NEWSLETTER

INTERNATIONAL FEDERATIONOF FERTILITY SOCIETIES

SPRING 2013

INSIDE THIS ISSUE :3 ‘Ovarian Reserve’ a term bound for confusion4 Online Educational Resource5 Education6 Historic Decision of the Inter- American Court of Human Rights7 IVF Pioneer Robert Edwards7 Women’s Health - Geneva 2014

The Spring IFFS Newsletter continues to highlight the myriad of activities within IFFS. Included in this issue are several interesting articles:

- Dominique de Ziegler and colleagues provide a succinct summary of age-related decline in oocyte quality and quantity and their well known correlation with infer-tility. Professor de Ziegler makes a strong case for a new term – ovarian response testing – to designate those medi-cal evaluations routinely used.

- Educational Director Paul Devroey (Belgian Soci-ety for Reproductive Medicine) recounts the continuing IFFS series of successful workshops. As discussed in more detail by Prof Devroey, recent workshops were held in the Philippines (October 1-3 2012), Peru (January 15-18 2013), and Romania (February 21-23 2013). All were well received and employed the standard format of three IFFS speakers working within a framework coordinated with na-tional member societies. The gracious support of Ferring Pharmaceuticals provides stability for continuation and expansion of this signature program.

- Professor Bruce Dumphy (Fertility Society of Australia) describes the exciting new online education-al resource with which IFFS is intercalated. Sponsored by Ferring through an award to Elsevier, this resource (http://www.iffs-uit.com) provides scientific articles of great relevance. Information provided at IFFS workshops may be placed online, leveraging the educational values of those programs.

- Fernando Zegers (Chilean Fertility Society) re-ports good news from the American Court on Human Rights. Laws precluding ART in Costa Rico were abrogated by the court. Not only that, but the government of Costa Rico was instructed that providing ART to its citizens was a component of their human rights. Although IFFS has no member society in Costa Rica, our organization has fol-lowed this case carefully given its potential ramifications, supporting the many individuals like Professor Zegers from our member societies who were involved.

IFFS officers are deeply involved in the scientific and social program for IFFS 2013, to be held October 11-17 and hosted by our member society American Society for Reproductive Medicine (ASRM). Its location in Boston, the hub of American history, is exciting. The city has a new and expansive convention center, located on the wa-

Message from the President

Joe Leigh SimpsonPresident of IFFS

terfront. Many new hotels and nearby restaurants assure comfortable surroundings and convenient dining options.

Of special note is the opening night (Sunday October 13) ceremony and reception, to be held in the conven-tion site among our exhibitors. On Wednesday October 16 a gala reception will be held in the Museum of Science. Food and drinks are provided on site, and the entire pan-oply is available for us to peruse--a giant Van den Graff generator, planetarium, I-Max movies, and innumerable brain-teasing exhibits for adults, children, and the child-within us. Space is limited, so remember to sign up when registering.

Cov

er: ©

Yur

i Arc

urs/

Shut

ters

tock

.com

2

OFFICERSJoe Leigh SimpsonRichard KennedyGabriel de CandolleEdgar MocanuMauricio AbraoBasil TarlatzisPaul Devroey

BOARD OF DIRECTORS MEMBER SOCIETIES

SCIENTIFIC COMMITTEE

SCIENTIFIC COMMITTEE MEMBER SOCIETIES

American Society for Reproductive MedicineArgentine Society of Reproductive MedicineColombian Association of Fertility and Reproductive MedicineFertility Society of AustraliaGerman Society of Reproductive MedicineIndian Society of Assisted ReproductionJapan Society of Reproductive MedicineJordanian Society for Fertility and GeneticsSwedish Society of Obstetrics and Gynecology

Basil TarlatzisJoe Leigh SimpsonLiselotte MettlerLinda GiudiceSerdar BulunDhiraj GadaNarendra MalhotraRichard KennedyPaul Devroey

Brazilian Society of Human Reproduction Artur DzikBritish Fertility Society Sue AveryFinnish Gynecological Association Antti PerheentupaJapan Society of Reproductive Medicine Osamu IshiharaFertility Society of Australia Cynthia FarquharKorean Society for Reproductive Medicine Seok Hyun Kim

Member Societies and readers are invited to send all comments, reports or articles of 800 - 1200 words no later than 1st February for the Spring Issue and 1st July for the Autumn Issue. The views expressed in articles in the IFFS Newsletter are those of the authors and do not necessarily reflect the official viewpoint of IFFS.

