ovarian club ii final book

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

www.comtecmed.com/OC/2012 • [email protected]

MENOPUR Multidose is now available,offering a more convenient treatment option

compared to MENOPUR 75 IU3



Ferring International Center SAChemin de la Vergognausaz 50CH 1162 St-PrexSwitzerlandwww.ferring.com

More live births with MENOPUR®

vs. rFSH following IVF1,2

A fact you can hold on to




OC II cover-RUN.indd 1 22/10/12 12:21:19

Ovarian Club IIMeeting

Friday, November 9th 201213.45 –14.15 h

Prague, Czech RepublicNovember 8 –11, 2012

Company Presentation on„New Horizons: The voice ofthe industry“

Julian Platon, MD PhD


Dupha_Anz_Ovarian_Club_RZ 11.10.2012 10:55 Uhr Seite 1

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

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

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 Léc iva, 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

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.


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

23



PROGRAM









01-12-OC II- part 1.indd 3 22/10/12 12:02:04

Fostimon®

Highly purified hFSH

Listen to the oocyte

Evidence of life

Adv Fostimon A4 2011_rev10_3_11.indd 1 10.03.11 08.18

01-12-OC II- part 1.indd 4 22/10/12 12:02:08


3

Fostimon®

Highly purified hFSH

Listen to the oocyte

Evidence of life

Adv Fostimon A4 2011_rev10_3_11.indd 1 10.03.11 08.18

TiMeTAble

THuRsDay, NovembeR 8, 2012

FRiDay, NovembeR 9, 2012

14:30-16:30 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

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


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


11:00-13:00 SeSSion 8: Metabolic programming during the preconception period and implications for subsequent fetal, neo-natal and adult health


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


16:45-18:45 SeSSion 10: Aging

suNDay, NovembeR 11, 2012

Travel day

01-12-OC II- part 1.indd 5 22/10/12 12:02:10


4

Table of ConTenTs

Welcome Note 5

Organizing Committee 6

Club Speakers 7

CME Accreditation 8

Sponsors 9

List of Sponsors 10

General Information 11

Scientific Program 13

Thursday, November 8, 2012 14

Friday, November 9, 2012 15

Saturday, November 10, 2012 17

Club Speakers’ Overviews 21

Posters 39

Index 49

01-12-OC II- part 1.indd 6 22/10/12 12:28:14


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-of-the–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

Dear Friends and Colleagues

P. bouchard, FranceP. Devroey, BelguimJ. eppig, USAb. Fauser, The NetherlandsR. Fleming, UKs. Hamamah, FranceK. Korach, USA

s. mashiach, IsraelJ. motlik, Czech RepublicG. schatten, USAZ. shoham, IsraelJ. smitz, Belgiume. Telfer, UKJ. Thompson, Australia

01-12-OC II- part 1.indd 7 22/10/12 12:02:14


6

ORGAnizinG COMMiTTee

Philippe bouchard France

Ken KorachUSA

Zeev shohamIsrael

Paul DevroeyBelgium

shlomo mashiachIsrael

Johan smitzBelgium

John eppigUSA

Jan motlikCzech Republic

evelyn TelferUK

bart FauserThe Netherlands

Richard FlemingUK

samir HamamahFrance

Gerald schattenUSA

Jeremy Thompson Australia

01-12-OC II- part 1.indd 8 22/10/12 12:02:20


7

David albertini, USAellen anckaert, Belgiumamir arav, Israelesther baart, The NetherlandsPiergiorgio Crosignani, ItalyRabindranath De La Fuente, USANava Dekel, IsraelDominique De Ziegler, Franceadrian ellenbogen, IsraelTom Fleming, UKshevach Friedler, IsraelNorbert Gleicher, USAsatish Gupta, Indiasamir Hamamah, FranceGeraldine Hartshorne, UKmary Herbert, UKJohn C. Herr, USAariel Hourvitz, IsraelPatricia Hunt, USAKenneth Korach, USAmaria Lalioti, USAshlomo mashiach, Israel marcos meseguer, Spain

