Publication of this monograph acknowledges great strides made in research on the zona pellucida during the past decade or so. The body of work presented testifies to a resurgence of interest in the zona pellucida, prompted largely by a renewed appreciation of its unique properties and its important functions during early mam malian development. It is gratifying to realize that the zona pellucida has at last achieved a well-deserved attention. Whereas extracellular coats of nonmammalian eggs have been studied intensively for many years, the zona pellucida by comparison, has until now taken a back seat. Fortunately, the research presented here signals an end to this situ ation. Many of the difficulties inherent in working with relatively small amounts of material have been overcome, paving the way for application of a wider variety of experimental approaches to the zona pellucida by a larger community of investigators. Hopefully, this monograph will serve as a catalyst in this regard. As revealed in these pages, application of contemporary experi mental methodologies has had significant impact on both pure and applied research on the zona pellucida. For example, modem im munological approaches have been used to assess molecular fea tures of zona pellucida structure and function, as well as to evalu ate the zona pellucida as a potential contraceptive target antigen."

The decision taken during the First International Congress on the Menopause in June 1976 to repeat the exercise 2 years later turned out to be a good one. In the last few years much work has been done on the subject of the menopause. I t is, of course, a subject of many facets, but of particular importance recently has been the work done as a result of the reports appearing in 1975 and 1976 alleging an increase in the incidence of endometrial carcinoma in women who had used oestrogens, and of other effects, some beneficial others deleterious, reportedly seen when oestrogens were administered. 1978 seemed the right time to re-assess the situation, and the Second Inter national Congress on the Menopause provided a good platform. The congress was held in Jerusalem in June 1978. It took the form of a series of 12 workshops, each of which, within a prescribed framework, was planned and presided over by a moderator experi enced in that particular field. The 12 moderators were free to organize their sessions in whichever way they wished, and to invite whoever they wished to present papers and to join in the discussions. In addition the workshops were open to anyone who wished to attend."

The progess in biological sciences and its applications in obstetrics in the last twenty years have formed the base for feto-placental semeiotics. In this way, it has been possible to diagnose placental insufficiency even in patients whose clinical conditions gave all the indications of a perfectly normal feto-placental condition. On the other hand, observations have shown that in certain conditions some deficiencies can im prove until normality is reached again. On the basis of the above one feels justified to talk about the therapy of feto-placental insufficiency. Until now this therapy has been aimed at the obstetrical pathology of the mother. Our aim is to illustrate the various steps which should be taken to execute an efficient therapy of the conditions relating to the pathology of the fetus, realizing full well that fetal pharmacology is only now being taken into consideration. The various steps to be taken, the length of therapy, and all the other correlated factors are still the object of individual ex periences, and we are fortunate to have amongst us researchers in this field who have accepted our invitation and can supply us with their personal experiences which can also be compared. The first international symposium on the therapy of feto-placental insufficiency has been organized in conjunction with the Samil-Pabyrn Foundation whom I would lik to thank, and especially so its president, Mrs. INGE SAXON-MILLS."

Since the discovery of LHRH in 1971, research into the physiology and therapeutics of this compound can be divided into three dis tinctly different phases. In the first phase, attention was paid chiefly to the natural sequence hormone; efforts were channeled to explore its diagnostic use; and nearly all the clinical investigations were coordinated by a single pharmaceutical company. The successes in this area were quite limited and the interest in the promise of this agent as a diagnostic test has long since waned. This phase of research con sumed roughly the first seven years of clinical testing after the isolation and characterization of the compound by the two groups involved in the Nobel effort. With the appearance of long-acting LHRH agonists, the second phase of research on LHRH began in the late '70's. LHRH agonists were the only compounds available during this period of research and paradoxical desensitization was the predominant therapeutic basis for the discoveries. An ever-widening number of therapeutic applications using this approach were unearthed. A second theme which emerged during this second 5-7 year period was that the pulsatile administration of the natural sequence LHRH could be used to treat LHRH deficiency in men and women."

