FRMC Program

THE FOUNDATION FOR REPRODUCTIVE MEDICINE CONFERENCE 2023 "THINK DIFFERENTLY."

DECEMBER 1-3, 2023

INTERCONTINENTAL TIMES SQUARE HOTEL, NEW YORK, NY

CONFERENCE VENUE AND HOTEL

InterContinental New York, Times Square 300 West 44th Street, New York, N.Y 10036 (212) 803-4500

CONFERENCE SPONSORS

The Foundation for Reproductive Medicine (FRM) A Not-For-Profit Research Foundation 21 East 69th Street, New York, N.Y 1021 T: (646) 882-0840, F: (212) 988-0250 www.foundationforreprodmed.com The Center for Human Reproduction (CHR) An International Fertility and Research Center 21 East 69th Street, New York, N.Y 1021 T: (646) 882-0840, F: (212) 988-0250 https://www.centerforhumanreprod.com The International Do No Harm Group in IVF (IDNHG-IVF) A Not-For-Profit Foundation 21 East 69th Street, New York, N.Y 1021 T: (646) 882-0840 F: (212) 988-0250 https://www.donoharmivf.com/

CONFERENCE ADMINISTRATION ComtecMED Medical Congresses, Israel Trebron Management, Inc. New York, N.Y.

COMMERCIAL SPONSORS

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A BRIEF INTRODUCTION TO THE FRMC 2023 In a mildly irreverent way, the FRMC over three conference days will again attempt to link evolving basic science with cutting-edge clinical practice, in the process facilitating translational connections between bench and clinic. The purpose is to demonstrate to clinicians what is possible and to inform basic scientists about what is needed. The intent is not to dream about the future, but to demonstrate what is possible now!

FRMC frequently premieres new paradigms and encourages the audience to think differently. As new findings are reported in basic sciences and clinical journals, the conference content, therefore, evolves over the preceding year by following the most current scientific and clinical developments. Since reproduction contains information about everything important, - life, death, regeneration, immune tolerance, etc.-, the earliest stages of embryo development never fall out of fashion. Worldwide declines in IVF live birth rates since 2013 have still not attracted the attention they deserve. Never bashful in addressing controversies, this represents a strong reason to raise the issue again at FRMC 2023. It does not take special insights to conclude that those declines must relate to changes in IVF practice patterns over the last decade, - in the USA increases in utilization of preimplantation genetic testing for aneuploidy (PGT-A) likely being the most consequential. What leads to the introduction of so many unvalidated “add-ons” to IVF, is, of course, also worth pondering, as many not only have failed to improve IVF outcomes but, in certain subpopulations, actually harm outcomes. With precision medicine increasingly replacing evidence-based medicine as medicine’s most favored “slogan,” the FRMC, of course, will jump right into the subject, even though the concept of IVF treatment individualization has been promoted by this conference since its inception.

The FMRC, therefore, more than ever before, promises a very memorable visit to NYC at one of the most beautiful times of the year to visit this city.

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CONFERENCE CHAIRS Eli Y. Adashi. MD, MS, MA Former Dean of Medicine and Biological Sciences, Professor of Medical Science, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; Member of the National Academy of Medicine (formerly the Institute of Medicine), The Association of American Physicians and the American Association for the Advancement of Science. 2018 recipient of the ASRM Lifetime Achievement Award.

David F. Albertini, PhD, USA Editor-in-Chief, Journal of Assisted Reproduction and Genetics (JARG), Senior Visiting Scientist, The Center for Human Reproduction-New York, New York, NY, USA; Visiting Researcher, Stem Cell Biology and Molecular Embryology Laboratory, The Rockefeller University, New York, NY, USA.

Ali H. Brivanlou, PhD, USA Robert and Harriet Heilbrunn Professor, Director, The Brivanlou Laboratory of Synthetic Embryology, Rockefeller University New York, NY, USA.

Norbert Gleicher, MD, USA Medical Director and Chief-Scientist, The Center for Human Reproduction- New York, NY, USA; Visiting Researcher, The Rockefeller University, New York, NY, USA; Professor (Adj.), Department of Obstetrics & Gynecology, University of Vienna Medical School, Vienna, Austria; President, The Foundation for Reproductive Medicine, New York, NY, USA.