Kelle H. moley, USAJan motlik, Czech RepublicNicole Noyes, USAJean-Pierre ozil, FrancePasquale Patrizio, USAPatrick Quinn, USACarmen Rubio, SpainDenny sakkas, USAGerald schatten, USAemre seli, USAaritro sen, USAZeev shoham, Israelsherman silber, USACarlos simón, SpainKevin sinclair, UKPeter svoboda, Czech Republicevelyn Telfer, UKJeremy Thompson, AustraliaJonathan Tilly, USAJonathan van blerkom, USADori Woods, USAGwo-Jang Wu, Taiwan

Club sPeAkeRs

01-12-OC II- part 1.indd 9 22/10/12 12:02:25


8

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 aCCReDiTaTioNeuropean Accreditation is granted by the eACCMe in order to allow participants who attend the above-mentioned activity to validate their credits in their own country.

aCCReDiTaTioN sTaTemeNTAccreditation 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 CReDiTseach 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.

01-12-OC II- part 1.indd 10 22/10/12 12:02:25


9

sPOnsORs

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

Institut Biochimique SA

01-12-OC II- part 1.indd 11 22/10/12 12:02:26


10

ACknOwledGeMenTs

Institut Biochimique SA

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, pain-management, dermatology and thyroid diseases.

abbott Products operations aGContact person: Julian V. PlatonHegenheimermattweg 1274123 AllschwilSwitzerlandTel: +41 61 487 0200Fax: +41 61 487 0299email: [email protected]

Ferring PharmaceuticalsFerring international Center S.ACh. de la Vergognausaz 50, 1162 Saint-Prex, SwitzerlandTel: +41 58 301 00 00Fax: +41 58 301 03 71www.ferring.com

ibsa institut biochimique saVia del Piano, P.o. Box 266, 6915 Pambio-noranco, Lugano, SwitzerlandTel: +41 58 360 10 00Fax: +41 58 360 16 47email: [email protected]

01-12-OC II- part 1.indd 12 22/10/12 12:02:27


11

GeneRAl infORMATiOn

meeTiNG veNuedorint Hotel don Giovanni Prague Vinohradská 157a13020 Prague, Czech Republic

LaNGuaGe english is the official language of the Meeting.

CLoTHiNGinformal for all occasions

ReGisTRaTioN aND HosPiTaLiTy DesK oPeNiNG HouRsThe 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 NameTaGnametags are included in your personal Meeting kit. Please wear your nametag during all sessions and social events.Key colors for nametags:

PRevieW RoomClub 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 DisPLaysPosters 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.

Dark blue: Club Members Orange: Club Speakers

Prague, CzeCh rePubliC • November 8-11, 2012


Prague, CzeCh rePubliC • November 8-11, 2012


01-12-OC II- part 1.indd 13 22/10/12 12:02:33


12

GeneRAl infORMATiOn

Cme aCCReDiTaTioNPlease 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.

LuNCHesBuffet lunch will be served for Club Members between 13:00-13:45 on both Friday, november 9, 2012 & Saturday, november 10, 2012.

CoFFee bReaKsCoffee/tea will be served in the Poster Board area during the coffee breaks between sessions as specified on the time table.

ovaRiaN CLub meeT & GReeTThe 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 membeRsA list of pre-registered club members is displayed on the notice board. Please correct or add your name and address wherever necessary.

CeRTiFiCaTioN oF aTTeNDaNCeyour Certificate of Attendance is included in your personal Meeting kit.

WiFiwifi internet will be available at the dorint Hotel Giovanni free of charge.

saFeTy aND seCuRiTyPlease do not leave any bags or suitcases unattended at any time, whether inside or outside the session halls.

