This book is based on the 20th Study Group of the Royal College of Obstetricians and Gynaecologists, which concerned the important topic of fetal growth. Basic scientific and both obstetric and paediatric aspects of the subject were addressed in contributions from many different disciplines. The deliberations covered the broad topics of normal fetal growth, fetal overgrowth and fetal undergrowth. Clinical implications of these entities, especially fetal undergrowth, played a large part in the proceedings as dictated by clinical concerns. Definitions, epidemiology, aetiology and screening were covered, as were technological developments, with special reference to blood flow and volume flow measurements, both fetal and placental. Other aspects of clinical fetal monitoring, including fetal activity measurements, and biophysical evaluation were rationalised and placed in context, and the important newly emerging areas of cordocentesis and therapy in IUGR addressed. Finally, neonatal management of the SGA baby, mortality and long-term morbidity were discussed.The formal papers presented by the members of the Study Group are given together with edited versions of the ensuing discussions and the Group's conclusions.

Almost all known tumors and tumor-like conditions of the fe- male lower genital tract are classified in this complete mo- nograph on the subject. Clinical features, treatment and prognosis ar included, making this book a practical refe- rence for the busy clinician.

ABOUT THE SUBJECT MATTER Adolescence is a time of significant change. The adolescent era spans the interval between childhood and adulthood. It is a time of physical, social, and even emotional upheaval. During this relatively brief period of time not only does physical growth accelerate but, of more significance in the biology of any species, the individual attains reproductive maturity. Within this time frame, the human being acquires the capacity to procreate and perpetuate our species. From a reproductive standpoint, throughout adeolescence the individual is being prepared for perhaps what might be considered the most important function an organism has during his/her brief sojourn on earth, namely to endow successor(s) with a minute quan tity of DNA to enable continuation of its form of life. The interlude be tween childhood and adulthood is not always socially or emotionally sim ple. The anatomic and physiologic modifications that come to pass during adolescence are not necessarily paralleled by a capacity to assume the societal responsibilities associated with reproductive maturity. Although the physiologic changes normally proceed in a predetermined fashion, adaptation to a changing role is a far more trying process. Accustomed to living in a child's world, the subject of adolescent change requires considerable time and understanding to facilitate exis tence in the adult world. The early stages of sexual awareness, for ex ample, are generally extremely confusing and, as evidenced by the in ordinately high frequency of teenage pregnancy and sexually transmitted diseases, can be extraordinarily dangerous."

Medical ethics is a difficult and controversial field and that part of it dealing with reproductive medicine is no exception. Our first conference on philosophical ethics in reproductive medicine (PERM 1) in 1988 discussed many of the controversies in this field. The acclaim it received encouraged us to organise PERM 2 but choosing a relevant and topical programme was a clairvoyant challenge in its own right. Since PERM 1 we have seen a number of developments, in the UK and internationally, that have thrown the problems that society must face into sharp relief. Drawing on the expertise of contributors from science, many medical specialities, philosophy, theology and economics, we have sought to address the issues raised by these new developments, as well as a number of long-standing issues that remain as contentious as ever, but of undiminished significance. On the scientific front, the long-predicted technique of embryo biopsy and diagnosis is now a reality. This has prompted the inclusion of some of the topics addressed by this second conference.

Sexual medicine is an interdisciplinary subject. Special knowledge of normal and disturbed sexuality is expected of general practitioners, gynecologists, dermato logists, urologists, specialists in internal medicine, neurologists, psychiatrists, and psychotherapists. Sexual dysfunctions may occur in connection with organic lesions or as psychosomatic phenomena. They are brought to the practicing physician's attention by the patient either directly or in the form of factitious symptoms. The disturbed sexual function generally causes suffering and so motivates the patient to consult a physician. Psychosomatic aspects are thus very much to the fore. In a significant number of cases, however the disturbances stem from a physical-functional handicap which not only affects the patient's general personality but also has a direct adverse effect on sexual function. The physical defect leads to disturbances of the body-image, and so can cause impairments in the sexual sphere both directly and indirectly. The diseases which result in sexual handicap and which can be treated by reconstructive surgery were examined and discussed at an international satellite symposium of experts on the occasion of the 8 th World Congress for Sexology in June 1987. The papers presented at this symposium have been collected and edited in this volume."