Raoul Orvieto, MD, Israel Professor and Head of Infertility and IVF Unit, Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat Gan, The Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation, Sackler Faculty of Medicine, Tel-Aviv University, Israel; Co-Editor-in-Chief, Reproductive Biology and Endocrinology, Tel Aviv, Israel.

Pasquale Patrizio, MD, USA Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miller School of Medicine, Miami, FL, USA; Visiting Scientist, The Center for Human Reproduction, New York, NY, USA.

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CONFERENCE FACULTY Eli Y. Adashi, MD, MS, MA Former Dean of Medicine and Biological Sciences, Professor of Medical Science, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; Member of the National Academy of Medicine (formerly the Institute of Medicine), The Association of American Physicians and the American Association for the Advancement of Science. 2018 recipient of the ASRM Lifetime Achievement Award.

David F. Albertini, PhD Professor, Bedford Research Foundation, Bedford, MA, USA; Visiting Senior Scientist, The Center for Human Reproduction – New York, Editor-in-Chief, Journal of Assisted Reproduction and Genetics (JARG) and a Visiting Researcher at Rockefeller University, New York, NY, USA.

David H. Barad, MD, MS, FACOG Director of Clinical ART and Senior Scientist, The Center for Human Reproduction, New York, NY, USA.

Samuel F. Bakhoum, MD, PhD Human Oncology and Pathogenesis Program and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States. He is also a scientific cofounder and a member of the board of directors of Volastra Therapeutics.

Howard Bauchner, MD Professor of Pediatrics and Community Health Sciences, Vice Chairman of Pediatrics, Assistant Dean of Alumni Affairs and Continuing Medical Education at Boston University School of Medicine, Boston, MA, USA, and between 2011-2021 the 16th Editor-in-Chief of JAMA, the Journal of the American Medical Association, and the JAMA Network. Since 2003, he also has been the first U.S.-based editor of the Archives of Diseases in Childhood, the official publication of the Royal College of Pediatrics and Child Health in the UK.

Juan Carlos Izpisua Belmonte, PhD Head of the San Diego division of the Altos Institutes of Science, former Professor at the Salk Institute in La Jolla, CA, USA.

Ali H. Brivanlou, PhD Robert and Harriet Heilbrunn Professor, Director, The Brivanlou Laboratory of Synthetic Embryology Biology, Rockefeller University New York, NY, USA.

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CONFERENCE FACULTY Eli Y. Adashi, MD, MS, MA Former Dean of Medicine and Biological Sciences, Professor of Medical Science, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; Member of the National Academy of Medicine (formerly the Institute of Medicine), The Association of American Physicians and the American Association for the Advancement of Science.

2018 recipient of the ASRM Lifetime Achievement Award.

David F. Albertini, PhD Professor, Bedford Research Foundation, Bedford, MA, USA; Visiting Senior Scientist, The Center for Human Reproduction – New York, Editor-in-Chief, Journal of Assisted Reproduction and Genetics (JARG) and a Visiting Researcher at Rockefeller University, New York, NY, USA.

David H. Barad, MD, MS, FACOG Director of Clinical ART and Senior Scientist, The Center for Human Reproduction, New York, NY, USA.

Samuel F. Bakhoum, MD, PhD Human Oncology and Pathogenesis Program and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

He is also a scientific cofounder and a member of the board of directors of Volastra Therapeutics.

Howard Bauchner, MD Professor of Pediatrics and Community Health Sciences, Vice Chairman of Pediatrics, Assistant Dean of Alumni Affairs and Continuing Medical Education at Boston University School of Medicine, Boston, MA, USA, and between 2011-2021 the 16th Editor-in-Chief of JAMA, the Journal of the American Medical Association, and the JAMA Network. Since 2003, he also has been the first U.S.-based editor of the Archives of Diseases in Childhood, the official publication of the Royal College of Pediatrics and Child Health in the UK.

Juan Carlos Izpisua Belmonte, PhD Head of the San Diego division of the Altos Institutes of Science, former Professor at the Salk Institute in La Jolla, CA, USA.

Ali H. Brivanlou, PhD Robert and Harriet Heilbrunn Professor, Director, The Brivanlou Laboratory of Synthetic Embryology Biology, Rockefeller University New York, NY, USA.

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Uri Elkayam, MD Clinical Professor of Medicine and Obstetrics and Gynecology, University of Southern California Keck School of Medicine. Los Angeles, CA, USA.

