Focus on REPRODUCTION European Society of Human Reproduction and // MAY 2010 // Crisis? What crisis?

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 ESHRE news  Papers which changed the world of ART  Meet ESHRE’s next chairman

EXECUTIVE COMMITTEE Focus on Chairman Luca Gianaroli (IT) Chairman Elect Anna Veiga (ES) REPRODUCTION Members Ursula Eichenlaub-Ritter (DE) Jean-François Guerin (FR)  Chairman’s introduction Timur Gürgan (TR) Antonis Makrigiannakis (GR) Carlos Plancha (PT) In my introduction to the January issue of Focus on Françoise Shenfield (GB) Reproduction I stated that 2010 was likely to be a Miodrag Stojkovic (RS) hectic year for ESHRE. Four months later, I can confirm Anne-Maria Suikkari (FI) Etienne Van den Abbeel (BE) that this is proving particularly true. Heidi Van Ranst (BE) Traditionally, ESHRE has always given its first Veljko Vlaisavljevic (SL) priority to education, but this year we have made even Ex-officio members extra efforts in this direction. The budget for Joep Geraedts (Past Chairman) Søren Ziebe (SIG Sub- educational activities has been increased by more than committee) 30% over the previous year and 27 Campus symposia and workshops have joined the annual meeting and FOCUS ON REPRODUCTION precongress courses to enrich the ESHRE calendar. EDITORIAL COMMITTEE So far, we have had extremely positive feed-back from all the activities that Paul Devroey Bruno Van den Eede have already taken place this year. Our Campus meeting on the ‘Prevention Hans Evers and treatment of in modern society’, held in Istanbul in February Joep Geraedts and reported in detail on page 28, formally inaugurated the public activities of Luca Gianaroli the Task Force Reproduction and Society, and created much interest. Hanna Hanssen Anna Veiga Another important event was the Campus consensus meeting on poor Søren Ziebe ovarian response held in Bologna in March. This was the first ever activity to Simon Brown (Editor) be organised through a collaboration of all ESHRE’s SIGs. The meeting Focus on Reproduction culminated with the development of common definition of poor ovarian is published by response, an issue that has so far has been the subject of much debate in the The European Society of Human Reproduction and Embryology scientific community. Meerstraat 60 There is also encouraging news to report from the embryology certification Grimbergen, Belgium committee, which will shortly introduce a process of certification renewal [email protected] www.eshre.eu through a scoring system similar to the CME scheme already in place in many European countries. All rights reserved. The opinions expressed in this As far as international relationships are concerned, a letter of intent has magazine are those of the been recently signed by ESHRE and the Chinese Society for Reproductive authors and/or persons interviewed Medicine to promote grants and exchanges between researchers from Europe and do not necessarily reflect the views of ESHRE. and China. We are hopeful that this collaboration will lead to significant results in the future. MAY 2010 The organisation of the annual meeting in Rome is now progressing in the

Cover picture: best possible way, and ESHRE 2010 will be another outstanding assembly of Getty Images/Hulton Archive clinicians, scientists and paramedics from all over the world. So I look forward to seeing you all in Rome! Luca Gianaroli ESHRE Chairman 2009-11

CONTENTS NEWS FEATURES 4 Scientific programme Rome 28 Europe’s demographic crisis 8 Honorary members 2010 Simon Brown on ESHRE’s role in Europe’s politics of population 9 This year’s AGM agenda 32 Papers which changed the world 10 Rome to celebrate 20 years of PGD of assisted reproduction 13 From the Paramedical Group Hans Evers with a commentary on 14 Fertility Europe some of the landmark papers 15 From the Special Interest Groups in the history of ART 36 Meet Anna Veiga 20 Sperm banking Campus report ESHRE’s Chairman Elect 24 Consensus in poor ovarian response talks about her career and 26 From the Task Forces ambitions for the Society

Focus on Reproduction May 2010 3 ANNUAL MEETING 2010 Abstracts go through the roof

Submissions up by an unprecedented 33%

The final programme for our annual meting in Rome is All abstracts were submitted to our standard review now confirmed, and this year the International Scientific procedure, which comprises a screening and a scoring Committee (ISC) has been faced with an unprecedented process. The aim of the screening is: increase in the number of abstracts submitted. The  to ensure that abstracts are generally designated to the committee has received a remarkable 33% more abstracts correct topic category this year than last, a rise from 1154 in 2009 to 1539 in  to eliminate all abstracts of obviously poor quality 2010. It is also clear that there is a wealth of new  to eliminate abstracts that deal with topics or subject developments now scheduled for the free communications, matters unrelated to the meeting either as oral or poster presentations. A total of 138 abstracts were rejected following the The submitted abstracts were arranged in the following screening process. In addition, there were five withdrawals. categories before review: This means that 1396 abstracts underwent the complete review procedure. Of these, there were: Category Total  359 abstracts submitted for poster presentation only Andrology 208  1037 abstracts submitted for oral/poster presentation Cross-border reproductive care 17 And from this latter total no more than 239 have now been Demography, epidemiology, registries, selected for oral presentation and 590 for poster. This and health economy 54 selection was done solely on the basis of the scores from Early 71 three reviewers scoring blinded abstracts. The 239 free Embryology ( selection) 184 communications have now been divided into 45 sessions, Endometriosis, endometrium, implantation 144 which each contains between four and seven oral Ethics and law 21 presentations. Fertility preservation 105 Others 202 Poster presentations Paramedical (nursing, laboratory) 30 With such a substantial increase in the number of abstracts Psychology and counselling 47 submitted, the ISC agreed to admit a higher percentage of Reproductive endocrinology 217 poster presentations than last year, with 590 authors now Reproductive 68 invited to present their posters electronically. Furthermore, Reproductive surgery 35 each presenter this year will be offered the additonal Safety & Quality 112 opportunity of a paper poster. These traditional posters will Stem cells 24 be presented in the ‘Poster Village’, according to subject, as Grand total 1539 was done last year. The number of posters in each category

4 Focus on Reproduction May 2010 Human Reproduction Topic (total posters) Poster discussion Poster Village keynote lecture, in honour of the best paper from our main Andrology (91) Tuesday Wednesday journal. The first presenter, Cross-border reproductive care (9) Monday Gayle Jones, has been Demography, epidemiology, registries and health economy (17) Monday selected on the basis of the Early pregnancy (23) Tuesday paper ‘Novel strategy with Embryology (103) Tuesday potential to identify Endometriosis, endometrium, implantation (64) Monday Tuesday developmentally competent Ethics and Law (4) Monday IVF blastocysts’, which was Fertility preservation (49) Wednesday Monday published in 2008. Gayle will Paramedical (6) Tuesday begin her presentation with Psychology & counselling (14) Tuesday the published work and then Reproductive endocrinology (97) Monday go on to deal with more Reproductive genetics (27) Monday recent developments. The Reproductive surgery (11) Wednesday second keynote lecture is by Safety & quality (63) Tuesday Wybo Dondorp, who will Stem cells (12) Wednesday discuss the risks and responsibilities associated as well as the days on which they will be presented in the with innovative reproductive technologies. Poster Village are indicated in the box above. In addition, Monday morning will also feature a PGD/PGS session each day of the meeting will feature a more formal poster during which the latest annual data from the PGD discussion, also as indicated in the table above. The time Consortium will be presented as well as the first results allocated to each presenting author will be restricted to from the PGS pilot study staged by ESHRE’s Task Force on two minutes only and thereafter three minutes will be PGS. available for discussion. In recent years our debate sessions have been well Continued over page Geographical distribution As ever, abstracts were received from all over the world. This year, no fewer than 65 countries (last year 60) will be represented. The ten most prolific countries are shown below: Total Selected Selected abstracts for oral for poster Spain 157 19 65 Italy 128 10 48 United Kingdom 114 29 39 USA 86 18 44 Netherlands 81 23 35 Japan 76 8 39 France 73 16 34 China 63 7 19 Where from? Selected oral presentations 2010. South Korea 60 3 22 Brazil 60 9 19

It is interesting to note that Belgium, which is not on this list, submitted 40 abstracts, of which 14 were selected for oral and 19 for poster presentation. As always, the main scientific meeting begins on the Monday morning (28th June). Before that, however, no fewer than 12 precongress courses will be held on the Sunday. The topics vary from ‘Patient-centred fertility care’, hosted by Fertility Europe, to ‘Fertility preservation in cancer’, organised by our Task Force on Fertility Preservation in Severe Diseases. Monday starts as usual with a keynote lecture session. This year, for the first time, one of the presentations is the Where from? Selected poster presentations 2010.

Focus on Reproduction May 2010 5 ANNUAL MEETING 2010

All aboard!

Take the bus, the train or the Metro in Rome

The congress venue in Rome, the Nuova Fiera di Roma, is  Shuttle buses located outside the city centre, between the city and Hotels officially booked by ESHRE and its agent, Fiumicino airport, which means that all participants this Meridiano Congress International, will be served by a fleet year - even those staying in hotels near the congress centre of shuttle buses running between the hotels and the - will need transportation. congress centre. The journey time from the city centre There are three public transport systems available: hotels will be around 45 minutes, so delegates planning an

Scientific programme, Rome Continued from previous page

received, and this year there will be at least one a day. This again combining the awards ceremony with summaries of year’s topics include natural cycle IVF vs. stimulation, the award-winning presentations and the closing ceremony. selection of male vs. female gametes and alternative All in all, this has been an unprecedented year in terms medicine. of interest and abstract submission, and there’s little doubt On Tuesday our historical lecture is topically devoted to where most investigators want to be at the end of June. We ‘Catholicism and human reproduction’ and will be in the ISC are looking forward to a very interesting and delivered by Norman Ford. rewarding programme, which we feel confident will deliver The number of invited sessions totals 25, and almost presentations of the highest quality. every one of ESHRE’s SIGs is represented. There are also Joep Geraedts, company symposia, our traditional live surgery session, Chairman International Scientific Committee and sessions covering themes related to ESHRE activities.  There is more graphic information on the geographical And as last year - since it proved such a success - we are distribution of abstracts on the ESHRE website.

6 Focus on Reproduction May 2010 early start at the congress will need to be on their way by 7.00! First results from ESHRE’s PGS pilot  Metro + Laurentina shuttle Rome’s Metro system is inexpensive study to be reported in Rome and easy to use, with just two lines First results from the amplification protocol crossing the city. These two lines - line PGS pilot study staged and the 24sure A and line B - cross at the Termini by ESHRE’s PGS Task microarray technology station. Those without access to Force will be presented provided by BlueGnome official hotel shuttle buses may take in Rome in a Monday of Cambridge, UK. The the line B Metro to Laurentina station morning session which images have been scored (at the end of the line), where a further also includes new data from the by two independent observers in fleet of shuttle buses will run to and ESHRE PGD Consortium. each centre. To estimate the from the congress centre. More than This PGS proof of principle (PoP) concordance of data between the 2000 seats a day will be available on study, which was first announced in polar bodies and corresponding the Laurentina shuttles. Amsterdam last year, began about a oocytes, there will be a blind analysis  Direct on the FR1 railway month later than originally planned. of those oocytes which are deemed Fiera di Roma has its own stop on the However, recruitment of patients aneuploid according to the result of FRI (Trenitalia) train line between the went successfully and the technical the polar body analysis. city and Fiumicino airport. You can part of the project will be completed The study began in September pick up the train at stations Termini, soon. A sufficient number of polar 2009 and it is expected that the Tuscolana, Trastevere or Ostiense in bodies have been biopsied by the two acquisition of the data will be the direction of Fiumicino and get off pilot centres in Bonn and Bologna. completed in May. At the moment all at Fiera di Roma. Departures are every First and second polar bodies have data are in the process of evaluation 15 minutes. been separately processed for by an independent data analysis team We also understand that some of our chromosomal analysis, which has at the University of Amsterdam. sponsoring companies with large hotel been performed at each of the two Joep Geraedts allocations will be providing their own centres using the SurePlex Co-ordinator PGS Task Force transport between hotels and the congress site. Our agents in Rome, Meridiano, European Court declares Austria’s ban have now devised a bus timetable, with schedules divided according to on gamete donation unjustified three clusters of hotels - ‘city centre’, ‘congress area’ and ‘residential area’. The European Court of Human gametes from the treated infertile The timetables are available on the Rights has ruled in favour of two couple. Legal restrictions had been ESHRE website. All buses will carry infertile Austrian couples who put in place to protect children from the ESHRE logo, and each will have a complained to the Court that ‘unusual family relationships’ and representative of Meridiano on board. Austria’s ban on sperm and egg the exploitation of donors. Filippo Maria Ubaldi donation in ART violated their right ‘It’s early to say what this means Chairman Local Organising Committee to respect for family life and that for other countries where gamete the difference in treatment available donation in IVF is banned,’ says to them (needing gamete donation) ESHRE’s Chairman Luca Gianaroli. and to other couples using ART ‘But this ruling appears to set a (without gamete donation) was precedent that any restriction on discriminatory. On this latter gamete donation in IVF is a violation complaint, the Court - while noting of two articles of the European that among EU member states there Convention on Human Rights - on was ‘no uniform approach’ to ART rights to family life and to non- nor any ‘obligation to allow it’ - discriminatory treatment. As in Italy, ruled by a majority of six to one that the challenge to restrictive the difference in treatment at issue legislation in ART has once again was not justified. come from patients.’ According to a 1st April press The Austrian government now has release from the Court, Austrian law three months in which to decide allows ART only with ‘homologous’ whether to appeal the judgement.

Focus on Reproduction May 2010 7 ANNUAL MEETING 2010 // HONORARY MEMBERS //

Meet ESHRE’s 2010 honorary members

Honorary memberships have been awarded annually to two luminaries from reproductive science and medicine at each of ESHRE journals: ESHRE’s annual meeting since 1985, one of them from the HR progresses ‘in host country. This year’s ‘local’ honorary membership will be awarded to the Italian gynaecologist Ettore Cittadini, who the right direction’ since the late 1950s has worked clinically and in research in The publisher’s report to gynaecological endoscopy, infertility and family planning at ESHRE’s journal sub- several hospitals in Italy and abroad, including the Hopital committee for 2009 shows that Broca in Paris and the O&G Clinic of Palermo. Professor the indices of performance for Cittadini was a member of ESHRE’s first temporary Human Reproduction ‘have all committee, which Robert Edwards formed in 1984 to steer moved in the right direction’. the fledgling society, and of ESHRE’s first Advisory The number of new Committee set up soon after. submissions was maintained ESHRE’s second honorary membership will be awarded to or increased, the time to a the French biologist Professor Luc Montagnier, who in 1983 first decision decreased, the led the group which first isolated the human acceptance rate declined, the immunodeficiency virus (HIV1) and identified it as the response times from associate causative agent of AIDS. In 1985 he isolated the second AIDS editors reduced, and the virus, HIV2, from West African patients. His laboratory in impact factor increased. Paris at the Institut Pasteur was also the first to show that a During the six-month period large fraction of white blood cells of HIV-infected patients of July-December 2009, the ESHRE’s two honorary were prone to die by apoptosis, a process of programmed cell journal received a total of 851 members for 2010: death attributed to oxidative stress in patients, possibly manuscripts, the vast majority above, Italian associated with infections. Besides his involvement in the original articles. The 9% gynaecologist Ettore design of new types of HIV vaccines, his current studies are Cittadini, and below, acceptance rate for 2009 French biologist aimed at microbial and viral factors associated with cancers, suggests that the decline Luc Montagnier. neurodegenerative and articular diseases. observed over the previous In 1987 Professor Montagnier was one of four guest four years (19, 15, 12 and lecturers at ESHRE’s third annual meeting, which Edwards 11%) may now be stabilising. organised in Cambridge, UK.