This monograph contains a selection of papers presented at the Xlth World Congress of Fertility and Sterility (Dublin, 1983); the central theme is ovarian function and treatment of its disorders. Cross-cultural research provides international congresses with their unique quality due to the world-wide exchange of views; we think this aim has been achieved and reflected in this book. During the past decade significant advances have been made in our understanding of the events surrounding human ovulation leading to the development of an increasing range of effective therapeutic agents and the more logical use of existing drugs. As a result infertile patients with disordered ovulation can now anticipate a more favourable out come. In addition more sophisticated diagnostic methods have revealed the presence of minor defects in ovarian function in some patients previously labelled as 'unexplained infertility'. The identification of such problems can only lead to further therapeutic success. The contents of this volume reflect many different aspects of the study of ovulation including the monitoring of both follicular growth and the luteal phase, the role of prolactin and the treatment of ovulatory dysfunction. We are sure that the wide range of topics will evoke continued interest in these subjects. We extend our thanks to the invited speakers for their excellent contributions in lecture and essay form and express our gratitude for the unfailing help we received from the staff of MTP Press in the preparation of this volume."

The role of prostaglandins in physiological events and pathological disorders related to human reproduction has been most actively investigated in the past decade. Their clinical use for fertility regulation, extensively evaluated, represents the most common clinical indication for the administration of these remarkable compounds. Thus, it is most appropriate to update the available information related to the use of prostaglandins in the regulation of human fertility to provide a background document for the benefit of clinicians and scientists. Invited experts of international reputation from various parts of the world have contributed, each in his own area of interest, to offer this book, which we hope will fill an existing gap. M. T. M. B. E. S. E. H. ix 1 Potential for prostaglandin use in controlling human reproduction K. T. KIRTON and F. A. KIMBALL BACKGROUND It was observed in 1930 that seminal plasma of a number of species contained very large amounts of substance(s) capable of altering uterine motility. These substances were subsequently demonstrated to be prostaglandins (PGs); this began the early and continued association of this group of compounds with reproduction. The activity was found to be associated with a fraction containing lipid-soluble acids, derived from prostanoic acid. Restrictions imposed by obscure sources and small amounts of material available for testing were initially impediments to their study.

These four volumes comprising "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at a landmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, Switzerland in February 1988. The Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of The International Committee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of Fertility and Sterility, The University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US Foundation for Studies in Reproduction Inc., and help from the World Health Organization. B. H. Vickery B. Lunenfeld June 1989 LIST OF CONTRIBUTORS TO THE SERIES H. Bartermann A. Abbondante First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" D-2300 Kiel 1, FRG Rome, ltaly M. Bartholomew P. Abel Department of Medicine/Endocrinology Department of Urology Milton S. Hershey Medical Center Hammersmith Hospital Pennsylvania State University DuCane Road PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck H.

These four volumes comprlslng "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at a landmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, Switzerland in February 19B8. The Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of The International Committee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of Fertility and Sterility, The University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US Foundation for Studies in Reproduction Inc., and help from the World Health Organization. B. H. Vickery B. Lunenfeld June 1989 xiii LIST OF CONTRIBUTORS TO THE SERIES A. Abbondante H. Bartermann First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" 0-2300 Kiel 1, FRG Rome, ltaly M. Bartholomew P. Abel Department of Medicine/Endocrinology Department of Urology Milton S. Hershey Medical Center Pennsylvania State University Hammersmith Hospital DuCane Road PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck H.

The image of obstetrics as a largely manipulative art has changed radically in recent years. The risk to a healthy mother of pregnancy and labour has been markedly reduced and morbidity not mortality is the yardstick by which the quality of maternal care is judged. We are now able to devote far more attention to the fetus whose growth patterns and behaviour in utero can be studied in detail by modern and sophisticated technical aids with a resultant improvement in perinatal mortality. A patient with a pre-existing general disease, however, still presents a problem which is best managed by close co-operation between obstetrician and physician. Essential hypertension, diabetes, heart disease, thyroid disease and epilepsy are examples of disorders which require great care throughout pregnancy and during labour if good maternal and fetal results are to be obtained. There are many questions still to be answered. What is the place of hypotensive therapy in essential hypertension complicating pregnancy? When should delivery take place in the pregnant diabetic? How should the patient be delivered? What should be her management during labour? What is the risk of fetal abnormality in the epileptic patient who becomes pregnant whilst on anti-epileptic drugs? These questions and others have been the subject of a recent symposium in the Institute of Obstetrics and Gynaecology.

