Ovarian Club II final book by Strata Media Group

More live births with MENOPUR® 1,2 vs. rFSH following IVF1,2

A fact you can hold on to

The fertilization process of the oocyte and embryo development in relation to various clinical conditions

Dorint Hotel Don Giovanni PRAGUE Prague, Czech Republic • November 8-11, 2012

MENOPUR Multidose is now available, offering a more convenient treatment option compared to MENOPUR 75 IU3

Ferring International Center SA Chemin de la Vergognausaz 50 CH 1162 St-Prex Switzerland www.ferring.com

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PROGRAM

www.comtecmed.com/OC/2012 • ovarian@comtecmed.com

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Dupha_Anz_Ovarian_Club_RZ

11.10.2012

10:55 Uhr

Seite 1

Ovarian Club II Meeting

Shortened summary of MENOPUR 1200 IU and 600 IU characteristics Name of the product: MENOPUR 1200 IU. Powder for solution for injection + solvent. MENOPUR 600 IU. Powder for solution for injection + solvent. Composition: Menopur 1200 IU: Highly purified HMG equal to 1200 IU FSH and 1200 IU LH in one vial. Menopur 600 IU: Highly purified HMG equal to 600 IU FSH

Prague, Czech Republic November 8 –11, 2012

and 600 IU LH in one vial. Indications: Treatment for infertility in women and men (in women with anovulation who fail to respond to treatment with clomiphene citrate; controlled ovarian hyperstimulation during assisted reproduction; in men with hypo/ normogonadotrophic hypogonadism). For details see SPC. Contraindications: Hormone-dependent cancers. Gynaecological haemorrhage of unknown aetiology, premature menopause, enlarged ovaries and cysts (polycystic ovarian syndrome), states incompatible with pregnancy. Pregnancy and lactation. Excessive sensitivity to any of the medicinal product ingredients. For details see SPC. Posology: individual, i.m. or s.c. administration. For details see SPC. Special warnings (and special precautions for use). Ovarian response to treatment ought to be monitored owing to threatened ovarian enlargement or development of OHSS. Potentially increased risk of thromboembolic disease developing in women at high risk. Pregnancy and lactation: see section Contraindications. Undesirable effects: Headache and abdominal pain, nausea, vomiting, enlargement of abdominal cavity, pelvic pain, OHSS, thromboembolic disease, reactions at the site of injection, hypersensitivity. Overdose: Threatened development of ovarian hyperstimulation. Interaction: No interaction studies have been undertaken. Special precautions

Friday, November 9 2012 13.45 –14.15 h th

Julian Platon, MD PhD

Company Presentation on „New Horizons: The voice of the industry“

for storage: Store in refrigerator (2°C - 8°C), after preparation the solution can be stored at up to 25°C for a maximum period of 28 days. Marketing authorisation holder: Ferring Lé˘civa, Inc. Jesenice u Prahy, Czech Republic. Marketing authorisation number: Menopur 1200 IU: 56/961/10-C, Menopur 600 IU: 56/960/10-C. Date of revision of the text: 01/06/2011. Available solely against medical prescription. No coverage from public health insurance funds. Prior to prescription, please seek full information on the medicinal product at the following address: FERRING Pharmaceuticals CZ s.r.o, K Rybníku 475, 252 42 Jesenice u Prahy. Telephone: +420 241 041 111

The fertilization process of the oocyte and embryo development in relation to various clinical conditions Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.gov.uk. Adverse events should also be reported to Ferring Pharmaceuticals Ltd.

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The fertilization process of the oocyte, embryo development and implantation in relation to various clinical conditions Dorint Hotel Don Giovanni Prague • Prague, Czech Republic • November 8-11, 2012

The fertilization process of the oocyte and embryo development in relation to various clinical conditions

Dorint Hotel Don Giovanni PRAGUE Prague, Czech Republic • November 8-11, 2012

PROGRAM

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Listen to the oocyte

Fostimon

速

Highly purified hFSH

Evidence of life 01-12-OC II- part 1.indd 4 Adv Fostimon A4 2011_rev10_3_11.indd 1

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Timetable Thursday, November 8, 2012 Session 1: Harvesting and Harnessing Human Ovarian Stem Cells Supported by an unrestricted grant by IBSA

16:30-17:00

Coffee Break/Poster Viewing

17:00-19:00

Session 2: The Mystery of Fertility Preservation

19:00 Ovarian Club Meet & Greet

Friday, November 9, 2012 08:30-10:30

Session 3: Recruitment, follicular development and oocyte competence Supported by an unrestricted grant by IBSA

10:30-11:00

Coffee Break/ Poster Viewing

11:00-13:00

Session 4: The Environmental Influence of Oocytes and Embryos

13:00-13:45

Lunch Break

13:45-14:15

New Horizons: The Voice of the Industry Company symposium sponsored by Abbott

14:15-15:45

Session 5: Oocytes and Embryos: Clinical Relevance

15:45-16:15

Coffee Break/ Poster Viewing

16:15-18:15

Session 6: Biomarkers: Clinical Relevance Endorsed by IVI

18:15 Ovarian Club Meet & Greet

Saturday, November 10, 2012 08:30-10:30

Session 7: Clinical implication of ICSI failure Supported by an unrestricted grant by IBSA

10:30-11:00

Coffee Break/ Poster Viewing

11:00-13:00

Session 8: Metabolic programming during the preconception period and implications for subsequent fetal, neo-natal and adult health

13:00-13:45

Lunch Break

13:45-14:15

New Horizons: The Voice of the Industry Company symposium sponsored by Ferring

14:15-16:15

Session 9: The Fertilization Process

16:15-16:45

Coffee Break/ Poster Viewing

16:45-18:45

Session 10: Aging

Sunday, November 11, 2012 Travel Day

11 08.18

14:30-16:30

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Table of Contents Welcome Note

Organizing Committee

Club Speakers

CME Accreditation

Sponsors

List of Sponsors

General Information

Scientific Program

Thursday, November 8, 2012

Friday, November 9, 2012

Saturday, November 10, 2012

Club Speakers’ Overviews

Posters

Index

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Dear Friends and Colleagues After the success of the 1st Meeting of the Ovarian Club (Barcelona, Spain, November 3-6, 2011), we would like to welcome you to the Ovarian Club II: The fertilization process of the oocyte and embryo development in relation to various clinical conditions, Prague, Czech Republic, November 8-10, 2012. The field of Reproductive Medicine is experiencing vast expansion in clinical trials and basic research as well as in emerging cutting-edge technology. New agents will be entering the clinical realm in the coming years. The "Ovarian Club" will function as a comprehensive forum where international experts share and present state-ofthe–art management issues with the participants in order to outline the optimal treatment for patients. Participants are provided the opportunity to discuss and brainstorm with well-known speakers and experts from all over the world. The "Ovarian Club" forum aims to help clinicians to reach reliable solutions that can be implemented in their daily practices. The "Ovarian Club" will allow researchers to present their new studies and findings in their fields of expertise creating an inter-active platform for discussions with the leading experts who will attend the Meeting. We hope you will enjoy the scientific program and the beautiful city of Prague! Sincerely yours, The Organizing Committee P. Bouchard, France P. Devroey, Belguim J. Eppig, USA B. Fauser, The Netherlands R. Fleming, UK S. Hamamah, France K. Korach, USA

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S. Mashiach, Israel J. Motlik, Czech Republic G. Schatten, USA Z. Shoham, Israel J. Smitz, Belgium E. Telfer, UK J. Thompson, Australia

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Organizing Committee

Philippe Bouchard France

Paul Devroey Belgium

Samir Hamamah France

John Eppig USA

Ken Korach USA

Gerald Schatten USA

Bart Fauser The Netherlands

Shlomo Mashiach Israel

Zeev Shoham Israel

Evelyn Telfer UK

Richard Fleming UK

Jan Motlik Czech Republic

Johan Smitz Belgium

Jeremy Thompson Australia

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Club Speakers Kelle H. Moley, USA Jan Motlik, Czech Republic Nicole Noyes, USA Jean-Pierre Ozil, France Pasquale Patrizio, USA Patrick Quinn, USA Carmen Rubio, Spain Denny Sakkas, USA Gerald Schatten, USA Emre Seli, USA Aritro Sen, USA Zeev Shoham, Israel Sherman Silber, USA Carlos Simón, Spain Kevin Sinclair, UK Peter Svoboda, Czech Republic Evelyn Telfer, UK Jeremy Thompson, Australia Jonathan Tilly, USA Jonathan Van Blerkom, USA Dori Woods, USA Gwo-Jang Wu, Taiwan

David Albertini, USA Ellen Anckaert, Belgium Amir Arav, Israel Esther Baart, The Netherlands Piergiorgio Crosignani, Italy Rabindranath De La Fuente, USA Nava Dekel, Israel Dominique De Ziegler, France Adrian Ellenbogen, Israel Tom Fleming, UK Shevach Friedler, Israel Norbert Gleicher, USA Satish Gupta, India Samir Hamamah, France Geraldine Hartshorne, UK Mary Herbert, UK John C. Herr, USA Ariel Hourvitz, Israel Patricia Hunt, USA Kenneth Korach, USA Maria Lalioti, USA Shlomo Mashiach, Israel Marcos Meseguer, Spain

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CME Accreditation

The Ovarian Club II: The fertilization process of the oocyte and embryo development in relation to various clinical conditions was granted 15 European CME credits (ECMEC) by the European Accreditation Council for Continuing Medical Education (EACCME). European Accreditation European Accreditation is granted by the EACCME in order to allow participants who attend the abovementioned activity to validate their credits in their own country. Accreditation Statement Accreditation by the EACCME confers the right to place the following statement in all communication materials including the registration website, the event program and the certificate of attendance. The following statements must be used without revision: The Ovarian Club II: The fertilization process of the oocyte and embryo development in relation to various clinical conditions' (or) 'Ovarian Club II: The fertilization process of the oocyte and embryo development in relation to various clinical conditions' is accredited by the European Accreditation Council for Continuing Medical Education (EACCME) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), www.uems.net. The 'Ovarian Club II: The fertilization process of the oocyte and embryo development in relation to various clinical conditions' is designated for a maximum of (or 'for up to') 15 hours of European external CME credits. Each medical specialist should claim only those hours of credit that he/she actually spent in the educational activity. Through an agreement between the European Union of Medical Specialists and the American Medical Association, physicians may convert EACCME credits to an equivalent number of AMA PRA Category 1 Credits™. Information on the process to convert EACCME credit to AMA credit can be found at www.ama-assn.org/go/internationalcme. Live educational activities, occurring outside of Canada, recognized by the UEMS-EACCME for ECMEC credits are deemed to be Accredited Group. Learning Activities (Section 1) as defined by the Maintenance of Certification Program of The Royal College of Physicians and Surgeons of Canada. EACCME credits Each medical specialist should claim only those hours of credit that he/she actually spent in the educational activity. The EACCME credit system is based on 1 ECMEC per hour with a maximum of 3 ECMECs for half a day and 6 ECMECs for a full-day event.

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The fertilization process of the oocyte, embryo development and implantation in relation to various clinical conditions Dorint Hotel Don Giovanni Prague â&#x20AC;˘ Prague, Czech Republic â&#x20AC;˘ November 8-11, 2012

Sponsors The Ovarian Club Meeting gratefully acknowledges the generous support of the Sponsors

Institut Biochimique SA

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Acknowledgements

Abbott Products Operations AG Contact person: Julian V. Platon Hegenheimermattweg 127 4123 Allschwil Switzerland Tel: +41 61 487 0200 Fax: +41 61 487 0299 Email: julian.platon@abbott.com www.abbott.com

Ferring Pharmaceuticals Ferring International Center S.A Ch. de la Vergognausaz 50, 1162 Saint-Prex, Switzerland Tel: +41 58 301 00 00 Fax: +41 58 301 03 71 www.ferring.com

Institut Biochimique SA

IBSA Institut Biochimique SA Via del Piano, P.O. Box 266, 6915 Pambio-Noranco, Lugano, Switzerland Tel: +41 58 360 10 00 Fax: +41 58 360 16 47 Email: info@ibsa.ch www.ibsa-international.com

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 91,000 people and markets its products in more than 130 countries. Abbott's news releases and other information are available on the company's Web site at www.abbott.com.

Ferring Pharmaceuticals is a research-driven biopharmaceutical company devoted to identifying, developing and marketing innovative products in the fields of reproductive health, urology, gastroenterology, endocrinology and osteoarthritis. The company’s research activities and products are connected by a common thread focused on the provision of tailored treatments that work on the body’s own terms to enable doctors to combat numerous diseases and medical conditions. The company has gained international recognition over the last 20 years for the creation of inventive medications that improve the quality of life of children and adults all around the world. To learn more about Ferring or our products please visit www. ferring.com. IBSA is an international pharmaceutical company headquartered in Lugano, Switzerland, delivering different therapeutic solutions for follicular stimulation and luteal support. IBSA developed an entirely new purification process to obtain a full range of highly purified, human gonadotrophins: hFSH, hMG and hCG. This unique patented process was conceived to ensure at the same time both high purity and the respect of the structure–correlate activities of the gonadotrophins (natural glycosylation). IBSA’s whole in-house manufacturing ensures the same global quality system in company owned plants, from the first steps of raw materials to the final lyophilized products. Other company's franchises include osteoarthritis, painmanagement, dermatology and thyroid diseases.