Continuing education for ESHRE-certified embryologists ESHRE's programme for the certification of embryologists improved, with different parts of the curriculum being is now in its third year, and this year's exams will be held linked to relevant syllabi from ESHRE workshops. in Rome on Saturday 26th June at 16.30. With the A questionnaire regarding the certification procedure, numbers of certified embryologists - and scientific and what ESHRE-certified embryologists have gained after developments - ever increasing, ESHRE will this year obtaining their certification, was sent out at the beginning introduce a Continuous Embryology Education (CEE) of the year. The results are currently being analysed, and system in which ESHRE-certified embryologists will be able will be presented shortly. to upgrade their certification on-line. This can be done The website also contains detailed instructions about the through examination in Rome - as well as details for aspiring  attending meetings, courses and workshops examinees of eligibity and logbook submission for next  publishing abstracts and articles year’s exam in Stockholm. The rules for certification of  presentations at meetings embryologists state that the applicant must be a member The embryology certification pages on the ESHRE website of ESHRE at the time of applying for certification. will shortly contain full information. Kersti Lundin The curriculum information on the website will also be EmCC Steering Group Co-ordinator

8 Focus on Reproduction May 2010 // ANNUAL GENERAL MEETING //

Balance sheet shifts towards higher expenditure

ESHRE’s financial report to be presented at the General Assembly of Members (AGM) in Rome will Income show - for the first time in many years - a small budget deficit for 2010. With income continuing to rise, the shortfall in Expenditure finances will be accounted for by a greater commitment to the activities of the SIGs and Task Forces, which in 2009 are set to represent 19% of Balance ESHRE’s total expenditure. The organisation of Campus events, for example, of which 27 have been scheduled for 2010, cost ESHRE 382,584 euro in 2008, but 418,567 euro in 2009, an increase of 8.6%. Currently, SIG and Task Force activities represent around 19% of the Society’s total 2008 2009 Budget 2009 Budget 2010 expenditure, but generate only around 7% of total Income 5,612,051 5,943,762 5,161,495 6,259,708 income. Attendance costs of Campus events are kept Expenditure 4,795,813 5,945,504 5,120,231 6,379,951 to a minimum to encourage participation from Balance +816,238 -1,742 +41,263 -120,243 students and young members. The annual meeting remains ESHRE’s greatest Financial results 2008-9; Budget 2009-10 (euro) source of income (67%) and greatest expenditure (50%). Publications represent 16% of the Society’s 1. Minutes of the last meeting income, and membership fees 7%. However, ESHRE 2. Future activities of the Society remains financially strong - despite the economic 3. Ratification of the honorary members for 2011: circumstances - and committed to its training nominees are Alan Trounson and Lars Hamberger programme and specialist groups. 4. Paramedical Group This year’s General Assembly of Members will take 5. Financial report place on Tuesday 29th June at 18.00 at the Fiera 6. Membership of the Society Roma (Hall 10, Room I), Rome; the agenda is as 7. Any other business summarised in the box opposite: 8. Date of the next General Assembly of Members

Make the most of Special Interest Group membership

There are 11 Special Interest Groups (SIGs) in ESHRE members (deputies), including a junior representative and all members are asked to indicate which is their and the recent past co-ordinator. The role of the SIG primary and secondary interest. Of course, this does not committee is to take suggestions for Campus events restrict you to participating only in the activities of your and PCCs and organise these activities, which may special interests, but will enable you to receive special often be combined as a joint course with other SIGs. alerts relating to topics of interest and forthcoming There are 25-30 workshops each year, across a range of Campus events and precongress courses (PCCs). The subjects and in different European countries. These SIGs are listed on the ESHRE website under the serve to provide both training and state-of-the-art heading ‘Speciality Groups’. In addition, there is the updates. Lecture notes are available on the ESHRE Paramedical Group, which was established to assemble website. The SIGs also hold a business meeting at each nurses, lab technicians and other support personnel annual meeting, which is open to all members. Here active in the field of and you may make suggestions for future activities. science. The PMG also organises Campus workshops If you are not a member of a SIG (or two), please and has dedicated sessions at the annual meeting. contact ESHRE and express your interest. Each SIG has a co-ordinator, who is nominated from Adam Balen the SIG committee, which usually comprises three other Co-ordinator SIG Reproductive Endocrinology

Focus on Reproduction May 2010 9 ANNUAL MEETING 2010 // PGD CONSORTIUM // Twenty years of PGD for celebratory post-congress course in Rome

ESHRE’s PGD Consortium and SIG Reproductive Genetics are this year organising a post-congress course to celebrate 20 years of PGD. The event will take place on 1st July in Rome. The first clinical PGD cases were performed at the Hammersmith Hospital in in 1989, and, although the first couple treated did not get pregnant at this first attempt, they did deliver twins in 1990 at their second try. However, more than 20 years before that, the first PGD Presentations from many had been performed by Richard Gardner and Robert Edwards - in 1967. They biopsied a small portion of the of the central figures in PGD trophectoderm from rabbit blastocysts, sexed the The celebration of 20 years of PGD will be held as an by identifying sex chromatin to identify females, and ESHRE post-congress course on Thursday 1st July in replaced the biopsied blastocysts back into recipient Rome and includes contributions from many of the key females. The offspring in these experiments were found to players in PGD. These include include Alan Handyside, be of the predicted sex.1,2 Joep Geraedts, Karen Sermon, Joyce Harper, Gary The first human PGD cases were performed at the Harton, Darren Griffin, Marilyn Monk, Montse Boada, Hammersmith Hospital in 1989, using cleavage stage Mark Hughes, Dagan Wells, Edith Coonen, Santiago biopsy for embryo sexing by PCR.3 Female embryos were Munné, Cristina Magli, Luca Gianaroli, Joe Leigh selectively transferred in five couples at risk of X-linked Simpson, Alison Lashwood, Inge Liebaers, Francesco disease resulting in two twin and one singleton pregnancy. Fiorentino, Stéphane Viville, Guido de Wert, Leeanda A total of 21 cycles were performed in two series and Wilton and Anver Kuliev (who will also pay tribute to included the above successes as well as one misdiagnosis. the late Yury Verslinsky). The programme is divided into At that time little was known about the pitfalls of single three sessions: The past, present and future of PGD; cell amplification, particularly allele dropout, cumulus cell PGD from the patient's perspective (which will include contamination or amplification failure from single cells. talks by two families who have benefitted from PGD In the USA several teams were also developing PGD in and 'saviour sibling' HLA matching); and Embryology the late 1980s. Yury Verlinsky did his first cases in and ethics as they relate to PGD. 1988/89.4 His team used the first polar body to detect a maternally transmitted alpha 1 antitrypsin deletion in one patient. Eight eggs were collected, seven polar bodies were PGD, with four in the USA. A total of 83 cycles were aspirated, six embryos fertilised, and PCR was successful in reported of sex selection for patients carrying X-linked five cases. Two embryos were transferred but the patient disease using PCR or FISH and 51 cycles of PGD for did not become pregnant. In the same year Yury’s team monogenic disorders, including . Three reported on preconception diagnosis for cystic fibrosis.5 centres dominated the field: the Hammersmith/UCL By 1994 there were eight centres worldwide performing group, the team at Cornell University Medical College in

Joyce Harper, Chair of the PGD Consortium, demonstrating embryo biopsy during a 1993 workshop organised by Leeanda Wilton Gary Harton, right, Deputy Chair of the PGD Consortium, with in Melbourne. Alan Handyside at the Genetics & IVF Institute, Fairfax, in 1995.

10 Focus on Reproduction May 2010 Accreditation the way to quality assurance in the PGD lab

According to an internationally recognised standard accreditation bodies for each country have been (ISO), accreditation is increasingly acknowledged as established, which will streamline the accreditation the most effective route to appropriate laboratory process. quality assurance, and most diagnostic and IVF At this year’s workshop 15 invited speakers provided laboratories are now moving towards accreditation. a detailed overview of current best clinical/laboratory ESHRE’s PGD Consortium, and some regulatory experience in quality management for PGD. This bodies including the HFEA in the UK, recommend that included training of PGD staff, auditing PGD activities, all PGD laboratories should be accredited according to external quality assessment, key quality indicators in ISO 15189, Medical laboratories - Particular PGD, emerging technologies in PGD and the role of the requirements for quality and competence. The PGD PGD Consortium. Since the first workshop of 2008, Consortium working-group on accreditation has recently several centres have become accredited and many described each point of the ISO and how it relates to others are working towards accreditation. PGD.1 Accreditation is an ongoing issue and the Consortium In order to help centres understand the benefits, and EuroGentest are developing further workshops. The advantages and profitability of being accredited, the Consortium will be conducting annual questionnaires of PGD Consortium, SIG Reproductive Genetics and its members to monitor the centres who have been EuroGentest organised a second Campus workshop on successful in accreditation. Successful centres will be accreditation for PGD in London in March, two years noted in the quarterly Consortium newsletter. after the first on accreditation in Brno, Czech Republic, Katerina Vesela, Chairman Accreditation working group in 2008. Since that time the conditions, availability Joyce Harper, Chair PGD Consortium and legislation across Europe have developed at a fast 1. Harper JC, Sengupta S, Vesela K, et al. Accreditation of the pace. From January this year clearly defined national PGD laboratory. Hum Reprod 2010; 25: 1051-1065.

Participants in the Campus workshop on accreditation for PGD held in London in March.

New York run by Jacques Cohen and Santiago Munné, and 2. Gardner RL, Edwards RG. Control of the sex ratio at full term the Reproductive Genetics Institute in run by Yury in the rabbit by transferring sexed blastocysts. Nature 1968; 218: 346-349. Verlinsky. The other centres were the University Hospital, 3. Handyside AH, Kontogianni EH, Hardy K, Winston RM. Ontario, Free Univeristy Hospital Brussels (VUB), the Jones from biopsied human preimplantation embryos sexed Institute, Norfolk, USA, the Genetics & IVF Institute, by Y-specific DNA amplification. Nature 1990; 344:768-770. Fairfax, USA, and GIEPH, Barcelona. 4. Verlinsky Y, Ginsberg N, Lifchez A, et al. Analysis of the first Joyce Harper and Gary Harton polar body: preconception genetic diagnosis. Hum Reprod 1990; Chair and Deputy Chair 5: 826-829. 5. Strom CM, Verlinsky Y, Milayeva S, et al. Preconception genetic ESHRE PGD Consortium diagnosis of cystic fibrosis. Lancet 1990; 336: 306-307. * For more details about the history of PGD see Preimplantation 1. Edwards RG, Gardner RL. Sexing of live rabbit blastocysts. Genetic Diagnosis, Ed Harper. JC, Cambridge University Press, Nature 1967; 214: 576-577. 2009.

Focus on Reproduction May 2010 11 ESHRE 2012 heads to Istanbul ‘. . . as far East as we can go’

ESHRE’s 2012 annual meeting - the medicine, but also its location as a limited number of cities in Europe Society’s 28th in total - will take place bridge between East and West. ‘It will able to provide what ESHRE now in Istanbul, and for the first time in provide a great opportunity for our expects - sufficient high quality Turkey, a country which is now well members in the Middle East, Asia and conference and exhibition space, represented in ESHRE’s membership. Australia,’ says ESHRE’s managing convenient transport connections and The local chairman will be Timur director Bruno Van den Eede, ‘and plentiful accommodation in all price Gürgan, who has been a member of make the 2012 meeting a little more ranges. Istanbul meets those criteria, ESHRE’s Executive Committee for the convenient. It’s another move in the with the annual meeting set to be past three years. right direction, but geographically it’s staged at the Istanbul Convention & The choice of Istanbul not only as far East as we can go.’ Exhibition Centre, a state-of-the-art reflects Turkey’s substantial With congress planning now having venue whose main auditorium can membership in ESHRE and its to consider 10,000 participants (in seat more than 2000 ‘in armchair prominent role in reproductive theory if not actually), there are a comfort’.

Ten years of ESHRE IVF monitoring to be marked by celebration meeting

The unique and far-reaching data collection of ESHRE’s European multiple rates below 20% for the first time. European IVF Monitoring (EIM) consortium is now in its However, the most striking trend in ten years of EIM 12th year and on 11th September in Munich the group data has been the proportional increase in the use of will celebrate the ten-year anniversary of its first ICSI, which is now double that of IVF in European publication. Ten-year trends reported by the EIM have practice. This is a complete reversal in trend from what shown a continuing increase in ART pregnancy rates, was apparent a decade ago - from 65% IVF and 35% despite the transfer of fewer and fewer embryos in each ICSI in 1997, to 37% IVF and 63% ICSI in 2005. cycle: from 26% to 30% for IVF and ICSI, and from 15% The September meeting programme has been put to 19% for frozen embryo cycles. And although the together by the present chairman of the EIM steering number of egg donation cycles remains low, pregnancy group, Jacques de Mouzon, and will feature the impact of rates have increased from 27% to 42%. ART databases over the past decade and experience from The data also showed a ten-year decline in multiple many of the local registries on which the annual EIM delivery rates, from 29.5% when records began to 20.5% reports are based. There will also be round-table sessions in 2005. Last year in Amsterdam, the EIM report noted on the practicalities of gathering and presenting EIM data.

12 Focus on Reproduction May 2010 NEWS // PARAMEDICAL GROUP //

Paramedic members encouraged to pursue their own research and submit abstracts

A two-day Campus workshop on ‘Research - theory and practice’ was staged by the Paramedical Group on 4/5th March in Brussels. The course, which attracted 55 participants, aimed to increase the number and the quality of abstracts submitted by paramedics, who today include nurses and laboratory technicians, counsellors, junior scientists and junior medics. Both the editors of Human Reproduction, André Van Steirteghem, and Human Reproduction Update, John

The first textbook designed for nurses in reproduction The past decade has seen the professional role of the specialist nurse evolve, through the development of More than 50 members of the Paramedical Group took part in a evidence-based protocols and a greater involvement in Campus workshop on the theory and presentation of research in research. The continuing education of nurses is reproduction. The course was designed to encourage research and increase the number and quality of abstracts and papers important to maintain this momentum and improve submitted to congresses and journals by paramedics. standards of care. As happened with our medical colleagues, more and Collins, took part, the latter describing the skills needed to more nurses are now specialising in just one field of write a meeting abstract, and the former a full manuscript. medicine, and in such cases a basic nursing education An introduction to descriptive statistics was given by is not enough to support the development of care in a Olivier Mairaisse, whose presentation covered specialty such as reproductive health. distributions, quantiles, measures of central tendency and In the Netherlands, under the lead of two nurses, variation and standard scores. Metty Spelt and Nicolette de Haan, several Van Steirteghem opened the second day with the professionals have now filled a gap in the education of selection of papers: how abstracts are reviewed and how nurses in reproduction with the development of a papers are chosen for publication. He noted that the textbook, the first to be written for nurses working in chances for acceptance of a congress abstract or a paper reproductive health. The book provides an overview of for publication might be better if potential researchers all the important issues - and junior doctors and lab know which standard should be met and what quality is technicians have also found it invaluable. expected. Herman Tournaye from the VUB in Brussels However, a lack of formal education and training for described the art of presenting data and making effective paramedics working in reproduction is not just an issue use of PowerPoint. in the Netherlands. Many countries in Europe are Facilitators for the afternoon workshops were actively unable to provide specific training - which is why involved in one type of research and proposed one of their ESHRE’s Paramedical Group has developed its basic own research projects. There were specific workshops on training course as a model suitable for members nursing research (presented by Valerie Peddie) and research throughout Europe. The next step in the support of in midwifery (covered by Mette Juhl). these training efforts was a translation of the textbook The objective of the course was to help participants into other languages. And we are pleased to report that understand the different approaches to research and to the textbook is now being translated into English and apply this knowledge in their own fields of practice. The will be ready for the annual meeting in Rome. ESHRE Paramedical Board hopes that those attending will feel has generoulsy agreed that every paramedical member more confident about their own research ideas and to will receive a free copy of the book. submit their abstracts to ESHRE Jolieneke Schoonenberg-Pomper Patricia Baetens and Heidi Van Ranst PMG Chair elect Paramedical Board

