Early embryonic loss is a continuing social and economic global problem. In human populations the estimates of interruptions early in pregnancy range from 35-60%. In animal husbandry (swine, ruminants) fully 30% of pregnancies fail to survive early events of gestation. The futility associated with this persistant high risk is even more unsettling because of advances made in assisted reproductive technology which, although this very selective methodology has added to our knowledge of embryo-endometrial interactions, has resulted in a birth rate of only 14%. These studies have instigated comparisons of the live relative contributions of the embryo and the uterus to the outcome of pregnancy. These analyses have shown that we have learned significantly less about the role of the uterus in deciding the outcome of either natural or assisted pregnancies. In 1979 a quotation by George Corner was used to set the tone of a meeting that was devoted to discussion of the cellular and molecular aspects of implantation. In spite of the proliferation in research activity which occurred in the following 15 years our real understanding of the embryo transfer process has fallen short of our expectations. We use the Corner quotation, once again, to preface this symposium so that we may recall that the fundamental nature of the process which regulates embryo-endometrial interactions still escapes us.

Volume 3 of this series is concerned with geriatric aspects of surgical specialties: gynecology, orthopedics, general surgery, otorhinolaryn gology, and ophthalmology. Closely associated with these specialties is anesthesiology. Dermatology has an intermediate position between surgical and nonsurgical fields. The peculiarities of physiological and pathological aging of otgans and the consequences for diagnosis and therapy - presented in the first two volumes - are of great significance, especially for surgical special ties. There are a large number of pre-, intra-, and postoperative problems in multimorbid geriatric patients, e. g., coronary insufficiency, brady arrhythmias, hypertonia, and hypotonia. While as recently as the tum of the century the age of 65 years was viewed as a contraindication for sur gery, today even older patients undergo operations on aortic aneurysms, bypass operations for coronary sclerosis, pulmonary resections, and abdominosacral resections of rectal carcinomas, for example. Pre requisite for successful surgery at an advanced age is good pre- and postoperative care of multimorbid patients. Physiological changes of the lungs with aging, the increased frequency in pneumonia and pulmonary just a few embolisms with age, and the decrease in receptors, to give examples, confront anesthetists with difficulties. The maxim "in old age a little less" is also applicable in this field. Only improved experimental gerontological research, possibly reaching even into anesthesia, will provide objective data for anesthesia in elderly patients. The skin is an organ that experiences characteristic qualitative and quantitative changes in old age."

The first few months of any pregnancy are of supreme importance to the success of that pregnancy. This statement is so obvious as to be almost a platitude, yet it must be said that no aspect of pregnancy has been more neglected in the human than the first three months. Little is known of the morphological changes that occur at that time and our knowledge of the mechanisms that control this vital stage of pregnancy is almost non-existent. The explanation for this neglect of what is an obvious area for study is the difficulty of obtaining normal material. It is rare to have material to study from a healthy first trimester pregnancy and the study by Hertig and Rock!l) of early conception found by chance in hysterectomy speci mens must be unique. The information that we do have about early pregnancy is mostly gained from animal studies or single miscarriages in humans. Chromosomal defects are common but are not an explanation for the majority of recurrent miscarriages. Obstetricians have hypothesised many causes for this condition and have deve loped numerous metQods for treating it, but the studies have been poorly con trolled so that our understanding of the cause(s) has not advanced. Treatment of women with a history of recurrent miscarriage by paternal leuco cyte infusion (immunotherapy) may be yet another form of treatment that is hailed as a new advance only to be rejected when subject to rigorous testing.

Various scientific evaluations taken from these chapters were presented during the international symposium, 'Carcinoma of the Cervix, ' which was held from September 4-7, 1980 in Kiawah Island, Charleston, South Carolina, U.S.A. An international selection of research investigators have contributed reviews designed to be informative to medical, graduate and post-graduate students, as well as clinicians, oncologists and investigators working in the area of female carcinoma. An attempt has been made to provide a total coverage of current progress in carcinoma of the cervix. In particular, the following major areas are included: Epidemiology, Histology & Histochemistry, Ultra structure, Physiology & Biochemistry, Genetics & Cytogenetics, Immunology, Diagnosis, and Patho physiology & Complications. Major changes have occurred in incidence and mortality rates for carcinoma of the cervix in the past decade. Mass screening programs and their ability to detect earlier stage diseases have attributed to a reduction in invasive diseases. Most cervical cancers could be prevented by an extension of cytologic screening programs in high risk areas. Greater resources must be provided to reach high risk areas in order to prevent the occurrence of cervical cancer."