Norbert Gleicher, MD, FACOG, FACS Medical Director and Chief Scientist, The Center for Human Reproduction – New York, President, The Foundation for Reproductive Medicine; Visiting Researcher Laboratory for Stem Cell and Molecular Embryology, The Rockefeller University, Prof. (Adj.), Department of Obstetrics and Gynecology, Vienna University School of Medicine, Vienna, Austria, Founding Editor-in-Chief Emeritus, Journal of Assisted Reproduction and Genetics (JARG) and American Journal for Reproductive Immunology (AJRI), New York, NY, USA.

Demián Glujovsky, MD Director and Founder of Fertility Argentina, Buenos Aires, Argentina, and Scientific Director at CEGYR - Eugin group, Buenos Aires, Argentina.

Jacob H. Hanna, MD, PhD Professor of Stem Cell Biology at the Weizmann Institute of Science in Rehovot, Israel.

Chaim Jalas, PhD CEO and Director of Technology Development at Juno Genetics U.S. in Brooklyn, NY, USA.

Robert J. Kiltz, MD Founder and Director of CNY Fertility, one of the larger and structurally most innovative fertility clinic chains in the U.S., propagating a holistic medical approach for fertility treatments that is also “affordable.”

Ashley Laughney, PhD Assistant Professor of Physiology and Biophysics, Weil Cornell Medicine, Physiology & Biophysics, and Assistant professor of Computational Cancer Genomics in Computational Biomedicine in the Institute of Computational Biomedicine, and she is a member of the Institute for Computational Medicine, Physiology, Biophysics and System Biology, TriInstitutional PhD Program in Computational Biology and Medicine, Weil Cornell Medicine Meyer Cancer center, all New York, NY, USA

Milton K. H, Leong, MDCM, DSc (McGill), FACOG, FROG, FHKCOG, FHKAM, FRCS(C) Clinic Director of the Women’s Clinic in Hong Kong and Professor, Mc Gill University, Montreal, Canada.

Limor Man, MD, M.Med Sci Assistant Professor of Research in OB/Gyn, Center for Reproductive Medicine, Weil Cornell Medicine, New York, NY, USA.

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Michelle N. Meyer, PhD, JD Chief Bioethics Officer, Associate Professor and Chair, Department of Bioethics and Decision Sciences in the College of Health Sciences, and Faculty Co-Director of the Behavioral Insights Team in the Steele Institute for Health Innovation at Geisinger in Danville, PA, USA.

Shoukhrat Mitalipov, PhD Director of the Oregon Health and Science University (OHSU) Center for Embryonic Cell and Gene Therapy Program in Molecular and Cellular Biosciences, Professor, Division of Reproductive & Developmental Sciences of the Oregon National Primate Research Center, and Professor of Obstetrics and Gynecology, at the OHSU School of Medicine.

Raoul Orvieto, MD Professor and Head of Infertility and IVF Unit, Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat Gan, The Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation, Sackler Faculty of Medicine, Tel-Aviv University, Israel; Co-Editor-inChief, Reproductive Biology, and Endocrinology.

Pasquale Patrizio, MD, MBE, HCLD FACOG Professor, Department of Obstetrics and Gynecology and Reproductive Sciences, Director, Division of Reproductive Endocrinology and Infertility, University of Miami School of Medicine, Miami, Florida, USA; Visiting Senior Scientist, The Center for Human Reproduction, New York, NY, USA.

Antonio Pellicer, MD, PhD is a founder of IVI/RMA Worldwide, the world’s most valuable company exclusively dedicated to IVF. He in addition and concomitantly had an illustrious academic career that led him to become a Distinguished (full) Professor of Obstetrics and Gynecology, Department Chair and, ultimately, Dean of the Medical School at the University of Valencia in Spain, while also serving for 10 years as Co-Editor-in-in Chief of Fertility and Sterility.

Paolo Rinaudo, MD, PhD Professor of Obstetrics & Gynecology, Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, CA, USA.

Nicolas Rivron, PhD Group Leader, Laboratory for Synthetic Development, Institute of Molecular Biotechnology, the Austrian Academy of Sciences (IMBA)/ the Vienna BioCenter (VBC), Vienna, Austria.

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Jared C. Robins, MD, MBA Current Chief Executive Officer of the American Society for Reproductive Medicine (ASRM). He until 2019 was Chief of the Division of Reproductive Endocrinology and Infertility at Northwestern University – The Feinberg School of Medicine and between 2019-2021, the Medical Director, International Health at Northwestern Memorial Healthcare Corporation, both in Chicago, IL, USA.