Focus on Reproduction May 2010 13 ‘Patient-friendly’ treatment from the patient point of view

Fertility Europe will organise this year’s Patient Session in the scientific programme for Rome under the title ‘How Fertility Europe’s association with ESHRE patient-friendly is patient-friendly?’ The session, with four  Why should FE and ESHRE work together? We are speakers, aims to present the patient’s view of what they experts in our own fields and complement each other. consider ‘patient friendly’ treatment to be. The perspective Patients and professionals should work in partnership is global, and, by presenting that view from East and and we both have relevant skills and experience. Western Europe as well as from a developing country, will  We have now grown from seven members to 25 consider strategies to improve the friendliness of the whole thanks to ESHRE’s support. journey that patients take in their clinical and holistic care.  FE is now the official partner patient organisation The first paper, presented by Guido Pennings from with ESHRE - something we are very proud of and ESHRE’s SIG Ethics & Law, will introduce an ethical take very seriously. approach to patient-friendly treatment in terms of the  Statistics we have from just 11 member patient and society. Three other papers will be presented, organisations show that we reach 229,400 unique by Italian psychotherapist Vincenza Zambaldi on a holistic visitors each month via our websites and 382,000 in approach to treatment, Denisa Priadková, chair of the civil terms of total visitors per month. A fantastic reach. association Stork (Bocian) in Slovakia and vice chair of  It’s important that our patient organisations across Fertility Europe, on how the rapid route to IVF is not Europe have reporting space in Focus on Reproduction always in the patient’s best interest, and Gamal Serour to bring our activities to everyone’s attention. from Egypt (and President of FIGO) on what patient-  Our precongress course in Rome will represent the friendly treatment means in developing countries. patient view on treatment - a fantastic opportunity for Fertility Europe will have a booth in the main exhibition FE to inform those working in the field about patient area in Rome, so we hope all ESHRE members will pass experience and views - exactly the sort of thing the by and find out a little more about us. Our own annual collaboration with ESHRE was aiming for. meeting will be held in Rome on Monday 28th June. And I should here express our appreciation to ESHRE for allowing our delegates entry to the congress and exhibition (Onskebarn), Poland (Nasz Bocian), Slovakia (Obcianske - something none of us would be able to afford without zdruzenie Bocian), Switzerland (Verein Kinderwunsch), and the generosity of ESHRE. Patient organisations too can UK (Infertility Network UK), with candidate members learn an awful lot from the scientific sessions at the annual present from Austria (Wunschkind-Kinderwunsch), meeting and contribute to them. Bulgaria (Iskambebe and Sdruzhenie Zachatie), France Our latest FE meeting in March saw a very active (Association Maia), Greece (Kiveli), Latvia (Fertilitas), attendance from representatives of full-member patient Romania (SOS Infertilitatea), Sweden (IRIS), and Spain groups in Belgium (De Verdwaalde Ooievaar Netwerk (Genera). Fertiliteit), Czech Republic (Nadace Materska nadeje), It was striking to hear, from the presentations of each, Finland (Lapsettomien yhdistys Simpukka ry), Israel how inequalities exist between East and West Europe, and (Chen), Italy (FIAPI), Netherlands (Freya), Norway how too their issues and priorities are different. One vital role for Fertility Europe is to help beneficiary organisations share best practices, including information on fertility and infertility, prevention, fundraising, increasing membership and attracting volunteers. Among Fertility Europe’s plans for 2010 is the launch of our ‘Special Families’ campaign in which ‘virtual’ greeting cards become real cards with real hope. These messages will be displayed in a central point in Rome as a reflection of the variety and importance of fertility treatment today. Patient groups in East and West Europe Clare Lewis-Jones are now represented in Fertility Europe Chair Fertility Europe

14 Focus on Reproduction May 2010 SPECIAL INTEREST GROUPS // EMBRYOLOGY // Oocyte and embryo scoring The design of a common system from ESHRE and ALPHA embryologists

The continuous exchange of morphological features as possible scientific and technical data Officers in relation to the time of among embryology laboratories is Cristina Magli (IT), Co-ordinator development, and to establish often hampered by the diversity of Rachel Levy (FR), Deputy Co-ordinator eventual correlations with viability experimental conditions and terms Kersti Lundin (SE), Deputy Co-ordinator and implantation potential, was of reference. The scoring of Josephine Lemmen (DK), Junior Deputy emphasised. This approach would oocytes and embryos is one such Etienne Van den Abbeel (BE), Past Co-ordinator make it possible to identify those example. Of course, there are Takashi Hiiragi (DE), Basic scientist aspects of morphology with many similarities in aspects and biological significance and for parameters of grading in each setting, but with large which systematic evaluation is critically relevant. differences of nomenclature. It is quite clear that a more The group met for two days in February in Istanbul at a uniform classification system would greatly help the meeting hosted by Basak Balaban, the current chair of integration of data for a better understanding of early ALPHA. A consensus document was drafted and is embryogenesis. currently being edited in its final version. The document With this concept in mind, the board of the SIG will be presented to the next ESHRE Executive Committee Embryology has been working towards the introduction of meeting and, after approval, published as an a comprehensive system for oocyte and embryo ESHRE/ALPHA document to be used as a common oocyte classification which could be shared throughout the and embryo grading system. scientific community. Our strategy was based on the idea of identifying those scoring criteria which could 2. The Atlas of Embryology unequivocally describe the morphological aspect of A new Atlas of Embryology was considered the best way oocytes, pronuclear stage and embryos and thereby reach to promote the new scoring system and illustrate the common definitions with a common language. We thus criteria for assessment. Working groups have now been planned to define an ESHRE scoring system to be shared organised to address the different chapters: oocytes, by all clinical embryologists - which might be realised in pronuclear stage, embryos and blastocysts. Gayle Jones has two steps: first, the compilation of evidence-based been appointed by the board of the SIG Embryology as co- evaluation data to formulate a common scoring system; ordinator of the working groups. and next, the dissemination of this new system through the During the SIGE’s business meeting in Rome there will be Atlas of Embryology. an update on the consensus document and 1. Consensus on the status of the The first step of the project. project was to gather a This initiative is the group of experts who result of a close could produce a collaboration between consensus document two embryology societies representing an evidence- and we both hope that the based guide to the proposed scoring system evaluation of oocytes, will soon become widely The SIG Embryology and ALPHA consensus development group, with pronuclear stage and all accepted, reinforcing the left to right, Alan Thornhill, Joe Conaghan, Aycan Isiklar, Lynette Scott, stages of embryo Jonathan Van Blerkom, Basak Balaban, Lisa Cowan, Kersti Lundin, idea that joint efforts can assessment. The Thorir Hardarsson, Etienne Van Den Abbeel, Cristina Magli, be very fruitful. importance of verifying Johan Smitz, Jim Catt, Dominique Royere, Sharon Mortimer and Cristina Magli the physiological David Mortimer. Not pictured are Santiago Munné, Thomas Ebner, Co-ordinator significance of as many Gloria Calderon and Daniel Brison SIG Embryology

Focus on Reproduction May 2010 15 SPECIAL INTEREST GROUPS // EARLY PREGNANCY //

Clarifying the evidence in recurring miscarriage

Annual meeting Rome and comparative genomic Our precongress course in Rome has Officers hybridisation (CGH) array, this been creatively constructed around Roy Farquharson (GB), Co-ordinator improved accuracy of chromosomal the theme of debate and audience Mariette Goddijn (NL), Deputy Co-ordinator abnormality detection has heralded interaction. In the field of recurring Ole Christiansen (DK), Deputy Co-ordinator a new era. With a wide spectrum of miscarriage there is a dearth of Eric Jauniaux (GB), Past Co-ordinator treatment interventions now used in evidence-based practice with no clear Marcin Rajewski (PL), Junior Deputy recurring miscarriage this session systematic review to guide and provides an ideal opportunity to inform best clinical practice (Level 1 question whether treatment failure evidence). As a result, this lack of remains a valid concept in the clarity allows considerable scope for absence of cytogenetic testing. In opinion to fill the vacuum. The particular, it suggests a new purpose of our precongress activity is standard for future RCT design to clarify existing evidence and allow when pregnancy loss occurs. These a more focused approach to emerge. topics are hot topics, and would The themes are currently hot topics allow the promotion of high impact in recurring miscarriage. areas of translational research and The SIGEP committee was clinical innovation. attracted to the debate forum (a fine SIG EP co-ordinators, left to right, Roy A plenary session during the Roman tradition) and invited a host Farquharson, Mariette Goddijn, scientific programme of the meeting of world class speakers to present a Ole Christiansen and Marcin Rajewski. on Monday 28th June at 17.00 will case for and against two distinct address the prevention of maternal themes. The first theme of heparin use in pregnancy will be death in early pregnancy. This session will feature two presented by Lesley Regan (London, GB) and Carl Laskin internationally recognised experts, James Neilson on (Canada). This subject continues to attract a good deal of maternal death from miscarriage and ectopic pregnancy, opinion, especially as a treatment intervention in and Michael Greaves on thromboembolism and early preventing early pregnancy loss in recurring miscarriage pregnancy. patients. There is emerging evidence based on RCT findings assessing the role of heparin, with recent Notes for your diary publication in 2010. In addition, the indications for  ESHRE joint SIG meeting Dubrovnik maternal thromboprophylaxis have recently been updated. On 24-25th September 2010 a joint SIG meeting with SIGs which in turn moves the debate wider. Reproductive Surgery and Reproductive Endocrinology The second theme of selective karyotyping will be will take place in in Dubrovnik. A full two-day debated by two similarly world-renowned speakers in programme has now been developed. Mary Stephenson (Chicago, USA) and Mariette Goddijn  ESHRE joint SIG meeting Valencia (Amsterdam, NL). Historically, the investigation of early On 2-3rd December 2010 a joint SIG meeting with SIGs pregnancy loss relied on parental chromosome testing and, Endometriosis and Endometrium and Stem Cells - on the more pertinently, failed pregnancy testing. Conventional ‘maternal embryonic interface’ - has been developed. Full cell culture techniques exhibited a high rate of maternal programme details will be available in shortly. cell contamination from failed pregnancy. With the Roy Farquharson appearance of innovative cytogenetic techniques, such as Co-ordinator SIG Early Pregnancy extended fluorescent in situ hybridisation (FISH), spectrum [email protected]

16 Focus on Reproduction May 2010 // ENDOMETRIOSIS AND ENDOMETRIUM //

A high profile for endometriosis in Rome

Annual meeting Rome poor responders. It is We hope to see as many of Officers accepted, he said, that in you as possible at this Hilary Critchley (GB), Co-ordinator over-responders, the very Anneli Stavreus-Evers (SE), Deputy Co-ordinator Endometrium year’s precongress course. high E2 levels (>20,000 Juan Garcia Velasco (ES) Gerard Dunselman (NL), Deputy Co-ordinator Endometriosis pmol/l) adversely affect and Paola Vigano (IT) have Annemiek Nap (NL), Junior Deputy endometrial development prepared an excellent Thomas D’Hooghe (BE), Past Co-ordinator and function and reduce programme on the theme of implantation rate. In ‘Endometriosis: How new technologies may help’. The normal responders, the moderately high E2 levels seem to course will provide participants with an understanding of affect endometrial morphology but do not have any major not only the pathogenesis of endometriosis but the detrimental effect on implantation rate (usually around importance of diagnosis and non-surgical approaches to 30%). In poor responders, however, E2 levels are lower management. We encourage all those involved in the care than normal responders but are still higher than those in of patients with endometriosis - and particularly those natural cycles - yet the implantation rate is reduced with needs of fertility and pain management - to attend. (~10%). Professor Li noted that there are no good quality We hope to see all SIG members there. data on endometrial function in poor responders, but It is splendid that the scientific programme of the annual nevertheless proposed that their reduced implantation rate meeting will provide a platform for presentations on topics is more likely a consequence of poor oocyte quality, endometriosis/endometrium, with oral contributions in because these same women usually have good implantation four sessions and a significant number of posters. Well rates when they have oocyte donation. done all for submitting your work! The Poster Village will have representation from our SIG on Tuesday lunchtime, Future activities and we’ll also be involved in an interactive poster A tripartite meeting of the SIGEE, SIG Early Pregnancy discussion on Monday lunchtime. and Stem Cells in Valencia is now scheduled for 2-3rd December. This exciting event should have wide appeal Endometriosis guidelines and provide a platform for state-of-the-art discussion on Revised ESHRE guidelines for the diagnosis and treatment complementary topics of implantation, stem cell biology of endometriosis were presented and interactively discussed and endometriosis. during a Campus course in Budapest in February. The We are also exploring a joint Campus meeting with the course was organised by Attila Bokor and Thomas SIG Reproductive Surgery on the subject of ‘Deeply D’Hooghe, who also spoke at the meeting, together with infiltrative endometriosis’; more details will follow in a other members of the Endometriosis Guideline future edition of Focus on Reproduction. Another Development Group - including Stephen Kennedy (GB), proposed Campus initiative will be on the topic of Daniela Hornung (DE), Robert Greb (DE), Ertan ‘Scarring and adhesion formation in the female Saridogan (GB), Charles Chapron (F) and Lone reproductive tract’. We hope to hold this meeting in Hummelshoj (DK). The course was attended by about 65 Edinburgh in late 2011/ early 2012. participants and rated as very good or excellent by the majority with respect to organisation, general information, Raising awareness of endometriosis educational value, and individual lectures by the invited Endometriosis support organisations across Europe drew speakers. This was the first time we had organised an much public attention to the disease during this year’s educational activity in Central/Eastern Europe, and we feel Endometriosis Awareness Week (8-14th March). MEP and that this format was interesting and can be repeated vice-president of the European Parliament, Diana Wallis, elsewhere upon request. called for more investment in research into endometriosis. Lone Hummelshoj continues to press the European Poor ovarian respsonse Parliament and Commission to acknowledge the need for The first inter-SIG Campus meeting considered poor investment in benign female diseases, especially those, such ovarian response and the contribution from the SIGEE was as endometriosis, which affect women during the prime delivered by Professor TC Li, from Hallam University, years of their lives. Sheffield, who reported that, while the implantation rate Hilary Critchley in normal responders is ~30%, it is reduced to ~10% in Co-ordinator SIG Endometriosis and Endometrium

Focus on Reproduction May 2010 17 SPECIAL INTEREST GROUPS // REPRODUCTIVE ENDOCRINOLOGY //