Starting in 1986, the European School of Oncology has expanded its activities in postgraduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meetings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminating the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It was decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a common problem in medical literature: that of the material being outdated even before publication. Umberto Veronesi Chairman, Scientific Committee European School of Oncology Table of Contents How to Read this Monograph F.CAvALLI ......... . 1 Experimental Strategies for Studying the Development of Breast Cancer with Special Reference to Steroid Hormones, Growth Factors and Oncogenes R.J.B. KING . . . . . . . . . . . . . . . . . . . . . . . . .. . . . 5 . . .

This series of volumes dealing with reproductive health care has as its primary objective the improvement of the quality of human reproduction. The of knowledge and new technology give us opportunities as never explosion before to accomplish this end. The Editor has brought together contributors who are outstanding scientists from around the world. A number of the authors have personally made significant contributions to our body of knowledge in reproductive medicine. Bringing all this information together in an easily readable format is a great service. This is essential reading for all concerned with the control and improvement of human reproduction and the correction of its many deficits. xv P'art I Physio-anatom-ical Parameters 1 Uterine microvasculature and spontaneous abortion M. TAKADA In the implantation and subsequent development of a fertilized ovum, its integrity is most significant. However, with maternal local factors, i.e., unsatisfactory uterine conditions, implantation may not succeed even if the integrity of the fertilized ovum is excellent; if implantation is made, the maturation of the fetoplacental unit following implantation is disturbed, which leads to abnormalities in fetal development or to miscarriage. Thus, the uteroplacental unit, as well as the fetoplacental unit, plays an important role in the establishment and maintenance of pregnancy. Among the mechanisms of the utero placental unit, most significant is the physiological mechanism of the uterine microvasculature and its correspon dence to gestation. In particular, homeostasis of simultaneous cooperative development of the uterine wall and the placenta is most important."

The original series, Advances in Prostaglandin Research, edited by Sultan M. M. Karim, was published by MTP Press in three volumes in 1975 and 1976. A glance at those books illustrates the progress that has been made since then. The thromboxanes were mentioned twice (first publication 1975) and prostacyclin not once (first publication 1976); leukotrienes were only on the horizon. The amazing generation of research data in the last 10-15 years has given new, broad insights into many areas, including asthma, inflammation, renal, cardiovascular and gastrointestinal diseases and in reproduction, and has led in some instances to real clinical benefit. This series, Advances in Eicosanoid Research, reflects the current understanding of prostaglandins , thromboxanes and leukotrienes. The aim is to provide an introductory background to each topic and the most up-to-date information available. Although each book stands alone, the eicosanoids cut across many boundaries in their basic actions; selected chapters from each book in the series will provide illuminating and productive information for all readers which will advance their education and research. In the production of this series, I must acknowledge with pleasure my collaboration with editors and authors and the patient endeavours of Dr Michael Brewis and the staff at MTP Press. KEITH HlLUER University of Southampton England ix Preface This book is an appraisal of areas in human reproduction where eicosanoid studies (prostaglandins, leukotrienes and thromboxanes) are contributing to physiological and pathological awareness and clinical advances.

The introduction of prostaglandins into clinical practice has been one of the most important advances in obstetrics and gynaecology in recent years. During the last decade obstetricians have become familiar with these drugs for inducing labour and for terminating second-trimester pregnancy. Within the last year their use has been extended, in association with antiprogestin, to first-trimester termi nation. Although the effectiveness of prostaglandins in these pharma cological roles is clear, their full potential has still to be explored, and much remains to be learned about their physiology. Prostaglandins playa central role in the initiation of labour. Further clarification of this role could lead to improvements in preventing or treating preterm labour, which still remains the most important cause of perinatal mortality in this country. Prostaglandins are also inti mately involved in the mechanism of menstruation. More detailed understanding of this role should lead to more effective treatments for menorrhagia and dysmenorrhoea. These substances also playa part in the mechanism of implantation, and further research in this area may lead to more effective therapy for infertility.