More often than not, progress in medicine occurs incrementally. The report of an 'important' new observation is typically greeted by a mixture of excitement and skepticism. Yet the true value of the discovery may not be known for several years until it is confirmed (or refuted) by independently conducted studies. In some cases, controversy may continue to shroud a topic due to the discordant results generated by different research groups. Since the last Gynecologic Oncology volume in the Cancer Treatment and Research series, a number of new areas have emerged that shed new light on the pathogenesis, diagnosis, and treatment of gynecologic malignancies. In this volume of the Cancer Treatment and Research series, I have attempted to integrate articles that highlight some of these newest developments with chapters that provide an overview of selected areas of controversy. This volume is not meant to be an abbreviated text of gynecologic oncology but rather a collection of selected works that can provide the reader with a better perspective on the areas of change within the field. The application of molecular biology to cervical cancer has allowed us to understand more completely the roles of human papilloma viruses and cellular oncogenes in the development of cancer of the uterine cervix.

Introduction to Mammalian Reproduction is a welcome contribution to the fields of gametogenesis, gamete transport, fertilization, and reproduction technologies. Key topics covered include:
*formation and maturation of male gametes;
*morphology and physiology of female gametes;
*how the sperm meets the egg;
*sperm-egg fusion, egg activation, and implantation of fertilized egg;
*assisted reproduction and environmental chemicals that have an effect on formation and function of male and female gametes. This book is for both researchers and students involved in reproductive biology.

Androgen Receptors is the most comprehensive and up to date volume on the topic, including discussions of the basic mechanisms of androgen-androgen receptor actions, their roles in the androgen-related diseases, and their potential clinical applications. Key topics covered include: -The discovery and cloning of the androgen receptor; -Androgen receptor coregulators; -Androgen related genes and their consensus DNA response elements; -Basic mechanism of action including functional analyses, cellular localization and phosphorylation studies; -Cross-talk to other signal transduction systems; -The recent connections of androgens to women's diseases, such as osteoporosis and ovarian cancer. This book is of interest to students, basic scientists, and clinicians as both a study guide and reference of research in the androgen field. It could also be used as an advanced level text in endocrinology, urology, OBGYN, or oncology.

The field of human artificial reproductive technology (ART) is continually advancing and has witnessed significant changes since the inception of Louise Brown in 1978. Though Louise Brown herself was conceived after the trans fer of a blastocyst, there remain significant confusion and debate regarding the stage at which the human embryo conceived in the laboratory should be replaced in the mother. Developments in culture media formulations, leading to the introduction of sequential media, have brought the role of the blasto cyst in human ART back into the spotlight. It was due to this resurgence of interest in the niche of extended culture in human infertility treatment that the symposium on "ART and the Human Blastocyst" was held. of this meeting within this volume bring to the forefront The proceedings the main issues raised with the transfer of embryos at the blastocyst stage. It is evident from the chapters that follow that ART needs to be perceived as a continuum of procedures, each one dependent on the preceding one, and all equally as important as each other. That is to say, the development of a com petent embryo is ultimately dependent on the quality of the gametes from which it was derived. With regard to the oocyte, this then places the emphasis on the physician to use a stimulation protocol that both produces quality oocytes and does not impair endometrial function. Maintenance of gamete and embryo quality is the laboratory's role.

I am very happy and honoured to have so many famous contrib utors from around the world presenting their knowledge and experience in this book, including Dr. Rufer who, as early as 1967, attempted to improve the pressure-volume curve of a child dying from RDS using dried surfactant from dogs; Drs. Enhorn ing and Robertson who were the first to treat rabbit fetuses with surfactant replacement and impressively demonstrated that sur factant improved lung mechanics; and Dr. Fujiwara who at the end of the 1970's had already successfully treated the first babies with surfactant replacement and published this work al ready in 1980. Thus, the idea of surfactant replacement therapy is now more or less 20 years old and almost 10 years have passed since the first publication by Dr. Fujiwara of his impressive clinical results. Up to now (September, 1988) about 2,200 babies have been treated worldwide with tracheal instillation of surfactant, with most promising results. The type of surfactant used varies from pure natural extracts from bovine or pig lungs, to surfactant extracted from human amniotic fluid, to pure phospholipids. To date, however, there is still no surfactant commercially available (except in Japan), in spite of the fact that it is urgently awaited by neonatologists and intensive care doctors throughout the world. This volume is based on the contributions presented at the international congress on Surfactant Replacement Therapy which was held in Rotterdam, The Netherlands, in November 1987."

