Concise, recent data are presented on obstetric problems arising in patients with cardiovascular diseases (not only congenital and acquired valvular heart diseases and hypertension, but also uncommon heart lesions) and on cardiological complications encountered in pregnant women. The goal of the book is to provide obstetricians with necessary cardiological information and cardiologists with essential obstetric information to enable both specialists to make optimal decisions regarding the permissibility of pregnancy, management of pregnancy and labour, or termination of pregnancy, and selection of an adequate form of contraception in women with heart and vascular diseases. Along with recent scientific findings, the book contains practical recommendations for examination diagnosis and treatment that is effective for the mother and safe for the fetus.

In the last decade of the 15th century a new and deadly disease called Morbus Gallicus, or syphilis, appeared and spread rapidly throughout Europe. The effects of syphilis were so severe that it, and those suffering from it, where regarded with horror and despair. It is difficult for the modern reader to appreciate the fog of confusion which surrounded sexually transmitted diseases in earlier times. Those suffering with these diseases were often condemned as victims of their own "sinful lust of the flesh"; a judgement attitude which hindered most of the early attempts at control and treatment. Despite this general attitude, there were some doctors who persevered in their attempts to understand the causes and discover treatments for syphilis and other sexually transmitted diseases. The Scars of Venus is illustrated with pictures of people, places, instruments and documents. It presents the historical background and achievements of the early venereologists through to the current venereologists' fight against HIV. This book will be of interest to anyone concerned with venereal diseases: doctors, nurses, counsellors, laboratory workers, medical historians, and those working in the areas of public/world health and the spread of infectious diseases.

The number of studies on chronic and recurrent pain bears no relation to the frequency of these complaints in gynecologic practice, nor to the clinical and scientific problems that still need solving in this area. Several factors stand in the way of progress in this field, such as the strongly subjective nature of the complaints, the frequent lack of correlation between them and objective findings, and the complexity of the psychosomatic interac tions involved. Although progress in our knowledge has been much slower than we would have wished, and although we are well aware of these many gaps, it was considered useful to gather in a book what we think we have learned during 3 decades of active interest in pain patients and pain problems in gynecologic practice and 12 years of supervision of a pain clinic in the Department of Obstetrics and Gynecology of Leuven University. As there are many differences between acute pain - clinical as well as experi mental - on the one hand and chronic pain symptoms on the other, it was felt preferable to limit the scope of this book essentially to chronic and recurrent pain in gynecologic practice. When presented with a complaint of lower abdominal and/or low back pain, the gynecologist should constantly be on the lookout for nongynecologic causes, of which the most frequent will be either gastroenterologic or orthopedic and sometimes urologic. I have been fortunate in obtaining the collaboration of Dr."

During the past ten years numerous new findings have been documented in the field of gynecological pathology, especially in respect of neoplasms. These findings have been generated by the application of recently developed techniques of immunology and molecular biology. However, clinicopathologic examinations. are still an absolute requirement for the morphologic evaluation of neoplasms, including gynecological tumors. The International Society of Gynecological Pathologists (ISGYP) has contributed greatly to the progress within gynecological pathology. The ISGYP Nomenclature Committee has promoted the International Histological Classification of Gynecological Tumors under the auspices of the W orid Health Organization. A new edition of the classification of tumors and tumor-like conditions of trophoblastic disease, uterine corpus, cervix, vagina, and vulva is currently in press. A second volume covering the ovaries, fallopian tubes, broad ligament, and female peritoneum will be published later. Organization of scientific symposia and seminars has also been an important activity of the ISGYP. The present editor organized and chaired a symposium entitled "Recent Progress in Diagnostic Pathology of Gynecological Tumors" held in Sendai, Japan on 11 April 1986 in close cooperation with Prof. T. Okagaki, University of Minnesota Medical School, and under the joint auspices ofthe ISGYP and the Japanese Society of Pathology. The following topics were discussed at this symposium: - Immunocytochemistry of gestational trophoblastic disease (Dr. R.J."