Edior in Chief : Gabriel de CandolleEditorial Board : Basil Tarlatzis; Paul Devroey; Moïse Fiadjoe

Please send your contribution to : Gabriel de Candolle6, rue de Candolle - 1206 Geneve - SwitzerlandPhone: +41 22 781 53 80 - Fax: +41 22 781 54 67E-mail : gabrieldecandolle@vtx.ch

G. David AdamsonMarcos HortonJose Ignacio Madero

Ossie PetruccoTina BuchholzDhiraj GadaMinoru IraharaMazen El-ZibdehPietro Gambadauro

GreeceUSAGermanyUSAUSAIndiaIndiaUKBelgium

2007 ˜162010 ˜192004 ˜13

2004 ˜132004 ˜132010 ˜192007 ˜162010 ˜192007 ˜16

ChairPresident2010 Chair Local SC2013 Congress Chair2013 Chair Local SC2016 Congress Chair2016 Chair Local SCSecretary General, ex officioDirector of Medical Education, ex officio

USAUKSwitzerlandIrelandBrazilGreeceBelgium

PresidentSecretary GeneralAssistant Secretary GeneralTreasurerAssistant TreasurerPast PresidentDirector of Medical Education

3

– has become a science in its own right. COS responses decline with age, with an increasing risk of so-called poor responses (COS yielding <3 oocytes) 4 in older women. A parallel was thus rapidly drawn between the age-related decline in oocyte quality and the meager COS responses often seen in these women5. Logically, the quality of COS response – an expression of oocyte quantity – was seen as predicting ART outcome and in a broader sense, the fe-cundity of women6. This ultimately gave credence to the concept – erroneous, as we will see – that oocyte quality (pregnancy chances in ART) and quantity (COS respons-es) are inherently linked7.

The ovarian endometriosis and fertile oocyte donor models

The COS response in ART does not predict oocyte quality and ART outcome in two models in whom the oo-cyte decrease is age-independent :

1. In ovarian endometriosis, the ovarian response to COS is dramatically reduced8, but ART outcome is equivalent to that of age-matched controls.

2. Certain fertile women – oocyte donors in France – have COS yields that are markedly below average without reduction in oocyte quality 9.

Ovarian reserve, a term bound for confusion Ovarian reserve parameters – basal FSH and AMH lev-

els and the antral follicle count (AFC) – predict the magni-tude of COS responses.

For simplicity sake, we use a three-color coding system for interpreting ovarian reserve data (Fig. 2). Any appar-ent link between COS response – by extension, ovarian re-serve testing – and ART outcome results from a confound-ing effect of age, not form a true independent association.

Ovarian reserve tests predict the magni-tude of ovarian responses in ART, not the fecundity of women. The confu-

sion stems from the fact that aging is a confounding fac-tor. This enduring confusion justifies replacing the term of ovarian reserve – too misleading – for that of ovarian re-sponse testing.

Age-related decline in oocyte quality

The results of ART decline in women 37 years of age and older (Fig. 1A)1. Conversely, the outcome of donor-egg ART (DE-ART) remains remarkably constant until the age of 45-50 years (Fig. 1A) and beyond1. This strikingly indi-cates that the poorer pregnancy rates seen in older women in regular ART result from an age-related decline in oocyte quality. The DE-ART data therefore distinctly and forceful-ly refute the belief that the sharp increase in miscarriage rates seen in older women stems from uterine aging.

Age-related decline in oocyte quantity

In an extensive work that took years to complete, Gou-geon et al. quantified by histological analyses the age-re-lated decline in primordial follicles (oocytes) present in the ovary2. These investigators reported that the oocyte decline is bimodal in nature2. First there is a ‘slow depletion’ phase followed by the ‘rapid depletion’ phase, starting in the late reproductive years (Fig. 1B)2. The accelerated oocyte loss, or rapid depletion, commonly starting at 37 years of age (Fig. 1B) is initiated by the number of primordial follicles remaining (<25,000 total), not by age itself3.

COS response and fecundity

From incept, ART has relied on ovarian stimulation for improving outcome through multiple ovulations and multiple-oocyte harvests. Over the years, ovarian stimula-tion for ART – known as controlled ovarian stimulation (COS)

‘Ovarian Reserve’a term bound for confusion

4

Conclusion

Ovarian reserve testing – any parameter used – pre-dicts the magnitude of ovarian responses in ART, not fecundity. Yet, an enduring confusion erroneously inter-twines the issues of oocyte quality and quantity in ART be-cause aging is a cofounding factor causing a concurrent decline of both oocyte quantity and quality. The term ovar-ian reserve, as catchy as it may be, is part of the confusion. It should be replaced for the more descriptive and less deceiving one of ovarian response testing.