The Third International Copenhagen Symposium on Detection of Breast Cancer afforded a further opportunity for scientists from all over the world to come together and present important papers con cerning breast cancer and early diagnostic procedures. The Sympo sium was an opportunity to learn from extensive screening proce dures carried out at outstanding centers in the United States, Sweden, the Netherlands, and England. Furthermore, the Sympo sium dealt with new modalities such as ultrasonography, magnifi cation techniques, and magnetic resonance; and very important contributions concerning self-examination, fine needle aspiration biopsy, and radiation risks were presented. A whole section was also dedicated to the highly important cooperation between radiologist, surgeon, and pathologist. It is our sincere hope that a study of the different aspects of breast cancer presented in this volume will encourage the reader to join in the struggle against this dreadful dis ease. December 1986 S. Brunner B. Langfeldt Contents B. Nielsen Image Quality in Mammography: Physical and Technical Limitations . 1 S. A. Feig, B. M. Galkin, and H. D. Muir Clinical Considerations in Selection of Dedicated Mammography Units . . . . . . . . . . . . . . . . . . . . 15 . . . E. A. Sickles The Role of Magnification Technique in Modern Mammography . . . . . . . . . . . . . . . . . . . . . . . . . . 19 B. M. Galkin, S. A. Feig, P. Frasca, H. D. Muir, and R. Z. Soriano Imaging Capabilities and Dose Considerations of Different Mammographic Units . . . . . . . . . . . . . . . . . . 25 . . . E. A. Sickles Computed Tomography Scanning, Transillumination, and Magnetic Resonance Imaging of the Breast . . . . . . . . . . . 31 A. G. Haus Recent Trends in Screen-Film Mammography: Technical Factors and Radiation Dose . . . . . . . . . ."

Endocrinologic investigations during pregnancy have focused in the last decades on placental hormones, the maternal endocrine system and maternal fetal interactions. Less is known about the fetus itself and the interaction of fetal hormonal response and physiological parameters. In this book physiologists, pediatricians and obstetricians active in experimental studies in both physiology and endocrinology combine both aspects of investigations. Historical remarks on the endocrine development of the fetus are followed by observations of the hormonal control of the cardiovascular system. Basic mechanisms of fetal endocrine control such as brain development, fetal growth, fetal behaviour, and thermoregulation are given particular consideration. Finally, carbohydrate metabolism and the mechanism of parturition are outlined.

H.-J. Senn Adjuvant Chemotherapy (ACT) of breast cancer has now emerged as one of the controversial su):>jects in clinical and also experimental oncology. Driven by growing frustration about stagnating cure rates in breast cancer [1,4] and stimulated by elegant demonstration of highly curative effects of adjuvant systemic therapy in animal models [6, 11] and in several childhood neoplasias [15], researchers introduced ACT to the primary treatment of breast cancer with great hope some 15 years ago. After a first wave of isolated "historic" trials with generally limited but in one case remarkable success [5, 9], a second generation of ACT studies was initiated by NSABP investigators and oncology centers in Europe [2, 6, 13]. These trials were well conducted statistically and diagnostically, and all in the early 1970s included a surgical control arm. Early and intermediate beneficial effects on relapse-free survival (RFS) after 2-3 years median observation time then prompted a whole series of ACT studies in breast cancer. These "third-gener ation" studies usually regarded some positive influence of ACT as a given fact, dropping surgical control regimens and comparing different ACT regimens, hopefully in a prospective, randomized way 1984 Fig. 1. The mushrooming of adjuvant studies in breast cancer XII Introduction [reviews in 3, 14]. The "mushrooming" of ACT studies in breast cancer during the last 10 and especially 5 years is demonstrated in Fig. 1, and it gets really cumbersome even for the insider to keep on top of the multitude of sometimes conflicting data.

Few subjects in gynecology, let alone in medicine in general, have provoked such inter est or study as cervical cancer. Although the wealth of monographs and books publish ed on the subject would seem to obviate the need for more, the great advances made in the medical sciences and in gynecological experience and techniques in recent years call for, if not require, a new book on cervical cancer to bring together the latest ideas and trends in its methods of study, diagnosis, and treatment. Although precancerous lesions have become more common, the number of women developing invasive cervical carcinomas has not increased, owing in part to programs of patient education, in part to screening examinations sponsored by the government. The gynecologist is now able to detect with well-tried and proved techniques precan cerous states of the cervix, and to treat these effectively before they become invasive cancer. Accordingly, recent interests in cervical cancer have shifted from the classic descrip tion of invasive carcinoma to newer studies of cause, diagnosis, therapy, and terminol ogy of its precursors. As the reader will learn, epidemiological studies as guides for the future account for, and justifiably so, an important part of this book. New knowledge about changes in the morphology of cervical carcinoma confirms its dependency on hormonal stimulation. Furthermore, modem experiences serve to explain which therapy is best. Overlapping of concepts and opinions between some chapters could not be avoided."