Extensive basic research and clinical trials have in some aspect of reproductive physiology, gyne been conducted on inert and medicated intrauterine cology, or family planning. There is in this volume devices. In the last decade, substantial progress has an attempt to provide a total coverage of current been made in understanding the modes of action progress in medicated intrauterine devices. The and the physiological mechanisms of IUDs - pro volume is intended for a broad readership, includ gress resulting from modern techniques and in ing physicians, medical workers, medical personnel, strumentation in microanatomy, immunology, pa and administrators in family planning. It is hoped thology, endocrinology, biochemistry and biophy that this volume will serve as a stimulus to basic sics. Such studies, however, are scattered in such a scientists and clinicians concerned with intrauterine wide spectrum of journals that the clinician and devices to intensify their research toward better family planner can hardly keep up to date with the contraceptive techniques. advances. An attempt is made in this volume to coordinate physiological and clinical parameters. Little is September 1980 known about the possible role of diet, diseases and environmental factors. E. S. E."

The motive to prepare this volume on antibiotics for the physician caring for women was based upon the editor's perception that the subject matter had never been fully developed for the obstetrician-gynecologist. Most textbooks of infectious disease have a small section devoted to antibiotics, which has little relevance for the physician caring for post-operative or post-partum infections. Basic antibiotic pharmacology is described and there is a reflex prohibition of antibiotics for the pregnant woman. Correctly, the reader assumes that the authors themselves do not care for women with bacterial infections of the pelvis. Recent texts in infectious disease in obstetrics gynecology have been little better. Although the focus has been more clini cally oriented, space requirements have too often kept the discussions at a superficial level. A total focus upon antibiotics in this volume eliminates the restraints of space in prior publications. The greatest reward in my task as editor of this volume is related to the quality of the individual authors. They range from former students, to con temporary colleagues, to respected peers in infectious disease. Since the quality of this volume is related to the sum total of the individual chapters, I wish to comment about each of the contributors. Philip Mead from the University of Vermont is an old friend, who brings to the question of prophylactic antibiotics, his wide clinical experience and encyclopedic knowledge."

The aim of this book is to transmit the message that asphyxia is the major cause of infant mortality in the ne asphyxia-if severe, caus onatal period. The sequelae of ing cerebral palsy; if mild, leading to MBD to seizures are all potential risks. It is important to make young physicians and nurses aware of this complication of the birth period, how to avoid it, and how to treat it. Facilitating such awareness is the chief purpose of this book. Alberto Lacoius-Petruccelli New York 7 Contents 1. Asphyxia: Definitions, History, and Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2. Occurrence in Utero, at Birth, and after Delivery ................................. 17 3. Physiopathology of Asphyxia and Its Staging .................................. 21 4. Work-up and Treatment in the Newborn: Delivery Room, Nursery, and Perinatal leU 25 5. Mechanical Ventilators .................... 31 6. Prognosis ................................ 37 7. Brain Asphyxia and Hemorrhage ., ........ 51 8. Types and Stages of Fetal Anoxia: Anoxic, Anemic, Stagnant, and Histotoxic ......... 57 9. Embryonic and Fetal Periods .............. 65 10. The Placenta: Origin and Functions ........ 77 9 CONTENTS 10 11. Fetal Circulation 87 12. Placental Insufficiency or Dysfunction ..... ."

This is a unique book in that it brings together the two key investigative techniques in Gynaecology and Obstetrics, namely ultrasound and endoscopy. So often in the past they were regarded by their exponents as rival techniques but it is now recognised that they are complementary to each other. Consequently future trainees in endoscopy should become efficient in transvaginal sonography and vice versa. Ultrasound can be used to study the morphology of the pelvic organs such as the endometrium, myometrium and ovaries, and being non-invasive, safe and convenient can be repeated as often as is deemed necessary to monitor changes over time; for example in the investigation of the infertile woman the development of the dominant follicle, the maturation of the endometrium and the formation of the corpus luteum can be documented throughout the menstrual cycle while growth of ovarian cysts can be precisely measured to determine the need for surgery. A seldom-mentioned strength of the ultrasound examination is its interactive quality, for example by performing abdominal palpation during the scan, the mobility of the uterus and ovaries can be assessed. Also the images as they appear can be shown to the patient to aid understanding. Ultrasound can also determine function and the use of Doppler has been used for example to access endometrial receptivity, follicular maturity and the likelihood of malignancy in the endometrium or ovary.