Old and new hormones reviewed in Budapest

Professor Janos Urbancsek proved the adrenal in health and disease, a tremendous host for our Campus Officers and current management of types workshop, ‘Old and new Adam Balen (GB), Co-ordinator 1 and 2 diabetes. The Leeds hormones’, held at Semmelweis Richard Anderson (GB), Deputy Co-ordinator contribution was completed by University, Budapest, in December Juan Garcia Velasco (ES), Deputy Co-ordinator myself on hyperandrogenism in last year. We had just over 80 Georg Griesinger (DE), Junior Deputy women - diagnosis and registrants from 22 different Nick Macklon (NL), Past Co-ordinator management - and not only in countries, with a very good PCOS! Thyroid physiology and representation from the host country Hungary. Every talk dysfunction were covered by George Griesinger (DE), was of the highest standard and the meeting provided a before we moved on to new data on the link between gut superb overview and update of recent advances and and adipose hormones and reproduction by Waljit Dhilo potential future research. (GB). Among a range of elegant and comprehensive reviews Our host, Professor Urbancsek, gave an elegant overview were presentations on: of the role of inhibins during the menstrual cycle and  Current understanding of the hypothalamic-pituitary- during ovarian stimulation for IVF and shared many years gonadal axis (John Marshall, USA), with comment on of carefully collected data. His key message was that recently derived pathways and neuropeptides such as measurement of inhibin B may indeed predict ovarian kisspeptin, GPR 54 and neurokinin B. response and pregnancy, whilst measurement of the other  Determinants of normal puberty (David Dunger, GB) on members of the inhibin/activin family does not warrant secular changes, epidemiology and the influence of routine assessment in clinical practice. The meeting birthweight and early infant growth on puberty and concluded with the latest endocrine marker for ovarian longer-term health. reserve, AMH, delivered by Frank Broekmans (NL).  Control of ovulation (Steve Hillier, GB), including the Whilst more data is still required, it appears that AMH is role of IL-1 and its regulation of enzymes such as not only the best predictor of ovarian response and 11betaHSD1 in controlling the conversion of cortisone to potentially oocyte quality but also, when measured at cortisol and the regulation of matrix metalloproteinases on intervals, may in future provide a better insight into the ovarian surface epithelium. declining ovarian reserve with age than other tests such as  Hormonal control of spermatogenesis and the antral follicle count. hypogonadal male (Richard Anderson, GB) on the action of androgens in the testis and their control by the HPT Future events axis. Our precongress course for Rome is on ‘The lost ART of  Hypothalamic disorders and their management (Pierre OI’. Many of us feel that the pathway to IVF is too swift Bouloux, GB) on the more and that a preferable aim is common and very rare causes to treat the underlying of Kallmann’s syndrome and causes of infertility. Special hypogonadotrophic skills are required when hypogonadism. performing ovulation  Pituitary tumours and the induction for anovulatory management of hyper- infertility, which require a prolactinaemia, in which degree of subtlety not Didier Dewailly (FR) needed for ‘controlled’ dispelled any notion of an ovarian hyperstimulation association with PCOS. for IVF. This course will Among other presenters cover the causes of were Philippe Bouchard (FR) anovulation and deal in turn with a fine update on FSH with management protocols, and LH receptor Speakers at our Campus workshop in Budapest. Seated are SIG predictors for response and polymorphisms, Eleanor Co-ordinator Adam Balen (left) and local host Janos Urbancsek, algorithms for treatment. Scott (GB) with two flanked by Ine Van Wassenhove and Veerle De Rijbel from Further ahead we have a endocrinological reviews of ESHRE’s Central Office. joint Campus with the Early

18 Focus on Reproduction May 2010 // PSYCHOLOGY AND COUNSELLING //

Collaborations with other SIGs prove valuable

The SIG Psychology and 22). In April, she introduced Counselling has a challenging Officers infertility counselling to junior precongress course planned for Petra Thorn (DE), Co-ordinator doctors, paramedicals and Rome with topics covering Christianne Verhaak (NL), Deputy Co-ordinator embryologists in Kiev, . current developments in ART and Jan Norré (BE), Deputy Co-ordinator This is clearly a valuable their impact on counselling. The Patricia Baetens (BE) Past Co-ordinator contribition to clinical meetings morning sessions will tackle Uschi Van den Broeck (BE), Junior Deputy and we hope to see more ethical dilemmas arising from collaboration with other SIGs. We recent advances, such as providing ART for HIV-affected can all benefit from a multidisciplinary approach. men and women, egg freezing and PGD. Afternoon Our second Campus workshop in Amsterdam on sessions will feature clinical issues such as counselling the December 3-4th will be a two-day course designed to infertile man, mourning rituals for couples remaining increase knowledge and competence in psychosocial care childless, internet-based support for infertility and finally by outlining the different perspectives of infertility discussion on whether interactive personal health records counselling and acquiring basic communication skills in can empower patients. The course will be chaired by SIG specific situations through in-depth case work. The course Co-ordinator Petra Thorn and Deputy Chris Verhaak. is aimed at all professionals involved in the psychosocial The SIG business meeting which follows welcomes care of people with infertility: psychologists, counsellors, members to join in the discussion. Topics this year will doctors, nurses, administrative personnel and other medical include collaboration on the update of guidelines as well as staff. The first day will focus on more theoretical issues in an overview of the first Campus workshop held in Basel the psychology of infertility, medical treatment from a last year and the upcoming event in Amsterdam later this patient-centered perspective, infertility counselling from a year. The annual dinner in conjunction with the cognitive-behavioural and systemic perspective, third party International Infertility Counsellors Organisation (IICO) reproduction and the difference between infertility will complete the day’s events in Rome. Participants counselling and psychotherapy. The second day will interested in joining the dinner can contact Jan Norré for provide discussion targeted towards medical and more information. administrative staff on the one hand and psychosocial staff We have been well represented by Petra Thorn, our Co- on the other. In-depth case work will guide the much more ordinator, in the past few months in other Campus events. hands-on discussion and promote interactive participation. In March Petra described the psychological perspectives of Uschi Van den Broek women diagnosed with poor ovarian response (see page Junior Deputy Co-ordinator 24) and counselling concepts for donor insemination (page SIG Psychology and Counselling

Pregnancy and Reproductive Surgery SIGs, entitled consensus workshop on ‘Medical problems associated with ‘Healthy start - The determinants of a successful PCOS’. The first consensus in Rotterdam, in 2003 pregnancy’. This will take place in Dubrovnic, Croatia, in provided definitions for PCOS which resulted in one of the September (on 24/25th). The meeting will start with the most cited publications in our field. The Thessaloniki diagnosis of congenital anomalies of the lower genital tract consensus on the management of infertility in PCOS also and evidence for surgical approaches (whether cervical produced a highly cited joint publication in Human cerclage should be vaginal or abdominal). We will move on Reproduction and Fertility and Sterility, so we anticipate to the problems of obesity and early pregnancy, the effects that this third consensus will be equally stimulating and of obesity on natural conception and fertility treatment, important in its outcome. and the topical issue of medical and surgical approaches to Towards the end of the year we will be running a the management of obesity. Pregnancy in the older woman Campus course in Madrid (3-4th December) on ‘GnRH will cover how we can best predict fertility, what we agonists for triggering of final oocyte maturation-time for a should do about fibroids and endometriosis, and how the paradigm shift’, so please mark this date in your diaries older mother is best managed. too. The third joint ESHRE/ASRM PCOS consensus meeting Adam Balen will take place in Amsterdam, beginning on 18th Co-ordinator SIG Reproductive Endocrinology November with an open meeting followed by a two-day [email protected].

Focus on Reproduction May 2010 19 SPECIAL INTEREST GROUPS // ANDROLOGY //

At last, the fifth WHO manual for semen analysis has finally arrived

The fifth edition of the long awaited WHO laboratory manual Officers for the examination and Roelof Menkveld (ZA), Co-ordinator processing of human semen was Jose Antonio Castilla (ES), Deputy Co-ordinator finally published on line in Sheena Lewis (GB), Deputy Co-ordinator March.1 Jessica Tu (SE), Junior Deputy The manual was originally expected in 2008, but one of the reasons for its delay may morphology. The new have been that the semen parameter ‘reference’ values, edition has been previously known as ‘normal’ values, had to be subject to considerably extended peer review in a journal. This finally happened at the end of and contains much in detailed 2009, when the report was published on line.2 procedures and notes on the different aspects of However, as with the past issues, the new reference values the whole process of the semen analysis. are likely to prove controversial, especially the very low As one of the main focuses of the SIG Andrology is to value of 4% morphological normal spermatozoa for sperm promote the performance of semen analyses to a high and

// REPRODUCTIVE SURGERY // Repeats this year and next for our popular endoscopy course

Our precongress course in Rome is determinants of a successful on NOTES (natural orifice Officers pregnancy’, will take place in transluminal endoscopic surgery) Marco Gergolet (IT), Co-ordinator Dubrovnik, Croatia, on 24-25th of and single access surgery. Interest Vasilios Tanos (CY), Deputy Co-ordinator September this year, followed by a in the course is growing following Rudi Campo (BE), Deputy Co-ordinator joint meeting with the SIG the revolution in endoscopic Stephan Gordts (BE), Past Co-ordinator Andrology in Treviso on 8-9th surgical access. There have been Pietro Gambadauro (IT), Junior Deputy October. criticisms of this pioneering Next year an interesting course surgery, but not unlike the criticism 20 years ago on on ‘Reproduction and the management of fibroids’ will laparoscopic surgery. The live surgery session in Rome be organised in Larnaca, Cyprus, on 15-16th April will take place on 29th June. 2011, followed in May (6-7th) by a workshop on ‘How Our course on ‘Endoscopy in reproductive surgery’ in surgery can increase the success rate in ART’. This February in Leuven was a great success! As usual, it was meeting will be held in Grado, Italy, an attractive island fully booked and participants came from 13 countries, in the northern Adriatic connected by a short bridge to from Czech Republic to Turkey, from Philippines to the mainland. Grado is also known as the ‘sunny island’ Kuwait. The hands-on suturing sessions with the pelvic and has been appreciated for its beautiful beaches since trainer were performed on chicken legs, pig bowel and the country was ruled by the Habsburg Empire. Its pig bladder. For the first time the location of the course intricate history is linked to the history of Aquileia from was at the new building of he European Academy of the time of the first barbarian invasions, and to the Gynaecological Surgery. The course will be repeated in Republic of Venice. November (24-26th) and twice in 2011 (23-25th Our precongress course in Stockholm in 2011 will be February and 23-25th November). on the prevention and management of adhesions. A joint meeting of SIGs Reproductive Surgery, Early Marco Gergolet Pregnancy and Endocrinology, ‘Healthy start - the Co-ordinator SIG Reproductive Surgery

20 Focus on Reproduction May 2010 uniform standard, not only in Europe but throughout the world, our committee for training now believes that our Funding for research in male semen analysis courses should be run according to the new WHO guidelines. For this reason the training committee is infertility seriously neglected planning an urgent course, possibly in September 2010 in Stockholm, to train the trainers. The training committee Falling birth rates are becoming a public health issue also runs the worldwide External Quality Control (EQC) in Europe. In 2008 the European Parliament programme for basic semen analysis and this too will be acknowledged that reduced fertility was a major updated. cause of its demographic decline and that ART might offer one solution. However, if ART is to be included Past events as a substantive part of a new population policy, As reported on the following pages, the SIG Andrology has there will need to be a government led and funded recenently hosted a very successful Campus meeting on programme for its enhancement. Although European ‘Sperm and testicular tissue banking’ in the picturesque city live birth rates are impressive, male infertility has of Granada, Spain. The meeting was well attended, with a been long neglected, and this is the area where even total of 18 presentations covering a whole range of subjects further rapid progress could be made. This will first from basic laboratory procedures and safety, to the require a re-examination of current assessments of theoretical aspects of sperm and tissue cryopreservation male fertility potential. Research will be needed to and the surgical retrieval of testicular and epididymal tissue improve prognostic sperm function tests with clinical and its use. The presentation by Petra Thorn (Co-ordinator relevance for each type of ART treatment. Since of the SIG Psychology and Counselling) on the counselling 1995 research into sperm dysfunction has been of donor semen recipients was very well received and sidelined by the success of ICSI. As live birth rates prompted a lively discussion - as well as the possibility of with ICSI are presently as good as or better than combining a joint meeting of the two SIGs. those with IVF, there has been little incentive to invest in the research and development of sperm Future events selection tests. However, in order to raise ART One of our main focus areas now - in addition to our success and ensure the long-term health of children precongress course in Rome - will be to organise a semen born by ICSI, we need novel sperm tests with high analysis trainers meeting later this year. This year’s prognostic strength. precongress course on ‘The environment and human male Conventional semen analysis is fundamental to the reproduction’ is a scientific course but has many interesting initial work-up of the male partner but is of limited topics for the more clinically minded congress attendee. value in predicting outcome. In contrast, sperm DNA The programme will cover what we know of the testing shows much promise in ART checkpoints. reproductive risks from occupational and environmental However, these tests have not been brought into pollutants. The precongress course will be followed clinical use because there is no funding to immediately by the SIG Andrology members business standardise them and perform the necessary clinical meeting, and later in the week will be the usual annual trials. In a position report from a recent ESHRE 1 meeting for participants in the external quality assessment Campus, the requirement for dedicated funding for (EQA) programme for semen analyses. research was highlighted as one of five Other activities this year recommendations: will include a basic semen 'A fundamental impediment to advancement over the past three decades has been the absence of reproductive analysis course in Barcelona medicine and infertility research as a strategic priority for from 20-23rd September and national governments and agencies. This has resulted in a a combined Campus meeting paucity of funding. A prerequisite of achieving the above with SIG Reproductive recommendations is for national and international agencies Surgery on ‘Surgery in female to realize the importance of both basic and clinical research in this area and, to deliver substantial and male infertility patients’ long-term financial support.' in Treviso, Italy, from 8-9th We in the SIG Andrology share October. this view and look forward to Roelof Menkveld ESHRE members’ comments on Co-ordinator SIG Andrology how it might be implemented. [email protected] Sheena Lewis Deputy Co-ordinator SIG Andrology 1.http://whqlibdoc.who.int/publications /2010/9789241547789_eng.pdf 1. Barratt CL, Aitken RJ, Björndahl L, et al. Sperm DNA: 2. Cooper TG, Noonan E, von Eckardstein S, et al. World Health organization, protection and vulnerability: from basic Organization reference values for human semen characteristics. science to clinical applications - a position report. Hum Hum Reprod Update. 2009; doi:10.1093/humupd/dmp048. Reprod 2010; 25: 824-838.

Focus on Reproduction May 2010 21 SPECIAL INTEREST GROUPS // ANDROLOGY //

Despite falling demand Donor insemination UK for donor insemination, Stimulated sperm donors are still and unstimulated cycles in very short supply

Although donor insemination as a treatment for male factor infertility has decreased considerably since the introduction of ICSI in the early 1990s, there is still a demand for donor sperm. According to presentations at a Campus event hosted by the SIG Andrology in Granada, As the graph above (taken from the HFEA’s database in Spain, in mid-March, the indications today are more in the the UK) suggests, the decline in the use of donor treatment - where permitted - of single and lesbian women, insemination seems inversely related to the increase in and men who wish to avoid passing on genetic disorders. the use of ICSI since the early 1990s. According to However, according to a former chairman of the SIG Vanessa Kay from Ninewells Hospital in Scotland, this Andrology, Chris Barratt, there still remains a shortage of is also reflected in a change in the profile of patients donor sperm in many countries despite a 20% fall in now receiving donor insemination. She told the demand since the 1990s. And the reasons, he proposed, are Granada Campus that donor insemination is now seen not just about ICSI. It has, he said, always been more in cases of severe male infertility and in couples 'challenging' to recruit sperm donors, but the challenge has with serious genetic conditions. However, she also grown in recent years over the rates of compensation to noted an increase in use in ‘social infertility’ - in same- donors, the attrition of donors during screening, the legal sex couples amd single women. She cited HFEA demands of the EU's Tissues and Cells Directives, and the register data showing an increase in DI for single vexed question of anonymity. This uncertainty has meant females from 508 treatments in 1999 rising to 705 that many centres have simply given up their efforts to treatments in 2006, and in lesbian couples from 284 recruit donors, and hence the continuing gap between treatments in 1999 to 767 in 2006. Conversely, the supply and demand. number of treatments in ‘other females’ fell from 3536 The UK, for example, in line with some other EU in 1999 to 2392 in 2006. countries such as Sweden and the Netherlands, changed its However, Kay also calculated that, despite the laws on donor anonymity in 2005 such that children decreased demand, there was still a chronic shortage of sperm donors in the UK, with no more than 384 formally registered with the HFEA in 2008. The result is that clinics continue to withdraw their DI services and that sperm is imported from overseas sources. The whole question of gamete donation is now under review in the UK, and Kay recommended that compensation to donors should be enhanced, with those targeted likely to be fertile and good screening candidates.