The account of "neonatal sterilization" is the story of the advocates of direct effect of steroids on the gonads and those who believed in the indirect influence, mediated through the hypothalamus and/or the pituitary gland. As often happens in biology, both convictions represent the same image seen from different perspectives. Prof DC Johnson (Kansas City, KS) reminisced the beginning of the story in a letter to me. I am paraphrasing parts of the letter with his permission. "As a starting point we could pick the life-long research of Emil Steinach ... " Steinach recognized the influence of testes on the develop ment of accessory sex organs in 1894, described virilization of females and feminization of males in 1913, and identified the controlling influence of the hypophysis on the gonads in 1928. He reviewed his work in a book Sex and Life, Forty Years of Biological and Medical Experience (E Steinach and L Loebe!; Faber and Faber, London, 1940). He got on the wrong road in later years and that is the reason everybody seems to have forgotten him. He presented his hypothesis that estrogen has a direct effect upon the testes, i. e. hormone antagonism, at the 1st International Congress on Sex Research in 1926.

The Interfaces of Perinatal Addiction Ira J ChasnofT In the last few years, problems associated with drug use in pregnancy have become endemic. As cocaine has become the drug of choice for millions of Americans, including pregnant women, as AIDS has become more commonly recognized in women and infants, and as legal cases have begun to raise the question of fetal abuse, no professional group has come forward to serve as advocate for this special population of substance abusers. Meanwhile, however, physicians, nurses, social service agencies and public health officials have all been faced with increasing numbers of infants showing the detrimental effects of their mothers' drug use. Although problems of substance abuse in pregnancy have received increasing attention in the medical literature since the early 1970s, there has recently been a very rapid increase in the number of articles published related to this field. The reasons for this new interest are easily understood when current statistics from the National Institute on Drug Abuse are reviewed 1. Although patterns of abuse of alcohol, marijuana, heroin and other substances by women of childbearing age have changed very little over the last ten years, the incidence of cocaine use in this special population has been rising rapidly, a reflection of cocaine's increasing popularity among the general population of the United States.

The examination of the human fallopian tubes was, until recently, restricted to observations on gross anatomical disposition and tubal patency. These studies, for decades, were the domain of doctors and physiologists whose primary interest was population control and family planning, funded largely by organisations and agencies seek ing alternatives to steroidal contraceptives. For a "worrying" but short period after the birth of Louise Brown in 1978 as the conse quence of successful in-vitro fertilisation and embryo transfer, the fallopian tube was considered to be "dispensable" given that the metabolic milieu in which human fertilisation takes place could be effortlessly reproduced in a Petri dish, in in-vitro fertilisation procedures. However, a number of factors have acted together to renew in terest in the fallopian tube, namely new techniques in cell biology, microinstrument developments (in particular in imaging), an inter disciplinary transfer of skills from interventional radiology and car diology to gynaecology, the surgeon's wish to improve surgical tech niques, and better techniques to monitor early pregnancy. These factors have led surgeons to develop the new diagnostic and ther apeutic strategies and techniques listed here. This volume contains contributions from the majority of keynote speakers at a conference held in London in April 1992 from which its title is derived. Better diagnostic procedures should lead to the implementation of rational effective treatments.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons }Vhy such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been 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 future developments in specific fields of oncology.

The most meaningful reward to clinicians and researchers is the absence of recurrent malignancy in their patients. While in some patients the disease will be cured by resection alone, in other similarly staged cases the disease will recur despite adequate loco regional and systemic therapies. Hence, risk assessment is a complex issue with many related or unrelated prognostic factors determining outcome. The purpose of this volume is to review some of the most relevant prognostic factors of newly diagnosed breast cancer, focusing on fea tures determining the magnitude of risk. The ultimate value of establishing the significance of each prognostic factor in a given patient will be the resulting ability to plan individu alized therapies for patients at different risk of recurrence at the time of diagnosis. To secure the maximum benefit for high-risk patients, while avoiding undue toxicity in those with low-risk lesions, a well-integrated analysis of all known prognostic factors will be essential in the early postdiagnos tic period. In addition to well-established staging criteria such as axillary nodes, tumor size, receptors, scanning and radiographic examinations, the more sophisticated labora tory techniques, as discussed by several authors herein, will playa crucial role in risk assessment. Most of them, - ploidy determination, oncogenes, tumor markers, monoclonal anti bodies, growth factors, etc. -are presently available in only a minority of treatment centers.