Zeev Shoham, MD Director Emeritus Reproductive Endocrinology Unit, Kaplan Hospital, Rehovot and Professor of Obstetrics and Gynecology Hadassah School of Medicine of Hebrew University, Jerusalem, Israel.

Sherman J. Silber, MD Medical Director, The Infertility Center of St. Louise, St. Louise, MO, USA.

Ilya Volodyaev, PhD Senior Researcher, Laboratory of Developmental Biophysics and Department of Embryologist, Faculty of Biology, Moscow State University, Moscow, Russian Confederation and Senior Embryologist, European Medical Center, Moscow, Russian Confederation.

S. Zev Williams, MD, PhD Wendy D. Havens Associate Professor of Women’s Health and Chief of the Division of Reproductive Endocrinology and Infertility at Columbia University Irving Medical Center, New York, NY, USA.

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DAY 1: FRIDAY, DECEMBER 1, 2023 08:30 – 08:35

Welcome Norbert Gleicher, MD

08:35 – 08:45

The Young Investigator Award David F. Albertini, PhD Norbert Gleicher, MD THE OPENING LECTURE What is wrong with current medical publishing?

Howard Bauchner, MD

08:45 – 09:30

This speaker served as the 16th Editor-in-chief of JAMA and the JAMA Network between 2011 and 2021 and is probably better suited than most other former editors of major medical journals to describe openly and unaffected by current-day political correctness what pains current medical publishing in a very rapidly changing world.

LITERATURE: Bauchner et al., Scientific misconduct and medical journals. JAMA, 2018;320 (19):1985-1987 Bauchner H. Conflict of interest: ubiquitous, unrelenting, and forever challenging. J Clin Epidem 2022S0895-4356(22)00148-2. Doi: 10.1016/jclinepi.2022.06.002

SESSION 1 : IMPORTANT NEW DEVELOPMENTS: PART I Chair: Norbert Gleicher, MD As has been tradition, every FRMC has one or two main themes: this year, as on occasions before, a dominant subject had to be, because of research breakthroughs over the last year, once again the early embryo. But what differentiates this year from earlier conferences is the development of early embryo models which have brought completely new dimensions to early-stage embryo research. The first two sessions of this conference 9and selected lectures in later sections of the program) are, therefore, dedicated to this subject, with one talk also pointing out the importance of this kind of research for regenerative medicine.

Toward penetrating the black box of gastrulation Jacob H. Hanna, MD, PhD 09:30-10:00

LITERATURE: Tarazi et al., Post-gastrulation synthetic embryos generated ex utero from mouse naïve ESCs. Cell 2022;185(18):32903306.e25 Amadei et al., Embryo model completes gastrulation to neurulation and organogenesis. Nature 2022;610(7830):143-153

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Human blastoid models to advance our understanding of earlystage embryos Nicolas Rivron, PhD 10:00-10:30

10:30-11-00

11:30-12:00

LITERATURE: Kagawa et al., Human blastoids model blastocyst development and implantation. Nature 2022;601:600-605 Ronghui et al., Time matters: Human blastoids resemble the sequence of blastocyst development. Cell 2022;185(4):581-584

Improving organ health and function by programmed rejuvenation Juan Carlos Izpisua Belmonte, PhD LITERATURE: Liao et al. In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. Nat Commun 2021;12(1):3094

COFFEE BREAK

SESSION 2 : DISCREPANT SCIENTIFIC REALITY AND CLINICAL PRACTICE Chair: Raoul Orvieto, MD The last few years have seen significant progress in our understanding why PGT-A simply cannot produce any of the originally proposed IVF outcome improvements; yet, somewhat surprising, changes in clinical practice as a consequence of these findings have not been as profound as one would expect and wish for. Granted, practice changes always significantly lag behind academic research disclosures; but in the U.S. PGT-A utilization has, indeed, continued to increase, even though it now appears established that PGT-A, in principle, does not improve IVF outcomes. Increasing evidence, indeed, suggests that PGT-A, in at least some patient populations, actually adversely affects IVF outcomes. This session, including today’s lunch SYMPOSIUM, therefore, is dedicated to a detailed review of the subject of PGT-A.