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GENERAL INFORMATION MEETING VENUE Dorint Hotel Don Giovanni Prague Vinohradská 157a 13020 Prague, Czech Republic LANGUAGE English is the official language of the Meeting. CLOTHING Informal for all occasions REGISTRATION AND HOSPITALITY DESK OPENING HOURS The registration desk will operate during the following hours: Thursday, November 8, 2012

12:00-18:30

Friday, November 9, 2011

07:30-18:00

Saturday, November 10, 2012

08:00-19:00

MEETING KIT AND NAMETAG Nametags are included in your personal Meeting kit. Please wear your nametag during all sessions and social events. Key colors for nametags:

The fertilization process of the oocyte and embryo development in relation to various clinical conditions

Prague, Czech Republic • November 8-11, 2012

Dark Blue: Club Members

Orange: Club Speakers

PREVIEW ROOM Club Speakers are required to visit the preview room. Please come to the Speakers preview room 24 hours before (or at least three hours prior to the lecture) with your slide presentations to be ready to be uploaded for your session. POSTER DISPLAYS Posters should be mounted for Group A: From Thursday, November 8, 2012 at 17:00 and are to be dismantled by the Poster Presenter no later than 18:15 on Friday, November 9, 2012. Posters should be mounted for Group B: From Friday, November 9, 2012 at 18:15 and are to be dismantled by the Poster Presenter no later than 18:45 on Saturday, November 10, 2012. Poster presenters should plan to be alongside their posters during the coffee breaks. The Organizing Committee is not responsible for posters that are not removed on time.

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GENERAL INFORMATION CME ACCREDITATION Please note that you have your CME Accreditation Form in your kit. In order to receive your accreditation points, please submit the completed form to the registration desk before the end of the Meeting. Your certificate will be sent to you directly. LUNCHES Buffet lunch will be served for Club Members between 13:00-13:45 on both Friday, November 9, 2012 & Saturday, November 10, 2012. COFFEE BREAKS Coffee/tea will be served in the Poster Board area during the coffee breaks between sessions as specified on the time table. OVARIAN CLUB MEET & GREET The Ovarian Club Meet and Greet gives all OC II participants an opportunity to mingle and interact with one another. Drink and snacks will be served. Come and join us. LIST OF CLUB MEMBERS A list of pre-registered club members is displayed on the notice board. Please correct or add your name and address wherever necessary. CERTIFICATION OF ATTENDANCE Your Certificate of Attendance is included in your personal Meeting kit. Wifi Wifi internet will be available at the Dorint Hotel Giovanni free of charge. SAFETY AND SECURITY Please do not leave any bags or suitcases unattended at any time, whether inside or outside the session halls. LIABILITY The Meeting Secretariat and Organizers cannot accept liability for personal accidents, loss or damage to private property of participants, either during or directly arising from The 2nd Meeting of the Ovarian Club. Participants are expected to make their own arrangements with respect to health and travel. Meeting Organizers

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The fertilization process of the oocyte and embryo development in relation to various clinical conditions

Dorint Hotel Don Giovanni PRAGUE Prague, Czech Republic • November 8-11, 2012

SCIENTIFIC PROGRAM

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SCIENTIFIC PROGRAM

Thursday, November 8, 2012 14:30-16:30 SESSION 1 Harvesting and Harnessing Human Ovarian Stem Cells Supported by an unrestricted grant by IBSA

Chairpersons: Carlos Simón, Spain; Zeev Shoham, Israel; Gerald Schatten, USA

14:30-15:00

Isolation and characterization of OSCs in human Jonathan Tilly, USA

15:00-15:30

Formation of new human follicles from OSCs in vitro Evelyn Telfer, UK

15:30-16:00

Testing genetic integrity of OSC formed oocytes David Albertini, USA

16:00-16:30

Modulation of Mouse Oogonial Stem Cell Fate Determination by Long-term Propagation Dori Woods, USA

16:30-17:00 Coffee Break/ Poster Viewing 17:00-19:00 SESSION 2 The Mystery of Fertility Preservation

Chairpersons: Sherman Silber, USA; Kenneth Korach, USA

17:00-17:30

The oocytes as the conductor of the reproductive symphony Pasquale Patrizio, USA

17:30-18:00

Directional freezing or vitrification; which child do I prefer? Amir Arav, Israel

18:00-18:30

Vitrification- as applied embryos and ovaries Sherman Silber, USA

18:30-19:00

Oocyte Cryopreservation for Cancer and Deferred Reproduction Nicole Noyes, USA

19:00

Ovarian Club Meet & Greet

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SCIENTIFIC PROGRAM

Friday, November 9, 2012 08:30-10:30 SESSION 3 Recruitment, follicular development and oocyte competence Supported by an unrestricted grant by IBSA

Chairpersons: Evelyn Telfer, UK; Jeremy Thompson, Australia; Ariel Hourvitz, Israel

08:30-09:00

Molecular characterization of human folliculogenesis and ovulatory events - from basic research to clinical application Ariel Hourvitz, Israel

09:00-09:30

What granulosa cell- and oocyte-specific ARKO mice can tell us about folliculogenesis and female fertility Aritro Sen, USA

09:30-10:00

CHK1 is involved in SAC satisfaction and preservation of DNA integrity in mouse oocytes Jan Motlik, Czech Republic

10:00-10:30 Appropriate meiotic segregation in oocytes: possible practical implications Nava Dekel, Israel 10:30-11:00 Coffee Break/ Poster Viewing 11:00-13:00 SESSION 4 The Environmental Influence of Oocytes and Embryos

Chairpersons: Satish Gupta, India; Patrick Quinn, USA; Maurizio Dattilo, Italy

11:00-11:30

Environmental exposures and gametogenesis: are exposures affecting our reproductive health? Patricia Hunt, USA

11:30-12:00

Late procreation in the main determinant of multiple pregnancies Piergiorgio Crosignani, Italy

12:00-12:30

Environmental Action on Ovarian toxicity Kenneth Korach, USA

12:30-13:00

Relationship of telomere length in human gametes and zygotes with semen analysis parameters, sperm DNA fragmentation, smoking status and treatment outcome: What are the clinical implications of telomere length for embryo viability? Geraldine Hartshorne, UK

13:00-13:45 Lunch Break

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SCIENTIFIC PROGRAM

Friday, November 9, 2012 13:45-14:15 New Horizons: The Voice of the Industry Company symposium sponsored by Abbott

Abbott's Research Activities in IVF

Julian V. Platon, MD, PhD Global Medical Director, Gastrointestinal & Women Health Strategic Medical Affairs Abbott Products Operations AG, Basel, CH 14:15-15:45 SESSION 5 Oocytes and Embryos: Clinical Relevance

Chairpersons: Shevach Friedler, Israel; Denny Sakkas, USA; Marcos Meseguer, Spain

14:15-14:45

In Vitro Maturation does not offer any advantage over current IVF for PCOS patients Samir Hamamah, France

14:45-15:15 Alterations in oocyte, embryo and/or endometrium quality in endometriosis: identifying the weak link Dominique De Ziegler, France 15:15-15:45

Ovarian stimulation for IVF, the oocyte and the embryo: possible detrimental effects Esther B. Baart, The Netherlands

15:45-16:15 Coffee Break/ Poster Viewing 16:15-18:15 SESSION 6 Biomarkers: Clinical Relevance Endorsed by IVI

Chairpersons: Carlos Simón, Spain; Samir Hamamah, France; Maria Lalioti, USA

16:15-16:35

Polymorphisms as biomarkers of ovarian reserve and oocyte quality Maria Lalioti, USA

16:35-16:55

Cumulus cells as markers of oocyte and embryo quality Emre Seli, USA

16:55-17:15

Clinical relevance of morphokinetics to assess embryo viability Marcos Meseguer, Spain

17:15-17:35

Non invasive metabolomic profiling of embryos using spectroscopy Denny Sakkas, USA

17:35-17:55 Use of Comparative Genomic Hybridization (CGH) for embryo assessment. Clinical results Carmen Rubio, Spain 17:55-18:15

Conclusion Carlos Simón, Spain

18:15

Ovarian Club Meet & Greet 16

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SCIENTIFIC PROGRAM

Saturday, November 10, 2012 08:30-10:30 SESSION 7 Clinical implication of ICSI failure Supported by an unrestricted grant by IBSA

Chairpersons: Shlomo Mashiach, Israel; Nicole Noyes, USA; Jonathan Van Blerkom, USA

08:30-09:00

The sperm-egg, fertilization and the embryo: Egg activation - calcium oscillations and outcome in pre and post implantation development Jean-Pierre Ozil, France

09:00-09:30

The mechanisms of mammalian sperm-egg interaction John C. Herr, USA

09:30-10:00

Cell cycle control in human embryos: Why all the aneuploidy? David Albertini, USA

10:00-10:30

Post-transciptional regulations during oocyte-to-zygote transition Petr Svoboda, Czech Republic

10:30-11:00 Coffee Break/ Poster Viewing 11:00-13:00 SESSION 8 Metabolic programming during the preconception period and implications for subsequent fetal, neo-natal and adult health

Chairpersons: Ellen Anckaert, Belgium; David Albertini, USA; Carlos Simón, Spain

11:00-11:30

Preconception protein levels and subsequent fetal growth Tom Fleming, UK

11:30-12:00

Cellular disruption within oocytes and early embryos caused by maternal diabetes – basic and clinical implications Kelle H. Moley, USA

12:00-12:30

O-linked glycosylation mediates the hyperglycemic pathology in oocytes and early embryos? Jeremy Thompson, Australia

12-30-13:00 Dietary methyl donors during the preconception period and their influence on subsequent development Kevin Sinclair, UK 13:00-13:45 Lunch Break

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SCIENTIFIC PROGRAM

Saturday, November 10, 2012 13:45-14:15 New Horizons: The Voice of the Industry Company symposium sponsored by Ferring

Why Health Care Professionals and Pharma Must Work Together to Identify and Meet Patients’ Needs

Julian Jenkins, DM, FRCOG Head of Global Medical Affairs Ferring International Center SA, St. Prex, Switzerland

14:15-16:15 SESSION 9 The Fertilization Process

Chairpersons: Norbert Gleicher, USA; Gwo-Jang Wu, Taiwan; Jan Motlik, Czech Republic

14:15-14:45

Membrane and cytoplasmic influences on penetration and post penetration development - Can basic science provide markers for the clinical embryologist Jonathan Van Blerkom, USA

14:45-15:15

Role of Chromatin Remodeling Proteins in Chromosome Segregation and the Transmission of Aneuploidy in Mammalian Oocytes. Basic research with clinical implications Rabindranath De La Fuente, USA

15:15-15:45

The Minimal Oocyte – or How to construct an artificial egg? what are the requirements for the oocyte to achieve it mission Gerald Schatten, USA

15:45-16:15

Human Tubal Fluid: In Vivo and In Vitro Patrick Quinn, USA

16:15-16:45 Coffee Break/ Poster Viewing

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SCIENTIFIC PROGRAM

Saturday, November 10, 2012 16:45-18:45 SESSION 10 Aging

Chairpersons: Dominique De Ziegler, France; Piergiorgio Crosignani, Italy; Zeev Shoham, Israel

16:45-17:15

How androgens and genes affect follicle maturation and ovarian aging Norbert Gleicher, USA

17:15-17:45

How do Oocytes Tell Time? (Oocyte Aging and Can the Chronology Sensing Machinery Be Reset) Gerald Schatten, USA

17:45-18:15

Female reproductive aging: new insights into an old problem Mary Herbert, UK

18:15-18:45

The impact of Y chromosome like regions of the X chromosome (palindromes and amplicons) on ovarian reserve Sherman Silber, USA

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Dorint Hotel Don Giovanni PRAGUE Prague, Czech Republic • November 8-11, 2012

Speakers Overviews (Order as per the Scientific Program)