This Campus meeting in Granada was yet another in 2010 conceived by donor sperm (or donor oocytes) had the right to attract a full house, with 135 registered participants, a from the age of 18 to know the identity of the donor. reflection of ESHRE’s ongoing commitment to expanding Sperm banks were thus obliged to collect identifying (and and supporting its Campus programme. Pictured above are non-identifying) information from their donors and lodge the meeting’s scientific committee, from left to right, the information with the regulatory authority. The result, Roelof Menkveld (SIG Andrology Co-ordinator), Jose with almost immediate effect, was a drop in the numbers Antonio Castilla (chairman) and Matt Tomlinson. The event of donors, such that the British Fertility Society, in marked the 30th anniversary of Spain’s third sperm bank proposing a national plan for sperm donation services, at Virgen de las Nieves in Granada. described the shortage as ‘critical’.

22 Focus on Reproduction May 2010 Spain takes one step nearer to a formalised, national IVF register; many clinics remain outside the voluntary scheme Although 2006 legislation in Spain ruled that all results from Spanish ART centres should be collected in a national register and a proportion audited, only one region (Catalonia) has implemented the law with any formality. The rest of the nation’s data collection and audit has been left to a voluntary programme undertaken by the Spanish Fertility Society, which, according to its co-ordinator Jose Antonio Castilla, accounts for only around 65% of Spanish clinics. Now, in recognition of the legal requirement and the ongoing work of the voluntary register, the Spanish Health Ministry has agreed to support some of the Fertility Society’s data collection and audit. ‘The Ministry wants transparency,’ says Castilla, ‘so patients can see for themselves how clinics perform. So we now have to give the data to the Ministry on a clinic by clinic basis. We are hoping to audit around 10% of the results.’ The latest results of the voluntary data collection - for 2007 - which have just been presented to the Ministry, recorded 54,620 treatment cycles, with a pregnancy rate per transfer of 39%. Fresh cycle IVF represented 34,449 cycles, frozen embryo transfer 9089 cycles, and egg donation 7925 cycles. Some of Spain’s clinics, however, have not supported the Fertility Society’s efforts, arguing that, if the Minstry wants the data, the Jose Antonio Castilla, organiser of the Minstry should collect it. Others, says Castilla, have even questioned the SIG Andrology Campus in Granada and need for a registry at all, noting that other medical disciplines are not co-ordinator of the Spanish Fertility subject to such demands. Society voluntary IVF register

However, Lars Björndahl, another former chairman of applicability, a detrimental effect on cell viability, the lower the SIG Andrology, insisted that the EU’s Directives on risk of infection from reproductive (than transplant) tissue, tissues and cells - which by now, he said, ‘should have been and the difficulty of ICSI in a Grade A environment. implemented in all EU countries’ - were intended to However, said Björndahl, once establishments are increase, not reduce, the availability of donor sperm compliant the safe transport of donor sperm should be throughout Europe. With the Directives setting uniform guaranteed and the risks to offspring minimised. Such baseline standards for air quality, quarantine, guarantees should make feasible the ‘hub-and-spoke’ cryopreservation, transportation and traceability, the system proposed for sperm supply in the UK, the measures should make sperm banking safer with quality international transport of sperm samples as is now seen guaranteed. These standards, Björndahl explained, were from Denmark, or the cross-border treatment of many baseline, with individual member states free to raise the bar couples now seeking donor insemination abroad. as they thought appropriate. Nevertheless, Roelof Menkveld described the recruitment The ‘mother’ Directive (2004:23), which had appeared in of semen donors as still ‘tedious’ because of the high drop- 2004, had thus set standards for the 'procurement' of out rate and continuing attrition. Screening requirements - sperm samples from donors which grouped sperm as reflected in the Tissue and Cell Directives or in local alongside all other tissues and cells (mainly for guidelines - will of course help ensure safety, but Menkveld transplantation) and their donors as ‘voluntary’ and also lamented a lack of consistent universally applicable ‘unpaid’. One of two later technical Directives (2006:17) semen parameters for sperm donors. Even the latest WHO required that non-partner donors were subject to safety manual (2010) has reduced its minimum concentration screening through medical history and biological testing for from >20 million/ml in 1999 to 15 million. There is a view, HIV1 and 2, hepatitis B and C, syphilis, chlamydia and said Menkveld, that semen parameters are declining, but other diseases (including some of genetic origin). this is not supported by all studies, which are anyway Björndahl reported that traceability requirements with characterised by ‘analytical variability’. The latest UK respect to both adverse reaction disclosure and coding had guidelines, developed by a consortium which included the still not been agreed, though are apparently under current British Fertility Society and British Andrology Society, discussion at the European Commission. ‘Nevertheless,’ he recommended that only men with pre-freeze semen quality said, ‘there is still no European coding system.’ Similarly, values above the 1990 WHO values should be accepted as the EU’s Grade A requirements for air quality in sperm donors, and of course providing they could meet the other banks remain controversial, with ESHRE and some safety screening tests for medical and genetic history and member states raising practical objections based on bacterial and viral infection.

Focus on Reproduction May 2010 23 SPECIAL INTEREST GROUPS // INTER-SIG CAMPUS //

Poor ovarian response: from the ‘unknown’ to consensus in definition and prognostic tests

Rarely can Donald Rumsfeld, the erstwhile architect of the US invasion of Iraq, have been the talisman for a meeting on reproductive medicine, nor his words cast such a long shadow. But it was Rumsfeld’s celebrated ‘known unknowns’ and ‘unknown unknowns’ which Nick Macklon - now back in his native UK as Professor of Obstetrics & Gynaecology at the University of Southampton - took as This was the first Campus meeting to his theme to describe the black hole of predicting poor be organised by all ESHRE’s SIGs and response to ovarian stimulation for ART. the timely theme attracted more than Poor ovarian response (POR) was the challenging but 150 registered participants to Bologna ever more evident theme of this first Campus course to be in March. The two-day programme was organised collectively by each of ESHRE’s SIGs. And on collated by the SIGs, with each one few other subjects could such a multidisciplined input be represented in the presentations. Local organiser Anna Pia more appropriate. Macklon’s case was that the emerging Ferraretti, from the SISMER centre in Bologna, proposed tests of ovarian reserve, such as measures of anti-Mullerian that a standard definition of poor ovarian response is hormone (AMH) or antral follicle count (AFC), do have a ‘urgently needed’ not only for appropriate individual justified place in individualising treatment and setting a patient management but also to provide a consistent starting dose of FSH, but their value in predicting background to clinical trials. ‘By using different criteria,’ pregnancy remains less clear. So, while such prognositic she said, ‘we are creating a mixed population from which factors as AMH or AFC may well provide therapeutic it is difficult to derive meaningful results.’ opportunities, there is little they can do in the face of a dramatically diminished oocyte supply or a patient of advanced maternal age (which, said Macklon, remains the found an inverse and significant correlation between the best predictor of a live birth). Data cited by him showed proportion of normal (euploid) oocytes and patient age, that only at extreme cut-off levels will results of AFC, suggesting that egg quality as well as quantity is AMH and basal FSH tests occasionally predict pregnancy contributing to outcome in poor responders. The SISMER with accuracy. Otherwise, as his fellow speaker Juan data indicated that the viability of oocytes in poor Garcia-Velasco from the IVI clinic in Madrid suggested, responders is especially compromised when associated with ovarian reserve testing remains important for little more advanced age, with outcome additionally related to the than counselling on outcome, tailoring stimulation opportunity for embryo (and oocyte) selection. protocols and predicting cycle cancellation. If both age and oocyte quality are beyond repair, how For Velasco too, age was the only realistic (and cost might treatment interventions help? Well, not much, efficient) marker of egg quality and outcome - and according to Basil Tarlatzis, a former ESHRE chairman and increasingly the major everyday challenge in ART. His joint author of a recent systemic review of interventions clinic in Madrid performed 2047 fresh cycles in 2009, of aiming to increase the chance of pregnancy in poor which 68% were in women over the age of 34. In responders. The study reviewed 15 interventions, ranging reflection of this challenge, a first polar body analysis of from added aspirin to added pridostigmine, from short more than 5000 oocytes performed by SIG Embryology co- agonist cycles to modified antagonist cycles. Of the studies ordinator Cristina Magli at the SISMER clinic in Bologna in the review - which were characterised by different

24 Focus on Reproduction May 2010 The consensus panel also concluded that ovarian reserve tests 'may add something' when prediction is based solely on age, with AFC and AMH deemed the most useful. However, there was little controversy in the group's conclusion that no individual treatment protocol appears to confer any clear advantage in POR, with the possible exceptions of added growth hormone and modified natural cycle IVF. The case for the latter was neatly demonstrated by Filippo Ubaldi, local chairman of this year's congress in Rome, whose own clinic began natural cycle treatment in POR patients in 2000. An analysis of 962 consecutive cycles (in 533 POR patients) achieved a pregnancy rate per cycle of 10%. A subsequent prospective study with a historical control found no significant difference between clinical pregnancy rates in modified natural cycles and Consensus - in definition and the use of prognostic tests stimulated cycles (5.6%/cycle natural and 4.7% of ovarian reserve - was steered by an expert group stimulated). However, the cost per baby was considerably comprising, from left to right, Antonio La Marca, Christina less in the natural cycles (and without the risk of OHSS or Bergh, Anna Pia Ferraretti, Bart Fauser, Geeta Nargund multiples); the major drawback was the risk of premature and Basil Tarlatzis. The ‘Bologna criteria’ defined POR (or LH surge and spontaneous ovulation, which occurred in expected POR) as the presence of two from 30-60% of cycles.  advanced maternal age or any other risk factor for POR With the outlook so poor for these patients, it was fitting  a previous poor response to stimulation that the SIGs Psychology & Counselling and Ethics & Law  an abnormal test of ovarian reserve were each represented. Petra Thorn, representing the ‘Poor’ ovarian reserve was preferred to ‘low’, even though former, said that women with POR were likely to poor is a less accurate converse of ‘high’ and rather more experience high levels of distress and self-blame, which an subjective. Age was unanimoulsy defined as the most understanding of the background and of the alternative predictive measure of pregnancy, with four (or fewer) family options, may alleviate somewhat. Francoise oocytes agreed as a definition of poor response to Shenfield, however, raised another salutary but harsh stimulation. Data presented by Anna Pia Ferraretti from an reality of poor response in warning that the provision of analysis of 2000 cycles at the SISMER centre showed ‘futile treatment’ is not ethically justified. She noted that that three oocytes retrieved was the cut-off point of the ASRM has recently defined ‘futile’ as having a 1% (or significance in the association of pregnancy rate per egg less) chance of live birth, while a 1-5% chance is defined as retrieval with the number of oocytes collected. ‘very poor’. Clinicians, she added, may refuse treatment in both cases. Thus, with so little encouragement for POR patients and inclusion criteria, limited evidence, and multiple definitions so little that conventional ART can do about age and of poor response - only the addition of growth hormone to oocyte quality, the meeting turned back to the unknown the stimulation protocol made any beneficial difference to (either known or unknown) for its look to the future. The outcome, with an odds ratio for live birth of 5.22. But, data on oocyte vitrification for fertility preservation were when challenged, even Tarlatzis was reluctant, on safety described by ESHRE’s chairman Luca Gianaroli as grounds, to recommend GH as a reliable intervention. ‘promising’, with comparable outcomes reported this year So one of the challenges for this meeting was to form a (from Rome) from fresh and vitrified oocyte cycles. The consensus on a uniform definition of POR as an aid to same study, said Gianaroli, suggested that 16 vitrified eggs clinical practice and trials, and to estimate its incidence were needed to produce a singleton fetal heart beat. (which Tarlatzis put at between 9 and 24% of all cycles). However, there was less immediate promise in another Consensus on a definition was reached with surprising ease possible way to overcome POR, the generation of gametes and the group settled on the presence of at least two of the from stem cells. Ana Marques-Mari, representing the SIG following three features: Stem Cells, reported that one or two recent studies had  advanced maternal age or any other risk factor for POR described both embryonic and somatic stem cell lines  a previous poor response to stimulation showing a small number of cells carrying a marker for  an abnormal test of ovarian reserve differentiation, but these, she emphasised, were still no The POR definition was modified with the addition of more than a tool for research, and still without any ‘expected’ in those cases where no previous response had certainty of safety. This indeed was the ‘unknown been recorded. In the risk factors additional to age, the unknown’ at its most Rumsfeldian. recovery of four or fewer oocytes was deemed an Simon Brown acceptable cut-off point consistent with POR. Focus on Reprodcution

Focus on Reproduction May 2010 25 TASK FORCES // FERTILITY PRESERVATION IN SEVERE DISEASE and BASIC REPRODUCTIVE SCIENCE //

An ambitious initiative for oncofertility in Europe

The Oncofertility Consortium is a network of researchers, national physicians, and scholars - which includes ESHRE’s Task biomaterials Forces for Fertility Preservation in Severe Disease and Basic core, and a team Science in Reproductive Medicine - aiming to advance of ethicists, fertility preservation options for young cancer patients. As economists, law a result of more aggressive and advanced treatment, more scholars, cancer patients are surviving their disease. However, these educationists, treatments are not without risks of infertility, sterility, or social and early menopause. Until recently, providers and patients behavioural alike seemed willing to tolerate these adverse effects, with scientists, the notion that surviving the disease was the only goal and patient any unintended consequence of treatment should be advocates, basic Members of the Task Forces Basic Science in endured. The desire to do something positive about post- reproductive Reproductive Medicine and Fertility Preservation in Severe Disease met for a ‘reflection’ earlier this year cancer infertility came to the fore some ten years ago as scientists, and to solidify an EU-US partnership in fertility patients began voicing their belief that the ability to have a clinical preservation before cancer treatment. child of their own should not be an afterthought. investigators. Mature technologies for both adult men (sperm banking) The Consortium also created mechanisms by which and women (hormonal stimulation followed by embryo patients receive rapid information such that more are now cryopreservation) are of course in place for cancer patients aware of the fertility effects of treatment. Additionally, concerned about their fertility, but structural barriers fertility clinics have been re-engineered to meet the special between practices limit patient access. Moreover, there are needs of cancer patients, which often cannot be addressed few options for young men and women unable to delay using the typical routines applied to infertility patients. cancer treatment, and for women and girls unable to At the same time, basic research discoveries have undergo hormonal intervention. expanded our knowledge of the fertility threat posed by Recent advances in ovarian tissue transplantation and in specific treatments, developed more robust fertility vitro follicle maturation offer new opportunities for preservation options, and led to medical interventions that fertility management. By unifying clinical teams at the protect the gonads from the lethal effects of certain cancer intersection of oncology and reproductive medicine and by treatments. All of this work coincides with the using discovery research to create the next generation of development of a team of healthcare providers who enable reproductive interventions, this trans-disciplinary team is the patient to make an informed decision about fertility working to ensure that young cancer survivors are interventions while ensuring the best outcome from cancer provided the best information and methods to protect their treatment. options for future families. Thus, the solution to the previously ‘intractable’ problem of fertility options for young cancer patients required The Oncofertility Consortium progress at the bench and bedside in concert with deep The Consortium (http://oncofertility.northwestern.edu/) is scholarship in the societal issues that frequently parallel funded by a new grant mechanism at the National reproductive intervention. The only way to make progress Institutes of Health, the NIH Roadmap Interdisciplinary in this area was to engage the bench, bedside and Research Consortium. These roadmap grants provide the community in an overarching programme, which is the significant resources to bring together the diverse groups mission of the Oncofertility Consortium. necessary to solve intractable problems. And the fertility needs of young men, women and children faced with a The opportunity in Europe cancer diagnosis and fertility-threatening treatment have It is clear that there is substantial interest from professional been identified as ‘intractable’ because, first, the science societies in creating a similarly robust network of clinicians and supporting technology are not mature, and second, and basic scientists to provide comparable fertility options solving the problem requires an interdisciplinary approach to those in EU countries. in research and clinical communities and at the NIH. ESHRE has two Task Forces committed to this special During the first three years under the grant, the interest: the TF Fertility Preservation in Severe Disease had Oncofertility Consortium expanded to include a 50-site a first well attended meeting in Heidelberg in 2008; now, National Physicians’ Cooperative and tissue repository, a the TF Basic Science in Reproductive Medicine has