The use of human in vitro fertilization in the management of infertility is the outgrowth of years of laboratory observations on in vitro sperm-egg interaction. "The editors of this work have themselves contributed significantly to basic knowledge of the mammalian fertilization process. The observations of Don Wolf on sperm penetration, the block to polyspermy and, most recently, sperm hyperactivation in the monkey and human, Gregory Kopf's elucidation of the mechanisms of sperm activation during penetration and the reciprocal dialogue between sperm and egg, and Barry Bavister's definition of culture conditions and requirements necessary for in vitro oocyte maturation, fertilization and development in model mammalian systems including nonhuman primates have contributed greatly to our understanding of the mammalian fertilization process. Wolf, Kopf and Gerrity have enjoyed substantial interaction with clinicians in Departments of Obstetrics and Gynecology and have been directly involved with successful IVF programs. Both Wolf and Kopf have served as research scientists in the Division of Reproductive Biology at the University of Pennsylvania, which, for more than 22 years, has fostered co-mingling of clinically oriented and basic science faculty. It is through such interaction, which clearly exists at many institutions including the University of Wisconsin, that the process of technology transfer is best served. Without an exquisitely coordinated laboratory, there can be no consistent success in human in vitro fertilization. Quality control is pivotal, but close collaboration between the laboratory and the clinic is also essential as information is shared and correlated.

Atrophy of gonadotrophin producing cells Exogenously LH synthesis administered androgens and release or anabolic steroids are decreased Prostate Testes Normal function. Testosterone synthesis in The deficit of endogenously Leydig cells is decreased. The synthesized testosterone is exogenously administered compensated for by the steroid is not able to exogenously administered compensate for the deficit of steroid endogenously synthesized testosterone Figure 2 Intratesticular and serum testosterone concentrations after treatment with andro gens or anabolic steroids in order to substitute for the peripheral androgen deficiency and to achieve azoospermia. Because this steroid is alkylated in position 17, toxic effects on liver function can not be excluded. Danazol offers no advantages as compared with other anabolic steroids; rather, disadvantages. Numerous experiments of this type have been performed during the last 40 or 50 years. The outcome in each case was more or less identical: with a certain dose of an androgen or anabolic steroid it is possible to inhibit spermatogenesis without interfering with other androgen-dependent func tions, including libido (potentia coeundi) and accessory sexual glands. On the basis of this pharmacological-endocrinological background, androgens and anabolic steroids can be used for male fertility control, and several clinical trials have been performed during the last 10-15 years. Some of 1 these studies 2-23 are mentioned in Table 2."

Infectious diseases remain a major problem for physicians and other health professionals dealing with problems of the reproductive system. Accordingly, this two-volume comprehensive presentation of infectious diseases involving the male and female reproductive systems promises to be a major contribution in this field and to fill a much-needed vacuum. During the past three decades, the introduction of antimicrobial therapy has dramatically altered both the clinical presentation and the therapeutic approaches employed in dealing with the traditional infections of the repro ductive system. In addition, the changing demographics of infectious problems in the industrial countries and the developing world have been a source of concern. A good deal of important information on this topic is included in this series. In recent years, considerable attention has been given to the role of Myco plasma and Chlamydia in both male and female infertility and the problems related to genital herpes and human papilloma virus infections. Current clinical information is included on these infections as well as on newer aspects of diagnosis, such as the use of laparoscopy in the diagnosis and treatment of pelvic inflammatory disease. Also addressed is new information regarding the role of actinomycosis in pelvic infections; current problems such as toxic shock syndrome and acquired immune deficiency syndrome (AIDS) are reviewed as well. New concepts are included in these volumes to complement the clinical information. The attachment of microbial organisms to sperm may help to explain access of these and other organisms to the upper female genital tract."

A little over 12 years ago I wrote a small volume entitled Infertility. It seemed to me at that time that significant advances in the field called for the publication of such a volume. The following is from the preface to that volume: During the past 15 years considerable progress has been made in the field of infertility diagnosis and management. It is perhaps a paradox that much of this increased knowledge has come about because of Western medicine's preoccupation with the search for a means to control reproduction. As a result, we have achieved new insights into the physiologic mechanisms involved in reproduction, and we have found better methods for measuring physiologic changes in reproductive health and disease. To these advances can be added improvements in the utilization of endoscopic and surgical techniques, in the diagnosis and treatment of infections and endometriosis, and in the treatment of hormonal disorders. During this period, too, through workshops and conferences and in journals and texts, these latest advances have been made available to physi cians, an outstanding example being the two volumes of Progress in Infer tility, edited by Drs. Jan Behrman and Robert Kistner. As necessary as these publications are, they do not offer an overall view of infertility diag nosis and management."