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ISOLATION AND CHARACTERIZATION OF OSC’S IN HUMAN Jonathan Tilly, USA For decades it was believed that mammalian females rely on primordial germ cell (PGC)-derived oogonia to generate their entire quota of oocytes during embryogenesis, leading to the endowment of a non-renewable pool of oocytecontaining follicles at birth. However, the recent discovery of mitotically active germ cells, referred to hereafter as oogonial (oocyte-producing) stem cells (OSCs), in adult mouse and human ovaries opens the prospects that the mammalian oocyte pool is actively replenished at least during early adulthood. Such a paradigm shift would draw strong parallels to maintenance of adult spermatogenesis by spermatogonial stem cells (SSCs) in the testes as well as to the continuous production of oocytes during adulthood in less evolved species such as flies and teleost fish. This presentation will highlight new advances in the field of mammalian OSC biology, including as-yet unpublished observations from our lab regarding the functionality of eggs generated by transplanted mouse OSCs, as tested in natural mating trials, as well as insights into the signaling pathways that guide the decisions of self-renewal (proliferation) versus differentiation (meiotic commitment) in OSCs in vitro and in vivo. Lastly, experimental evidence supporting a central role for OSC dysfunction with age to deterioration of the ovarian reserve, and eventual ovarian failure, will be overviewed. IN VITRO FOLLICLE FORMATION AND GROWTH FROM HUMAN OSC’S Evelyn Telfer, UK Recent work from Jon Tilly‟s group has demonstrated the isolation and identification of oocyte-producing germline stem cells [oogonial stem cells (OSC)] from ovaries of reproductive age woman. The isolation of such rare cells from adult human ovaries makes this work significant in a biological context, providing a model to study human oocyte development at the earliest stages. This presentation will focus on work that our lab has been conducting in collaboration with Jon Tilly‟s group to characterise the ability of human OSCs to form primordial follicles within a human ovarian cortex culture system and their subsequent ability to grow within a multi-step culture system developed to support human oocyte growth and development. These studies demonstrate that new primordial follicles are formed from these OSCs and that the limitation to formation is the somatic cell availability. Our results show that follicles formed from OSC‟s are capable of growth to multi-laminar stages and significant oocyte growth can be achieved. Whilst the in vivo significance of these cells has yet to be determined, our system will facilitate their characterisation and allow us to define the potential of OSC derived putative oocytes in vitro. TESTING GENETIC INTEGRITY OF OSC FORMED OOCYTES David Albertini, USA With several reports now in the literature having claimed to have made oocyte-like cells from stem cells of various sources, an urgent call for quality control measures is now upon us before clinical applications can be realized. From a cell cycle point of view, stem cells and oocytes have a checkered history owing to their remarkable predisposition towards aneuploidy, just one of the many forms of genetic instability that have been well characterized in human oocytes, embryos, and ES cells. The need for methodology that will allow the assessment of genetic integrity on oocyte-like cells will be discussed in the context of liabilities obtained from meiotic re-entry and or periods of amplification at a somatic cell level prior to transformation into gametic progenitors.

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LONG-TERM IN VITRO CULTURE OF MOUSE OOGONIAL STEM CELLS INFLUENCES CELL FATE DETERMINATION Dori C. Woods, USA Recent studies have reported that adult mouse and human ovaries contain a rare population of oogonial stem cells (OSCs) which have the ability to generate new oocytes during reproductive life. Among the properties of OSCs is the ability to self-renew and produce daughter cells that undergo differentiation into oocytes. Like their male counterparts (spermatogonial stem cells or SSCs), OSCs can be established as propagating cells in culture, and in mice such cultured cells returned to adult mouse ovaries produce developmentally competent eggs. Studies of mouse SSCs maintained ex vivo have shown that a subpopulation of the cells undergoes a transformation process producing testicular multipotent adult germline stem cells (maGSCs), as defined by a number of endpoints including tumor formation following transplantation in vivo. While freshly-isolated mouse OSCs exhibit a single fate (oocyte formation) with no capacity to generate tumors, prolonged ex-vivo expansion of these mouse cells produces a multi-potent phenotype similar to that described for mouse SSCs cultured ex vivo, as revealed by the in vivo tumor formation assay. Interestingly, OSCs isolated from ovaries of reproductive age women do not undergo this multi-potential transformation, even after long-term propagation for many months, with 100% of the cell lines tested from multiple subjects failing to show tumorigenic potential in vivo. Thus, while the change in cell fate determination towards multi-potentiality associated with long-term culture of OSCs is mouse-specific (as appears to be the case for SSCs as well), these studies nonetheless provide a defined in vitro model system to help elucidate events and pathways responsible for governing germline identity and stem cell potentiality. THE OOCYTES AS THE CONDUCTOR OF THE REPRODUCTIVE SYMPHONY Pasquale Patrizio, USA Human oocytes represent one of the most important variables for the success of IVF. Since inception of IVF and despite progress in clinical and laboratory protocols, the rate of live birth per retrieved oocyte is still disappointingly low (about 5%). The majority of oocytes obtained during IVF are either chromosomally or genetically abnormal. A number of new, non-invasive, technologies aiming at deciphering the transcriptome of the cumulus cells and the associated oocyte, the follicular fluid and oocyte culture media content, have the potential to improve identification of competent oocytes. Understanding genetic pathways important for oocyte intrafollicular maturation and for the completion of meiotic processes would enable the selection of oocytes (and subsequently embryos) with the greatest reproductive potential and would represent the next breakthrough in ART.

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DIRECTIONAL FREEZING OR VITRIFICATION; WHICH CHILD DO I PREFER? Amir Arav, Israel Directional freezing is a technique which permits accurate control of the heat transfer and ice crystal propagation velocity during the freezing process. In the last 20 years we applied this technique on sperm of different species, oocytes embryos, tissue and even whole organs freezing and we published our achievements. Vitrification is becoming the golden standard for oocytes and embryos cryopreservation since the method of minimal volume ("minimum drop size") which allows reducing cryoprotectant concentration to non toxic levels, developed by us. I will demonstrate the state of the art in both methods and speculate on future applications in the reproduction field. VITRIFICATION AS APPLIED TO EMBRYOS AND OVARIES Sherman Silber, USA The aim of this lecture is to summarize the state-of-the-art of embryo and ovarian tissue cryopreservation with vitrification. Ten of ten fresh ovary transplants were successful, resulting in twelve healthy babies in eight of the ten recipients. Recipients always reinitiated ovulatory menstrual cycles and normal Day 3 serum FSH levels by 4-1/2 months. Grafts of just modest portions of ovarian tissue have lasted more than 7 years. The same surgical techniques were then applied to frozen ovary tissue transplants, up to 14 years after the ovary had been frozen, all resulting in normal ovulation and a total of 30 healthy babies worldwide, whereas, in no cancer patients have any babies thus far resulted from egg freezing. Slow freeze has resulted in only a 50% loss of oocytes, and vitrification has resulted in no loss. With vitrification, embryos can be frozen with impunity, whereas with slow freeze (like with ovarian tissue) there is some viability loss. Vitrification may thus eventually obviate the growing worldwide epidemic of female age-related decline in fertility, and even could eliminate menopause. OOCYTE CRYOPRESERVATION FOR CANCER AND DEFERRED REPRODUCTION Nicole Noyes, USA In 2012, more than a million new female cancers will be diagnosed worldwide; ~10% in women of reproductive age. This, combined with a global delay in childbearing threatens the ability of women to reproduce. Recent advances in cryobiology have resulted in >1500 live births as a result of oocyte cryopreservation, with pregnancy/live-birth rates matching those of conventional IVF in some centers, thus, providing the option for autonomous fertility preservation (FP) and the chance for successful reproduction at a time more conducive to childbearing. Dr. Noyesâ&#x20AC;&#x;s lecture will cover oocyte cryopreservation topics such as treatment indications an modifications, special considerations, and successes to date.

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MOLECULAR CHARACTERIZATION OF HUMAN FOLLICULOGENESIS AND OVULATORY EVENTS - FROM BASIC RESEARCH TO CLINICAL APPLICATION Ariel Hourvitz, Israel Ovarian follicular development and ovulation in mammals is a complex and highly regulated process. Most advances in the understanding of the ovulatory process have come from animal models, mainly the rodent. These experimental findings should be validated in human study. IVM/IVF procedures allow us to obtain follicular fluid and granulosa cells from follicles in different developmental stages. Using the cells and fluids obtained in IVM/IVF procedures allowed us to characterize human ovulatory gene expression during antral folliculogenesis and ovulation, examine gene expression in luteinized and non-luteinized granulosa cells in vivo and in vitro and to use cumulus granulosa cells genes as biomarkers for oocyte and embryo maturity and competence. Using global transcriptome sequencing we were able to generate a library of genes regulated during cumulus expansion and oocyte maturation processes. Analysis of these genes, will allow us to identify new important genes involved in cumulus oocyte complex maturation and cumulus expansion, and may contribute to improve the process of in vitro maturation of immature oocytes aspirated during IVM cycles. We will present an extensive review of the currently available literature in this field together with our preliminary results. WHAT GRANULOSA CELL- AND OOCYTE-SPECIFIC ANDROGEN RECEPTOR KNOCKOUT (ARKO) MICE CAN TELL US ABOUT FOLLICULOGENESIS AND FEMALE FERTILITY Aritro Sen, USA Androgens have traditionally been considered detrimental to women‟s health and associated with deregulated ovarian function and infertility. However lately, many clinical studies have reported benefits of androgen priming prior to IVF cycles in women with decreased ovarian reserve. Intriguingly, through the generation of a granulosa cell (GC)- and an oocyte-specific androgen receptor (AR) knockout (ARKO) mouse model, we have recently pioneered a new concept that critical androgen actions in GCs, but not in the oocyte are absolutely essential for normal ovarian function and female fertility. Our studies indicate that ARs expressed in GCs control preantral follicle growth and development to antral follicles, while preventing follicular atresia. However, to date, the underlying mechanism of AR actions in the ovary has remained elusive. It is well established that androgen functions are mediated by both “genomic” and “membrane-initiated” actions of ARs. Using our GC-specific ARKO mouse model, we have now uncovered two novel regulatory pathways that may account for the AR actions in GCs. First we have found that ARs regulate the expression of a microRNA (miR) that may contribute to androgen-induced follicular survival. The expression of this miR in GCs requires a synergistic action between the nuclear and extra-nuclear AR signaling. Secondly, ARs exclusively through a non-genomic pathway augment FSH actions during follicular development. This lecture will discuss recent findings of AR actions in normal follicular development and how the studies in GC-specific ARKO mouse model help in understanding some of the recent clinical data regarding androgen effects in infertility treatment.

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CHK1 IS INVOLVED IN SAC SATISFACTION AND PRESERVATION OF DNA INTEGRITY IN MOUSE OOCYTES Jan Motlik, Czech Republic We have shown that Check point kinase 1 (CHK1) is involved in timely correct spindle assembly checkpoint (SAC) satisfaction but it is not SAC component. More importantly, CHK1 deficient oocytes have higher level of DNA damage leading to chromosome breaks and loss of DNA fragments in anaphase I. Female conditionally deficient for CHK1 in oocytes are highly subfertile and more often completely unfertile. APPROPRIATE MEIOTIC SEGREGATION IN OOCYTES: POSSIBLE PRACTICAL IMPLICATIONS Nava Dekel, Israel Meiosis in oocytes includes two asymmetric cell divisions. The first meiotic division, during which the homologous chromosomes segregate, is particularly error prone, leading to aneuploidy and genetic malformations. Completion of this division, characterized by the formation of the first polar body (PBI), is fully dependent on proteasomal protein degradation and the subsequent CDK1 inactivation. We identified the polyubiquitin signal that mediates proteasomal action at this stage of meiosis and characterized the role of CDK1 inactivation during PBI extrusion. Shedding light on the complexity of meiosis these results may potentially contribute to our understanding of unfaithful chromosome segregation. ENVIRONMENTAL EXPOSURES AND GAMETOGENESIS: ARE EXPOSURES AFFECTING OUR REPRODUCTIVE HEALTH? Patricia Hunt, USA Experimental studies in rodents suggest that environmental endocrine disruptors impact the developing reproductive tract of both males and females. In the female, at least three distinct stages of egg development are vulnerable, and it appears that exposures can affect both reproductive success and longevity. In the male, exposure to environmental estrogens during testis development causes a drop in testis size, a reduction in sperm counts, and permanently alters the process of spermatogenesis in the adult testis. Taken together, experimental studies suggest that BPA adversely impacts gametogenesis and fertility in both sexes, and more recent findings from studies in the rhesus monkey make it likely that these effects extend to humans.

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LATE PROCREATION IN THE MAIN DETERMINANT OF MULTIPLE PREGNANCIES Piergiorgio Crosignani, Italy Monozygotic twins arise from the fertilization of a single oocyte, with the resulting embryo splitting during early development to form two separate embryos. In contrast, dizygotic twins result from the fertilization of two separate oocytes, which subsequently develop as two separate embryos. The dizygotic twinning rate varies in different populations and its incidence has risen in the last 30 years on account of the current tendency to postpone childbearing and the increased use of ovarian stimulation. The risk of dizygotic twinning is linked to the postponement of childbearing, as increased maternal age is associated with a decline in ovarian feedback capacity and elevations in FSH. Therefore, il older women, there is a tendency towards multile follicular development and an increased prevalence of twinning. As higher numbers of women delay reproduction, for understandable social reasons, an additional 5-8 twins per 1000 births will be born every year. On the other hand pharmacologic ovarian stimulation induces the simultaneous growth of multiple follicles, leading to the ovulation of more than one egg, and hence, multiple pregnancies. The milder ovarian stimulation used in IUI cycles and the choice of single embryo transfer for IVF cycles can largely prevent iatrogenic twinning. On the contrary there seems to be no way to stop the increase in risk of natural twinning due to the current widespread choice of late procreation. ENVIRONMENTAL ACTION ON OVARIAN TOXICITY Kenneth Korach, USA Estrogen receptors (ER) are thought to play a crucial role in development, reproduction and normal physiology. We produced lines of mice homozygous for phenotype occurs developmentally due to elevated LH and can be reversed by a GnRH antagonist similar to PCOS. Ovarian gonadotropin receptor levels, serum breeding studies and superovulation show arrested function similar to clinical LUF syndrome. Granulosa cell cultures indicate poor target gene stimulation in a/b knockout shows a unique ovarian phenotype of transdifferentiation of granulosa to sertoli cells and altered gene expression pattern, suggesting that both ER signaling mechanisms must be functional in order to maintain the proper differentiation state of the granulosa cells and oocyte developmental viability.