26 Focus on Reproduction May 2010 // CROSS-BORDER REPRODUCTIVE CARE //

Setting consistent and safe standards of care

The first step of our cross-border reproductive care project regulators from France, Italy, Greece, Portugal and the UK, is now complete with our paper published online.1 With and national society members who are committed to the 1230 questionnaires analysed in Central Office, we have care of infertile people from Belgium, Czech Republic, estimated our snapshot picture, limited by the voluntary Denmark, Italy, Germany, Slovenia and Spain. Fertility nature of our study, to represent some 12,000-15,000 Europe will represent the patients, and Jacques Milliez the cycles of cross-borders treatments - ART and IUI whether interest of FIGO, whose ethics committee has recently with spouse or donor semen - over a full calendar year. discussed the matter. Since Amsterdam, where preliminary results were reported, Many members of ESHRE know of, or have had, several researchers in the UK and France have already patients wishing to go abroad for all the varied reasons contacted us, keen to have more details of this first confirmed in our study, aiming either to avoid restrictive gathering of facts from several European countries, whilst legislation or have better access because of long waiting they study psychosocial or legal aspects. Press attention has lists at home, always looking for quality treatment and also been sustained. sometimes expecting a more moderate cost. In Paris, we Our next step involves an important meeting in Paris in will discuss the most appropriate approach to meet our May, where many national regulators, and /or aim of high standards of care (including ethical) and safety professionals involved in the gathering of data for national for all concerned. The choice lies probably between setting societies, as well as other stakeholders including patient up a code of practice and a certification scheme, or perhaps groups, will exchange views about achieving a good first a code and then the latter. We will also discuss the standard of care for those seeking fertility treatments means of informing members and others involved, and how outside their own national borders. Under the aegis of a code or certification scheme might be implemented. ESHRE, our aim is to take a lead in establishing standards Our foremost concern, of course, is safety for patients for this phenomenon, which is not about to stop, and and participant donors, which cannot be achieved by consider the most appropriate means for informing and merely observing the EU tissue directives. Good protecting patients and other participants, such gamete communication between professionals needs to be donors or surrogates. We are also privileged to be joined addressed, as well as the matters of perennial interest such by a regulator from Canada, which was the host last year as the prevention of multiple pregnancy. to the first international forum on reproductive health care. Finally, of course, these concerns are relevant to all our Indeed, such cross-border exchanges are now happening members, and any strong feelings on the matter should be throughout the world, not only in Europe. sent to the Co-ordinator of the Task Force. It is also exciting to us that, if ESHRE can establish a Françoise Shenfield model which ensures safe care in cross-border reproductive Co-ordinator Task Force Cross-border Reproductive Care treatments, we might strengthen our links with other international societies facing the same concerns. 1. Shenfield F, de Mouzon J, Pennings G, et al. Cross border reproductive care in six European countries. Hum Reprod 2010; The May meeting, held in the French national agency doi:10.1093/humrep/deq057. offices of l’Agence de la Biomedecine, will gather

brought together a group of researchers from the USA and 26/27th September this year, organised by Teresa Woodruff ESHRE to solidify an EU-US partnership in oncofertility. A (http://oncofertility.northwestern.edu/events/2010- first ‘reflection meeting’ was organised by ESHRE in oncofertility-consortium-conference-international- January 2009 in Brussels and a landmark paper perspectives) and two precongress courses are planned for summarising the state of the art in fertility preservation 2011 in Stockholm: one on basic research and one on technologies has been recently published.1 organisational issues. Several European research teams are joining forces to Johan Smitz submit an ambitious project for EU funding which aims to Co-ordinator TF Basic Science in Reproductive Medicine solve basic scientific problems and implement new technologies into the procedures of oncofertility centres. 1. Smitz J, Dolmans MM, Donnez J, et al. Current achievements The US Consortium, being three years ahead of us in this and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility endeavour, has offered full support. preservation. Hum Reprod Update 2010; The next organisational meeting is being planned for doi10.1093/humupd/dmp056, 2010.

Focus on Reproduction May 2010 27 COVER STORY // REPRODUCTION AND SOCIETY // Europe’s demographic crisis is over - unofficial ESHRE seeks to clarify its role with the population policymakers

It’s not yet official, but Europe’s demographic crisis is over. 0.1 increase forecast At least, that’s the impression gathered from demographers by the year 2030 - speaking at a symposium organised by ESHRE’s newly and thus still well renamed Task Force on Reproduction and Society in below the 2.1 fertility Istanbul in February. Demographer Tomas Kucera, a rate deemed necessary member of the Task Force from Charles University in for population Prague, showed that, while mean age at childbirth was still replacement. The consequences, warned the report, would rising in the Czech Republic (to 29.5 years in 2008, the be a ‘spectacular’ increase in the number of old people highest ever recorded), total fertility rate, at 1.5, was now needing social and financial support, especially those in climbing back from its all-time low of under 1.2 in 1999. their 80s and 90s. The impact of this greying population Similarly, Tomas Sobotka from the Vienna Institute of would reverberate into the labour market and economic Demography, arguing that Europe’s universal trend for growth, into social security and public finance. postponed childbearing would have only a temporary However, for the clinicians of ESHRE toiling in the impact on fertility rates, showed that when this ‘tempo treatment of infertility, there were two more immediate effect’ was applied Europe’s (EU27) adjusted fertility rates messages to emerge from the demography of this actually began rising towards 1.5 in 2004. This tempo symposium: first, that despite this marginal reverse in a effect, said Sobotka, would explain the upward trend seen trend of falling fertility rates, the march towards late in the Czech Republic. motherhood continues, with no apparent change in a social Such news, no doubt, will be welcome to the politicians phenomenon which began in the 1970s and today shows in Brussels, who have identified Europe’s declining fertility no sign of abating; and second, the prevalence of infertility rate - alongside advancing life expectancy - as one of their is likely to increase as a direct result of this evolving social hot potatoes, even though a white paper for the European trend. Another of the Task Force members, Henri Leridon Commission in 2006 described Europe’s demographic from INED in France, has already reported a 6% estimate decline as a ‘challenge’, not a crisis. Overall fertility rate of permanent childlessness when female pregnancy was put at 1.5 children per woman, with no more than a attempts begin at age 30, of 14% when those attempts begin at 35, and 35% when they begin at 40. Leridon has Definitions from the demographer’s dictionary also shown that the postponement of a first conception attempt from age 25 to 30 years is associated with a mean Fertility Frequency of live births, as in number of children reduced from 2.0 to 1.77, an increase - age-specific fertility rate = number of in infertility prevalence from 9.8 to 15.8%, and an increase births/population in a given age group in the number of couples with fewer children than desired - total fertilty rate = sum of ASFRs in a from 14.8 to 24%. given year = the number of children per For ESHRE, the purpose of this meeting was not just to woman check the demographic evidence but also for the Society’s Infertility Absence of births, voluntary or involuntary Fecundity Biological ability to conceive Executive Committee to ask if ESHRE itself had any place Fecundability Monthly risk of conception in this hugely political arena. Certainly, no-one was - can be measured as percentage or doubting the clinical implications of the evidence, but more estimated from distribution of time to debatable was what ESHRE could do about it, other than conception witness the ever increasing age of patients and respond in from Henri Leridon its usual clinical and scientific ways.

28 Focus on Reproduction May 2010 The ‘tempo effect’ on total fertility rates: why the crisis is over?

Total fertility rate is reduced when the tempo of births is slowing down, and boosted when the tempo accelerates. The very low TFRs seen in Europe in the past two decades are partly because the postponement of childbearing temporarily depresses the number of births and has a tempo effect on fertility rates. The recent increases in total fertility rate seen in some countries - as in Czech Republic, right - is to a large extent explained by a slowing-down in the trend to postpone fertility. However, according to Tomas Sobotka, the postponement transition is not over yet.

Søren Ziebe, Co-ordinator of the Task Force, in if - ESHRE should involve itself in public education reviewing the evidence for the Executive Committee, campaigns about sexually transmitted diseases or described the whole demographic question as ‘important’, occupational pollutants was less easily answered. and firstly advised that ESHRE, as a reference point in For example, Bill Ledger, from the University of reproductive medicine, should continue to forge its links Sheffield, UK, described the net effect of different lifestyles with the EU and make public with authority the simple on fertility as ‘not much’. ‘Most people who eat too much, message that delaying pregnancy beyond the age of 35 drink too much, smoke too much and have too much sex increases the risk of infertility. Most agreed that large-scale with too many people,’ he said ‘don’t often end up with public education campaigns were beyond the resources (or fertility problems.’ But even the pragmatic Professor Ledger remit) of ESHRE, but that need not exclude the formal conceded that overweight oligospermic men or anovulatory statement or position paper. Certainly, no other women should indeed be encouraged to lose weight, just as organisation in the world can say with more authority than women who smoke should be encouraged to stop. But ESHRE that ART is not the magic bullet for age-related individual advice is a big step away from a public health infertility or cannot be guaranteed to reverse the infertility campaign. And the only public message to emerge from risks of a delayed pregnancy attempt. Ledger’s presentation was one echoed by many speakers at Ziebe and ESHRE’s Chairman Luca Gianaroli were also this symposium (especially the clinicians), that IVF cannot insistent that the Task Force had a solve the fertility problems of the older responsibility to collect the data, or at least patient. It couldn’t in 1994, when the huge provide an umbrella for data collection and database of the HFEA was analysed (an 8% review within its framework. The databases pregnancy rate per cycle in 40-year-olds), and of ESHRE - in PGD, cross-border still couldn’t in 2007 (when the rate had reproductive care and ART monitoring - are edged forward to 12% per cycle). already a valuable and unique reference And even when millions of dollars are source, whether within the ART, poured into public education campaigns, the demographic or political sectors. results may not turn out as planned. Carina However, the question of ESHRE’s Bjartling from Malmö University Hospital responsibilities in the prevention of infertility described a steep rise in ectopic pregnancies was less easily answered. in Sweden in the 1980s Thus, while the provision BILL LEDGER: ‘MOST PEOPLE WHO EAT and 1990s many of which, of a voice of reference TOO MUCH, DRINK TOO MUCH, SMOKE TOO she proposed, were and evidence in support associated with earlier was accepted as desirable MUCH AND HAVE TOO MUCH SEX WITH chlamydia infection. Yet by all the Committee, the TOO MANY PEOPLE DON’T OFTEN END UP screening strategies for question of how - or even WITH FERTILITY PROBLEMS.’ chlamydia - whether

Focus on Reproduction May 2010 29 The demographic effects of infertility and ART

 Based on ESHRE’s IVF monitoring data Observed TFR UK TFR Maximum TFR (availability and outcome) for the UK and TFR 2002 without ART with DK with ART Denmark in 2002, RAND Europe availability estimated the empirical and potential 1.62 1.68 impact of ART on fertility rates in these United Kingdon 1.64 1.84 two countries. At the base of the Denmark 1.72 1.65 - 1.89 calculation was an availability rate of 2106 cycles per million population in From Hoorens S, Gallo F, Cave JA, Grant JC. Can assisted reproductive technologies help to Denmark, and 625 cycles per million in offset population ageing? An assessment of the demographic and economic impact of ART UK. Results showed that ART has the in Denmark and UK. Hum Reprod 2007; 22: 2471-2475. potential to contribute to a country’s fertility rate; the study also showed that  Demographer Tomas Kucera reported that the demographic losses the costs associated with adopting ART as (live births) attributed to infertility were in the order of 10-11%. In the a population policy are comparable with EU27 countries these losses (the ‘real consequence of infertility’) those of existing policies commonly used represent a shortfall of some 0.5-0.6 million live births per year, by governments to influence fertility. calculated at recent levels of ART performance

selective or universal - have so far proved inefficient and become well accepted reasons for either having or not largely ineffective, she said. having children. And these, he implied, are trends with Similarly, the role of occupational and environmental deep social roots, whose advance will be little influenced by pollutants in male fertility remains subject to doubt, deomographers or well-meaning clinicians. Indeed, it was conflicting results, and tenuous associations. Jens Peter striking to hear Sobotka identify the over-40s as the only Bonde from Copenhagen University Hospital agreed that age group since 1985 to see an increase in fertility rate male reproductive health was at risk from environmental within the EU25 countries. Similarly, a survey conducted pollutants, but only in specific occupational settings. The by Sobotka in Austria last year found that 59% of childless effect of more generalised environmental toxins, he said, women aged between 35 and 39 still had plans to have a was ‘more difficult’ to measure. Thus, the effect of working baby, as had 30% of those aged 40 to 45! (And just weeks directly with lead might have a measurable effect on sperm after this symposium Britain’s national statistics office counts or time to pregnancy in an exposed individual, but reported that conception rates decreased in all age groups would be less easily measured universally. Nevertheless, between 2007 and 2008, with the exception of women several studies - though reportedly in different populations over 40, where conceptions remained at 12.6 per 1000.) and with different models of assessment - have suggested And so - as ESHRE’s IVF monitoring data continue to that sperm concentrations have declined with some degree confirm - the demand for fertility treatment grows from of consistency to ‘suboptimal levels’ in some men. As yet, one year to the next. Anders Nyboe Andersen, a former said Bonde, we don’t know if trace levels of pollutants in chairman of ESHRE’s EIM data gathering consortium, the environment have any harmful effect on reproduction. reported ART cycles in Europe rising to almost 450,000 in However, the one clear dominating theme of this 2006, with comparable increases found in the USA (to symposium was the universal trend towards delayed first almost 140,000) and Japan (to 160,000 in 2007). The pregnancy - and that now seems a social phenomenon expansion of ART in Japan, said Nyboe Andersen, has almost beyond the reach of any public health been especially remarkable, climbing from campaign. Its cornerstones are found in the almost zero in just 18 years, much of it greater availability of higher education (the link accounted for in frozen embryo transfers and between educational attainment and delayed low-cost modified natural cycles. pregnancy is unequivocal), a greater emphasis The availability of such data will surely define on career and consumption, reduced ESHRE’s role within the ‘reproduction and relationship stability, and more economic society’ debate. And ESHRE agreed in Istanbul uncertainty. Moreover, as Tomas Sobotka that it does indeed have a responsibility to take emphasised, even the notion of ‘family value’ part, and at least represent the clinical sector. has changed in the past few However, there was little decades, from one defined less TOMAS KUCERA: ‘BECAUSE ANY enthusiasm at this meeting for by marriage than by children as INCREASE IN FERTILITY IN EUROPE IS the politicising of infertility some form of self-fulfilment. treatment within that Indeed, said Sobotka, ‘leisure ASSUMED TO BE LOW, ALL demographic debate. Indeed, and self-realisation’ have now CONTRIBUTIONS ARE WELCOME.’ Henri Leridon cast a somewhat

30 Focus on Reproduction May 2010 Playing fertility roulette by Søren Ziebe, Co-ordinator Task Force Reproduction and Society