Due to the introduction of molecular and cellular biology approaches, our understanding of ovarian physiology has reached a new level during the last few years. The present volume provides a new perspective on the ovary from molecular and cellular to whole organ levels, from non-mammalian and rodent to human levels and from paracrine, neuroendocrine and endocrine levels as well. These papers represent the proceedings of the Ninth Ovarian Workshop sponsored by Serono Symposia, USA, July 9-11, 1992 in Chapel Hill, North Carolina.

This volume contains the proceedings of the Symposium on Molecular and Cellular Aspects of Periimplantation Processes, held July 15 - 18, 1994, in Boston, Massachusetts. Despite considerable research, the molecular and cellular bases of embryo-uterine interactions are still poorly understood. The papers included in this volume address recent advances in several areas in the field of implantation, including uterine receptivity, hormonal regulation, cell-cell interaction, growth factors/cytokines, immunobiology, and trophoblast invasion.

Sex Hormone Replacement Therapy addresses important issues in contemporary endocrinology. Its major emphasis is on the consequences of the menopause and on androgen deficiency in the absence of overt disease of the hypothalamus and/or pituitary in men. The use of hormone therapy for the primary prevention of cardiovascular disease in post-menopausal women has become an area of major debate, and the pros and cons are examined in detail. Secondary prevention also remains controversial and is addressed in this volume. An issue of particular concern is the treatment of estrogen deficiency symptoms in women with the diagnosis of breast cancer. Whether older men with some androgen deficiency symptoms and equivocally low plasma testosterone concentrations should be treated with androgens is also a matter of great debate, as is the efficacy and safety of plant estrogens in the treatment of menopause-related complaints. Sex Hormone Replacement Therapy will be of interest to students and non-specialists, as well as a wide range of medical practitioners including endocrinologists, gynecologists, rheumatologists and cardiologists.

Neuroendocrine Perspectives, Volume 7, is part of an international book series designed to keep clinicians and researchers appraised of important trends and new data in basic and clinical neuroendocrinology. It focuses on four very rapidly evolving major topics: - the role of dopaminergic regulation of the intermediate pituitary lobe in elucidating intracellular signal transaction pathways and other regulatory mechanisms involved in transsynaptic regulation of peptide biosynthesis, post-translational processing, and hormone secretion; - the physiological and clinical implications of corticotropin releasing factor for such areas as diagnosing Cushing's syndrome, defining the hypothalamic and pituitary origins of secondary adrenal insufficiency, and distinguishing Cushing's syndrome from psychiatric states associated with hypercortisolism; - the large number of neurotrophic factors that affect CNS neurons and of neurite promoting factors that modulate neuronal performance, with emphasis on their mechanisms of action and their possible therapeutic applications to peripheral neuropathies and central diseases; - and the many factors that regulate changes in female reproductive cycles during middle age, with careful distinction between neuroendocrine and ovarian components and special attention to the possible cause-and-effect relationship within the cascade of events resulting in acyclicity and infertility.

Bernard (Barney) Berelson had a major influence in the application of social science concepts and methods to population policy during the period from 1962 to 1980. This was the period when concern with population problems spread from a relatively small group of scholars and population activists to a much larger, diverse, international group of political and intellectual leaders and to the general public as well. There was an exponential growth in the number of scholars and service personnel in vari ous population and family specialities in this period. Barney came into the field with his appointment as Director of the Com munication Research Program of The Population Council in 1962. He had no previous training or experience in demography. Frank Notestein, Presi dent of The Population Council at the time, had the wisdom to appreciate the value and relevance of Barney's itTIpressive background in communica tion research and other social science areas, as well as his creative mind and leadership qualities. His influence on the Council's rapidly expanding program was so immediate and impressive that within a year, he was named Vice President. When Frank Notestein retired in 1968, Barney became President, a post he held for 6 very productive years."