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RELATIONSHIP OF TELOMERE LENGTH IN HUMAN GAMETES AND ZYGOTES WITH SEMEN ANALYSIS PARAMETERS, SPERM DNA FRAGMENTATION, SMOKING STATUS AND TREATMENT OUTCOME: WHAT ARE THE CLINICAL IMPLICATIONS OF TELOMERE LENGTH FOR EMBRYO VIABILITY? Geraldine Hartshorne, UK This paper will present new data on telomere length in human individual spermatozoa, oocytes at different stages of maturation, and both male and female pronuclei in newly formed zygotes. Telomere lengths in sperm samples donated by an unselected group of men have been tested for relationships to sperm DNA fragmentation and routine semen analysis criteria and analysed in relation to the menâ&#x20AC;&#x;s smoking status and eventual outcome of treatment. Sperm DNA fragmentation was related to clinical parameters, however telomere length was not. We show that telomere length in human oocytes reduces with maturation, and that mature oocytes and female pronuclei have similar length telomeres, as do sperm and male pronuclei from the same donor. Telomeres in sperm and male pronuclei were, on average, significantly shorter than those in oocytes and female pronuclei.

IN VITRO MATURATION DOES NOT OFFER ANY ADVANTAGE OVER CURRENT IVF FOR PCOS PATIENTS Samir Hamamah, France Patients suffering from PCOS benefit from assisted reproduction techniques (ARTs) adopted to induce multiple follicle maturation under controlled ovarian stimulation (COS). Although sufficient oocytes are usually retrieved for IVF, there are accumulated data suggesting that the oocyte developmental competence is altered in PCOS. To date, the gene expression profile of CCs from women with PCOS has been rarely investigated. The aim of this lecture is (i) to establish the gene expression profile of human CCs at different stages of oocyte maturation following in vivo and in vitro oocyte Maturation and (ii) to investigate the gene expression profile of human CCs isolated from mature metaphase II oocytes from a homogeneous group (age, weight and similar COS protocol) of patients with or without PCOS. we report the down-regulation of genes involved in cumulus expansion (TNFAIP6, PTGS2 and PTX3) as well as of genes related to oocyte maturation, including several EGF-like growth factors (EREG, AREG and BTC) in CCs from in vitro matured oocytes in comparison with CCs from in vivo matured oocytes. On the other hand, In PCOS CCs, 65% of genes related to the TGFb signalling pathways were down-regulated, including several members of the TGFb superfamily (INHBC, INHBB, TGFB1 and TGFB1I1), type II TGFb receptors and their targets SMAD1/5, as well as the TGFb receptor III. Also, estrogen receptor signalling was altered in CCs from the PCOS group compared with the control group. In conclusion, the comparison of the gene expression profiles of CCs from PCOS and non-PCOS patients suggests that, in women with PCOS, CC competence is strongly affected. Specifically, major signalling pathways that play a key role in the gradual acquisition of developmental competency by the oocyte (particularly the TGFb and the estrogen receptor signalling cascades) are altered in CCs from women with PCOS. Moreover, many genes, the expression of which is influenced by environmental and extra-ovarian factors, are also deregulated in PCOS CCs and their alteration may play a role in PCOS pathophysiology.

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ALTERATIONS IN OOCYTE, EMBRYO AND/OR ENDOMETRIUM QUALITY IN ENDOMETRIOSIS: IDENTIFYING THE WEAK LINK Dominique De Ziegler, France Endometriosis – an ailment of unknown origin – causes pain and infertility. Women suffering from endometriosis perform less well in assisted reproductive technologies (ART). From the sum of existing reports, we know that the responses to controlled ovarian stimulation (COS) and embryo implantation rates are diminished in endometriosis. Remarkably, all the studied alterations of the eutopic endometrium – notably, CYP-19 activation and resistance to P4 – are normalized by a temporary suppression of ovarian function. ART data indicate that the timely use of GnRH-a or OC normalizes embryo implantation in endometriosis. In conclusion, the responses to COS are altered in ovarian endometriosis, but without alteration in ART outcome. These alterations can be normalized by timely use of OC or GnRH-a, allowing to achieve similar ART outcome despite poor ovarian response to COS. OVARIAN STIMULATION FOR IVF , THE OOCYTE AND THE EMBRYO: POSSIBLE DETRIMENTAL EFFECTS Esther B. Baart, The Netherlands We have previously demonstrated that mild stimulation reduces the number of oocytes retrieved, but significantly increases the proportion of chromosomally normal embryos. By now, other studies have observed a similar correlation between attenuation of the ovarian response and euploidy. Taken together, these observations suggest that selection of better quality embryos may be achieved by applying milder stimulation approaches, by allowing only the most mature follicles to develop. Alternatively, the observed differences may be due to a direct effect of the GnRH analogue or gonadotrophin used. This presentation will explore possible underlying mechanisms and implications for embryo quality and selection. POLYMORPHISMS AS BIOMARKERS OF OVARIAN RESERVE AND OOCYTE QUALITY Maria Lalioti, USA Optimal ovarian function is necessary for gonadal development and maturation at puberty and for gamete production during the reproductive phase of life and therefore for fertility. Inactivating mutations in critical genes, such as the FSH-beta, FSH receptor (FSHR), LH-beta, and LH receptor (LHR), cause infertility, while activating mutations can cause ovarian hyperstimulation. Unlike these mutations that define the two extremes of the spectrum, single nucleotide polymorphisms (SNPs) that result in amino acid substitutions within the promoter or coding regions have been associated with variability in ovarian response to FSH, Polycystic Ovary Syndrome, and ovarian cancer. Moreover, genome-wide studies have pinpointed associations with SNPs in several genes. However, each one of the SNPs has only a small contribution to the phenotype, attesting the multifactorial nature of the problem. Pharmacogenomics is the branch of pharmacology that aims to study the influence of genetic variability to drug efficiency or toxicity and ultimately, optimize therapy to suit the patient's genotype. Pharmacogenomics profit immensely from the vast advances in the study of the genome, which includes population distribution of polymorphisms, and technological advances, which make patient genotyping easy and affordable. However, it is imperative to study the change that each SNP confers to the function in the molecular level, because this will be the key to unravel the optimal match to a drug. This lecture will summarize the findings linking genome variation to ovarian reserve and oocyte quality.

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CUMULUS CELLS AS MARKERS OF OOCYTE AND EMBRYO QUALITY Emre Seli, USA The high success rates seen following in vitro fertilization (IVF) are attained in many cases through the simultaneous transfer of multiple embryos at the expense of multiple pregnancies. Multiple pregnancies, in turn, are associated with significant morbidity and mortality, primarily due to their propensity to result in preterm birth. Consequently, decreasing multiple gestations while maintaining or improving overall pregnancy rates remains the most significant contemporary goal in the treatment of infertility. In order to achieve this goal, an improvement over our current embryo assessment strategies (largely based on embryo morphology and cleavage rates) would be useful. Oocytes are in close contact with granulosa/cumulus cells throughout folliculogenesis. Genes exclusively expressed in oocytes (such as GDF9 and BMP15) are required for normal follicle growth and cumulus function. Therefore, (1) cumulus cell transcriptome is likely to reflect oocyte quality and viability, and (2) analysis of cumulus cells in women undergoing IVF could potentially be used as a non-invasive approach to assess oocyte and embryo viability. Within this context, independent investigators have identified specific cumulus cell transcripts associated with oocyte or embryo viability. The clinical validation of these biomarkers in IVF setting is awaited. CLINICAL RELEVANCE OF MORPHOKINETICS TO ASSESS EMBRYO VIABILITY Marcos Meseguer, Spain Time-lapse observation presents an opportunity for optimizing this embryo selection based on morphological grading as well as providing novel kinetic parameters, which may further improve accurate selection of viable embryos. We are presenting the largest set of transferred embryos after time-lapse analysis and thus a novel opportunity to correlate morphokinetic parameters to implantation and ongoing pregnancy. We have generated and evaluated a tool for the selection of viable embryos based on the exact timing of embryo development events together with morphological patterns by using an automatic time-lapse system to monitor embryo development. We have elaborated a hypothesis, trying to elucidate whether time-lapse monitoring system together with embryo selection by morphokinetics is able to improve reproductive outcome. To undergo this objective we compared the result of an incubator with a built-in time-lapse video system (TMS) to our standard procedure involving normal incubators (SI) and sequential assessment by microscopy. The study employs logistic regression model to compare the clinical pregnancy for incubations in the TMS with incubations in a SI. Ultimately, several variables were evaluated as confounding factors (CF) that could possibly affect the outcome. The analysis revealed that TMS had a significant positive impact on chance of clinical pregnancy. Our intention is to calculate and demonstrate the extent of the positive impact of TMS on pregnancy. Possible explanations for the observed increase could be : i) strictly controlled conditions, ii) reduced handling, iii) occasional observation of abnormal cleavages ; or iv) selection by morphokinetics related to embryo implantation.

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NON INVASIVE METABOLOMIC PROFILING OF EMBRYOS USING SPECTROSCOPY Denny Sakkas, USA Although the clinical IVF Laboratory has undergone numerous radical changes in the past 30 years, improving the ability to quickly identify the best single embryo for transfer remains a critical goal. A number of technologies including the non-invasive measurement of glucose, lactate, pyruvate and amino acids have been present for over 20 years but were not adapted to clinical practice. The assessment of the embryo and correlation to viability using, genomic and proteomic profiling, and more recently, analytical examination of the embryonic metabolome has shown greater promise. Metabolomic profiling of embryo culture media using optical and non-optical spectroscopy associated with bioinformatics is providing greater insight into the identification of embryos with increasing reproductive potential. Numerous instrumentation techniques examining the metabolome including, Near Infra Red, Raman, Nuclear Magnetic Resonance and Mass Spectroscopy will be discussed. The pitfalls and benefits of their development and clinical results will be presented showing that although some technologies may show initial promise there global clinical application can still be hindered with numerous hurdles. In the next decade the IVF laboratory will be a very different location featuring automated embryo culture and imaging systems and a range of technologies that will allow the possibility of both invasive and non-invasive single embryo profiling to more accurately assess which embryo will lead to a normal live birth. USE OF COMPARATIVE GENOMIC HYBRIDIZATION (CGH) FOR EMBRYO ASSESSMENT. CLINICAL RESULTS Carmen Rubio, Spain Preimplantation Genetic Diagnosis (PGD) is offered in many IVF centres to improve the reproductive outcome of specific groups of patients. PGD is used to discard affected embryos in carriers of monogenic diseases and structural chromosome anomalies. Preimplantation Genetic Screening (PGS) is a variant of PGD applied to the screening of numerical chromosome anomalies in couples with normal karyotype, but with infertility problems. Current indications for PGS are: advanced maternal age (AMA), recurrent miscarriage (RM), repetitive implantation failure (RIF), and severe male factor infertility (SMF). In PGS programs, the technique most widely employed for the cytogenetic analysis of blastomeres has been fluorescence in situ hybridization (FISH) for a selected panel of chromosomes. Using FISH, prospective randomized trials (RCT) concluded that PGS should not be recommended in AMA patients. Other authors have argued that there are some important methodological pitfalls in the published RCTs, such us patientsÂ´s inclusion criteria, the embryo biopsy procedure, embryo culture conductions as well as the type of genetic analysis performed. It has been proposed that higher benefits would be reached if the whole set of chromosomes could be tested. The best approach seems to be array-CGH, which would offer the most complete analysis of the embryo, giving information about all 24 chromosomes. In this presentation, we will present current data with array-CGH analysis for different indications. In general using this technology pregnancy rates per transfer in our clinical programs has increased to over 60% for all PGS indications, including advanced maternal age with day-3 embryo biopsy. The experience of other s groups with blastocyst biopsy will be also introduced.