This book is the product of long years of close collaboration between two physicians, a pediatric endocrinologist and a pediatric surgeon, who are interested in the complex field of human malformations. Their efforts have set a new standard in the treatment of children with intersexual or mal formed female genitalia. It is impossible to convey the details of complex surgical procedures without the help of meticulous illustrations. It is fortunate that happened to meet an academically trained artist, Mrs. Siri Mills, M.A., while visiting in the United States. Her excellent knowledge of anatomy, her remarkable skills as an artist and technical illustrator, and her readiness to include all details of interest to the surgeon have found their fruitful expression in the illustrations of this book. We express our thanks to Springer-Verlag and especially to Prof. Diet rich Goetze, at whose suggestion this book was written, for their amiable compliance with all our wishes, and particularly for their willingness to retain Mrs. Mills as our illustrator. Munich, May 1985 WALDEMAR HECKER Contents In trod ucti on 1 Part 1: Endocrinologic Diagnosis in Pediatric Patients with Genital Anomalies General Rules . . . . . . . . . . . 4 Endocrinology of Antenatal Sex Differentiation 6 Male Differentiation 6 Female Differentiation 7 Specific Endocrinologic Diagnosis and Therapy 8 Virilization of the Female External Genitalia 8 Congenital Adrenogenital Syndrome with a Defect of 21-Hydr- ylase . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Intersexual Genitals Due to Deficient Androgenization of the Male 11 Defects of Testosterone Biosynthesis 11 Androgen Receptor Defects . . ."

March 23 and 24, 1983 saw the fIrst international symposium held under the auspices of the Wilhelm Vaillant Foundation for the Advancement of Pro- phylactic Medicine in the I. Frauenklinik der Ludwig Maximilians Univer- sitiit Miinchen. This symposium was concerned with Advances in Early Detection and Treatment of Breast Cancer and brought together patholo- gists, gynecologists,and radiologists from Denmark, England,France, Italy, Sweden, Switzerland, the German Democratic Republic, and the Federal Republic of Germany. The fIrst session dealt with problems concerned with the biology, patho- genesis, and histopathology of early carcinoma of the breast, with special reference to the clinical aspects. The second session was taken up with topi- cal developments in the early diagnosis of breast carcinoma and indicated the present limitations of early diagnosis. In the third session the latest results of the experiences by groups working on the treatment of early carci- noma of the breast in France, the United Kingdom, Italy, the United States of America, and the Federal Republic of Germany were discussed. The main emphasis lay on conservative treatment methods with complete or partial preservation of the breast. These vary quite widely. Some of the conclusions presented on the basis of long-term clinical studies must be regarded as signifIcant breakthroughs, and at the stage these have reached they must no longer be overlooked. The symposium has highlighted numerous unsolved problems and made it clear that conflicting opinions abound.

A variety of new techniques that promise to revolutionize the clinical management of early pregnancy are fully detailed in this state-of-the-art book. Leading international researchers describe fast-moving topics such as embryo manipulation and the diagnosis of congenital abnormalities. The technology of assisted reproduction has made it possible to study living embryonic material for the first time, which has led to rapid advances in our understanding of the human embryo's early development. For example, study of the embryo in the test tube has pointed to early pregnancy loss as a possible cause of later infertility. Even more important, diagnostic tests using sophisticated techniques of molecular biology can be run on single cells before the embryo is replaced in the uterus. Another area of advance is the diagnosis of congenital abnormalities in the first and second trimesters of pregnancy. Great improvements have been made in the techniques of chorion villus biopsy and ultrasound imaging. A spectrum of simple biochemical tests performed on the mother's blood can greatly improve the detection of Down syndrome and other chromosome defects. Together with other developments in the fields of molecular biology and endocrinology, these new diagnostic techniques are the beginning of a new age in clinical human genetics and embryology.

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.

A close look at stories of maternal death in Malawi that considers their implications in the broader arena of medical knowledge. By the early twenty-first century, about one woman in twelve could expect to die of a pregnancy or childbirth complication in Malawi. Specific deaths became object lessons. Explanatory stories circulated through hospitals and villages, proliferating among a range of practitioners: nurse-midwives, traditional birth attendants, doctors, epidemiologists, herbalists. Was biology to blame? Economic underdevelopment? Immoral behavior? Tradition? Were the dead themselves at fault? In Partial Stories, Claire L. Wendland considers these explanations for maternal death, showing how they reflect competing visions of the past and shared concerns about social change. Drawing on extended fieldwork, Wendland reveals how efforts to legitimate a single story as the authoritative version can render care more dangerous than it might otherwise be. Historical, biological, technological, ethical, statistical, and political perspectives on death usually circulate in different expert communities and different bodies of literature. Here, Wendland considers them together, illuminating dilemmas of maternity care in contexts of acute change, chronic scarcity, and endemic inequity within Malawi and beyond.

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.