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Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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Page viii Cite
Suggested Citation:"Front Matter." Institute of Medicine and National Research Council. 1989. Medically Assisted Conception: An Agenda for Research : Report of a Study. Washington, DC: The National Academies Press. doi: 10.17226/18586.
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REFERENCE copy FOR UUMW uSEOHif MEDICALLY ASSISTED CONCEPTION An Agenda for Research Report of a Study by a Committee of the INSTITUTE OF MEDICINE^.Sj Division of Health Sciences Policy NATIONAL RESEARCH COUNCIL Board on Agriculture National Academy Press Washington D.C. 1989 Ordef national Technical Information Servict. Springfield, Va. 22161 Ordw No..

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competencies and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an advisor to the federal government and its own initiative in identifying issues of medical care, research, and education. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. This project received support from the National Academy of Sciences Basic Science Fund and the U.S. Department of Agriculture (Contract 59-32U4-8-63/R). 2101 Constitution Avenue, N.W. Washington, D.C. 20418 (202) 334-3300 IOM 89-08

INSTntTTE OF MEDICINE NATIONAL RESEARCH COUNCIL Board on Agriculture OMGTIEE ON THE BASIC SCIENCE FUUNDATICNS OF MEDICALLY ASSISTED CONCEPTION KENNETH J. RYAN,* (Chairman) , Professor and Chairman, Department of Obstetrics and Gyneoology, Harvard Medical School, Boston, JCHN D. BIGGERS, Professor of Physiology, Harvard Medical School, Boston, Massachusetts MARIAN D. DAMEWDOD, Assistant Professor, Department of Gyneoology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland CLAUDE DESJARDINS, Professor of Physiology, Department of Physiology, University of Virginia School of Medicine, Charlottesville, Virginia NEAL L. FIRST,** Professor of Reproductive Physiology, Meat and Animal Science Department, University of Wisconsin, Madison, Wisconsin GARY D. HODGEN, Professor and Scientific Director, Eastern Virginia Medical School, Norfolk, Virginia ROBERT B. JAFFE,* Professor and Chairman, Department of Obstetrics, Gynecology and Reproductive Science, School of Medicine, University of California, San Francisco HOWARD W. JONES, Jr., Professor of Obstetrics and Gynecology, Eastern Virginia Mflrtical School, Norfolk, Virginia STANLEY P. LEIBO,*** Research Associate Professor, Departments of Obstetrics, Gynecology and of Urology, Baylor College of Medicine, Houston, Texas *Member, Institute of Medicine **Member, National Academy of Sciences ***During the study, Dr. Leibo was in the Research and Development Division of Rio Vista International, Inc. - iii -

JONATHAN VAN BLERKCM, Professor of Molecular, Cellular, and Developmental Biology, Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado EDWARD E. WALLACH, Professor and Chairman, Department of Gynecology, The Johns Hopkins Medical Institutions, Baltimore, Maryland STUDY STAFF Institute of Medicine BOTH ELLEN BULGER, Director, Division of Health Sciences Policy JESSICA TCWNSEND, Study Director CONSTANCE M. PECHURA, Meeting Rapporteur WALLACE K. WATERFALL, Editor, Institute of Medicine Board on Agriculture JAMES TAVARES, Associate Executive Director - iv -

TABLE OF (UNIUflS PAGE PREFACE vii SUMMARY i SCOPE OF THE STUDY 1 I. IN VITRO FERTILIZATION AND EMBRYO TRANSFER AND SOCIAL CONCERNS 15 Infertility 15 Contraception 20 Agriculture 20 Biodiversity 21 Primates for Research 22 II. ADVANCES IN THE PRACTICE AND SCIENCE BASE OF MEDICALLY ASSISTED CONCEPTION 25 Developments in Human In Vitro Fertilization 25 Developments in Assisted Conception in Food-Producing Animals 27 Gametogenesis and Gametes 30 Fertilization 45 Prelmplantation Development 50 Implantation 58 III. BARRIERS TO PROGRESS IN IN VITRO FERTILIZATION AND EMBRYO TRANSFER 66 Ethical and Social Issues 67 Other Barriers to Scientific Progress 78 IV. RESEARCH AGENDA AND REOTMENDATIONS 86 Research Agenda 86 Conclusions and Recommendations 90 - v -