Contraceptives have always provided ground for controversy. This book describes and discusses latest findings concerning the advantages as well as hazard and risk factors of contraception. The clinical impact of oral contraceptives on metabolism is particularly highlighted. In addition, behavioral methods, intrauterine devices, implants and modern approaches in animal and clinical research in the field of immunization against pregnancy are considered. Last, but not least, the book summarizes the complex ethical, religious and political aspects of family planning and contraception.

The anticipation of seeing and having to manage patients suffering from sensory disorders of the urinary tract brings dismay and foreboding to the urologist. This stems from his experience of the time that these patients take up, both at the stage of initial interview and subsequently during numerous consultations over periods of months and years. This and the largely unsatisfactory response to various forms of therapy in the past are reason enough for this bold attempt to define with objectivity the notoriously subjective disorders of interstitial cystitis, urethral syndrome and prostatodynia. In writing this book the principal aim of the authors has been to define these three entities concisely and to describe the investiga tional methods which are required to establish the diagnosis in each case. The importance of this cannot be overestimated since, when the label of one or other of these conditions is attached to a patient, further objective consideration of the case is-endangered. The casual attribution of these sensory diagnoses to inappropriate cases is already on record as having dulled clinical awareness and led to oversight of progressive disease and its sometimes avoidable conse quences."

It is about 15 years since the first presentation on uteroglobin was given to a group of developmental biologists, reproductive physiologists, and geneticists who had gathered in November 1966 at Konstanz (Germany). In the following decade so much knowledge was accumulated that a special symposium seemed appropriate. This was organized as a satellite symposium to the International Congress of Endocrinology at Hamburg and brought together 50 scientists at Aachen. These scientists, working in the field of pro teins and steroids, in early pregnancy, recognized the impact of what had been reported, and many of them later agreed to contribute to this booN. and thus to present their research d, ta available until December 1980. The present volume covers a relatively broad spectrum of data and observations which shed some light on preimplantational embryonic life and on the supports and obstacles provided by the maternal organism with respect to final accomplishment of normal im plantation and establishment of pregnancy. The book will serve both as a textbook and as a scientific dictionary for Ph.D. students, postdoctoral fellows and advanced scientists working in this area. The course of early pregnancy depends very much on a proper balance of steroid hor mones, and the induction of protein synthesis by steroid hormones is one of the well known fundamental processes in cellular differentiation and embryonic development."

I am honored to have been invited to write a foreword for this book, because tumors of the yolk sac have been a preoccupation of mine since the days of my residency, now more than 3 decades ago. At that time, a 3-year-old boy died of a testicular cancer of unknown histo genesis. It was bad enough that the child died, but it bothered me even more that medical science did not know the histogenesis of the tumor that destroyed him, and I decided to study testicular cancer. For re search training I sought out F. J. Dixon, who had written the Armed Forces Fascicle on testicular tumors. Dr. Dixon and I showed that embryonal carcinoma was a multipoten tial malignant stem cell that differentiated into the three embryonic germ layers of murine teratocarcinoma. This led to the idea that the normal counterpart of embryonal carcinoma must also be multi potent, and we focused on the preimplantation embryo for the histo genesis of the tumor. This idea was strengthened by the discovery that embryonal carcinoma cells made embryoid bodies in the ascites and it was possible to observe the development of these bodies in vitro. These observations led to the idea that embryonal carcinoma was a caricature (gross misrepresentation) of early development, and car cinomas in general were a caricature of the process of renewal of their normal counterpart."

The epididymis has great significance in the reproductive biology of the male and it is gaining recognition as an organ worthy of study in its own right - where the secretory and absorptive activities of one tissue (the epithelium) profoundly modify the function of another (the spermatozoon). Apart from cases of epididymal agenesis or physical blockage, however, it is not yet known to what extent mal functions of the epididymis contribute to "unexplained" male infer tility, but its importance as a target for antifertility agents in the male is now widely appreciated. This monograph evolved from two lectures on epididymal func tion given at the National Research Institute for Family Planning, Beijing and the Sichuan Provincial Family Planning Research Insti tute, Chengdu, China in 1983. In order to stress for this audience the central importance of the epididymis in fertilisation, and so highlight its potential for attack by antifertility agents, the talks attempted to put the epididymis in reproductive perspective by stressing the func tional development of the sperm cells during their sojourn in the epididymis, rather than merely listing the changes observed in them."