This volume represents the Proceedings of the World Conference on Embryo Transfer, In Vitro Fertilization and Instrumental Insemination held on September 24-27, 1980 in Kiel, West Germany. Professor Dr. L. Mettler and Dr. H. H. Riedel of Frauenklinik der UniversiUit in Kiel were the local co chairpersons, who contributed very richly to the program. Basic research, clinical trials, preparation of manuscripts, editorial assistance and presentation of results were generously supported by the following institutions and organizations: Kulturministerium des Landes Schleswig-Holstein Medizinische FakuItat der Christian-Albrechts-UniversiUit, Kiel Wayne State University School of Medicine; Detroit, Michigan, USA C. S. Mott Center for Human Growth and Development; Detroit, Michigan, USA Universitats-Frauenklinik und Hebammenlehranstalt; Kiel, West Germany Serono GmbH; Freiburg, West Germany Hutzel Hospital; Detroit Medical Center; Detroit, Michigan, USA Deutsche Gesellschaft fUr Gynaekologie und Geburtshilfe; West Germany Deutsche Gessellschaft zum Studium der Fertilitat und Sterilitat; Sektion Andrologie Thanks are also due to Aponti GmbH (5000 Koln 21), Bayropharm GmbH (5000 Koln 80), Deutsche Lufthansa (5000 Koln), Organon GmbH (8024 Oberschleissheim), Winthrop GmbH (6080 New Isenburg), and Wisap GmbH (8029 Sauerlach), for financial assistance. Sincere appreciation and gratitude are due to the contributors who meticulously prepared their chapters; to Ms Jackie Mucci for editorial skills and assistance, and Ms. Jackie Smieska for editorial help. Thanks are also due to Dr. H. D. Brackebusch for his assistance during the conference; to Ms. E. Seiss for her secretarial assistance; and to Mr."

The Fourth International Congress on the Menopause was held in Lake Buena Vista, Florida, USA in October - November 1984. It was different from the previous meetings held under the auspices of the International Menopause Society in three respects: the duration of the Congress was extended to five days, plenary sessions were held on each day, and the scope of the subject matter was expanded to provide a total or holistic overview of the subject - hence the theme for the Congress 'Climacteric Medicine and Science: A Societal need. ' In recent years there has been an increased interest in the menopause and middle year aging by scientists and clinicians in fields as diverse as anthropology, urodynamics, nutrition and exercise physiology, while 'newer' issues in clinical medicine, such as osteoporosis prevention and management, attracted specialists in nuclear immaging techniques and internal medicine. Over 120 invited speakers plus numerous contributors to the free communication, special lectures and the poster sessions provided a virtual cornucopia of information on the menopause, that has indeed brought a newer perspective to a subject previously the domain of a single specialty, the gynecologist, and dominated by a single therapy, estrogen replacement.

In vitro fertilization has resulted in an estimated 4000-5000 births in the world. The procedure has been accepted in Europe, America and Australia and several hundred IVF clinics are operating successfully. The newer procedures of GIFf, embryo freezing and donor oocyte IVF have become established and are dealt with in several chapters. GIFf has become the procedure of choice for patients with infertility of unknown origin. Oocyte freezing represents an important new technology which is being developed. The routine IVF procedure has improved slightly; variation in results can be reduced by quality control of laboratory and clinical techniques. Male factor infertility has been dealt with by IVF in mild and moderate cases, but newer techniques will be required to deal with severe problems in the male. Most countries have accepted that the straightforward IVF pro cedure is ethical. Limitations concerning the use of donor oocytes and embryo experimentation exist in some religions and countries; legal control of the new reproductive technologies ranges from the passage of statutes to no control at all. Many countries are still considering the need for legislative control. The text endeavours to indicate new areas of importance and to guide those organizing services as to how to introduce newer technolo gies.