LiabiLiTyThe 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

01-12-OC II- part 1.indd 14 22/10/12 12:02:34


23



SCIENTIFIC PROGRAM


13-21-OC II- part 2.indd 1 22/10/12 12:03:55


14

SCIENTIFIC PROGRAM

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


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

Thursday, November 8, 2012

13-21-OC II- part 2.indd 2 22/10/12 12:03:56


15

SCIENTIFIC PROGRAM

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


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


Friday, November 9, 2012

13-21-OC II- part 2.indd 3 22/10/12 12:03:56


16

SCIENTIFIC PROGRAM

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


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


13-21-OC II- part 2.indd 4 22/10/12 12:03:57


17

SCIENTIFIC PROGRAM

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


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


Saturday, November 10, 2012

13-21-OC II- part 2.indd 5 22/10/12 12:03:58


18

SCIENTIFIC PROGRAM

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



13-21-OC II- part 2.indd 6 22/10/12 12:03:59


19

SCIENTIFIC PROGRAM

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


13-21-OC II- part 2.indd 7 22/10/12 12:03:59

IVF-Worldwide.com is the largest and most comprehensive in-vitro fertilization (IVF)-focused websitefor doctors, embryologists, nurses and social workers.IVF-Worldwide.com has been constructed with a vision of improving patient care by encouragingdiscussion between professionals, advancing research and promoting publication of educationalmaterials.Enjoy the wealth of information offered by IVF-Worldwide. Register to receive our newsletter and stayupdated on new developments in the field of IVF. Tune in to the IVF-Worldwide Blog to read posts byleading experts. Join our Linked In and Facebook group and take part in the dialogue regarding specialtreatments and advance research issues. Enter our Business Directory and learn about medical equipmentmanufacturers.Be part of our community of IVF specialists dedicated to promoting excellence in reproductive medicine.

THE WORLD'S LARGEST IVF DIRECTORYincluding national and international sperm banks

WWW.IVF-WORLDWIDE.COM

www.ivf-worldwide.com Be part of our global network...

IVF-Worldwide.com is built with the vision to give to its members the ability to locateIVF units anywhere in the world and to communicate directly with the unit. In additionIVF-Worldwide.com will be home to a large section of educational material includingrecent publications, abstracts, PowerPoint presentations and newsletters.

13-21-OC II- part 2.indd 8 22/10/12 12:04:01


23



SPEAkERS OvERvIEwS


(order as per the Scientific Program)

IVF-Worldwide.com is the largest and most comprehensive in-vitro fertilization (IVF)-focused websitefor doctors, embryologists, nurses and social workers.IVF-Worldwide.com has been constructed with a vision of improving patient care by encouragingdiscussion between professionals, advancing research and promoting publication of educationalmaterials.Enjoy the wealth of information offered by IVF-Worldwide. Register to receive our newsletter and stayupdated on new developments in the field of IVF. Tune in to the IVF-Worldwide Blog to read posts byleading experts. Join our Linked In and Facebook group and take part in the dialogue regarding specialtreatments and advance research issues. Enter our Business Directory and learn about medical equipmentmanufacturers.Be part of our community of IVF specialists dedicated to promoting excellence in reproductive medicine.

THE WORLD'S LARGEST IVF DIRECTORYincluding national and international sperm banks

WWW.IVF-WORLDWIDE.COM

www.ivf-worldwide.com Be part of our global network...

IVF-Worldwide.com is built with the vision to give to its members the ability to locateIVF units anywhere in the world and to communicate directly with the unit. In additionIVF-Worldwide.com will be home to a large section of educational material includingrecent publications, abstracts, PowerPoint presentations and newsletters.

13-21-OC II- part 2.indd 9 22/10/12 12:04:06

S-1

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 oocyte-

containing 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.

S-2

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 multi-

potent 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.

S-3

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. Noyes‟s lecture will cover oocyte cryopreservation topics such as treatment indications an

modifications, special considerations, and successes to date.

S-4

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 pre-antral 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 micro-RNA (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.

S-5

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.

S-6

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.

S-7

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 men‟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.

S-8

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.

S-9

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.

S-10

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 patients´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.

S-11

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 co-

localized 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 two-hybrid, 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.

S-12

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-TO-ZYGOTE 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 post-transcriptional 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.

S-13

CELLULAR DISRUPTION WITHIN OOCYTES AND EARLY EMBRYOS

CAUSED BY MATERNAL DIABETES – 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 peri-

conception 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.