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THE SPERM-EGG, FERTILIZATION AND THE EMBRYO: EGG ACTIVATION - CALCIUM OSCILLATIONS AND OUTCOME IN PRE AND POST IMPLANTATION DEVELOPMENT Jean-Pierre Ozil, France There is compelling evidence that the earliest stages of fertilization in mammalian eggs are sensitive to perturbation arising from in vitro conditions. Alterations at the adult age, such as body size, hypertension or organ: body-weight ratios reflect some hidden mechanisms that are imprinted in the genome in the early stages. The linkage between very early quantitative changes in egg metabolism and post-natal effects is still poorly understood. In mammals, fertilization triggers various regimes of Ca2+ oscillations that stimulate the egg metabolism more or less. The variability and the enslavement of the redox potential within the process of ATP synthesis makes it difficult to discriminate specific impacts of the egg redox and energetic profiles on offspring health. To overcome such difficulties we take the advantage of the zygote's period of transcriptional inactivity to handle egg functioning solely by changing the composition of the culture media. We used various carbohydrate compositions to vary the redox potential and the energetic metabolism differently but only during the pronuclear stage. The results show that the adult weight can be up or down regulated by manipulating the redox potential but only when the activity of the mitochondria is maintained high for a few hours during the PN stage. Therefore, minute manipulation of the egg metabolism will make it possible to identify the metabolic sensor(s) that orient(s) the developmental processes and program(s) the adult phenotype during egg activation. THE MECHANISMS OF MAMMALIAN SPERM-EGG INTERACTION John C. Herr, USA Molecular mechanisms by which fertilization competent acrosome-reacted sperm bind to the oolemma remain an area of great interest. To identify oolemmal binding partner(s) for sperm acrosomal ligands, affinity panning was performed with mouse oocyte lysates using sperm acrosomal protein, SLLP1 as a target. An oocyte specific membrane metalloproteinase, SAS1B (Sperm Acrosomal SLLP1 Binding Protein [a.k.a. ovastacin]; encoded by the ASTL gene), was identified as a SLLP1 binding partner. SAS1B has 6 splice variants, each containing a zinc binding active site and a putative transmembrane domain, with signal peptides in three variants, resulting in protein microheterogeneity in the oocyte. SAS1B transcripts were ovary specific. SAS1B protein was first detected in early secondary follicles in day 3 ovaries. Immunofluorescence localized SAS1B to the microvillar oolemma of M2 oocytes. After fertilization, SAS1B decreased on the oolemma and became virtually undetectable in blastocysts. In transfected CHO-K1 cells SAS1B localized to the surface of unpermeabilized cells. Recombinant and native SLLP1 colocalized with SAS1B to the microvillar domain of ovulated M2 oocytes. Molecular interactions between mouse SLLP1 and SAS1B were demonstrated by surface plasmon resonance, far-western, yeast twohybrid, recombinant- and native- co-IP analyses. SAS1B bound to SLLP1 with high affinity. SAS1B had protease activity, and SAS1B protein or antibody significantly inhibited fertilization. SAS1B knockout female mice showed a 34% reduction in fertility. SAS1B-SLLP1 is one of the few sperm-egg binding partner pairs where both the oolemma and intra-acrosomal compartment proteins are known. Because SAS1B appears to be restricted among all normal tissues to growing oocytes in secondary and subsequent follicular stages, and because SAS1B appears on the oolemma, consideration has been given to SAS1B as a candidate female contraceptive drug target. A cell model will be described for screening immunotoxin biological drugs targeted to SAS1B.

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CELL CYCLE CONTROL IN HUMAN EMBRYOS: WHY ALL THE ANEUPLOIDY? David Albertini, USA Cell cycle checkpoints in normal tissues serve to maintain genetic integrity so as to eliminate progeny carrying imbalanced chromosome numbers or damaged DNA. This talk will focus on the propensity for human embryos to sustain levels of aneuploidy during preimplantation development without compromising the developmental potential of the conceptus unless it bears extreme cases of genetic imbalance. When considered in the context of a DNA damage checkpoint, it becomes apparent that human embryos have a limited capacity to repair DNA double strand breaks of either maternal or paternal origin.

POST-TRANSCIPTIONAL REGULATIONS DURING OOCYTE-TOZYGOTE TRANSITION Petr Svoboda, Czech Republic In mouse, a major portion of time during the oocyte-to-zygote transition occurs in the absence of transcription, and thus depends on posttranscriptional control of the maternal mRNA pool synthesized during oocyte growth. Many maternal mRNAs are stored in the cytoplasm and are translationally inactive. In somatic cells, the translationally repressed mRNAs are targeted to different RNA granules, such as stress granules or Processing bodies (P-bodies). P-bodies are cytoplasmic foci enriched in mRNA-destabilizing proteins, translational repressors and other RNA binding proteins, and microRNAs (miRNAs). This lecure will provide an overview of the regulation of maternal mRNA storage, recruitment, and degradation in the mouse model system. A particular attention will be paid to behavior of RNA binding proteins during acquisition of developmental competence in fully-grown GV oocytes and to induction of maternal mRNA degradation. PRECONCEPTION PROTEIN LEVELS AND SUBSEQUENT FETAL GROWTH Tom Fleming, UK Our research concerns the interaction between environmental factors and early embryos and oocytes, both in vivo and in vitro using rodent models. These interactions include those mediated through the quality of maternal diet and health status in vivo and the conditions of in vitro culture as used in IVF treatment. Our work has shown that poor diet or sickness or suboptimal culture conditions can induce developmental plasticity leading to long-term phenotypic effects ultimately increasing disease risk in adult life. These effects concern the cardiovascular, metabolic and immune system functioning in particular. Concerns associated with an adverse periconceptional environment will be discussed including consideration of developmental mechanisms of induction and propagation of early programming.

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CELLULAR DISRUPTION WITHIN OOCYTES AND EARLY EMBRYOS CAUSED BY MATERNAL DIABETES â&#x20AC;&#x201C; BASIC AND CLINICAL IMPLICATIONS Kelle H. Moley, USA The negative impact of obesity on reproduction and pregnancy outcome is well known, but the mechanisms and time course responsible for developmental failure remain unclear. The high fat diet induced mouse model for obesity has identified altered mitochondrial activity as one of the mechanisms of obesity-associated reproductive failure. Our data confirm that maternal obesity adversely affects oocyte mitochondrial morphology and function. In addition, mice maintained on a high-fat diet produce oocytes with meiotic spindle and chromosome alignment abnormalities, which lead to aneuploid embryos. Finally, embryos from high-fat fed obese mice that developed normally to the blastocyst stage and are transferred into non-obese dams experience growth retardation and brain abnormalities in the resulting fetuses, demonstrating that the initiating defect occurred earlier than the blastocyst stage, possible in the oocyte. Our results suggest that reduced fertility in obese females is, at least in part, oocyte specific. Further studies are needed to elucidate the reversibility of this phenomenon and whether these defects in mitochondrial energy metabolism are carried over to the next generation .

O-LINKED GLYCOSYLATION MEDIATES THE HYPERGLYCEMIC PATHOLOGY IN OOCYTES AND EARLY EMBRYOS? Jeremy Thompson, Australia Perturbations in the homeostasis of the maternal environment during the periconception period are known to cause alterations to subsequent fetal growth and health of offspring. Maternal peri-conception hyperglycaemia, especially as a result of obesity-induced insulin resistance leading to Type II diabetes, is one such perturbation known to have these effects. However, the causal pathways leading to this developmental programming are only now being examined and understood. Hyperglycaemia is known to cause up-regulation of a relatively minor glucose metabolic pathway, the hexosamine-biosynthesis pathway, the activity of which is also essential for the process of cumulus expansion. However, a consequence of hyperglycaemic induction of this pathway is the up-regulation of a protein post-O-linked glycosylation, of specific target proteins. This -O-linked glycosylation can change protein function, leading to changes in cellular function. These concepts will be developed in the presentation, and potential clinical therapies for the treatment of maternal hyperglycaemia will also be -O-linked glycosylation.

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DIETARY METHYL DONORS DURING THE PRECONCEPTION PERIOD AND THEIR INFLUENCE ON SUBSEQUENT DEVELOPMENT Kevin Sinclair, UK Compelling evidence exists, both from epidemiological studies in humans and direct interventionist studies in animals, to indicate that many non-communicable diseases of adulthood originate from aberrant developmental events that occur in utero. Emerging evidence indicates that maternal malnutrition around the time of conception can predispose offspring to metabolic and cardiovascular diseases in later life. Studies at Nottingham focus on the peri-conceptional period and consider the effects of maternal nutrition with an emphasis on one-carbon metabolism and epigenetic programming of offspring health. Studies extend from rodents to large animals, and utilize embryonic and somatic cells and tissues of human origin. We have demonstrated that physiologically relevant reductions in specific dietary B-vitamins (i.e. B12, folate) and methionine to intending mothers (sheep) can epigenetically modify DNA methylation in their progeny, leading to adult offspring with elevated blood pressure, exhibiting signs of â&#x20AC;&#x17E;metabolic syndromeâ&#x20AC;&#x;; effects most pronounced in male offspring. Parallel studies in the rat reveal common phenotypic effects which were also male specific. Our more recent studies have considered the effects of folate deficiency in women during IVF. Similar phenotypic effects, with respect to ovarian responses to gonadotrophin treatments, to that observed in sheep were reported. On-going studies in sheep using MBD-Seq are attempting to identify those loci associated with hypertension and insulin resistance in offspring. Future studies will focus on the genetics of one-carbon metabolism and the sexually dimorphic phenotypes observed.

MEMBRANE AND CYTOPLASMIC INFLUENCES ON PENETRATION AND POST PENETRATION DEVELOPMENT-- CAN BASIC SCIENCE PROVIDE MARKERS FOR THE CLINICAL EMBRYOLOGIST Jonathan Van Blerkom, USA The molecular architecture of the human oocyte plasma membrane that is consistent with normal fertilization is shown in this presentation to be organized into unique lipid-raft microdomains containing molecules involved in sperm attachment/docking and penetration. These microdomains are subject to different modes of cytoplasmic regulation and fertilization competence is a function of their distribution and density. The function of certain fertilization-associated lipid raft microdomains is dependent upon the bioenergetic state of the subjacent cytoplasm, with ATP levels regulated directly by the magnitude of the membrane potential across the inner membrane in mitochondrial localized in the subplasmalemmal cytoplasm. Dynamic imaging of sperm interactions with the oolemma revealed that one type of lipid raft microdomain is likely responsible for the cessation of sperm head motion at the docking site. Cessation of motion is necessary for robust membrane binding between oolemma and sperm membrane and is a prerequisite for membrane fusion and penetration. This step involves lipid raft microdomains enriched in the tetraspanin membrane protein CD9, which is exposed following the cessation of motion. Studies of failed interactions between sperm and oolemma in morphologically normal MII human oocytes have identified specific causes of sperm binding and penetration failure that can be attributed to specific phenotypes of lipid microdomain organization that (i) are cohort-specific, (ii) account for failure of sperm to attach to the oolemma, and (iii) can be related to both the protocol of ovarian hyperstimulation and maternal reproductive age. Present findings indicate that live cell imaging with developmentally benign fluorescent-tagged lipid microdomain reporters could be used to identify fertilization competent phenotypes for fertilization, and is already effective in diagnosing causes of unexpected fertilization failures after conventional IVF cycles with no male factor and with morphologically normal MII oocytes.

S-14

ROLE OF CHROMATIN REMODELING PROTEINS IN CHROMOSOME SEGREGATION AND THE TRANSMISSION OF ANEUPLOIDY IN MAMMALIAN OOCYTES. BASIC RESEARCH WITH CLINICAL IMPLICATIONS Rabindranath De La Fuente, USA Transmission of an abnormal chromosome complement, a condition called aneuploidy is a major cause of congenital birth defects and early pregnancy loss. Human embryos are particularly susceptible to aneuploidy, which in the majority of cases is due to abnormal chromosome segregation in the oocyte. The molecular mechanisms involved in this process are not known. Chromatin configuration in the nucleus or germinal vesicle (GV) of mammalian oocytes undergoes dynamic epigenetic modifications during oocyte growth. A crucial developmental transition at the culmination of oogenesis, large-scale chromatin remodeling in the GV is essential to confer the female gamete with meiotic and developmental potential. Using several models for the experimental manipulation of chromatin structure and function, our current work seeks to determine the signaling pathways and factors that are involved in chromosome segregation in the mammalian oocyte. Using RNA interference (RNAi) we have begun to explore the role of ATRX, (a chromatin remodeling protein) during meiosis. ATRX becomes exclusively associated with the centromeres of meiotic chromosomes, where it is required to mediate chromosome stability. Loss of ATRX function results in chromosome segregation defects leading to aneuploidy and severely reduced fertility. This lecture will discuss the role of ATRX and associated chromatin remodeling proteins in the epigenetic control of centromere function in mammalian oocytes and embryos as well as potential clinical implications to prevent the onset of aneuploidy in the human oocyte and pre-implantation embryo.

THE MINIMAL OOCYTE â&#x20AC;&#x201C; OR HOW TO CONSTRUCT AN ARTIFICIAL EGG? WHAT ARE THE REQUIREMENTS FOR THE OOCYTE TO ACHIEVE IT MISSION Gerald Schatten, USA With dramatic advances is stem and somatic cells entering into gametogenesis lineages, the previously strict distinction between the mortal somatic lineage and the potentially immortal germ line is now blurred. In this talk, the merits, challenges and possibilities of generating oocytes either in vitro or via xenografts as well as the utilities of these biomanufactured gametes.