by Dr. Donald L. King The past decade has seen the ascent of ultrasonography to a preeminent position as a diagnostic imaging modality for obstetrics and gynecology. It can be stated without qualification that modern obstetrics and gynecology cannot be practiced without the use of diagnostic ultrasound, and in particular, the use of ultrasonogra phy. Ultrasonography quickly and safely provides detailed, high resolution images of the pelvic organs and gravid uterus. The quality and quantity of diagnostic information obtained by ultra sonography far exceeds anything previously available and has had a revolutionary impact on the management of patients. High resolution static images permit the intrauterine diagnosis of fetal growth retardation and fetal abnormalities. In addition to tradi tional images, newer dynamic imaging techniques allow observa tion of fetal motion, cardiac pulsation, and respiratory efforts. The use of ultrasonography for guidance has greatly augmented the safety and utility of amniocentesis. One of the great virtues of diagnostic ultrasound has been its apparent safety. At present energy levels, diagnostic ultrasound appears to be without any injurious effect. Although all the availa ble evidence suggests that it is a very safe modality and that the benefit to risk ratio is very high, the actual safety margin for its use Vll as yet remains unknown. As a consequence, practitioners are urged to limit its use only to those situations in which genuine clinical indica tions exist and real benefit to the patient is likely to result."

This volume contains all the invited papers, symposium contributions and workshop reports of the 7th International Congress of Human Genetics, held in West Berlin from September 22 to 26, 1986. The organizers of this congress made sure to gain the cooperation of the leading scientists in the field from all over the world. These contributions therefore document the enormous progress made in human genetics research in recent years. The volume covers a wide range of topics, from analysis of the human genome to basic mechanisms, diagnosis and therapy of hereditary diseases, and to distribution of normal and pathological genes and DNA variation in human populations. Ethical issues raised by modern developments are discussed thoroughly. The volume is a must for all scientists and medical doctors working in human genetics research, its teaching and practical applications.

Conceptual advances in the biological sciences are marked by the applica tion of new techniques and experimental strategies. Nowhere has this ge neric principle been more apparent than in the study of testicular cells, as judged by the evolution of themes presented at the Testis Workshop over the past 23 years. Like its predecessors, the 1995 Testis Workshop was structured to offer fresh insights and approaches for understanding the mechanisms of spermatogenesis and steroidogenesis. The chapters pre sented in this book emphasize three aspects of testicular cell function: first, the molecular analysis of the cell cycle; second, examination of the cell cycle, including the function and identification of specific macromolecules that direct the proliferation and differentiation of germ cells; and third, the development of Leydig cells and the role of specific macromolecules in the formation of testicular steroids. Each chapter is based on a lecture presented at the XIIIth Testis Work shop held on March 30 to April 1, 1995, at the Radisson Plaza Hotel in Raleigh, North Carolina. The selection of topics reflects the recommenda tions of the workshop'S organizing committee. Sincere thanks are due to the speakers who agreed to lecture and prepare chapters."

Each new volume of this publication brings the privilege of expressing some of my thoughts on subjects of interest to its readers. In the past year or so public concern about environmental and societal dangers has largely turned to those of cosmic proportion-Chernobyl, the thinning ozone layer, AIDS, and the like-and thankfully our subject matter has been allowed a respite. Even the miniepidemic of craniofacial and other malformations caused by the retinoid antiacne drug Accutane made no headlines. Incidentally, this might have been a tragedy of far greater proportions had it not been nipped in the bud by the historical ground work that quickly permitted it to be recognized as due to an environ mental teratogen-the sort of fact the public and authorities inadequately appreciate. But there is a warning connected with this abeyance of media focus on teratological matters. Disquiet over cosmic imbalances will sub side as they are corrected or horrendous projections fail to materialize, and even cures for dread infectious diseases, or Puritan revolution in terdicting such plagues, will be forthcoming, and these things will occur long before congenital malformations are no more. And as the year-in and year-out recurrence of over 100,000 an nual births of seriously malformed infants in the United States alone continues to force itself on the public consciousness, we can expect a heightened demand that "a cure" be found, because "if we can land a man on the moon, if we can prevent polio, why can't we . . ."

Polycystic ovarian disease, or polyfollicular ovarian disease, as Dr. Fut terweit prefers to call it, is a disease of uncertain etiology and for which numerous modes of therapy have been advanced. Understanding of its pathophysiology should shed light on factors regulating normal ovarian function; the converse is also true. Recent years have brought about great understanding of the neuro endocrine regulation of gonadal function, as well as of factors in the microenvironment of the ovary which affect its function. It is also ap preciated that cases classified as polycystic ovarian disease actually rep resent a clinical and pathological spectrum which may reflect the effects of diverse etiological factors. In the present volume, Dr. Futterweit presents the fruits of his long interest in and extensive experience with this disease. He thoroughly and thoughtfully reviews the vast amount of basic and clinical information that has been garnered with regard to this condition over the past decade. The numerous theories that have been advanced to explain its etiology are presented in balanced fashion, in addition to a hypothesis, which is well formulated and amenable to clinical testing. His clinical interests and judgment are well represented by his presentation of the diverse manifestations of this condition, the approach to proper diagnosis, and the available therapeutic options. Patients with this disease represent diagnostic and therapeutic prob lems in a situation where manifestations of disease may lead to major emotional stress."