Dominique de Ziegler, MD1, 3

Anna Raggi, MD1

Nicolas Vulliemoz, MD2

Pietro Santulli, MD1

Vanessa Gayet, MD1

Charles Chapron, MD1

1 Université Paris Descartes, Paris Sorbonne Cité – Assistance Publique Hôpitaux de Paris, CHU Cochin, Deptof Ob Gyn and Reproductive Medi-cine, Paris, France. 2 Unité de médecine de la reproduction (UMR) – Centre Hospitalier Uni-versitaire Vaudois (CHUV), Lausanne Suisse.3 Address for correspondence:Dominique de Ziegler, MDProfessor and Head Reproductive Endocrinology and InfertilityService de Gynécologie Obstétrique IIGroupe d’hôpitaux ParisCentre Cochin Broca Hôtel DieuHôpital Cochin53, Avenue de l’Observatoire75014 Paris, FranceE-mail: ddeziegler@orange.fr

References

1. Sunderam S, Kissin DM, Flowers L, et al. Assisted reproductive technology surveillance--United States, 2009. MMWR Surveill Summ 2012;61:1-23.2. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 1992;7:1342-6.3. Charleston JS, Hansen KR, Thyer AC, et al. Estimating human ovarian non-growing follicle number: the application of modern stereology techniques to an old problem. Hum Reprod 2007;22:2103-10.4. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of ‘poor response’ to ova-rian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011;26:1616-24.5. Howles CM, Saunders H, Alam V, Engrand P. Predictive factors and a corresponding treatment algorithm for controlled ovarian stimulation in patients treated with recombinant human follicle stimulating hormone (follitropin alfa) during assisted reproduction technology (ART) procedures. An analysis of 1378 patients. Current medical research and opinion 2006;22:907-18.6. van den Boogaard NM, Hompes PG, Barnhart K, et al. The prognostic profile of subfertile couples and treatment outcome after expectant management, intrauterine insemination and in vitro fertilisation: a study protocol for the meta-analysis of individual patient data. BJOG 2012;119:953-7.7. Holte J, Brodin T, Berglund L, Hadziosmanovic N, Olovsson M, Bergh T. Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries. Fertil Steril 2011;96:594-9.8. de Ziegler D, Borghese B, Chapron C. Endometriosis and inferti-lity: pathophysiology and management. Lancet 2010;376:730-8.9. de Ziegler D, de Mouzon J, Fauque P, et al. Multiplying recipients paired with oocyte donors optimizes the use of donated oocytes. Fertility and sterility 2011;95:1633-8.

Online Educational ResourceBruce Dunphy MDThe Elsevier IFFS-UIT Resource Cen-

tre was launched in May 2012 and is funded by the International Federa-

tion of Fertility Societies (IFFS) and Ferring Pharma-ceuticals. It contains a number of educational tools, such as the Netter image bank, from where you can

download Netter imag-es as PDF files or by uti-lizing the slide making tool easily create image slides for presentation. The resource centre is published by Elsevier under the umbrella of Reproductive Bio-medicine Online and hosts open-access and peer-reviewed educa-tional material on in-fertility treatment. Pro-fessor Bruce Dunphy has been appointed as

the Editor and the editorial board is expanding with experts from around the globe.

Content was initially published in English, and is now available in Japanese, Chinese, Spanish, Portuguese and Russian. The resource centre contains feature and origi-nal peer-reviewed research articles, presentations in au-dio, slides and video material from IFFS, UIT and other academic symposia, interviews with experts, high resolu-tion Netter images, news and a list of conferences. Netter images can be downloaded for personal use such as for patient education, conference posters and presentations provided the source of the image is acknowledged. We anticipate developing a Resource Centre App in the near future.

The resource centre can be found at http://www.iffs-uit.com. We invite you to explore and make full use of this wonder-ful and growing educational resource. We also welcome any suggestions regarding additional content.

5

On October 1-3, 2012, the second Joint IFFS-PSREI meeting was held in Ma-nila, the Philippines.This event was

supported in part by an educational grant from Ferring Pharmaceuticals, inc. During this meeting several topics were presented including: Polycystic Ovarian Syndrome, Endometriosis, Controlled Ovarian Hyperstimulation, Controversies in Infertility, Concerns in ART and the Sci-ence of ART. A Ferring Luncheon Symposium was organ-ised on the Megaset study.