S-14

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 „metabolic syndrome‟; 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-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

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 – 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-16

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 heart-

breaking 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: “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?”

S-17

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.


23



POSTERS


39-49-OC II- part 3.indd 1 22/10/12 12:06:07


P-1

LIST OF POSTERS


1 INSUFFICIENCY OF SPINDLE ASSEMBLY CHECKPOINT IN MOUSE OOCYTES M. Anger1,2, J. Sebestova1,2, A. Danylevska1,2

1CEITEC - Veterinary Research Institute, Brno, Czech Republic; 2Institute of Animal Physiology and Genetics, Libechov, Czech Republic

2 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

3 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

1Fertilitat Centro de Medicina Reprodutiva; 2Departamento de Ginecologia, Faculdade de Medicina, PUCRS Porto Alegre, RS, Brasil

4 MARKERS OF OOCYTE QUALITY FOR OOCYTE CRYOPRESERVATION M. Barberi1, G. Gioacchini2, O. Carnevali2, E. Giorgini2, V. Bianchi1, M.A. Bonu1, R. Canipari3, A. Borini1

1Centre for Reproductive Health, Bologna, Italy; 2Università Politecnica delle Marche, Ancona, Italy; 3‘La Sapienza’ University of Rome, Italy

5 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

1University Tiradentes; 2Federal University of São Francisco Valley, Brazil

6 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

1Chungbuk National University, Chungbuk, South Korea; 2Chittagong Veterinary and Animal Sciences University, Pahartali, Bangladesh

7 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

Board # GROuP A

39-49-OC II- part 3.indd 2 22/10/12 12:06:08


P-2

LIST OF POSTERS


8 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

1AV CR, Libechov, CR; 2EMBL, Heidelberg, Germany; 3Institute of Animal Physiology, Kosice, Slovakia

9 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

10 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

1Charles University in Prague, Plzen, Czech Republic; 2Institute of Reproductive Medicine and Endocrinology, Plzen, Czech Republic

11 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

12 DISTRIBUTION OF THE INSLQ VARIANT IN LUTEINIZING HORMONE RECEPTOR (LHCGR) IN FERTILE CZECH MALE AND FEMALE CONTROLS J. Chrudimská, P. Krenková, 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

13 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 1Department of Comparative Biomedical Science, University of Teramo, Teramo, Italy; 2Department of Experimental Embryology, Institute of Genetics and Animal Breeding of the Polish Academy of Science, Jastrzebiec, Poland

14 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

1University of Pennsylvania, Philadelphia, USA; 2Children's Hospital of Philadelphia, Philadelphia, USA; 3University of North Carolina, Chapel Hill, USA; 4Children's Memorial Hospital, Chicago, USA

Board # GROuP A

39-49-OC II- part 3.indd 3 22/10/12 12:06:09


P-3

LIST OF POSTERS


15 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

1INRA UMR 1198, Jouy en Josas. France; 2Faculty of Veterinary Medicine, Brasilia, Brasil

16 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

17 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

1North Central Thames Foundation School - UCL, UK; 2Nottingham University Medical School, UK

18 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

1North Central Thames Foundation School; 2Nottingham University Medical School, UK

19 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 1Tecnobios Procreazione, Centre for Reproductive Health, Bologna, Italy; 2Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, Ancona, Italy; 3SISSI Beamline, Elettra Synchrotron Light Laboratory, Trieste, Italy

20 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

21 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

1Prague 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

Board # GROuP A

39-49-OC II- part 3.indd 4 22/10/12 12:06:10


P-4

LIST OF POSTERS


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

23 IMPACT OF DHEA ON CLINICAL OUTCOME IN POOR RESPONDERS P.R. Jirge1,2, S.M. Chougule1, V. Sawant1, D.A. Bhomkar1

1Sushrut Assisted Conception Clinic, Kolhapur, India; 2Rajeev Gandhi University, Bangalore, India

