In Vitro–Derived
Human Gametes
as a Reproductive
Technology
Scientific, Ethical, and
Regulatory Implications
_____
Emily Packard Dawson,
Chanel Matney, and
Katherine Bowman, Rapporteurs
Board on Health Sciences Policy
Health and Medicine Division
Proceedings of a Workshop
NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by grants between the National Academy of Sciences and the American Society for Reproductive Medicine, Burroughs Wellcome Fund (grant 1022869), Howard and Georgeanna Jones Foundation for Reproductive Medicine, and Open Philanthropy (grant 2022-250884). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-71080-0
International Standard Book Number-10: 0-309-71080-4
Digital Object Identifier: https://doi.org/10.17226/27259
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. In vitro–derived human gametes as a reproductive technology: Scientific, ethical, and regulatory implications: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/27259.
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PLANNING COMMITTEE1
ELI ADASHI, Professor of Medical Science, Brown University, Providence, Rhode Island
AMANDER CLARK, Professor, Molecular, Cell, and Developmental Biology, University of California, Los Angeles
I. GLENN COHEN, Deputy Dean and Professor of Law, Harvard Law School, Cambridge, Massachusetts
SUSAN CROCKIN, Founder, Crockin Law and Policy Group, Washington, DC
UBAKA OGBOGU, Professor and Katz Group Chair in Health Law, Faculty of Law, University of Alberta, Canada
KOTARO SASAKI, Assistant Professor, Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania
MELISSA SIMON, Vice Chair for Research, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois
HUGH TAYLOR, Professor of Obstetrics, Gynecology, and Reproductive Sciences and Professor of Molecular, Cellular, and Developmental Biology, Yale School of Medicine, New Haven, Connecticut
Health and Medicine Division Staff
KATHERINE BOWMAN, Senior Program Officer, Board on Health Sciences Policy
CHANEL MATNEY, Program Officer, Board on Health Sciences Policy
ASHLEY BOLOGNA, Senior Program Assistant, Board on Health Sciences Policy
CLARE STROUD, Senior Director, Board on Health Sciences Policy
Fellow
EMILY PACKARD DAWSON, Christine Mirzayan Science and Technology Policy Graduate Fellow, Board on Health Sciences Policy
__________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
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Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
DAVID CYRANOSKI, Kyoto University
DEBORAH HURSH, Hursh Cell Therapy Consulting, LLC
VANESSA GRUBEN, University of Ottowa
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings, nor did they see the final draft before its release. The review of this proceedings was overseen by ELLEN WRIGHT CLAYTON, Vanderbilt University Medical Center. She was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies. We also thank staff member LAURA BLASI for reading and providing helpful comments on this manuscript.
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4 SOCIAL, ETHICAL, AND LEGAL CONSIDERATIONS RAISED BY IVG
“A Solution in Search of a Problem?”
Ethical Issues Related to Potential Clinical Trials
Potential Implications of Embryo Creation via IVG
Societal Structures Impacting Human Reproduction
Using IVG to Answer Research Questions
5 EQUITY, ACCESS, AND COST CONSIDERATIONS ASSOCIATED WITH IVG
The Potential Demand for Surrogacy Driven by IVG
Issues at the Intersection of Equitable Access and Cost
Distinguishing Between Cost and Price
6 IMAGINING A POTENTIAL CLINIC RESEARCH PATHWAY FOR HUMAN IVG IN THE UNITED STATES
U.S. Policy and Legal Approaches to ART
An Industry Perspective on a Potential Path to Clinical Research
Potential U.S. Regulatory Frameworks for IVG
7 PARTICIPATORY PUBLIC ENGAGEMENT AROUND REPRODUCTIVE SCIENCE ADVANCES
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Figures
FIGURES
2-1 Human germ cell development
2-2 Three essential elements for reconstituting gametogenesis in culture
2-3 Schematic of human in vitro gametogenesis
2-4 Schematic of mouse and human spermatogenesis
2-5 Spermatogonial stem cell transplantation
2-6 DNA methylation across germ cell development in mice
2-7 Opportunities for de novo mutations are increased in male versus female germ cell development
3-1 Infertility coverage by state in the United States in April 2023
3-2 2020 National ART summary—number of ART cycles by egg or embryo source, United States, 2011–2020
7-1 Recruitment fliers for focus group discussions on in vitro gametogenesis
7-2 Schematics used to communicate IVG to study participants
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Acronyms and Abbreviations
ART | assisted reproductive technology |
DNM | de novo point mutation |
DSB | double strand break |
ESC | embryonic stem cell |
FDA | Food and Drug Administration |
iPSC | induced pluripotent stem cell |
ISSCR | International Society for Stem Cell Research |
IVF | in vitro fertilization |
IVG | in vitro gametogenesis |
MRT | mitochondrial replacement therapy |
NIH | National Institutes of Health |
PGC | primordial germ cell |
PGCLC | primordial germ cell–like cell |
PGT | preimplantation genetic testing |
PSC | pluripotent stem cell |
SSC | spermatogonial stem cell |
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