Under the guidance of the organising committee, an interactive meeting was planned. Dr. Joan Tan-Garcia was the General Chair. More than two hundred delegates at-tended.

The topic of research activities was addressed with a session on the “ART” of research. In this session, the main focus was improved performance in scientific activities. In considering publishing research, it is of paramount im-portance to decide what topic to focus on. With this in mind, the first presentation of the session was related to the design of a study. Several aspects can be analyzed such as: a mechanistic study to find the interaction between sev-eral points of research, a pilot study to confirm feasibility, and finally the role of a randomized controlled trial. If the study design is very well planned, it lends itself to be-ing published. It is also beneficial for a prospective ran-domized trial to be performed according to the existing standards. The methodology of performing a prospective randomized trial was presented at the meeting, especially as related to the study design. The most interesting study design is a two arm study with one primary endpoint. De-pending on the outcome, it is easy to calculate the num-ber of patients who have to be included in the two arms. It was discussed during the meeting that this study design is crucial. As an example of a correct study design, one could analyze the delivery rate of a day three versus day five embryo in women less than thirty-six years of age,

Education

undergoing the same stimulation protocol and replacing only one embryo. The only variable in this condition is a day three versus day five embryo. This study answers very clearly if the replacement of day three versus day five em-bryos initiates similar, significantly lower or higher ongo-ing pregnancy rates.

If the study design provides interesting data, there are different aspects which have to be taken into account: how to write an abstract, how to write a paper, how to pres-ent an abstract and how to give a lecture. For any young researcher, either a clinician or scientist, their perfor-mance in these previously described tasks is of vital im-portance.

One of the most neglected aspects related to the topic is, how to give a lecture. Most scientific organisations do not address the logistics of the presentation, most of the podia are badly organised, slide projections are not han-dled properly, the mobility of the speaker is restricted and the interaction with the audience is limited. Needless to say, the time limitation has to be respected. The golden rule is one slide per minute and seven lines per slide. Care has to be taken regarding color distribution. During this session all these topics were explained in depth.

The feedback from the members of the audience con-firmed the value of this session and suggested that this ex-periment be repeated. The presenters of this session were Dr. Nicholas Polyzos, MD, PhD and Dr. Dominic Stoop, MD, PhD and Prof. Dr. Paul Devroey, MD, PhD.

Early this year an IFFS-UIT Meeting was held in Cluj Napoca Romania the 21-23 of February 2013. The meet-ing was organised by the Romanian Society of Obstetrics and Gynaecology in collaboration with the Polish Gynae-cology Society. The meeting was extremely well attended by more than 200 participants. There were five sessions in total. The sessions dealt with several aspects of repro-ductive medicine, such as Evidence-based Medicine, From

IFFS Director of Medical Education

Paul Devroy MD, PhD

6

ESHRE 30th Annual MeetingJune 29 - July 2, 2014

Munich, Germanywww.eshre.eu

10th Women’s Health CongressJanuary 9 - 19, 2014Geneva, Switzerland

www.meeting-com.ch

IFFS / ASRM Conjoint MeetingOctober 12 - 17, 2013

Boston, Massachusetts, USAwww.iffs-reproduction.org

www.asrm.org

International Calendar

Costa Rica is the only country where a Su-preme Court has ruled against the use of ART for infertility treatment by arguing

that human embryos had rights of actual persons and IVF challenged that.

After almost 10 years of appeals the case reached the Inter American Court of Human Rights. As independent Expert to the court I can report on the December 20th verdict obliging Costa Rica to restore ART and make it available in the national health system on the grounds of non-discrimination against those who cannot pay.

The verdict goes further and explicitly establishes that: - reproductive rights are part of human rights and that

the rights to found a family and to privacy and autonomy to live one’s life must prevail.

Historic Decision of the Inter-American Court of Human Rights

- infertility is a disease (the WHO definition) that generates disability and forbidding IVF is discrimination against those with disability.

- the protection to which embryos are entitled is achieved by the protection of pregnant women from im-plantation, the time from which the pregnant woman, and not the embryo, has the right to life.

-the rights of women to be protected by international laws do not equally apply to embryos and women’s rights should not be jeopardized by actions to protect embryos.

This historic decision will open new avenues in the de-fense of women’s rights in the Americas.

Fernando Zegers-Hochschild MD

Consensus to Clinical Practice, Meet the Experts, From Efficacy to Safety, and PCOS. The question and answer sessions were very lively and debated on the different topics. Understanding evidence was discussed at length while, Embryo Quality and Implantation, Assessing Em-bryo Competence, the Role of AMH, and Ovarian Endo-metriosis evoked lively debate.