24 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

25 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

1Charles University in Prague, Plzen, Czech Republic; 2Institute of Reproductive Medicine and Endocrinology, Plzen, Czech Republic

26 GROUP IVA PHOSPHOLIPASE A2 COOPERATES WITH CYCLOOXYGENASE-2 TO OPTIMIZE OVULATION AND FERTILIZATION IN RODENTS S. Kurusu1, A Sapirstein2, J.V. Bonventre3

1Kitasato University School of Veterinary Medicine, Towada, Japan; 2Johns Hopkins University, Baltimore, USA; 3Brigham and Women's Hospital, Boston, USA

Board # GROuP A

39-49-OC II- part 3.indd 5 22/10/12 12:06:11


P-5

LIST OF POSTERS


1 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

1Seoul National University Bundang Hospital, Seongnam, Korea; 2Seoul National University College of Medicine, Seoul, Korea

2 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

3 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

1University of Bari Aldo Moro, Italy; 2Texas A&M University, College Station, Texas, USA

4 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 1Federal University of San Francisco Valley, Petrolina, Brazil; 2State University of Ceara, Fortaleza-CE, Brazil

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

6 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

Board # GROuP B

39-49-OC II- part 3.indd 6 22/10/12 12:06:11


P-6

LIST OF POSTERS


7 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

1Fondazione 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

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

9 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

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

11 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 1Institute of Experimental Endocrinology Slovak Academy of Sciences, Bratislava, Slovak Republic; 2Department of Toxicology Slovak Medical University, Bratislava, Slovak Republic

12 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

1National Institute of Immunology, New Delhi, India; 2Indian Immunologicals Limited, Hyderabad, India

13 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 1Centre de recherche en biologie de la reproduction, Université Laval, Québec, QC, Canada; 2Centre de Fertilité d’Ottawa, Canada

Board # GROuP B

39-49-OC II- part 3.indd 7 22/10/12 12:06:12


P-7

LIST OF POSTERS


14 ANTI-ENDOMETRIAL DEVELOPMENTAL ACTION OF A SYNTHETIC GLUCOCORTICOID: INVOLVEMENT OF DECIDUAL PARACRINE AND OVARIAN ENDOCRINE MECHANISMS F. Spencer1, M.L. Thompson1, L. Qi2

1Southern University, Biological Sciences & Health Research Center, Baton Rouge, Louisiana; 2University of Illinois, Biomedical and Therapeutic Sciences, Peoria, Illinois, USA

15 INTERACTIVE ROLES BETWEEN OVARIAN AND UTERINE MECHANISMS IN THE REGULATION OF ENDOMETRIAL DEVELOPMENT F. Spencer1, M.L. Thompson1, L. Qi2

1Southern University, Biological Sciences & Health Research Center, Baton Rouge, Louisiana; 2University of Illinois, Biomedical and Therapeutic Sciences, Peoria, Illinois, USA

16 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

17 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 1Clinic for Obstetrics and Gynecology Clinical Centre of Serbia, Belgrade, Serbia; 2University of Belgrade, Belgrade, Serbia

18 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

19 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

Board # GROuP B

39-49-OC II- part 3.indd 8 22/10/12 12:06:13


P-8

LIST OF POSTERS


20 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

1University Medical Center, Rotterdam, The Netherlands; 2Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

21 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

1Clinica EUGIN, Barcelona, Spain; 2Fundaciò EUGIN, Barcelona, Spain

22 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

1Department of Obstetrics and Gynecology, Holbaek Hospital; 2University of Copenhagen, Herlev Hospital, Denmark

23 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 1Seoul National University Bundang Hospital, Seongnam, Korea; 2Seoul National University College of Medicine, Seoul, Korea

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

25 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 1Graduate Institute of Medical Sciences, National Defense Medical Center; 2Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan

26 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

1Seoul National University Bundang Hospital, Seongnam, Korea; 2Seoul National University College of Medicine, Seoul, Korea