In most European countries too few children are being problems, we can never make oocytes younger. born. There are many reasons for this, not least the Those who play this waiting game with their families increasing age of women at the time they decide to are playing fertility roulette; these are choices which have children, and the impact of lifestyle factors. But depend on biology and ultimately affect one’s chances other reasons may play a part, such as a decline in of parenthood. In most cases, as Professor Ledger said semen quality or an increase in the prevalence of in Istanbul, there is no problem. However, more and sexually transmitted diseases. They may all have an more couples will remain involuntarily childless or have influence on when and if we can have children. fewer children than they originally desired, even with The main explanation for today’s increasing demand fertility treatment. for assisted reproduction is the older age of women as Against this background, we believe it’s important a consequence of postponing the birth of their first that ESHRE continues to drive reproductive science children. Similarly, we all know and acknowledge the and medicine such that the treatments available to major reasons for this - education, career concerns, affected couples are effective and safe. Our statement financial demands, housing, problems, the lack of a on good clinical practice in ART published in 2008 was suitable partner . . . a benchmark of these standards. However, despite all we know about these social But ESHRE also has a social responsibility and this trends, it is important to realise that biology remains will be usefully expressed in the provision of ignorant of them, and the biological clock just keeps information to the public on how we can reduce the ticking no matter how people prioritise their lives. number of couples needing our techniques; most We should also be aware that the problem is not only importantly, the public should be aware that we, the related to this ever increasing age of the fertility experts, simply cannot compensate oocytes, but also that the longer we live for any age-related decline in fecundity. the more it is likely that lifestyle factors or Perhaps we should all consider what illness will affect our fecundity and further signals each of us as parents is giving to lower our chances of having children. our own children – do we advise them to Clinicians working in reproductive have children early or should they wait medicine are more aware than most that until their education, income and housing there is a prevalent and growing attitude are all in order, and then to play fertility among young couples that if they have roulette? Of course, they will all have to difficulties in conceiving they can ‘just go decide for themselves – but we should be to a fertility clinic’. This is of SØREN ZIEBE: ‘WE CANNOT aware of the potential great concern to all of us, and, consequences and enusre that while we may be able to COMPENSATE FOR AN AGE- as many others as possible are compensate for some fertility RELATED DECLINE IN FECUNDITY.’ as well.

scornful doubt on the ability of ART to have any significant and, according to the consensus of ESHRE’s Executive effect on fertility rates, and even on the view that infertility Committee in Istanbul, the ART sector should at least be is a ‘disease’ - especially today when so much of its represented in the development of those policies. aetiology is age related. And whatever the role of ART within the demographics Nevertheless, it remains a fact that in countries like of Europe, infertility (and its treatment) does make a Denmark or Belgium, where the availability of ART per difference. As demographer Tomas Kucera told this million population lies somewhere above 2000 cycles and symposium: ‘Everyone counts and will count. And beause seems directly related to a generous funding policy, ART any increase in fertility in Europe is assumed to be low, all does at least appear able to have its say in how couples contributions are welcome. We should not forget that, plan their families. It also remains a fact that ART is on the even if the relative contribution of ART to the number of policymakers’ agenda, especially in Europe, and that the births in Europe is low, it still represents the annual ART sector requires representation. The diversity of ART number of births of one European country with a total policy and legislation in Europe - as in Germany and the population of between 5 and 10 million inhabitants.’ UK, Italy and Belgium - already has clinical repercussions in Simon Brown the explosive pattern of cross-border reproductive care, Focus on Reproduction

Focus on Reproduction May 2010 31 FEATURE // FIRSTS IN THE HISTORY OF IVF // Original papers which changed the world of assisted reproduction

There’s no dispute about the first report of an IVF baby, nor of the first ICSI birth. But many of the world’s firsts in ART remain lost in the literature, their significance sometimes forgotten. With the commentary of Hans Evers - whose Human Reproduction report on ‘100 papers to read before you die’ caused so much interest - we catalogue for the record ESHRE’s own selection of world firsts in assisted reproduction, and the top ten reproductive biology papers from Hans Evers.

1. In the beginning 3. The first IVF pregnancies 4. The first live birth Well . . . more The Melbourne group Louise Brown, born shortly before precisely, where to of Carl Wood in 1973 midnight at Oldham and District General begin? The story of described two very early Hospital, UK. Weighing 5lb 12oz (2.61 kg) human IVF surely IVF pregnancies, both the baby was delivered by Caesarean began with Robert lost after less than one section. Since then, estimates are that more Edwards, who in the week. According to than 4 million IVF babies have been born summer of 1965 spent Alan Trounson, who worldwide. six weeks with would join the group in  Steptoe PC, Edwards RG. Birth after the Howard and 1977, these ‘chemical’ reimplantation of a human embryo. Lancet Georgeanna Jones in Baltimore where - pregnancies, signified by rising levels of 1978; 2: 366. according to Howard and despite a hCG, showed that IVF embryos could HE: Why were the Swedes never brave ‘negative’ report from Edwards - ‘it seems develop in vivo and probably initiate enough to give Edwards and Steptoe the scarcely doubtful that human fertilization implantation. It is also likely that around Nobel prize? IVF provided more insight into was indeed obtained at the Johns Hopkins now Edwards and Steptoe had started life itself and produced more Quality Adjusted Hospital by Bob and his associates’. transferring embryos, unreported at the Life Years than any other medical treatment.  Edwards RG, Donahue RP, Baramki TA, time and with no sign of implantation Jones HW. Preliminary attempts to fertilize ‘except for a few very early ’. human oocytes matured in vitro. Am J  De Kretzer D, Dennis P, Hudson B, et al. Obstet Gynecol 1966; 96: 192–200. Transfer of a human zygote. Lancet 1973; Hans Evers: Bob's superb monograph 302: 728-729. Conception in the Human Female showed HE: ART discoveries have followed the same me the way into reproductive medicine. I track; first a biochemical pregnancy, then a have devoured it. Several times. From cover clinical , next an ectopic, and finally to cover. The first time Bob remembered my someone in a case report can boast the first name my heart skipped a beat. live birth.

2. Ovulation induction 5. Gonadotrophins in IVF The first pregnancy following ovulation induction with hMG Although Louise Brown and Australia’s first IVF baby were born (Pergonal) was in Israel in 1961. Carl Gemzell’s group had following egg retrieval from a natural cycle, the USA’s first IVF reported the first gonadotrophin pregnancy in the previous year. birth was in a cycle stimulated with hMG; Trounson in Melboure  Lunenfeld B, Sulimovici S, Rabau E, Eshkol A. L’induction de had described the first cycles stimulated with clomiphene citrate. l’ovulation dans les amenorrhees hypophysaires. C R Soc Franc  Lopata A, Brown J, Leeton J, et al. In vitro fertilization of gynecol 1962; 32: 407-415. preovulatory oocytes and embryo transfer in infertile patients  Gemzell CA, Diczfalusy E, Tillinger G. Human pituitary follicle treated with clomiphene and HCG. Fertil Steril 1978; 30: 27–35. stimulating hormone (FSH). Ciba Found Colloq Endocrinol 1960;  Trounson AO, Leeton JF, Wood C, et al. Pregnancies in humans 13: 191. by fertilization in vitro and embryo transfer in the controlled HE: There was no PubMed in the 1960s, no impact factors, so ovulatory cycle. Science 1981; 212:6 81–682. investigators published in obscure journals - which is why some  Jones HW, Jones GS, Andrews MC, et al. The program for in questions of who was first may never be answered. vitro fertilization at Norfolk. Fertil Steril 1982; 38: 14–21.

32 Focus on Reproduction May 2010 6. Ultrasound-guided aspiration 7. Oocyte donation 9. GnRH agonists in IVF Oocyte collection guided by ultrasound - The first report of a After the pulsatile administration of GnRH and not from laparoscopic puncture - was pregnancy resulting was established as a safe and effective way first described in 1981 by Suzan Lenz and from the transfer of a to treat hypogonadotropic hypogonadal colleagues in Copenhagen. An ultrasound fertilised donor oocyte anovulation, reports of its use for the scanner with a puncture transducer guided came from the Monash prevention of a premature LH surge during a steel needle through a full bladder for group in 1983, whose ovarian stimulation appeared in the early follicle puncture. The authors later report to the BMJ raised 1980s. Pituitary down-regulation resulted described the technique as ‘atraumatic and the issue of what to do in reduced cancellation rates, improved inexpensive’ and therefore valuable for with the excess eggs and IVF outcome and more convenient timing harvesting oocytes for IVF. embryos generated in a stimulated IVF of oocyte retrieval. The use of GnRH  Lenz S, Lauritsen JG, Kjellow M. cycle: ‘If more oocytes are recovered than agonists in combination with Collection of human oocytes for in vitro are needed they may be left unfertilised, gonadotrophins in IVF was highlighted by fertilisation by ultrasonically guided preserved, or donated to a recipient couple the group of Howard Jacobs in London. follicular puncture. Lancet 1981; 318: from whom oocytes cannot be obtained.’  Fleming R, Adam AH, Barlow DH, et al. 1163.  Trounson A, Leeton J, Besanko M, et al. A new systematic treatment for infertile  Gleicher N, Friberg J, Fullan N, et al. Pregnancy established in an infertile patient women with abnormal hormone profiles. Egg retrieval for by after transfer of a donated embryo Br J Obstet Gynaecol 1982; 89: 80–83. sonographically controlled vaginal fertilised in vitro. Br Med J 1983; 286:  Porter RN, Smith W, Craft IL, et al. culdocentesis. Lancet 1983; 322: 508-509. 835-838. Induction of ovulation for in vitro HE: Real progress in IVF came of course from HE: The uterus is not a demanding organ. fertilisation using buserelin and vaginal ultrasound monitoring of vaginal Provide it with estrogens and progesterone gonadotropins. Lancet 1984; 324: 1284- oocyte retrieval. And that was introduced by and it will let a young donor embryo implant, 1285. Matts Wikland's group in Gothenburg. From even at the age of 65. Alan Trounson is an HE: Testing urine samples every four hours, now on, IVF would be a less invasive icon. From sheep (in 1974) he went to cows detecting LH-surges at 4 am, performing procedure. (1976), horses (1976), rabbits (1977), mice laparoscopies in the small hours of darkness,  Wikland M, Nilsson L, Hamberger L. (1980) and humans (1980). From follicles to seven days a week, with ovulations on the The use of ultrasound in a human in vitro eggs to sperm to embryos to stem cells. And run; everything changed when GnRH agonists fertilization program. Ultrasound Med Biol finally to law, ethics, religion and clinical without histaminergic side effects became 1983; 2: 609-613. translation in the 21st century. available. IVF got safer and more convenient.

8. Cryopreservation of embryos 10. Vitrification and the cryopreservation of oocytes Gerard Zeilmaker (1936- The first successful attempt at 2002), pictured with freezing and thawing a human oocyte Robert Edwards in 1986, was reported by Christopher Chen recorded in his laboratory from Adelaide in 1986. A twin book in Rotterdam that a pregnancy was achieved after human embryo was frozen fertilisation and transfer. Chen in July 1979 and thawed in reported that 80% of 40 oocytes October; one blastomere frozen (to -196oC) showed survived. Of embryos morphological survival after thawing. frozen from three patients Thirty were inseminated; 83% in February 1983, one transferred in May resulted in the birth of retained their capacity to be fertilised, monozygotic twins. Zeilmaker recorded that this birth in the and 60% proceeded to cleavage Netherlands ‘took place considerably before such a baby was born division. in Australia’.  Chen C. Pregnancy after human oocyte cryopreservation.  Trounson A, Mohr L. Human pregnancy following Lancet 1986; 327: 884-886. cryopreservation, thawing and transfer of an eight-cell embryo. Experiments with embryo vitrification in animal models (mice, Nature 1983; 305: 707-709. sheep) date back to the mid-1980s. In 1990 Stephan Gordts and  Zeilmaker GH, Alberda AT, van Gent I, et al. Two pregnancies colleagues in Leuven, Belgium, described the ‘ultrarapid feezing’ following transfer of intact frozen-thawed embryos. Fertil Steril and thawing of 237 fertilised human oocytes, of which 34 were 1984; 42: 293-296. transferred to 20 patients, four of whom became pregnant. The HE: High quality embryo freezing is now a pivotal requirement for the first live birth following vitrification of a human oocyte was clinical feasibility of elective single embryo transfer (eSET), a reported by Gianaroli and colleagues from Bologna working with technique introduced by the Fins that has physiologised assisted Trounson in 1999. reproduction. Through eSET and cryopreservation, IVF finally became  Gordts S, Roziers P, Campo R, Noto V. Survival and pregnancy a safe and effective way of helping infertile couples. outcome after ultrarapid freezing of human embryos. Fertil Steril  Vilska S, Tiitinen A, Hydén-Granskog C, Hovatta O. Elective 1990; 53: 469-472. transfer of one embryo results in an acceptable pregnancy rate and  Kuleshova L, Gianaroli L, Magli C, et al. Birth following eliminates the risk of multiple birth. Hum Reprod 1999; 14: 2392- vitrification of a small number of human oocytes: case report. 2395. Hum Reprod 1999; 14: 3077-3079.

Focus on Reproduction May 2010 33 11. GIFT 14. Ultrasound-guided embryo transfer The first pregnancy following gamete intrafallopian transfer The use of ultrasound to guide (GIFT) was reported from California in 1984, with a live birth embryo transfer was first announced from the same group the following year. Two years described by Strickler et al in earlier Ian Craft in London had reported a pregnancy from the 1985. Ultrasonographic transfer transfer of gametes to the uterus. was found to be easier and  Craft I, McLeod F, Green S, et al. Human pregnancy following associated with less catheter oocyte and sperm transfer to the uterus. Lancet 1982; 319: 1031- distortion than the ‘blind’ 1033. transfers which were used until  Asch RH, Ellsworth LR, Balmaceda JP, Wong PC. Pregnancy then. after translaparoscopic gamete intrafallopian transfer. Lancet  Strickler RC, Christianson C, Crane JP, et al. Ultrasound 1984; 324: 1034-1035. guidance for human embryo transfer. Fertil Steril 1985; 43: 54–61  Asch RH, Ellsworth LR, Balmaceda JP, Wong PC. Birth HE: How world-shattering was US-guided ET? Everyone did it, it following gamete intrafallopian transfer. Lancet 1985; 326: 163. seemed to work, but did it really offer something extra? Not in the HE: : It must have been the alluring acronym that made GIFT so hands of an experienced operator apparently. successful in some parts of the world (especially Australia). How else  Kosmas IP, Janssens R, De Munch L, et al. Ulrasound-guided could you explain the appeal of a technique which still required embryo transfer does not offer any benefit in clinical outcome: a laparoscopy and general anaesthesia? randomized controlled trial. Hum Reprod 2008; 23: 457-458.

12. ZIFT 15. PZD and zona drilling 16. ICSI Zygote intrafallopian The first description of ICSI was transfer, another tubal partial zona dissection developed - transfer technique, was (PZD) of human somewhat first reported by Paul oocytes to encourage accidentally - at Devroey in Brussels in sperm penetration in the VUB in 1986 and was said to IVF (especially in male Brussels and it combine the advantages infertility) was first rapidly took of IVF (proof of reported from Atlanta over from SUZI as the microinjection fertilisation, exclusion by the group of technique of choice for conception in male of polyploid embryos) with the advantages Jacques Cohen; a report on zona drilling infertility. By 2006, just 14 years after of GIFT (higher pregnancy rates). followed in the same year. In time, as a Brussels reported the first births, around  Devroey P, Braeckmans P, Smitz J, et al. Cochrane review would show, ICSI was two-thirds of all ART fertilisations in Pregnancy after translaparoscopic zygote found to be a much more efficient Europe were with ICSI. intra-Fallopian transfer in a patient with technique in male infertility tha PZD, zona  Palermo G, Joris H, Devroey P, Van sperm antibodies. Lancet 1986; 327: 1329 drilling and SUZI. Steirteghem AC. Pregnancies after HE: GIFT made way for all manner of  Cohen J. Malter H. Fehilly C, et al. intracytoplasmic injection of single combinations and permutations: ZIFT, PROST, Implantation of embryos after partial spermatozoon into an oocyte. Lancet 1992; TET, transferring gametes, zygotes or opening of oocyte zona pellucida to 340: 17-18. embryos via the vagina, the bladder, the facilitate sperm penetration. Lancet 1988; HE: A revolution! How did they have the guts tube. Not all were unequivocally successful, 332: 162. to do it? What about the chromosomes and but this should not divert attention from the  Gordon JW, Grunfeld J, Garrisi GJ, et the spindles? What we do know is that 1-2% fundamental contributions of the Brussels al. Fertilization of human oocytes by sperm of all children born nowadays are the result team of André Van Steirteghem and Paul from infertile males after zona pellucida of ICSI and they seem to do well. Would we Devroey to the development of our specialty. drilling. Fertil Steril 1988; 50: 68-73. still have sperm banks if not for ICSI?