HUMAN TUBAL FLUID: IN VIVO AND IN VITRO Patrick Quinn, USA The physico and chemical environment in the human fallopian tube nourishes and protects the oocyte and early preimplantation embryo from the time of ovulation, through fertilization to the early morula stage on day 3 after ovulation. A major aspect of ART since it was first performed in both humans and other mammals has been to create a culture fluid to support this early embryogenesis in vitro. In my talk I will discuss not only how the chemical composition of media used for fertilization and the culture of early cleavage stage human embryos has been developed but also physical aspects of the culture system including pH and temperature parameters. Emerging technologies with respect to new media formats, embryo selection and refinements of culture systems will round-out the talk.

S-15

HOW ANDROGENS AND GENES AFFECT FOLLICLE MATURATION AND OVARIAN AGING Norbert Gleicher, USA For the longest, androgens have been considered detrimental to follicle maturation. Due to observations in rodents and humans, this view has, however, in recent years undergone considerable change. From work in androgen receptor knock out mice (ARKO) mice, it has now become abundantly clear that androgens, indeed, are essential for normal follicle growth. Since androgen receptors are present on granulosa cells only at small growing follicle stages, beneficial androgen effects have to occur at these early follicle development stages. These rodent data also offer explanation for the reported success of dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve (DOR), a treatment now widely utilized all over the world. Our research, therefore, suggests two potentially new directions in reproductive endocrinology and infertility: By apparently successfully treating small growing follicles with androgens, weeks to month before these follicles reach pre-ovulatory gonadotropin-sensitive stages, we, after over 50 years of concentration on only the gonadotropin-sensitive stage of folliculogenesis, point toward the possibility of earlier intervention into follicle maturation. Our DHEA data, indeed, suggest that such earlier interventions may, for the first time, offer the opportunity of still being able to influence egg quality. Our FMR1 data, in turn, suggest that such interventions can be selected based on a patient's genetic make up.

HOW DO OOCYTES TELL TIME? (OOCYTE AGING AND CAN THE CHRONOLOGY SENSING MACHINERY BE RESET) Gerald Schatten, USA The consequences of reproductive aging in women are far too often heartbreaking and it is an enormous societal problem at which many sophisticated and emerging ART treatments are directed. Against background, the fundamental mechanisms of aging at the cellular and molecular levels are being elucidated, so biological solutions for these demographic challenges could be envisioned. At the heart of the question is: â&#x20AC;&#x153;how do oocytes know that they are to remain viable

within the ovaries of a 38 year old woman, and why do their reproductive potentials largely expire once the woman is 42 years old?â&#x20AC;?

S-16

FEMALE REPRODUCTIVE AGING: NEW INSIGHTS INTO AN OLD PROBLEM Mary Herbert, UK Female reproductive lifespan is curtailed by depletion of the germ cell pool and by a prevalence of meiotic segregation errors resulting in aneuploid oocytes and a dramatically increased incidence of infertility, miscarriage, and birth defects. Despite its importance to human reproductive health, the biological basis for the association between meiotic errors and the decline in the germ cell pool during female ageing has until recently remained poorly understood. Recent findings from our lab (Lister et al, 2010, Curr. Biol., 20) and others (Chiang et al, 2010, Curr. Biol. 20) indicate that female ageing is accompanied by depletion of cohesin proteins, which mediate cohesion between sister chromatids. Cohesion between sisters is essential for maintaining the bivalent chromosome structure required for accurate segregation of dyads during the first meiotic division (MI). Consistent with this, two key features of bivalent structure – physical linkages at chiasmata and tightly associated sister centromeres – were disrupted in oocytes from aged mice. This was associated with a dramatically increased incidence of anaphase defects during MI. Our findings give ground to the hypothesis that gradual depletion of chromosomal cohesin in oocytes results in loss of the chromosome architecture required for accurate segregation during MI. Our current investigations are focused on determining the clinical significance of cohesin depletion and deciphering how it is related to germ cell depletion during female aging.

THE IMPACT OF Y CHROMOSOME LIKE REGIONS OF THE X CHROMOSOME (PALINDROMES AND AMPLICONS) ON OVARIAN RESERVE Sherman Silber, USA The Y chromosome contains 60 multicopy genes composed of nine different gene families concentrated in remarkable repeat regions of DNA sequence called amplicons, arranged in mirror images called palindromes. This pattern is very susceptible to deletions caused by homologous recombination with itself. In fact the most common types of mutation would not be those found in conventional regions of sequence that harbor simple single gene polymorphisms but rather in these areas of repeat sequence and multicopy genes that have thus far only been well described for the Y. For most of the human genome (which has been incorrectly thought to be fully sequenced), these regions of amplicons and palindromes are like the “dark side of the moon.” Twelve percent of the X chromosome has this Y-type structure and is likely to harbor many genes that control ovarian reserve. One could also speculate that a loss of genes responsible for de novo male dominant expression (such as autism) are most likely to be on the X chromosome, have not yet been ascertained, and they could very well be located in these ampliconic regions of the X chromosome that have heretofore been undeciphered.

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The fertilization process of the oocyte and embryo development in relation to various clinical conditions

Dorint Hotel Don Giovanni PRAGUE Prague, Czech Republic • November 8-11, 2012

POSTERS

www.comtecmed.com/OC/2012 • ovarian@comtecmed.com 23

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LIST OF POSTERS

Friday, November 9, 2012 Board #

Group A

INSUFFICIENCY OF SPINDLE ASSEMBLY CHECKPOINT IN MOUSE OOCYTES M. Anger1,2, J. Sebestova1,2, A. Danylevska1,2 1 CEITEC - Veterinary Research Institute, Brno, Czech Republic; 2Institute of Animal Physiology and Genetics, Libechov, Czech Republic

PCBS EXPOSURE CAUSES EPI/GENETIC DEFECTS OF SHEEP FOETAL FIBROBLASTS D.A. Anzalone, S. Sampino, M. Czernik, D. Iuso, P. Loi, G. Ptak University of Teramo, Teramo, Italy

EFFICIENCY OF FROZEN OOCYTES FOR POOR RESPONDER’S PATIENTS M. Badalotti1,2, V. Reig1, A. Tagliani-Ribeiro1, D. Kvitko1, L. Okada1, R. Azambuja1, F. Badalotti1, R. Petracco1, J. Michelon1,2, A. Petracco1,2 1 Fertilitat Centro de Medicina Reprodutiva; 2Departamento de Ginecologia, Faculdade de Medicina, PUCRS Porto Alegre, RS, Brasil

MARKERS OF OOCYTE QUALITY FOR OOCYTE CRYOPRESERVATION M. Barberi1, G. Gioacchini2, O. Carnevali2, E. Giorgini2, V. Bianchi1, M.A. Bonu1, R. Canipari3, A. Borini1 1 Centre for Reproductive Health, Bologna, Italy; 2Università Politecnica delle Marche, Ancona, Italy; 3‘La Sapienza’ University of Rome, Italy

ANALYSYS OF OVARIAN FOLLICULAR DEGENERATION CAUSED BY CHRONIC INGESTION OF ETHANOL IN WISTAR RATS I. Bezerra Lima-Verde1, J.C. Santos1, M. Dos Santos Silva1, F. De Santana2, G. Calado De Melo1, M.H. Tavares De Matos2, R.C. Cavalcanti De Albuquerque Jr1, J. Cordeiro Cardoso1 1 University Tiradentes; 2Federal University of São Francisco Valley, Brazil

SUPPLEMENTED EFFECTS OF VASCULAR ENDOTHELIAL GROWTH FACTOR DURING IN VITRO MATURATION OF PORCINE CUMULUS OOCYTE COMPLEXES AND EMBRYOS PRODUCED BY SOMATIC CELL NUCLEAR TRANSFER D. Biswas1,2, S.H. Hyun1 1 Chungbuk National University, Chungbuk, South Korea; 2Chittagong Veterinary and Animal Sciences University, Pahartali, Bangladesh

CYCLIC GUANOSINE MONOPHOSPHATE DOES NOT INHIBIT MITOGEN-ACTIVATED PROTEIN KINASE SIGNALING AND EXPRESSION OF CUMULUS EXPANSION-RELATED GENES IN PORCINE CUMULUS-OOCYTE COMPLEXES M. Blaha, R. Prochazka, L. Nemcova Academy of Sciences of the Czech Republic, Libechov, Czech Republic

P-1

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LIST OF POSTERS

Friday, November 9, 2012 Board #

Group A

POLO-LIKE KINASE I CONTROLS NUCLEAR ENVELOPE BREAK DOWN AND CHROMOSOME DYNAMICS IN MEIOSIS I A. Brzáková1, P. Šolc1, T. Kitajima2, V. Baran3, V. Mayer1, P. Šámalová1, J. Motlík1, J. Ellenberg2 1 AV CˇR, Libeˇchov, CˇR; 2EMBL, Heidelberg, Germany; 3Institute of Animal Physiology, Kosice, Slovakia

GONADAL FOXO EXPRESSION IN THE GERMLINE AND SOMATIC COMPARTMENTS OF DIVERSE MAMMALIAN SPECIES D. H. Castrillon, E. Tarnawa, M. D. Baker, G. Aloisio UT Southwestern Medical Center, Dallas, TX, USA

COMPARISON OF PROLACTIN, FREE T3 AND FREE T4 LEVELS IN THE FOLLICULAR FLUID OF INFERTILE WOMEN AND HEALTHY FERTILE OOCYTE DONORS M. Cedikova1, V. Babuska1, N. Zech2, M. Kralickova1 1 Charles University in Prague, Plzen, Czech Republic; 2Institute of Reproductive Medicine and Endocrinology, Plzen, Czech Republic

IMPROVED BLOOD SUPPLY BY SUBCUTANEOUS INJECTION OF HUMAN ENDOTHELIAL PROGENITOR CELLS (HEPCS) MAY INCREASE SURVIVAL OF TRANSFERRED VITRIFIED/ WARMED MOUSE OVARY S.K. Cha, M.K. Kim, D.H. Shin, J.M. Kim, W.S. Lee, T. K. Yoon, D.R. Lee CHA University College of Medicine, Seoul, Korea

DISTRIBUTION OF THE INSLQ VARIANT IN LUTEINIZING HORMONE RECEPTOR (LHCGR) IN FERTILE CZECH MALE AND FEMALE CONTROLS J. Chrudimská, P. Krˇenková, M. Macek jr., M. Macek sr. Department of Biology and Medical Genetics, Charles University Prague – 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic

ULTRASTRUCTURE ANALYSIS OF BLASTOCYSTS PRODUCED BY SOMATIC CELL NUCLEAR TRANSFER (SCNT) M. Czernik1, F. Zacchini1, F. Di Egidio1, D. Iuso1, J. Modlinski2, P. Loi1, G. Ptak1 1 Department of Comparative Biomedical Science, University of Teramo, Teramo, Italy; 2 Department of Experimental Embryology, Institute of Genetics and Animal Breeding of the Polish Academy of Science, Jastrze˛biec, Poland

OVARIAN STIMULATION PRECEDING CANCER THERAPY DOES NOT EFFECT OVARIAN RESPONSE TO SUBSEQUENT GONADOTOXIC TREATMENT K.E. Dillon1, M.D. Sammel1, J.P. Ginsberg3, Y. Gosiengfiao4, M. Prewitt1, C.R. Gracia1 1 University of Pennsylvania, Philadelphia, USA; 2Children's Hospital of Philadelphia, Philadelphia, USA; 3University of North Carolina, Chapel Hill, USA; 4Children's Memorial Hospital, Chicago, USA

P-2

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LIST OF POSTERS

Friday, November 9, 2012 Board #

Group A

DYNAMICS OF DNA METHYLATION LEVELS IN RABBIT PREIMPLANTATION EMBRYOS DEVELOPED IN VIVO OR IN VITRO V. Duranthon1, A. Reis e Silva1, C. Bruno1, R. Fleurot1, N. Daniel1, P.G. Adenot1, C. Archilla1, N. Peynot1, C.M. Lucci2, N. Beaujean1 1 INRA UMR 1198, Jouy en Josas. France; 2Faculty of Veterinary Medicine, Brasilia, Brasil

IN VITRO EMBRYO DEVELOPMENT AFFECTS MATURATION OF PLACENTAL VESSELS A. Fidanza, P. Toschi, C. Palmieri, P. Loi, G. Ptak Department of Biomedical Sciences, University of Teramo, Italy

PROTEOMIC BIOMARKERS OF PRETERM BIRTH RISK IN WOMEN WITH POLYCYSTIC OVARY SYNDROME (PCOS): A SYSTEMATIC REVIEW AND BIOMARKER DATABASE INTEGRATION N. Galazis1, N. Docheva2, K. Nicolaides1, W. Atiomo2 1 North Central Thames Foundation School - UCL, UK; 2Nottingham University Medical School, UK

PROTEOMIC BIOMARKERS FOR OVARIAN CANCER RISK IN WOMEN WITH POLYCYSTIC OVARY SYNDROME (PCOS). A SYSTEMATIC REVIEW AND BIOMARKER DATABASE INTEGRATION N. Galazis1, S. Drymiotou2, S.N. Thoukididou2, W. Atiomo2 1 North Central Thames Foundation School; 2Nottingham University Medical School, UK

