic for both partners.Focus on Reproduction January 2011 37

Table 3. 2009 results for IVF, ICSI and IVF/ICSI as a function of embryo quality and number transferred.’ Each centre provides information used during patient counselling to centres and registered treatments has twice a year (on average) and the explain the effect of age. As can be greatly increased, but further published data not only report a seen, treatment of women over the improvement is still required. Our clinic’s own results but also a age of 34 shows a significant decrease introduction of ideal patient comparison with all other in the likelihood of pregnancy - modelling has gone some way to participating centres. especially with ‘non-ideal’ embryos. removing variations in Since the registry requests data for Each year the annual report also reimbursement or availability, and both the current year as well as past includes ‘special’ statistics which vary our registry data cannot be combined years, our loss to follow-up - 13% from year to year. In 2009 we with prenatal medical data or cancer after a year - is generally low. included data on pregnancy rates in registries. The creation of follow-up However, as in other European patients with an ideal prognosis (and ID statistics on infant births is countries, many foreign couples are other patients too) as a function of extremely difficult. also treated in Germany, making it centre size over ten years (2000- And now, as its cumulative total somewhat difficult to obtain 2009). We defined ideal prognosis as heads towards 1 million cycles, our complete information on the outcome age under 35 years and having a first D.I.R report will for the first time be of pregnancy. stimulation cycle for ART. We published in English and we are now The pale blue column in Table 2 demonstrated that for both ideal able to research specific angles such describes the ‘ideal’ couple. To patients and others the larger centres as lifestyle factors (smoking, weight) overcome geographical differences in (more than 500 cycles per year) or reproductive history (former reimbursement or availability of offered a trend of higher pregnancy pregnancies, miscarriages). However, services the registry has generated a rates than the smaller centres. from our perspective the greatest model pregnancy rate when two Consumer demands for advance of the German registry lies in embryos are transferred with at least information and clarity in this highly the decision of nearly every IVF unit two more at the 2PN stage sensitive area of human reproductive to support its work through (cryopreserved or destroyed). Overall, medicine are more than justified. The prospective data collection and this ‘ideal’ pregnancy rate was success of these treatments will only payments made to maintain such calculated to be 37.5% per embryo be socially acceptable and comprehensive files. transfer. misunderstandings can only be Our data have also confirmed that prevented once a reliable assessment Markus S Kupka is Reader in the age of female partner represents and an open discussion of the Reproductive Medicine & Endocrinology the most confounding factor for attainable results have been carried at the Ludwig-Maximilians-Universität, outcome, and the D.I.R provides out. And this is why national Munich, a director of the Deutsches IVF detailed statistics on this. Table 3, for registries in nearly every European Register, and member of the EIM Consortium steering committee. example, shows success rates as a country have collected and are function of the number and quality of analysing their data. In Germany, this embryos transferred in each of four has been our aim since 1982. Over age groups. This table is frequently the years, the number of participating38 Focus on Reproduction January 2011

The European Society of Human Reproduction and Embryology Meerstraat 60 Grimbergen, Belgium info@eshre.eu www.eshre.eu

Focus on Reproduction ESHRE, ianuarie 2011

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Focus on Reproduction ESHRE, ianuarie 2011 — Document Transcript