12:00-12:30

THE INTERNATIONAL DO NO HARM GROUP IN IVF (IDNHG-IVF) LECTURE Breaking symmetry in human embryo models and consequences Ali H. Brivanlou, PhD LITERATURE: Simunovic et al., In vitro attachment and symmetry breaking of a human embryo model. Cell Stem Cell 2022;29(6):962-972

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12:30-13:00

Developing novel computational tools to infer cell interactions from single cell transcriptomics and applications toward embryonic development Ashley Laughney, PhD LITERATURE: Adler et al., Modelling collective cell behavior in cancer.

Perspectives from an interdisciplinary conversation. Cell Syst 2023;14(4):252-257

13:00-13:20

GET YOUR BOXED LUNCH

SYMPOSIUM: Transferring chromosomal “abnormal” embryos?

13:20-14:00

There are three intense debates underway within the infertility field, regarding PGT-A: (i) Should PGT-A be offered at all as a routine clinical test in association with IVF or not and, (ii) If PGT-A utilization is continuing, can some by PGT-A described as “abnormal” reported embryos be safely transferred; and (iii) if some embryos can be transferred, which embryos and in which sequence? Under the assumption that PGT-A will remain in many IVF centers an integral part of their IVF practice, we here concentrated on questions (ii) and (iii) and will also include polygenic risk scoring into the discussion.

Chair: David H. Barad, MD, MS Panelists: Chaim Jalas, PhD Michelle N. Meyer, PhD, JD Raoul Orvieto, MD Pasquale Patrizio, MD S. Zev Williams, MD, PhD

SESSION 3 : ABOUT THE CLINICAL FUTURE OF IVF Chair: Pasquale Patrizio, MD

Can non-invasive PGT-A save PGT-A? Raoul Orvieto, MD 14:00-14:30

LITERATURE: Orvieto et al., Is there still a rational for non-invasive PGT-A analysis of cell-free DNA released by human embryos into culture medium? Hum Reprod 2021;36(5):1186-1190

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What is the pregnancy potential of unused and/or discarded “abnormal” Embryos after PGT-A? David H. Barad, MD, MSc 14:30-15:00

LITERATURE: Barad et al., IVF outcomes of embryos with abnormal PGTa biopsy previously refused transfer: a prospective cohort study. Hum Reprod 2022;37(6):1194-1206 Barad et al., In science truth ultimately wins, and PGT-A is no exception.

Hum Reprod 2022;37(9):2216-2218

15:00-15:30

In vitro gametogenesis, - producing eggs and sperm from buccal smears: A summary of the 2023 workshop of the National Academy of Medicine Eli Y. Adashi, MD, MS, MA

15:30-16:00

COFFEE BREAK

SESSION 4 : “GROUPTHINK,” THE ANTI-THESIS TO “PRECISION MEDICINE” Chair: Eli Y. Adashi, MD, MS, MA “Groupthink” is widely defined as the practice of thinking and/or making decisions as a group. Though on first impression this may appear not only appropriate but even desirable, it ignores important downsides, - namely individual creativity and personal responsibility and, moreover, is antithetical to “precision medicine,” mandating highly individualized patient care. Psychologically “groupthink” has been defined as the desire for conformity within a group, which then, unfortunately, often results in irrational and dysfunctional decision-making. In medicine, as the COVID-19 pandemic is well demonstrated, consequences can be dire. A few practice patterns potentially dictated by “groupthink,” are discussed in this session.

16:00-16:30

16:30-17:00

Is the concept of embryo selection in IVF still sustainable?

David F. Albertini, PhD LITERATURE: Gleicher N, Albertini DF. Embryo selection in human IVFnarrowing the gap between basic science and clinical practice. ______

Why are we using extended embryo culture to blastocyst for almost all IVF cycles?

Demián Glujovsky, MD LITERATURE: Glujovsky et al., Cleavage-stage versus blastocyst-stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 2022;5(5):CD002118

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Another critical look at elective single embryo transfer Norbert Gleicher, MD 17:00-17:30

LITERATURE: Gleicher N, Orvieto R. Transferring more than one embryo simultaneously is justifiable in most patients. Reprod Biomed Online 2022;44(1):1-4

17:30-18:00

THE DAILY SUMMARY: QA with the day’s faculty Howard Bauchner, MD; Jacob H. Hanna, MD, PhD; Nicolas Rivron, PhD; Juan Carlos Izpisua Belmonte, PhD; Eli Y. Adashi, MD, MS, MA; Norbert Gleicher, MD; Raoul Orvieto, MD; David H. Barad, MD, MSc, David F. Albertini, PhD; Damián Glujovsky, MD