A NEW APPROACH TO EVALUATE AGING EFFECTS ON HUMAN OOCYTES: FPA FTIR IMAGING ANALYSIS G. Gioacchini1,2, E. Giorgini2, V. Bianchi1, P. Ferraris3, C. Conti2, L. Vaccari3, O. Carnevali2, A. Borini1 1 Tecnobios Procreazione, Centre for Reproductive Health, Bologna, Italy; 2Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, Ancona, Italy; 3 SISSI Beamline, Elettra Synchrotron Light Laboratory, Trieste, Italy

FERTILITY PRESERVATION COUNSELING PRIOR TO GONADOTOXIC TREATMENT A.R. Han, T.H. Lee, S.S. Jeon, Y.J. Cho Kyungpook National University Hospital, Daegu, Korea

THE TIMING OF EARLY EMBRYO CLEAVAGES–OBJECTIVELY MEASURABLE PREDICTOR OF HUMAN EMBRYO VIABILITY D. Hlinka1, S. Lazarovska1, M. Pichlerova1, I. Hamplova1, M. Stevikova1, J. Rutarova2, J. Razacova2, M. Dudas3 1 Prague Fertility Centre, Prague, Czech Republic; 2Institute for the Care of Mother and Child, Prague, Czech Republic; 3P. J. Safarik University Institute of Biology and Ecology, Kosice, Slovakia

P-3

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LIST OF POSTERS

Friday, November 9, 2012 Board #

Group A

TREATMENT OF SOMATIC CELLS WITH BIO IMPROVES THE NUCLEAR REPROGRAMMING OF SHEEP FIBROBLASTS D. Iuso University of Teramo, Teramo, Italy

IMPACT OF DHEA ON CLINICAL OUTCOME IN POOR RESPONDERS P.R. Jirge1,2, S.M. Chougule1, V. Sawant1, D.A. Bhomkar1 1 Sushrut Assisted Conception Clinic, Kolhapur, India; 2Rajeev Gandhi University, Bangalore, India

2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN(TCDD) INCREASES THE EXPRESSION OF CYCLOOXYGENASE-2 AND AROMATASE CYTOCHROME P 450 IN HUMAN ENDOMETRIUM Y.A. Kim, J.Y. Kim, K.C. Jun, D.Y. Chang, J.W. Park, Y.J. Choi, J.A. Jang Inje University Ilsan Paik Hospital, Goyangsi, S. Korea

COMPARISON OF HOMOCYSTEINE LEVELS IN THE FOLLICULAR FLUID OF INFERTILE WOMEN AND HEALTHY FERTILE OOCYTE DONORS M. Kralickova1, V. Babuska1, M. Cedikova1, B. Wirleitner2, N.H. Zech2 1 Charles University in Prague, Plzen, Czech Republic; 2Institute of Reproductive Medicine and Endocrinology, Plzen, Czech Republic

GROUP IVA PHOSPHOLIPASE A2 COOPERATES WITH CYCLOOXYGENASE-2 TO OPTIMIZE OVULATION AND FERTILIZATION IN RODENTS S. Kurusu1, A Sapirstein2, J.V. Bonventre3 1 Kitasato University School of Veterinary Medicine, Towada, Japan; 2Johns Hopkins University, Baltimore, USA; 3Brigham and Women's Hospital, Boston, USA

P-4

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LIST OF POSTERS

Saturday, November 10, 2012 Board #

Group B

CONCENTRATIONS OF FOLLICULAR FLUID LEPTIN AND ADIPONECTIN CAN PREDICT QUALITY OF ENSUING OOCYTE AND EMBRYO J.H. Lee1, J.R. Lee1,2, H.J. Chang1, B.C. Jee1,2, C.S. Suh1,2, S.H. Kim2 1 Seoul National University Bundang Hospital, Seongnam, Korea; 2Seoul National University College of Medicine, Seoul, Korea

CENTRALLY LOCATED GRANULAR CYTOPLASM OF THE OOCYTE: THE ULTRASTRUCTURAL ANALYSIS N. Makarova, L. Kazaryan, E. Kalinina, V. Polyakov, G. Baranova Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov, Russia

BIOENERGY/OXIDATIVE STATUS OF EQUINE OOCYTES HELD IN THE ABSENCE OF MEIOSIS INHIBITORS BEFORE IN VITRO MATURATION N.A. Martino1, M.E. Dell'Aquila1, G.M. Lacalandra1, M. Filioli Uranio1, K. Hinrichs2 1 University of Bari Aldo Moro, Italy; 2Texas A&M University, College Station, Texas, USA

PRESERVATION OF CAPRINE OVARIAN TISSUE USING DIFFERENT MEDIA AND INCUBATION PERIODS: EFFECTS ON MORPHOLOGY, APOPTOSIS AND DEVELOPMENT OF PREANTRAL FOLLICLES IN VITRO M.H.T. Matos1, R.J.S. Gonçalves1, A.Y.P. Cavalcante1, B.B. Gouveia1, T.L.B. Lins1, R.S. Barberino1, V.G. Menezes1, V.R.P. Barros1, L.P. Santos1, J.M.S. Santos1, J.R. Figueiredo2 1 Federal University of San Francisco Valley, Petrolina, Brazil; 2State University of Ceara, Fortaleza-CE, Brazil

ANTI-MÜLLERIAN HORMONE DYNAMICS DURING CONTROLLED OVARIAN HYPERSTIMULATION L. Melado Vidales1, V. Fernandez Villafañez1, V. Verdú Merino1, J.M. Bajo Arenas1, I. Bruna Catalán2 1 Clínica Ginefiv, Madrid; 2Hospital Universitario Montepríncipe, Madrid, Spain

AMH IS USEFUL TO PREDICT IVF/ICSI OUTCOME, OOCYTE MATURATION AND EMBRYO QUALITY L. Melado Vidales, V. Fernandez Villafañez, V. Verdú Merino, J.M. Bajo Arenas Clínica Ginefiv, Madrid

P-5

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LIST OF POSTERS

Saturday, November 10, 2012 Board #

Group B

MOUSE ANTRAL NSN OOCYTE DEVELOPMENTAL ARREST IS ASSOCIATED WITH DEFICIENCY OF MATER AND CYTOPLASMIC LATTICES M. Monti1, M. Zanoni2, A. Calligaro3, M.S.H. Ko4, P. Mauri5, C.A. Redi1,2 1 Fondazione IRCCS Ospedale San Matteo, Pavia, Italy; 2Laboratory of Developmental Biology, University of Pavia, Pavia, Italy; 3Department of Experimental Medicine, Histology and Embryology Unit, University of Pavia, Pavia, Italy; 4Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD, USA; 5Proteomics and Metabolomics Unit, Institute for Biomedical Technologies (ITB-CNR), Segrate, Italy

LAPATINIB THROUGH EGFR TYROSINE KINASE INHIBITION AFFECTS OOCYTE MATURATION E. Nagyova1, L. Nemcova1, A. Mlynarcikova2, S. Scsukova2, J. Kalous1 1 Institute of Animal Physiology and Genetics, Libechov, Czech Republic; 2Institute of Experimental Endocrinology, Bratislava, Slovakia

EFFECTIVENESS OF DIFFERENT MEIOTIC TRIGGERS UPON IN VITRO GROWN FOLLICLES APPEARS TO BE LINKED TO REGULATION OF THE CNP-NPR2 SYSTEM S. Romero, F. Sánchez, J. Smitz Vrije Universiteit Brussel, Brussels, Belgium

PATERNAL AGING INDUCE TRANSGENERATIONAL COMUNICATIVE DISFUNCTIONS IN MICE S. Sampino1, F. Zacchini1, J. A. Modlinski2, A.H. Swiergiel2, P. Loi1, G. Ptak1 1 University of Teramo, Italy; 2Institute of Genetic and Animal Breeding, Italy

ALTERATION OF OVARIAN STEROIDOGENESIS BY THE ACTION OF POLYMERIC NANOPARTICLE POLY (ETHYLENE GLYCOL)-BLOCK-POLY (LACTIC ACID) (PEG-B-PLA) S. Scsukova1, A. Mlynarcikova1, K. Smolikova1, J. Jurcovicova1, E. Rollerova2 1 Institute of Experimental Endocrinology Slovak Academy of Sciences, Bratislava, Slovak Republic; 2Department of Toxicology Slovak Medical University, Bratislava, Slovak Republic

GAMETE SPECIFIC RECOMBINANT PROTEINS BASED CONTRACEPTIVE VACCINE A. Shrestha1, N. Gupta1, D. Munshi1, V.A. Srinivasan2, S. Rajan2, R. Matur2, A.K. Panda1, S.K. Gupta1 1 National Institute of Immunology, New Delhi, India; 2Indian Immunologicals Limited, Hyderabad, India

FOLLICLE SIZE AND TRANSFERABLE EMBRYOS IN WOMEN, FOLLICULAR MARKERS TO IDENTIFY THE BEST MEDIUM SIZE FOLLICLES M.A. Sirard1, A.L. Nivet1, I. Dufort1, M.C. Leveillé2 1 Centre de recherche en biologie de la reproduction, Université Laval, Québec, QC, Canada; 2Centre de Fertilité d’Ottawa, Canada

P-6

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LIST OF POSTERS

Saturday, November 10, 2012 Board #

Group B

ANTI-ENDOMETRIAL DEVELOPMENTAL ACTION OF A SYNTHETIC GLUCOCORTICOID: INVOLVEMENT OF DECIDUAL PARACRINE AND OVARIAN ENDOCRINE MECHANISMS F. Spencer1, M.L. Thompson1, L. Qi2 1 Southern University, Biological Sciences & Health Research Center, Baton Rouge, Louisiana; 2University of Illinois, Biomedical and Therapeutic Sciences, Peoria, Illinois, USA

INTERACTIVE ROLES BETWEEN OVARIAN AND UTERINE MECHANISMS IN THE REGULATION OF ENDOMETRIAL DEVELOPMENT F. Spencer1, M.L. Thompson1, L. Qi2 1 Southern University, Biological Sciences & Health Research Center, Baton Rouge, Louisiana; 2University of Illinois, Biomedical and Therapeutic Sciences, Peoria, Illinois, USA

EFFECT OF THE FORM AND TEMPORAL ADDITION OOCYTE-SECRETED FACTORS DURING IN VITRO MATURATION OF MOUSE OOCYTES ON SUBSEQUENT EMBRYO AND FETAL DEVELOPMENT J. Sudiman, L. Ritter, D. Feil, D. Mottershead, J. Thompson, R. Gilchrist Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, Australia

HOW THE EMBRYO DEALS WITH OOCYTE LEGACY: EARLY INSPECTING OF MITOCHONDRIAL POOL L. Surlan1, I. Golic2, M. Vucetic2, K. Velickovic2, V. Stankovic1, J. Micic1,2, J. Stojnic1,2, I. Tulic1,2, V. Otasevic2, B. Korac2, A. Korac2 1 Clinic for Obstetrics and Gynecology Clinical Centre of Serbia, Belgrade, Serbia; 2 University of Belgrade, Belgrade, Serbia

CHANGES IN CUMULUS CELL METABOLISM & MOTILITY IMMEDIATELY FOLLOWING FERTILIZATION DURING BOVINE IVF J. Thompson, M. Sutton-McDowall The Robinson Institute, School of Pediatrics and Reproductive Health, The University of Adelaide

TWO DIFFERENT WAYS TO DIE: APOPTOSIS AND AUTOPHAGY IN SHEEP MONOPARENTAL PLACENTAE P. Toschi, A. Fidanza, M. Czernik, P. Loi, G. Ptak Department of comparative biomedical sciences, University of Teramo, Italy

P-7

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LIST OF POSTERS

Saturday, November 10, 2012 Board #

Group B

SPERM-DERIVED HISTONES CONTRIBUTE TO PERICENTRIC HETEROCHROMATIN IN HUMAN PRE-IMPLANTATION EMBRYOS C. Van de Werken1, G.W. Van der Heijden1, C.J.H. Van Veen-Buurman1, J.S.E. Laven1, A.H.F.M. Peters2, E.B. Baart1 1 University Medical Center, Rotterdam, The Netherlands; 2Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

LONG AND REGULAR MENSTRUAL CYCLES IN OOCYTE DONORS LEAD TO HIGHER PREGNANCY RATES IN IVF/ICSI RECIPIENTS R. Vassena1, A. Obradors1, R. Vidal1, O. Coll1, V. Vernaeve1,2 1 Clinica EUGIN, Barcelona, Spain; 2Fundaciò EUGIN, Barcelona, Spain

SLOWER PRE-EMBRYO DEVELOPMENT WITH INCREASING SERUM LEVELS OF YKL-40 IN WOMEN UNDERGOING IN VITRO FERTILIZATION M.L. Wissing1, M. Aziz2, S.O. Skouby2, T. Hoest1, A.L. Mikkelsen1 1 Department of Obstetrics and Gynecology, Holbaek Hospital; 2University of Copenhagen, Herlev Hospital, Denmark