Board # GROuP B

39-49-OC II- part 3.indd 9 22/10/12 12:06:14


48

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 UK Ukraine

Uruguay USA

39-49-OC II- part 3.indd 10 22/10/12 12:06:26


23



InDEX


39-49-OC II- part 3.indd 11 22/10/12 12:06:31

I

PPrrooggrraamm

PPaaggee AAbbssttrraacctt

PPaaggee PPrrooggrraamm


PPaaggee

AA CC ((ccoonn''tt))

Adenot, P.G. P-3 Cho, Y.J. P-3 Albertini, A. 14, 17 S-1, S-12 Choi, Y.J. P-4 Aloisio, G. P-2 Chougule, S.M. P-4 Anckaert, E. 17 Chrudimská, J. P-2 Anger, M. P-1 Chu, P.W. P-8 Anzalone, D.A. P-1 Coll, O. P-8 Arav, A. 14 S-3 Conti, C. P-3 Archilla, C. P-3 Cordeiro Cardoso, J. P-1 Atiomo, W. P-3 Crosignani, P. 15, 19 S-6 Azambuja, R. P-1 Czernik, M. P-1, P-2, P-7 Aziz, M. P-8 DD

BB Daniel, N. P-3 Baart, E.B. 16 S-8, P-8 Danylevska, A. P-1 Babuska, V. P-2, P-4 Dattilo, M. 15 Badalotti, F. P-1 De La Fuente, R. 18 S-15 Badalotti, M. P-1 De Santana, F. P-1 Bajo Arenas, J.M. P-5 De Ziegler, D. 16, 19 S-8 Baker, M. D. P-2 Dekel, N. 15 S-5 Baran, V. P-2 Dell'Aquila, M.E. P-5 Baranova, G. P-5 Di Egidio, F. P-2 Barberi, M. P-1 Dillon, K.E. P-2 Barberino, R.S. P-5 Docheva, N. P-3 Barros, V.R.P. P-5 Dos Santos Silva, M. P-1 Beaujean, N. P-3 Drymiotou, S. P-3 Bezerra Lima-Verde, I. P-1 Dudas, M. P-3 Bhomka, D.A. P-4 Dufort, I. P-6 Bianchi, V. P-1, P-3 Duranthon, V. P-3 Biswas, D. P-1 EE Blaha, M . P-1 Ellenberg, J. P-2 Bonu, M.A. P-1 FF Bonventre, J.V. P-4 Feil, D. P-7 Borini, A. P-1, P-3 Fernandez Villafañez, V. P-5 Bruna Catalán, I. P-5 Ferraris, P. P-3 Bruno, C. P-3 Fidanza, A. P-3, P-7 Brzáková, A. P-2 Figueiredo, J.R. P-5 CC Filioli Uranio, M. P-5 Calado De Melo, G. P-1 Fleming, T. 17 S-12 Calligaro, A. P-6 Fleurot, R. P-3 Canipari, R. P-1 Friedler, S. 16 Carnevali, O. P-1, P-3 GG Castrillon, D. H. P-2 Galazis, N. P-3 Cavalcante, A.Y.P. P-5 Gilchrist, R. P-7 Cavalcanti De Albuquerque Jr, R.C. P-1 Ginsberg, J.P. P-2 Cedikova, M. P-2, P-4 Gioacchini, G. P-1, P-3 Cha, S.K. P-2 Giorgini, E. P-1, P-3 Chang, D.Y. P-4 Gleicher, N. 18, 19 S-16 Chang, H.J. P-5, P-8 Golic, I. P-7 Chen, I.C. P-8 Gonçalves, R.J.S. P-5

II

PPrrooggrraamm

PPaaggee

AAbbssttrraacctt

PPaaggee

PPrrooggrraamm

PPaaggee

AAbbssttrraacctt

PPaaggee

GG ((ccoonn''tt)) LL Gosiengfiao, Y. P-2 Lacalandra, G.M. P-5 Gouveia, B.B. P-5 Lalioti, M. 16 S-8 Gracia, C.R. P-2 Laven, J.S.E. P-8 Gupta, N. P-6 Lazarovska, S. P-3 Gupta, S. 15 P-6 Lee, D.R. P-2 HH Lee, J.H. P-5 Hamamah, S. 16 S-7 Lee, J.R. P-5, P-8 Hamplova, I. P-3 Lee, T.H. P-3 Han, A. R. P-3 Lee, W.S. P-2 Hartshorne, G. 15 S-7 Leveillé, M.C. P-6 Herbert, M. 19 S-17 Lins, T.L.B. P-5