The ccranittee appreciates the generous contribution of time and knowledge of those who presented papers at the ocnmittee's workshop at the Arnold and Mabel Beckman Center, Irvine, California, August 21-23, 1988. The thought-provoking papers contributed to the workshop, and the presence of exceptional scientists and clinicians stimulated outstanding discussions. The ocnmittee gained invaluable knowledge and insight into issues in research in reproductive and developmental biology that provided the basis for its deliberations. I want to extend the gratitude of the ocnmittee to all who attended the workshop. By offering those resources that we all value — time and knowledge — the ocunittee's work was greatly facilitated. Kenneth J. Ryan Chairman Permittee on the Basic Science Foundations of Medically Assisted Conception - vi -

PREFACE This report is the result of a study by a committee of the Institute of Medicine (ICK) and the National Research Council's Board on Agriculture. The study results from a 1984 meeting of an ad hoc group convened by the National Academy of Sciences to Hianigg aspects of genetic engineering of the human germline. It was noted that because of a policy that, in effect, prohibited the use of federal funds for research involving human embryos, the clinical practice of in vitro fertilization and embryo transfer (IVFET) was in danger of outstripping its scientific foundations. Moreover, the United States had not systematically reviewed the current state of knowledge and practice of IVFET. In 1986, the ICM's Board on Health Sciences Policy convened a meeting of experts in the fields of human and animal research, clinical practice, law, ethics, and public policy to consider some of the issues raised at the earlier meeting. This group was asked to advise the ICM on whether it should pursue a study in any of the areas in which difficult issues had been raised by the practice of medically assisted conception—namely, professional, social, legal, and ethical issues, in addition to questions of science policy. The group identified several topics to which the ICM could make a substantial contribution. An important result of the meeting of this group was to highlight the scientific contribution of research relating to animal uses of medically assisted conception, and the lack of comnunication between those working to further human clinical IVFET and those working in the animal sciences. This study of the basic science foundations of medically assisted conception results from the recccmendations made by this group of experts. Scope of the Study A committee was appointed whose membership included individuals with expertise in the clinical practice of in vitro fertilization, research in animal and human reproductive and developmental biology, and physiology. The committee was asked to examine the basic science foundations of medically assisted conception, and develop an agenda for basic research in reproductive and developmental biology that would contribute to advances in the clinical and agricultural practice of IVFET. This research would also be applicable to other concerns in human and animal reproduction such as male and female infertility and contraception. Because of limitations on research using human embryos, the committee was also asked to identify animal systems that provide useful models for specific aspects of medically assisted conception. In addition, the committee was asked to yMFPSs ways of diminishing barriers to progress in reproductive research and consider ways of fostering communication between investigators oriented to human clinical questions and those interested in studies of animals. - vii -

Although the charge to the oonmlttee Includes consideration of ways of lowering barriers to progress in research, sane of which are caused by legal and ethical concerns, the ocnmittee was not constituted to resolve or make reccmnendaticns on such JRBues. Rather, it was to confine its deliberations to consideration of ways that scientists night contribute to the furtherance of the debate on legal and ethical issues related to medically assisted conception. The permittee held two meot ings. At the first, a plan was developed for a workshop that would bring together clinicians and investigators to review the status of assisted conception in animals and humans, and suggest productive areas for future research. One ocnmittee carefully reviewed current research directions in reproductive science, and selected research areas and investigators to present them at the workshop. The committee was aware that it was neither feasible nor desirable to provide a oomprehensive view of reproductive research. Rather, the committee selected areas of research that show particular promise or describe particularly problematical areas in relation to IYFET. This workshop was also conceived as a major effort in bringing together representatives from the human and animal research worlds to enable them to exchange ideas, enhance their understanding of ways in which they can contribute to each other's work, and together participate in a joint activity that might establish continuing ties. The committee's second meeting, after the workshop, was spent in developing this report and its reocnraendaticns. - viii -

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