The perimenopause is an extremely important time in a woman's life. In a similar but reverse sequence to puberty, it signals a change in ovarian status. Although some women pass through this transition without symptoms or concern, for many women, the perimenopause, which can last several years, is of great concern. Symptoms of estrogen deficiency, menstrual irregular ity, concerns over changes in mood, as well as reproductive concerns lead to anxiety and frustration. Because it is poorly understood, many clinicians are equally frustrated in finding ways to help their patients and question the appropriateness and/or need for treatment. This Serono Symposia USA, Inc., meeting was designed to help address some of these issues from both a basic science and a clinical perspective, and to provide a forum for discussion. The waning of ovarian function can be divided into two events that are dissociated: gametogenic and endocrine failure. Thus, the symposium was divided into three parts to address these two phenomena and to discuss treatment options. An outstanding international group of clinicians and investigators assembled to first address oocyte depletion and possible markers. Next the complex endocrine changes were discussed as well as the physiologic consequences of these changes. This included a discussion of hot flushes, bone and cardiovascular changes, menstrual irregularity, mood disturbances and depression, and anatomical changes in the ovary and breast. The third part of the symposium addressed treatment options, both in terms of symptoms as well as reproductive and fertility concerns."

Ultrasonic surgical techniques were first used by Dr. Kelman in the 1960s to fragment cataracts through a 2-mm incision allowing for minimally invasive surgery. The results from this procedure stimulated the development of a larger, move powerful ultrasonic unit that was used in neurosurgery. This instrument allowed the neurosurgeon to selectively remove tumor tissue with decreased blood loss and tissue trauma. The ability now of ultrasonic equipment to selectively fragment, irrigate, and aspirate tissue with minimal coagulation effect spurred its rapid use in surgery on the liver, spleen, kidney, and other intra-abdominal organs. This instrument has been invaluable in ovarian cancer cytoreduction and intricate segmental organ resection. The newest technical developments include electro cautery capability built into the hand piece and extended hand pieces for laparoscopic surgery. The impetus for assembling this volume has been to provide an extensive review of the field of ultrasonic surgery as it has currently developed including principles, equipment features, and surgical tech niques. It is hoped that the information will be of use to physicians in training and surgeons in practice. The book takes a multidisciplinary approach with chapters authored by a diversity of subspecialists in gen eral surgery, urology, surgical oncology, and gynecologic oncology. Each chapter contains basic information on surgical techniques. Together, these chapters cover surgery of the GI tract, kidney, liver, and lower genital tract, and present a number of personal approaches."

Since the awarding of the Nobel Prize to Drs. Guillemin and Schally iJ) 1971 for isolation and chemical characterization of gonadotropin releasing hormone, we have experienced a remarkable period of growth of interest in this hormone. The last 20 years have been characterized by a swift translation of basic science discovery into clinical utility. Approval of GnRH and its analogs for treatment of prostate cancer, endometriosis, of ovulation indicate the range and precocious puberty and for induction of these agents. of usefulness In order to bring together the leaders in the basic and clinical science of GnRH, a conference was organized on "Modes of Action of GnRH and GnRH Analogs" and held in Scottsdale, Arizona, February 26 to March 2, 1991. The presentations, given as chapters in this volume, show both the advances in the body of information in this discipline and the efforts underway to reduce basic science to clinical practice. The audience was a combination of representatives from universities, government, industry, and physicians in practice. The lively discussions and insightful questions indicated the interest in the topics discussed and frequently served to catalyze planned interactions of the meeting participants. The organizers are grateful to the speakers and poster presenters for their contributions and for the timely preparations of the manuscripts included in the present volume. We are also thankful to the staff of Serono Symposia, USA, for the organizational skills and support that allowed the meeting organizers to focus on the science and medicine presented.