Herr, J.C. 17 S-11 Loi, P. P-1, P-2, P-3, P-6, P-7

Hinrichs, K. P-5 Lucci, C.M. P-3 Hlinka, D. P-3 MM Hoest, T. P-8 Macek jr., M. P-2 Hourvitz, A. 15 S-4 Macek sr, M. P-2 Hunt, P. 15 S-5 Makarova, N. P-5 Hyun, S.H. P-1 Martino, N.A. P-5

II Mashiach, S. 17 Iuso, D. P-1, P-2, P-4 Matos, M.H.T. P-5

JJ Matur, R. P-6 Jang, J.A. P-4 Mauri, P. P-6 Jee, B.C. P-5, P-8 Mayer, V. P-2 Jenkins, J. 18 Melado Vidales, L. P-5 Jeon, S.S. P-3 Menezes, V.G. P-5 Jirge, P.R. P-4 Meseguer, M. 16 S-9 Jun, K.C. P-4 Michelon, J. P-1 Jurcovicova, J. P-6 Micic, J. P-7

KK Mikkelsen, A.L. P-8 Kalinina, E. P-5 Mlynarcikova, A. P-6 Kalous, J. P-6 Modlinski, J. P-2, P-6 Kazaryan, L. P-5 Moley, K.H. 17 S-13 Kim, J.M. P-2 Monti, M. P-6 Kim, J.Y. P-4 Motlik, J. 15, 18 S-5, P-2 Kim, M.K. P-2 Mottershead, D. P-7 Kim, S.H. P-5, P-8 Munshi, D. P-6 Kim, Y.A. P-4 NN Kitajima, T. P-2 Nagyova, E. P-6 Ko, M.S.H. P-6 Nemcova, L. P-1, P-6 Korac, A. P-7 Nicolaides, K. P-3 Korac, B. P-7 Nivet, A.L. P-6 Korach, K. 14, 15 S-6 Noyes, N. 14, 17 S-3 Kralickova, M. P-2, P-4 OO N�hqnry «/#S1# P-2 Obradors, A. P-8 Kurusu, S. P-4 Okada, L. P-1 Kvitko, D. P-1 Otasevic, V. P-7 Ozil, J.P. 17 S-11

III

PPrrooggrraamm


PPaaggee PPrrooggrraamm


PPaaggee

PP SS (con't) Palmieri, C. P-3 Shrestha, A. P-6 Panda, A.K. P-6 Silber, S. 14, 19 S-3, S-17

Park, J.W. P-4 Simón, C. 14, 16, 17

Patrizio, P. 14 S-2 Sinclair, K. 17 S-14 Peters, A.H.F.M. P-8 Sirard, M.A. P-6 Petracco, A. P-1 Skouby, S.O. P-8 Petracco, R. P-1 Smitz, J. P-6 Peynot, N. P-3 Smolikova, K. P-6 Pichlerova, M. P-3 ý rof /#S1# P-2 Platon, J.V. 16 Spencer, F. P-7 Polyakov, V. P-5 Srinivasan, V.A. P-6 Prewitt, M. P-2 Stankovic, V. P-7 Prochazka, R. P-1 Stevikova, M. P-3

Ptak, G. P-1, P-2, P-3, P-6, P-7 Stojnic, J. P-7

QQ Sudiman, J. P-7 Qi, L. P-7 Suh, C.S. P-5, P-8 Quinn, P. 15, 18 S-15 Surlan, L. P-7