18:00-20:00

WELCOME RECEPTION

DAY 2: SATURDAY, DECEMBER 2, 2023 SESSION 5 : DISCOVERIES WITH POTENTIAL FUTURE APPLICATIONS TO “PRECISION MEDICINE” Chair: David F. Albertini, PhD Precision medicine denotes, mostly based on an individual’s genetic constitution, a highly individualized approach to every patient. Most advanced in oncology, the contamination is spreading and is also finding its first applications in infertility practice.

This session presents new physiological discoveries with potential to advance precision medicine in reproductive medicine.

08:30-09:00

THE FOUNDATION FOR REPRODUCTIVE MEDICINE LECTURE The function of micronuclei in cancer cells: Is there relevance to the preimplantation-stage embryo?

Samuel F. Bakhoum, MD LITERATURE: Agustinus, AS et al. Epigenetic dysregulation from chromosomal transit in micronuclei. Nature 2023; 619: 176–183.

09:00-09:30

Chromosomal analysis of extruded cells/fragments in preimplantation-stage embryos.

Raoul Orvieto, MD LITERATURE: Aizer et al. Can expelled cells/debris from a developing embryo be used for PGT? J Ovarian Res 2021;14(1):104

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How follicles and oocytes change with advancing female age: Highly Individualized Egg Retrieval (HIER) as an important step toward “precision medicine” Norbert Gleicher, MD 09:30-10:00

LITERATURE: Nicholas et al. Changing relevance of oocyte maturity grading with advancing female age propels precision medicine in IVF. iScience 2023; 26(8), 107308.

Wu et al., Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval. J Endocrinol 2015;226(3):167-180 Wu et al., With low ovarian reserve, Highly Individualized Egg Retrieval (HIER) improves IVF results by avoiding premature luteinization. J Ovarian Res 2018;11(1):23

Polygenic risk scoring in IVF—overview, public opinions, and some ethical considerations Michelle N. Meyer. PhD, JD

10:00-10:30

10:30-11:00

LITERATURE: Meyer et al., Public views on polygenic screening of embryos. Science 2023;379(6632):541-543 Gleicher et al., The uncertain science of preimplantation and prenatal genetic testing. Nat Med 2022;28(3):442-444 Polyakov et al., Polygenic risk score for embryo selection-not ready for prime time. Hum Reprod 2022; 10:37(10:2229-2236 Pereira et al., Polygenic embryo screening: four clinical considerations warrant further attention.

COFFEE BREAK

SESSION 6: WITH INFERTILITY PATIENTS GETTING OLDER, PREEXISTING DISEASES ARE BECOMING INCREASINGLY IMPORTANT Chair: Zeev Shoham, MD Every potential maternal disease increases in prevalence with advancing female age and, because of third-party egg donation leading to even women in their 50s routinely conceiving, different diseases must now be managed in preparation for IVF. This mandates closer diagnostic workups, better preparation of patients, detailed collaboration with medical colleagues from other specialties and, of course, with our perinatology and neonatology colleagues. That maternal diseases can affect pregnancies, and that pregnancies can affect medical disease has been known for decades. To what degree maternal diseases, however, can affect offspring, has only in recent years started to become more apparent.

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11:00-11:20

THE CENTER FOR HUMAN REPRODUCTION LECTURE As the primary cause of maternal mortality in pregnancy, why are so many women still dying in pregnancy from cardiovascular diseases?

Uri Elkayam, MD LITERATURE: Ellkayam U. Cardiac Problems in Pregnancy. WileyBlackwell, 560 pages, 4th Edition, November 2019

11:20-11:40

Does pregnancy affect DNA methylation and, therefore, biological age?

Paolo Rinaudo MD, PhD LITERATURE: Lira-Albarrán et al., DNA methylation profile of liver of mice by in vitro fertilization. J Dev Orig Health Dis 2022;13(3):358-366

Germline editing for genetic diseases: The 2023 state-of-thearts.