Ovulation Induction gives an integrated view of basic ovarian physiology, pathophysiology, and the clinical management of ovulatory disorders. It provides core information upon which specialists can base clinical decisions. The most important feature is the inclusion of newer agents now available for ovulation induction. Newer clinical applications for older medications as well as various treatment combinations (including GnRH analogs) are thoroughly discussed. There is a frank discussion of risks, side effects, and the expense related to ovulation inducing agents. Many of the results in this book have never before been published in book form. Topics examined include the neuroendocrine regulation of the menstrual cycle, ovarian physiology and in vitro fertilization, the diagnosis of ovulation and the role of ultrasound in monitoring the follicular response, the use of clomiphene citrate for ovulation induction, and the role of bromocriptine and related compounds for ovulation induction in hyperprolactinemia.

Progress in biomedical science has called for an international discussion of the medical, ethical, and legal problems that confront physicians, medical researchers, infertile couples, pregnant women, and parents of premature or disabled infants. In addition, the unprecedented technological developments in obstetrical, perinatal, and neonatal medicine in recent years have indicated a need for an international forum for interdisciplinary dialogue regarding the definition of early human life, the neurological development of early human life, the value of early human life, the obligations for its protection and prolongation, and the limits to these obligations.

Leading workers in the field of human reproduction provide both basic knowledge and useful practical information in this book about the most critical phase in the development of a new human being: the first twelve weeks of life. The period from fertilization and implantation to the end of the first trimester is still insufficiently understood and marks a new frontier. The knowledge necessary for applying our present diagnostic capabilities and for venturing into the problematic areas of fertilization technology and embryonic treatment is made easily available in this comprehensive textbook. The book is divided into two parts. The first presents basic information about physiology, anatomy, in vivo investigations, biochemistry and legal aspects. The second part focuses on pregnancy development, monitoring and the clinical diagnosis and management of disorders in the early stages of life. A full section is devoted to assisted conception and the newest possibilities in fertilizationtechnologies, whereby the ethical aspects are also discussed.

The modern gynaecological patient is much more knowledgeable about the menopause and the therapeutic options, with information that is obtained from a variety of sources. Some of this information is unscientific, and many of the so-called remedies are unproven. The modern gynaecologist therefore needs to have confidence in being able to discuss, evaluate and manage women with menopausal problems. This review provides the MRCOG trainee with an excellent insight and with more than enough current facts and figures, but it will also be extremely useful for anyone else wishing to be up-to-date in this increasingly important area.

Interest in bone densitometry methods has recently experienced a resurgence within the medical community. Physicians have become more interested than ever before in the diagnosis and treatment of degenerative diseases of bone such as osteoporosis. The public perception of osteoporosis and its prevention has been recently heightened. Because osteoporosis is widespread, especially in women, and leads to an increase in fractures in our population, many re searchers and clinicians are strongly motivated in their search for more sensi tive and accurate methods of diagnosis. This book was written for physicians, scientists, engineers, medical phy sicists, and others desiring an introduction or further understanding of this exciting field. Beginning with the early development of x-ray film methods for assessing bone status, the field has steadily grown throughout the years. Novel and interesting devices have been designed for the measurement of bone mass, bone density, cortical thickness, and other parameters of bone changes. Both qualitative and quantitative bone methods are described. The techniques include imaging devices such as CT and radiography as well as fixed point methods in which bone characteristics of a region of interest are analyzed."

SIDNEY CALLAHAN AND DANIEL CALLAHAN This book, like many other things to do with abortion, is a product of long controversy. Though carried out with cooperation, it was conceived in conflict. The conflict between the coeditors has per sisted for years-in fact, for at least half of their thirty-year marriage. One, Sidney, is prolife; the other, Daniel, is prochoice. Ever since the topic of abortion became of professional interest to us, in the 1960s, we have disagreed. At one time, while Daniel was writing a book on the subject, Abortion: Law, Choice and Morality (1970), we talked about the subject every day for the four years of the book's gestation. On many occasions during the 1970s, prolife articles writ ten by Sidney were passed out at Daniel's lectures in order to refute his pro choice views. Over the years, every argument, every statistic, every historical example cited in the literature has been discussed by the two of us. As Eliza Doolittle says about "words" in My Fair Lady, "There's nota one I haven't heard. " And yet we still disagree. How can it be, we ask ourselves, that intelligent people of goodwill who know all the same facts and all the same arguments still come down on different sides of the con troversy? As we well know, it is possible to agree about many things and have great love and respect for an opponent, and still differ."