13. Microinjection and male infertility 17. PGD The first report of a pregnancy following the injection of a single The technique of sexing embryos from the DNA of a biopsied cell sperm cell beneath the zona pellucida of an oocyte came from the by amplification of a repeat sequence specific for the Y Monash group in 1987, who said ‘the technique has profound chromosome was first reported by Alan Handyside and colleagues implications for the possible treatment of severe male infertility’. in London, who described the technique as ‘may be valuable for The first live birth following subzonal insemination (SUZI) came couples at risk of transmitting X-linked disease’. The same group from Singapore the following year. Male infertility was at the time reported the first pregnancies using this same technique in couples defined as the largest diagnosed cause of infertility, accounting for at risk of transmitting recessive x-linked diseases. around 30% of cases (according to Hull et al, 1986).  Handyside AH, Pattinson JK, Penketh RJ, et al. Biopsy of  Laws-King A, Trounson A, Sathananthan H, Kola I. human preimplantation embryos and sexing by DNA Fertilization of human oocytes by microinjection of a single amplification. Lancet 1988; 1: 347-349. spermatozoon under the zona pellucida. Fertil Steril 1987; 48: HE: PGD was a formidable step ahead, both for our understanding of 637-642. early embryo development and for clinical infertility care. Its  Ng SC, Bongso A, Ratnam SS, et al. Pregnancy after transfer of commercialised little nephew, PGS, was nipped in the bud by several sperm under zona. Lancet 1988; 332: 790. robust clinical trials.

34 Focus on Reproduction May 2010 18. In vitro maturation 19. Surgical sperm retrieval 20. Fertility preservation Cha and colleagues in Seoul were the first The first report of live biths following a The restoration of fertility after the to describe a pregnancy from an oocyte technique of sperm aspiration came from transplantation of frozen–thawed ovarian matured in vitro. The paper reported that the Irvine group of Ricardo Asch working tissue was reported for the first time in the 270 immature oocytes had been incubated with Sherman Silber in 1988. The same sheep in 1994, but not until 2000 was with either mature follicular fluid or fetal group later confirmed the genetic link ovarian autotransplantation (orthotopic cord serum, the former showing a higher between CAVD and cystic fibrosis, while and heterotopic) described on an maturation rate than the latter. Five Silber, working with the VUB in Brussels, experimental basis in the human. embryos transferred to a woman with POF reported the first pregnancies with sperm According to recent reports, there have so resulted in birth of ‘healthy’ triplet girls. obtained from testicular biopsies in men far been nine deliveries from pregnancies  Cha KY, Koo JJ, Ko JJ, et al. Pregnancy with CAVD or obstructive azoospermia. derived from frozen-thawed ovarian tissue. after in vitro fertilization of human  Patrizio P, Silber S, Ord T, et al. Two  Oktay K, Karlikaya G. Ovarian follicular oocytes collected from births after microsurgical sperm aspiration function after transplantation of frozen, nonstimulated cycles, their culture in vitro in congenital absence of vas deferens. banked autologous ovarian tissue. N Engl J and their transfer in a donor oocyte Lancet 1988; 332: 1362. Med 2000; 342: 1919. program. Fertil Steril 1991; 55: 109-113.  Silber SJ, Van Steirteghem AC, Liu J, et HE: Fertility preservation by freezing ovaries HE: Soon after the first few publications on al. High fertilization and pregnancy rate or eggs is ART’s answer to ever more IVM in (ovine and bovine) animal models, after intracytoplasmic sperm injection with successful cancer treatments. Its 'social' the first successful human attempt was spermatozoa obtained from testicle biopsy. application - in older women who have not announced. Several more followed. The Hum Reprod 1995; 10: 148-152. yet found their Mr Right - is still elusive. A obstetric and perinatal outcomes were good, HE: No guts, no glory - or chance favours the 1-5% chance of a retrieved egg becoming a the mean birthweight was normal, and the prepared mind? Immature spermatozoa used pregnancy would require between five and children's development has so far been in human fertility treatment. Every cloud has 25 pick-up procedures in a 35-40 year old inconspicuous. a Silber lining. to take care of her 'fertility insurance'.

The top ten citation classics in ‘reproductive biology’ (so far) Journal impact factors will soon be a thing of the past. Citation scores of individual scientific papers will replace them. Page ranking, named after Larry Page, has been developed by for its Internet search engine that assigns a numerical weighting to each element of a hyperlinked set of documents found on the Internet with the purpose of establishing its relative importance within the set. By the same token, scientific publications may be ranked by their citation alone and by gathering weight from citation by authors who are frequently cited themselves. This may refine the present fledgling system of publication metrics and allow for the placement of scientific publications in (peer-reviewed?) web-based repositories. In order to see what these new developments might mean to publishing in our specialty, I checked the citation scores of the 100 most cited papers in the reproductive biology journals. - HE  Evers JL. 100 papers to read before you die. Hum Reprod 2010; 25: 2-5. Rank (citations) Author, paper 1 (841) Van Steirteghem AC, Nagy Z, Joris H, et al. High fertilization and implantation rates after intracytoplasmic sperm injection. Hum Reprod 1993; 8: 1061-1066. 2 (451) Kimura Y, Yanagimachi R. Intracytoplasmic sperm injection in the mouse. Biol Reprod 1995; 52: 7097-20. 3 (429) Wells DN, Misica PM, Tervit HR. Production of cloned calves following nuclear transfer with cultured adult mural granulosa cells. Biol Reprod 1999; 60: 996-1005. 4 (428) Van Steirteghem AC, Liu J, Joris H, et al. Higher success rate by intracytoplasmic sperm injection than by subzonal insemination. Report of a second series of 300 consecutive treatment cycles. Hum Reprod 1993; 8: 1055-1060. 5 (409) Munné S, Alikani M, Tomkin G, et al. Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities. Fertil Steril 1995; 64: 382-391. 6 (390) Eppig JJ, O'Brien MJ. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod 1996; 54: 197-207. 7 (377) Pursley JR, Mee MO, Wiltbank MC. Synchronization of ovulation in dairy cows using PGF2alpha and GnRH. Theriogenology 1995; 44: 915-923. 8 (375) Faddy MJ, Gosden RG, Gougeon A, et al. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 1992; 7: 1342-1346. 9 (373) Gosden RG, Baird DT, Wade JC, Webb R. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at -196 degrees C. Hum Reprod 1994; 9: 597-603. 10 (321) Gardner DK, Lane M, Spitzer A, Batt PA. Enhanced rates of cleavage and development for sheep zygotes cultured to the blastocyst stage in vitro in the absence of serum and somatic cells: amino acids, vitamins, and culturing embryos in groups stimulate development. Biol Reprod 1994; 50: 390-400.

Focus on Reproduction May 2010 35 PROFILE // ESHRE’S CHAIRMAN ELECT //

Hola Anna

ESHRE’s Chairman Elect, Anna Veiga, talks to Focus on Reproduction about her career and her ambitions for the Society

nna Veiga, Chairman Elect of ESHRE, seems at something I could do, so I made contact with him and first glance to be that feisty, energetic kind of asked if he might have a place for me. He didn’t, but said, woman who is still driven by the fun and come along and we’ll see.’ A enthusiasm of her student days. No baggage, no ESHRE too, as well as IVF, has long figured in Anna’s cynicism, no hidden agendas. But scratch the surface of professional life. Not only was Barri a founder member of ESHRE’s next Chairman - who will take up her post at the ESHRE, but Anna’s PhD supervisor in Barcelona, the late 2011 annual meeting in Stockholm - and what you’ll find geneticist José Egozcue, would become a member of is a whole lot more than just Little Miss Sunshine. ‘I’m ESHRE’s first Executive Committee in 1985, and really excited about being Chairman,’ she says with her Chairman of the Society ten years later. ‘I always had a usual wide-eyed enthusiasm, but mindful too that ‘fun’ very close working relationship with José,’ says Anna. ‘We might not be the only challenge ahead. collaborated after our first IVF pregnancies at Dexeus, For there’s an old head on Anna Veiga’s youthful when he was already becoming a prominent figure in shoulders. Her experience in reproductive science goes ESHRE - and I must admit that even then he raised the back to the earliest days of IVF, when, as a postgraduate possibility of me getting more involved with the Society, from the Universitat Autònoma de Barcelona, she made though I never really thought of the chairmanship. But contact in 1979 with Pedro Barri about a job at the when I returned to Barcelona after being selected as Dexeus Institute. ‘I’d read an article about Pedro, and he Chairman Elect, the first person I called was José’s widow, was being asked about IVF,’ Anna recalls. ‘Here I was, a to tell her how happy he would have been. biologist interested in genetics, so I thought, that’s ‘So I was very lucky to be involved in the early days of

36 Focus on Reproduction May 2010 IVF and to have this connection with ESHRE. Then, of course, it was a much more concentrated Figures of influence society than today. But even then I saw ESHRE as  Pedro Barri, head of the something trying to bring us all together.’ Department of Obstetrics, Luck, Anna freely admits, has played a large part Gynecology and Reproduction of in her life, but a strong vein of determination has Institut Universitari Dexeus, was also run through her career, right from her first a founding father of ESHRE and days at Dexeus. Then, she recalls, there were no member of the original temporary precedents in a medical environment which was committee under Robert quite new to her. ‘There was so much to learn,’ she Edwards. He was a member of says. ‘I just had to keep training and studying. I had the Executive Committee from a couple of weeks in Vienna and Montpellier, a 1989 to 1993 and made week in Jacques Testart’s lab in Paris to learn chairman of the first SIG sub-committee in 1990. cryopreservation, but mainly we just had to learn as  The record of the late José Egozcue with ESHRE went we went along. There was so much we didn’t know. back to the founding of the Society; he also represented So we went forward by trial and error - with Spain on the temporary committee and became a member surplus oocytes and mice but also keeping in touch of the first Executive Committee in 1985. He was joint with the pioneers to make sure we were on the chairman of the international right track.’ scientific committee for the That training and learning culminated in Spain’s fourth annual meeting in first IVF pregnancy in late 1983, and first delivery Barcelona in 1988, a member of in July 1984. ‘It was a great achievement for us,’ the editorial board of Human says Anna, ‘because what we put in place was the Reproduction, a founder of the beginning of IVF in Spain. IVF simply didn’t exist SIG Reproductive Genetics in before we began. But we built the lab and after the 1994, and Chairman of ESHRE first pregnancies began teaching all the other young in 1995. He was made an groups in Spain. Most of them came to us to be honorary member of ESHRE in trained. There was nobody else. And it struck me 2003. then that they all recognised the value of what we were doing in the lab - IVF wasn’t just something for the medical doctors. Of course, this was the original the philosophy of ESHRE - that clinical professional life, when the CMRB made contact medicine and science have to go together in IVF if with Dexeus about the derivation of stem cells from you want good results in terms of pregnancy and human embryos. ‘It’s a natural evolution,’ she says, publications. Today, I would say that this is still the ‘and I’m certainly not the first to move into stem case in most groups, but not in all. More and more cells from IVF. We have the confidence and I see an imbalance between science and medicine. knowledge to work with embryos, and that’s a But this wasn’t our experience in Barcelona.’ valuable asset in a stem cell laboratory.’ There were also challenges to face in her personal Now, of course, ESHRE is set to lay even more life. ‘At certain times there have been difficulties,’ claims on Anna’s time and energy. The she admits. ‘But I was lucky because my mother chairmanship, said former Chairman Arne Sunde, and father were very supportive and I could leave ‘takes six years out of your life’, but Anna is not my son with them when I had to be away. I wasn't anticipating any such life-changing upheavals. happy about it, that I wasn’t home, but I couldn’t ‘Being Chairman will have an impact,’ she admits, be home all the time. It was the support from my ‘but no more than my other commitments have had. family that enabled me to be so active in my I’ve always travelled a lot, so this is the life I’ve led. professional career.’ My career, what I do, has always been the driving Today, more than 30 years later, Anna Veiga still force in my life, and my work is very important. But holds a position at the Dexeus University Institute - I’m lucky to be able to work in something that I with responsibility now for the centre’s research really like. So I don’t think being Chairman of output - and still leads a life which is largely driven ESHRE will make a lot of difference to my personal by her career. But her working life is now shared life, because this is the life I’ve always led.’ between Dexeus and her new role as director of the Anna’s more back-seat role at Dexeus means that stem cell bank of the Centre for Regenerative ESHRE can now take a more prominent place in Medicine in Barcelona (CMRB). And luck too, that working life, which is what her colleagues smiles Anna, was behind this latest addition to her welcome and recognise as an honour for them and

Focus on Reproduction May 2010 37 ANNA VEIGA: challenges but how we face them doesn’t just ‘ESHRE IS IN A depend on me. We are in a continuous process, and CONTINUOUS I’ll be guided by the past and present chairmen. ‘ESHRE’s relationship with the EU is something PROCESS AND we’ve been working on very hard, and I think this I’LL BE GUIDED will continue. We have already been involved in BY THE PAST implementation of some of the Directives and with AND PRESENT people working on them in Brussels. I believe this CHAIRMEN.’ will continue and consolidate. ‘It’s fair to say that growth has always been one of our goals, but I’m not sure if we really want an annual meeting of 10,000 people. What I am sure of is that you learn more at smaller special interest meetings. Our big congresses have become more of an event, where you meet everybody, have your business meetings, enjoy the social occasions - but it’s very difficult to learn something new. That’s why the precongress courses have become so popular.’ Anna Veiga will be ESHRE’s second female chairman. The first, Lynn Fraser, began her term in 1999 with a commitment to increase the representation of women in ESHRE’s various committees, but that - as a glance at ESHRE’s activists suggests - seems no longer necessary today, nor of concern to Anna. ‘I think women should be where they are because they deserve it,’ she says. ‘If they belong in the SIGs or are active in committees or are good scientists, then that’s what they’ve deserved. I don’t like the idea that there should be a fixed number of women on a committee. Now in our profession there are probably more women for Spain. Now, as ESHRE’s 27th annual meeting in than men, and it’s inevitable that they will be Rome approaches, she has one more year before represented according to their merits. But I don’t becoming Chairman in Stockholm. ‘There are many like the idea of positive discrimination. I don’t think things to be done,’ she concedes, ‘and many it does women any favours. directions to take. But the organisation of the ‘Of course, it can be very difficult for a woman Society - with a Chairman Elect, a Chairman and with young children. At least in Spain. Maybe it’s Past Chairman - provides a continuous momentum different in other countries, but probably not so which in a way sets the direction. So ESHRE has its much. Women still have more responsibility in the home than men. So combining their working life with their domestic life can be very challenging. I Flying the flag for Spain certainly found it so bringing up my own son.’ Now, however, Anna has both the time and the Anna lists two of her achievements as helping set up the Spanish opportunity for ESHRE, and she’s under no association of clinical embryologist (ASEBIR) in 1990, whose illusions about what that involves. ‘ESHRE is not membership today has grown to around 800, and the MSc course in an exceptionally big society, but when you go to the embryology now provided at Dexeus. Says Anna: ‘I have a very good meetings you’re aware that it is becoming relationship with the embryologists in Spain, and with the Spanish something really important. I think there’s no doubt Fertility Society. So I’m sure they’ll be very happy that I’ll be that today ESHRE is the leading society in Chairman of ESHRE. Spain has made important progress in ART - reproduction in the world. That’s for sure. We now in the number of centres and in the quality of treatment. We are have an ESHRE Campus every ten days - that’s certainly at the level of most European countries - and in many how important ESHRE is for training. And it’s cases even better. I'd say that Spain is becoming a country which is these events and the activities of the SIGs and Task recognised for its standards and where things are done properly. So Forces that are the real heart of ESHRE - and why I’m proud to represent Spain in ESHRE’s Executive Committee.’ I’m so excited at the prospect of being the next chairman.’

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The European Society of Human Reproduction and Embryology Meerstraat 60 Grimbergen, Belgium [email protected] www.eshre.eu