Eli Y. Adashi, MD, MS, MA

11:40-12:10

12:10-12:30

LITERATURE: Sherkow et al., Governing human germline editing trough patent law. JAMA 2021; 326(12):1149-1150 Walters et al., Governing heritable human genome editing: A textual history and a proposal for the future. CRISPR J 2021;4(4):469-476 Turoci et al., Heritable human genome editing: Research progress, ethical considerations, and hurdles to clinical practice. Cell 2021;184(6):1561-1574 Adashi et al., Heritable human genome editing. The public engagement imperative. CISPR J 3(6):434-439

Is pregnancy primarily an endocrine or an immunological condition, - and why this matters?

Norbert Gleicher, MD LITERATURE: __________________________________________________________

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For how long IVF cycles can be safely delayed in cancer patients to pursue fertility preservation?

Pasquale Patrizio MD, MBE

12:30-12:50

12:50-13:10

LITERATURE: Romanski et al. Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve. Hum Reprod 2020;35(7):1630-1636 Wang et al., Risk of recurrence and pregnancy outcomes in young women with breast cancer who do and do not undergo fertility preservation. Breast Cancer Res Treat 2022;195(2):201-208 Crown et al., Fertility preservation in young women with breast cancer: Impact on treatment and outcomes. Ann Surg Onc 2022;29(9):57865796

GET YOUR BOXED LUNCH

SYMPOSIUM: After all, how effective is oocyte cryopreservation in extending a woman’s reproductive lifespan?

13:10-14:00

In efforts to extend the reproductive lifespan of older women, a whole industry over the last decade has grown up around the concept of fertility preservation through oocyte cryopreservation. To a large degree, the effectiveness of this concept has, however, remained unknown since only too few adequate follow-up studies to reach conclusions have been reported so-far. Recently colleagues from NYU’s IVF program, indeed, published a first such study with somewhat disappointing outcomes.1 Their study reemphasized the importance of oocyte cryopreservation at younger ages by demonstrating especially poor results when oocytes were cryopreserved at older ages. How well the concept of elective oocyte cryopreservation to extend reproductive lifespan performs, therefore, remains open to discussion. ________________________ 1 Druckenmiller Cascante et al. Fifteen years of autologous oocyte thaw outcomes from a large university-based fertility center. Fertil Steril 2022;118(1):158-166

Chair: David H. Barad, MD, MSc Panelists: Sherman Silber, MD Norbert Gleicher, MD Raoul Orvieto, MD Pasquale Patrizio, MD. Paolo Rinaudo, MD, PhD

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SESSION 7 : IMPORTANT NEW RESEARCH DEVELOPMENTS: PART 1 Chair: Ali Brivanlou, PhD

14:00-14:30

mtDNA transfer can be horizontal: A mechanism to restore compromised mitochondrial function in embryos?

Shoukhrat Mitalipov, PhD LITERATURE: Marti Guiterrez N et al. Horizontal mDNA transfer between cells is common during mouse development. iScience 2022;25(3):103901 Shining some light into the black box of implantation by using human stem cell-derived blastoids Nicolas Rivron, PhD

14:30-15:00

15:00-15:30

15:30-16:00

LITERATURE: Kagawa et al. Protocol for human blastoids modeling blastocyst development and implantation.

J. Vis Exp 2022;(186). Doi: 10.3791/63388 Seong et al. Epiblast inducers capture mouse trophectoderm stem cells in vitro pattern blastoids for implantation in utero. Cell Stem Cell 2022;29(7):1102-1118

In vitro germ cell induction from fertile and infertile monozygotic twins Sherman Silber, MD LITERATURE: Pandolfi et al.,In vitro germ cell induction from fertile and infertile monozygotic twin research participants. Cell Reports Med 2022;3:100782

COFFEE BREAK

SESSION 8 : IMPORTANT NEW RESEARCH DEVELOPMENTS: PART 2 Chair: Nicolas Rivron, PhD

16:00 – 16:30

The importance of Artificial Intelligence (A.I.) for medical research TBD LITERATURE: ____________________________________________________

16:30 – 17:00

Some tips and tricks after over 1,000 nuclear transfers in mice Ilya Volodyaev, PhD

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17:30 - 18:00

The importance of insulin-like growth factor 1 (IGF-1) in follicular physiology – an important consideration in using human growth hormone (HGH) in IVF Limor Man, MD, M. Med Sci MSc LITERATURE: Man et al., Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice. F S Sci 2021;2(3):237247