LATE LUTEAL PHASE START CONTROLLED OVARIAN HYPERSTIMULATION FOR EMERGENCY FERTILITY PRESERVATION H.R. Wi1, J.R. Lee1,2, H. Youm1, B.C. Jee1,2, C.S. Suh1,2, S.H. Kim2 1 Seoul National University Bundang Hospital, Seongnam, Korea; 2Seoul National University College of Medicine, Seoul, Korea

EFFECTS OF Г-SECRETASE INHIBITOR ON MOUSE EMBRYO IMPLANTATION G.J. Wu1,2, P.W. Chu1,2, Y.P. Wang2, I.C. Chen2 1 National Defense Medical Center; 2Tri-Service General Hospital, Taipei, Taiwan

EFFECTS OF Г-SECRETASE INHIBITOR ON EMBRYO IMPLANTATION AND EARLY PLACENTATION G.J. Wu1,2, P.W. Chu1,2, Y.P. Wang2, I.C. Chen2 1 Graduate Institute of Medical Sciences, National Defense Medical Center; 2 Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan

EFFECT OF NECROSTATIN ON OVARIAN CRYOPRESERVATION AND TRANSPLANTATION H. Youm1, J.R. Lee1,2, H.J. Chang1,2, B.C. Jee1,2, C.S. Suh1,2, S.H. Kim2 1 Seoul National University Bundang Hospital, Seongnam, Korea; 2Seoul National University College of Medicine, Seoul, Korea

P-8

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Ovarian Club II Participants came from... 38 countries

Argentina

Australia

Austria

Bangladesh

Belgium

Brazil

Bulgaria

Canada

Chile

China

Czech Republic

Denmark

Finland

France

Germany

Hungary

India

Ireland

Israel

Italy

Japan

Korea

Norway

Poland

Romania

Russia

Serbia

Slovak Republic

South Korea

Spain

Sweden

Switzerland

Taiwan

The Netherlands

Ukraine

Uruguay

USA

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The fertilization process of the oocyte and embryo development in relation to various clinical conditions

Dorint Hotel Don Giovanni PRAGUE Prague, Czech Republic • November 8-11, 2012

INDEX

www.comtecmed.com/OC/2012 • ovarian@comtecmed.com 23

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A Adenot, P.G. Albertini, A. Aloisio, G. Anckaert, E. Anger, M. Anzalone, D.A. Arav, A. Archilla, C. Atiomo, W. Azambuja, R. Aziz, M.

Program Page

Abstract Page

14, 17

P-3 S-1, S-12 P-2

Calado De Melo, G. Calligaro, A. Canipari, R. Carnevali, O. Castrillon, D. H. Cavalcante, A.Y.P. Cavalcanti De Albuquerque Jr, R.C. Cedikova, M. Cha, S.K. Chang, D.Y. Chang, H.J. Chen, I.C.

Cho, Y.J. Choi, Y.J. Chougule, S.M. Chrudimská, J. Chu, P.W. Coll, O. Conti, C. Cordeiro Cardoso, J. Crosignani, P. Czernik, M.

Baart, E.B. Babuska, V. Badalotti, F. Badalotti, M. Bajo Arenas, J.M. Baker, M. D. Baran, V. Baranova, G. Barberi, M. Barberino, R.S. Barros, V.R.P. Beaujean, N. Bezerra Lima-Verde, I. Bhomka, D.A. Bianchi, V. Biswas, D. Blaha, M . Bonu, M.A. Bonventre, J.V. Borini, A. Bruna Catalán, I. Bruno, C. Brzáková, A.

C (con't)

P-1 P-1 S-3 P-3 P-3 P-1 P-8

Program Page

15, 19

Daniel, N. Danylevska, A. Dattilo, M. De La Fuente, R. De Santana, F. De Ziegler, D. Dekel, N. Dell'Aquila, M.E. Di Egidio, F. Dillon, K.E. Docheva, N. Dos Santos Silva, M. Drymiotou, S.

S-8, P-8 P-2, P-4 P-1 P-1 P-5 P-2 P-2 P-5 P-1 P-5 P-5 P-3 P-1 P-4 P-1, P-3 P-1 P-1 P-1 P-4 P-1, P-3 P-5 P-3 P-2

15 18

Dudas, M. Dufort, I. Duranthon, V.

S-15 P-1 S-8 S-5 P-5 P-2 P-2 P-3 P-1 P-3 P-3 P-6 P-3

Ellenberg, J.

P-2

Feil, D. Fernandez Villafañez, V. Ferraris, P. Fidanza, A. Figueiredo, J.R. Filioli Uranio, M. Fleming, T. Fleurot, R. Friedler, S.

P-7 P-5 P-3 P-3, P-7 P-5 P-5 S-12 P-3

16, 19 15

Galazis, N. Gilchrist, R. Ginsberg, J.P. Gioacchini, G. Giorgini, E. Gleicher, N. Golic, I. Gonçalves, R.J.S.

P-3 P-4 P-4 P-2 P-8 P-8 P-3 P-1 S-6 P-1, P-2, P-7 P-3 P-1

P-1 P-6 P-1 P-1, P-3 P-2 P-5 P-1 P-2, P-4 P-2 P-4 P-5, P-8 P-8

Abstract Page

17 16

18, 19

P-3 P-7 P-2 P-1, P-3 P-1, P-3 S-16 P-7 P-5

G (con't) Gosiengfiao, Y. Gouveia, B.B. Gracia, C.R. Gupta, N. Gupta, S.

Program Page

Abstract Page

P-2 P-5 P-2 P-6 P-6

Hamamah, S. Hamplova, I. Han, A. R. Hartshorne, G. Herbert, M.

Herr, J.C. Hinrichs, K. Hlinka, D. Hoest, T. Hourvitz, A. Hunt, P. Hyun, S.H.

15 19

15 15

L Lacalandra, G.M. Lalioti, M. Laven, J.S.E. Lazarovska, S. Lee, D.R. Lee, J.H. Lee, J.R. Lee, T.H. Lee, W.S. Leveillé, M.C. Lins, T.L.B.

S-7 P-3 P-3 S-7 S-17 S-11 P-5 P-3 P-8 S-4 S-5 P-1

P-1, P-2, P-4

Jang, J.A. Jee, B.C. Jenkins, J. Jeon, S.S. Jirge, P.R. Jun, K.C. Jurcovicova, J.

P-4 P-5, P-8 18 P-3 P-4 P-4 P-6

Kalinina, E. Kalous, J. Kazaryan, L. Kim, J.M. Kim, J.Y. Kim, M.K. Kim, S.H. Kim, Y.A. Kitajima, T. Ko, M.S.H. Korac, A. Korac, B. Korach, K. Kralickova, M. N� hqnry «/#S1# Kurusu, S. Kvitko, D.

14, 15

Loi, P. Lucci, C.M.

Iuso, D.

Program Page

P-5 P-6 P-5 P-2 P-4 P-2 P-5, P-8 P-4 P-2 P-6 P-7 P-7 S-6 P-2, P-4 P-2 P-4 P-1

Macek jr., M. Macek sr, M. Makarova, N. Martino, N.A. Mashiach, S. Matos, M.H.T. Matur, R. Mauri, P. Mayer, V. Melado Vidales, L. Menezes, V.G. Meseguer, M. Michelon, J. Micic, J. Mikkelsen, A.L. Mlynarcikova, A. Modlinski, J. Moley, K.H. Monti, M. Motlik, J. Mottershead, D. Munshi, D.

Obradors, A. Okada, L. Otasevic, V. Ozil, J.P.

P-5 S-8 P-8 P-3 P-2 P-5 P-5, P-8 P-3 P-2 P-6 P-5 P-1, P-2, P-3, P-6, P-7 P-3 P-2 P-2 P-5 P-5

17 15, 18

Nagyova, E. Nemcova, L. Nicolaides, K. Nivet, A.L. Noyes, N.

Abstract Page

P-5 P-6 P-6 P-2 P-5 P-5 S-9 P-1 P-7 P-8 P-6 P-2, P-6 S-13 P-6 S-5, P-2 P-7 P-6

14, 17

P-6 P-1, P-6 P-3 P-6 S-3

P-8 P-1 P-7 S-11

Program Page

Abstract Page

S (con't)

Palmieri, C. Panda, A.K.

P-3 P-6

Shrestha, A. Silber, S.

Park, J.W. Patrizio, P. Peters, A.H.F.M. Petracco, A. Petracco, R. Peynot, N. Pichlerova, M. Platon, J.V. Polyakov, V. Prewitt, M. Prochazka, R.

P-4 S-2 P-8 P-1 P-1 P-3 P-3

Simón, C. Sinclair, K. Sirard, M.A. Skouby, S.O. Smitz, J. Smolikova, K. ý rof /#S1# Spencer, F. Srinivasan, V.A. Stankovic, V. Stevikova, M.

Ptak, G.

P-5 P-2 P-1 P-1, P-2, P-3, P-6, P-7

Qi, L. Quinn, P.

P-7 S-15

Q R

Rajan, S. Razacova, J. Redi, C.A. Reig, V. Reis e Silva, A. Ritter, L. Rollerova, E. Romero, S. Rubio, C. Rutarova, J.

15, 18

Sakkas, D. ý «p dory «/#S1# Sammel, M.D. Sampino, S. Sánchez, F. Santos, J.C. Santos, J.M.S. Santos, L.P. Sapirstein, A. Sawant, V. Schatten, G. Scsukova, S. Sebestova, J. Seli, E. Sen, A. Shin, D.H. Shoham, Z.

14, 18, 19

16 15

P-6 P-3 P-6 P-1 P-3 P-7 P-6 P-6 S-10 P-3

Stojnic, J. Sudiman, J. Suh, C.S. Surlan, L. Sutton-McDowall, M. Svoboda, P. Swiergiel, A.H.

Program Page

14, 19 14, 16, 17 17

Tagliani-Ribeiro, A. Tarnawa, E. Tavares De Mato, M.H. Telfer, E. Thompson, J. Thompson, M.L. Thoukididou, S.N. Tilly, J. Toschi, P. Tulic, I.

S-10 P-2 P-2 P-1, P-6 P-6 P-1 P-5

14, 15 15, 17

Vaccari, L. Van Blerkom, J. Van de Werken, C. Van der Heijden, G.W. Van Veen-Buurman, C.J.H. Vassena, R. Velickovic, K.

P-5 P-4 P-4 S-15, S-16 P-6 P-1 S-9 S-4 P-2

14, 19

III

Verdú Merino, V. Vernaeve, V. Vidal, R. Vucetic, M.

17, 18

Abstract Page

P-6 S-3, S-17

S-14 P-6 P-8 P-6 P-6 P-2 P-7 P-6 P-7 P-3 P-7 P-7 P-5, P-8 P-7 P-7 S-12 P-6 P-1 P-2 P-1 S-1 S-13, P-7 P-7 P-3 S-1 P-3, P-7 P-7 P-3 S-14 P-8 P-8 P-8 P-8 P-7 P-5 P-8 P-8 P-7

W Wang, Y.P. Wi, H.R. Wirleitner, B. Wissing, M.L. Woods, D. Wu, G.J.

Program Page

Abstract Page

14 18

P-8 P-8 P-4 P-8 S-2 P-8

Yoon, T. K. Youm, H.

P-2 P-8

Zacchini, F. Zanoni, M. Zech, N.

P-2, P-6 P-6 P-2, P-4

The Inverse Pyramid: Regulating Follicle Number and Oocyte Quality

PARIS, FRANCE • NOVEMBER 14-17, 2013 ORGANIZING COMMITTEE P. Bouchard, France P. Devroey, Belguim J. Eppig, USA B. Fauser, The Netherlands R. Fleming, UK

N. Gleicher, USA S. Hamamah, France K. Korach, USA S. Mashiach, Israel J. Motlik, Czech Republic F. Olivennes, France

G. Schatten, USA Z. Shoham, Israel J. Smitz, Belgium E. Telfer, UK J. Thompson, Australia

www.comtecmed.com/OC/2012 • ovarian@comtecmed.com

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NOTES

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Dupha_Anz_Ovarian_Club_RZ

11.10.2012

10:55 Uhr

Seite 1

Ovarian Club II Meeting

Prague, Czech Republic November 8 –11, 2012

Friday, November 9 2012 13.45 –14.15 h th

Julian Platon, MD PhD

Company Presentation on „New Horizons: The voice of the industry“

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More live births with MENOPUR® 1,2 vs. rFSH following IVF1,2

A fact you can hold on to

The fertilization process of the oocyte and embryo development in relation to various clinical conditions

Dorint Hotel Don Giovanni PRAGUE Prague, Czech Republic • November 8-11, 2012

MENOPUR Multidose is now available, offering a more convenient treatment option compared to MENOPUR 75 IU3

Ferring International Center SA Chemin de la Vergognausaz 50 CH 1162 St-Prex Switzerland www.ferring.com

OC II cover-RUN.indd 1

PROGRAM

www.comtecmed.com/OC/2012 • ovarian@comtecmed.com

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