There was a sharp debate concerning ovarian stimu-lation protocols with mixed protocols or mono therapy. The hormonal aspects of the role of progesterone and the occurrence of OHSS were also presented. Full atten-tion was given to PCOS syndrome especially as related to the Rotterdam Criteria. The day before the meeting, a rehearsal for interested speakers was organized. It was fascinating to observe that the speakers expressed the benefits of this rehearsal. The rehearsal focused on how to do the study, how to write the slides and how to pres-ent the slides.

7

The IFFS (International Federation of Fertility Soci-eties) together with Women’s Health (The Swiss Societ-ies for Reproductive Medicine and for Menopause) are organizing a congress with technical support from rele-vant Departments within the World Health Organization, Headquarters, Geneva. “Life style, toxicants and environ-ment: Influence throughout Reproductive life” will take place January 9 and 10, 2014 in Geneva, Switzerland, at the Centre International de Conférence Genève, CICG.

International and national specialists in the field, in-

cluding clinicians, reproductive endocrinologists, embry-ologists and toxicologists will together address and debate these issues. Adverse effects of known or suspected factors on reproductive life, from conception to menopause, will be presented and discussed. An attempt will be made to reach consensus on current status and gaps in basic and clinical knowledge.

IVF pioneer, Robert Edwards, passed away on April 10, 2013. Commenting on behalf of the International Federation of Fertility Societies, IFFS President Professor Joe Leigh Simpson said:

“The International Federation of Fertility Societies mourns the death of Nobel Laureate Sir Robert G Ed-wards, who with Patrick Steptoe produced the world’s first IVF baby and contributed to reproductive biology in nu-merous other ways. His success in IVF was one of the 20th century’s great medical feats, pursued at long odds and despite great opprobrium. He laid the groundwork for in-fertile couples worldwide to have children, with 1-4 per cent of all babies in Europe, North America and Australia now born by assisted reproductive technologies started by Professor Edwards. He will be greatly missed”.

IFFS Board Member, Dr David Adamson (Palo Alto, CA, USA) said:

“Professor Sir Robert Edwards’ death marks the pass-ing of an era he created with Dr. Patrick Steptoe when their research and treatment resulted in the birth of Lou-ise Brown, the world’s first IVF baby in 1978.

Bob Edwards was a brilliant pioneer who devoted his life to challenging established scientific perceptions about reproductive biology. He was innovative, persistent and exciting in his work and discoveries, all of which was recognized with his being award-

ed the Nobel prize for physiology or medicine in 2010.

Professor Edwards created a new medical technology that has resulted in the birth of approximately 5 million babies from IVF, but also changed how we saw our world and human reproduction. He also inspired a new genera-tion of physicians and scientists to continue on with the work he started. He was revered and loved by those who knew him.

Bob, as he was widely known, was a colleague, friend, supporter and inspiration to many. His sense of humor and wonder was enjoyable and contagious. He made all around him better. His genius, compassion and commit-ment will be missed by many, many physicians, scientists, patients, and ordinary people whose lives he has touched and changed around the world”.

IVF Pioneer Robert Edwards Dead at Age 87

10th Women’s Health Congress 20149  -10 JANUARY/JANVIER

Life style, toxicants and environment : Infl uence throughout Reproductive life.

Online registrationInscriptions en ligne

www.meeting-com.ch

Congress SecretariatSecrétariat du congrès

Meeting.com S.àr.l.Case postale 100

CH-1033 Cheseaux-sur-LausanneT +41 21 312 92 61F +41 21 312 92 63

sabine.gisler@meeting-com.chwww.meeting-com.ch

Genève - CICGCentre International de Conférences Genève17 rue de Varembé - CH - 1211 Genève 20

Women’s HealthGeneva 2014

8

Photographs courtesy of the Greater Boston Convention & Visitors Bureau.

2013_Announcement.indd 1 7/20/10 12:20 PM

INTERNATIONAL FEDERATION OF FERTILITY SOCIETIES

IFFS SECRETARIAT OFFICE19 MANTUA ROAD, MT. ROYAL, NJ. 08061TEL.:+ 1 856 423 7222, FAX:+ 1 856 423 3420E-MAIL: SECRETARIAT@IFFS-REPRODUCTION.ORGWEBSITE : WWW.IFFS-REPRODUCTION.ORG

Contact Information for IFFS Secretariat