THE DAILY SUMMARY: QA with the day’s faculty 18:00– 18:30

19:00 19:30-23:00

Samuel F. Bakhoum, MD; Limor Man, MD, M. Med Sci MSc; Raoul Orvieto, MD; Norbert Gleicher, MD; Michelle N. Meyer, PhD, JD; Uri Elkayam, MD; Paolo Rinaudo MD, PhD; Eli Y. Adashi, MD, MS, MA; Pasquale Patrizio MD, MBE; Shoukhrat Mitalipov, PhD; Nicolas Rivron, PhD; Sherman Silber, MD; Ali Brivanlou, PhD; Ilya Volodyaev, PhD

BUS PICK UP AT HOTEL FOR FACULTY DINNER FACULTY DINNER

DAY 3: SUNDAY, DECEMBER 3, 2023 SESSION 9 : WHAT WE MAY WANT TO RECONSIDER IN CLINICAL IVF PRACTICE Chair: Pasquale Patrizio, MD, MSc

Are Rotterdam PCOS phenotypes out of date?

Norbert Gleicher, MD 08:30-09:00

09:00-09:30

LITERATURE: Gleicher et al., Reconsidering the Polycystic Ovary Syndrome (PCOS). Biomedicines 2022;10(7):1505 Cedars MI. Is it time to revisit Rotterdam? Fertil Steril 2022;117(4):696697

“It starts with the egg:” Grading not only embryos but also oocytes David F. Albertini, PhD LITERATURE: Albertini DF. The Oocyte’s Role in Embryo Development.

Chapter 5 _________________________________ pp 43-52

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Issues arising for mankind from increasing utilization of IVF Paolo Rinaudo, MD, Ph.D. 09:30-10:00

10:00-10:30

LITERATURE: Rinaudo P. Preimplantation embryo: the first physical exam. F S Sci 2021;2(1):11-12 Lee et al., Murine blastocysts generated by in vitro fertilization show increased Warburg metabolism and latered lactate production. eLife 2022;11:79153

COFFEE BREAK

SESSION 10 HOW THE CLINICAL PRACTICE OF IVF EVOLVED INTO AN INDUSTRY In this closing session of the Conference, the CEO of the ASRM, Jared C. Robins, MD, MBA will offer the audience a glimpse into the future of infertility practice from the ASRM’s vantage point. As used in this section, the term “industrialization” should be understood as the change in ownership of IVF centers from individual physicians and small physician partnerships to equity investors and/or other large corporate entities. Concomitantly, the term “commoditization” describes efforts to add “sales” in the form of added services to standard IVF practice in efforts to improve revenues, involving a wide range of offerings, from so-called clinical “add-ons” to health spa services. This section, moreover, will offer insights from some of the worldwide most successful colleagues in the field who developed uniquely new and economically very successful IVF practice models.

Chair: Paolo Rinaudo, MD, PhD

10:30-11:00

11:00-11:30

The future of clinical infertility practice in the U.S. Jared C. Robins, MD, MBA

Unintended consequences of industrialization and commoditization of IVF practice: PGT-A as an example Pasquale Patrizio, MD, MSc LITERATURE: Patrizio et al., The changing world of IVF: the pros and cons of new business models offering reproductive technologies. J Assist Reprod Genet 2022;39(2):305-313

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Propagating the impossible in IVF: “Ovarian rejuvenation” as an example David H. Barad, MD, MSc

11:30-12:00

LITERATURE: Barad DH, et al., Preliminary report of intraovarian injections of autologous platelet-rich plasma (PRP) in extremely poor prognosis patients with only oocyte donation as alternative: a prospective cohort study. Hum Reprod Opem 2022(3):hoac027 Rinaudo P, Albertini D. Will PRP therapy find a niche in reproductive medicine? Not ready for prime time. J Assist Reprod Genet 2021;38(5):1013-1014 Aagard Lunding S et al., Biopsying, fragmentation and auto transplantation offresh ovarian cortical tissues in infertile women with diminished ovarian reserve. Hum Reprod.2019; 34(10): 1924-1936 Steiner AZ. Evidence that biopsying, fragmentation and autotransplantation of ovarian tissue should be abandoned as treatment of diminished ovarian reserve. Hum Reprod 2019;34(10): 1853-1854

12:00-12:30

Why IVF does not have to be as expensive as it is Robert J. Kiltz, MD

12:30– 13:00

THE CLOSING LECTURE Building the most valuable IVF clinic network in the world.

Antonio Pellicer, MD, PhD

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