RR Sutton-McDowall, M. P-7 Rajan, S. P-6 Svoboda, P. 17 S-12 Razacova, J. P-3 Swiergiel, A.H. P-6 Redi, C.A. P-6 TT Reig, V. P-1 Tagliani-Ribeiro, A. P-1 Reis e Silva, A. P-3 Tarnawa, E. P-2 Ritter, L. P-7 Tavares De Mato, M.H. P-1 Rollerova, E. P-6 Telfer, E. 14, 15 S-1 Romero, S. P-6 Thompson, J. 15, 17 S-13, P-7 Rubio, C. 16 S-10 Thompson, M.L. P-7 Rutarova, J. P-3 Thoukididou, S.N. P-3

SS Tilly, J. 14 S-1 Sakkas, D. 16 S-10 Toschi, P. P-3, P-7 ý «p dory «/#S1# P-2 Tulic, I. P-7 Sammel, M.D. P-2 VV Sampino, S. P-1, P-6 Vaccari, L. P-3 Sánchez, F. P-6 Van Blerkom, J. 17, 18 S-14 Santos, J.C. P-1 Van de Werken, C. P-8 Santos, J.M.S. P-5 Van der Heijden, G.W. P-8

Santos, L.P. P-5 Van Veen-Buurman, C.J.H. P-8

Sapirstein, A. P-4 Vassena, R. P-8 Sawant, V. P-4 Velickovic, K. P-7

Schatten, G. 14, 18, 19 S-15, S-16 Verdú Merino, V. P-5

Scsukova, S. P-6 Vernaeve, V. P-8 Sebestova, J. P-1 Vidal, R. P-8 Seli, E. 16 S-9 Vucetic, M. P-7 Sen, A. 15 S-4 Shin, D.H. P-2 Shoham, Z. 14, 19

IV

PPrrooggrraamm


PPaaggee

WW Wang, Y.P. P-8 Wi, H.R. P-8 Wirleitner, B. P-4 Wissing, M.L. P-8 Woods, D. 14 S-2 Wu, G.J. 18 P-8

YY Yoon, T. K. P-2 Youm, H. P-8

ZZ Zacchini, F. P-2, P-6 Zanoni, M. P-6 Zech, N. P-2, P-4

The Inverse Pyramid: Regulating FollicleNumber and Oocyte Quality

PARIS, FRANCE • NOVEMBER 14-17, 2013

ORGANIZING COMMITTEE

P. Bouchard, FranceP. Devroey, BelguimJ. Eppig, USAB. Fauser, The NetherlandsR. Fleming, UK

N. Gleicher, USAS. Hamamah, FranceK. Korach, USA S. Mashiach, IsraelJ. Motlik, Czech RepublicF. Olivennes, France

G. Schatten, USAZ. Shoham, IsraelJ. Smitz, BelgiumE. Telfer, UKJ. Thompson, Australia


ABSTRACT SUBMISSION DEADLINE:AUGUST 27, 2012

54-56-notes.indd 2 22/10/12 12:50:41


55

The Inverse Pyramid: Regulating FollicleNumber and Oocyte Quality

PARIS, FRANCE • NOVEMBER 14-17, 2013

ORGANIZING COMMITTEE

P. Bouchard, FranceP. Devroey, BelguimJ. Eppig, USAB. Fauser, The NetherlandsR. Fleming, UK

N. Gleicher, USAS. Hamamah, FranceK. Korach, USA S. Mashiach, IsraelJ. Motlik, Czech RepublicF. Olivennes, France

G. Schatten, USAZ. Shoham, IsraelJ. Smitz, BelgiumE. Telfer, UKJ. Thompson, Australia


ABSTRACT SUBMISSION DEADLINE:AUGUST 27, 2012

NOTES

54-56-notes.indd 3 22/10/12 12:50:44


56

NOTES

54-56-notes.indd 4 22/10/12 12:50:45








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

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

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 Léc iva, 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

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.




PROGRAM






Ferring International Center SAChemin de la Vergognausaz 50CH 1162 St-PrexSwitzerlandwww.ferring.com








ovarian club ii final book

Documents

iu fsh

iu characteristics

ovarian enlargement

ovarian response

shortened summary of

convenient treatment

ovarian club iimeetingfriday

embryo development