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.

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."

For the third time, specialists from all over the world met to present their most recent scientific results and to update their knowledge in the expand ing field of nutrition and, osteoporosis. Major nutrition-al factors, such as calcium and vitamin D, were reexamined, with special attention on the ef fects of calcium, given either as a supplement or in dairy products in chil dren and adolescents, and to vitamin D supplementation in the elderly. The RDA for calcium was questioned, and the calcium requirement was rede fined. Special attention was paid to proteins and their growth promoting action via IGF-l, as well as to the profound effects on calcium and bone metabolism of vegetarian diets or diets rich in acidic or alkaline foods. Although considered an environmental factor influencing the pathogenesis of osteoporosis, nutrition was discussed in relation to genetic conditions, because certain genetic conditions modifY patients' responses to nutritional deficiencies and to supplementary interventions. These proceedings report the wide spectrum of research currently being undertaken and the new perspectives this presents and emphasize the sig nificant and important impact of nutrition on bone health and disease."

Early Life Origins of Health and Disease is a new book which presents and discusses the many factors that may have impact on normal development. In a concise and readable manner, the authors consider both the proven and suggestive evidence that the high prevalence of hypertension, diabetes, obesity and, in some populations, kidney disease, may not be all due to genetics or adult environment alone. There is good evidence that stress and more subtle dietary deficiencies, as well as placental malfunction, may increase the risk that the offspring will develop these problems in later life. Finally, new and emerging evidence for other areas of human health and disease such a motor control and mental health is critically reviewed for the first time. The book is a 'must' for all scientists interested in researching these areas, as there is a critical evaluation of the methodology used and suggestions for the 'optimal' way in which to investigate these phenomena.

ThisbookcomprisesthescientificproceedingsoftheInternationalWorkshop onDigitalMammography(IWDM),heldinBremen,Germany,fromJune22 toJune25,2002. Sinceitsinceptionin1992,IWDMhasgrownintotheIn- ternationalForumonDigitalMammography. TheuniquenessofIWDMisits attractivenesstoresearchers,medicalpractitioners,andindustrialdevelopers. F6rmerworkshopswereheldinSanJose,USA(1992),York,UK(1994), Chicago,USA(1996),Nijmegen,NL(1998),andToronto,Canada(2000). Each ofthesescientificeventshasbeencombinedwithverysuccessfulandfocused industrialandresearchexhibits,whichdemonstratedthemilestonesofdigital mammographyhard-andsoftware. Now,thatdigitalmammographyisenteringroutineclinicaluse,wewitness itsstrongimpactonscreeninganddiagnosticmammography,computeraided detection,minimallyinvasiveprocedures,andthedevelopmentofsystemicand integrateddisease-orientedbreastcare. Inviewofthis,the2002workshoppro- videdawindowtogiveusaglanceatthefuture,andtheworkwhichwas presentedintalks,postersandexhibitshasdemonstratedthatIWDM2002will takeaspecialplaceintheverysuccessfulsequenceofIWDMevents. Finally,asconferencechair,Iwouldliketothankallwhohavehelpedtopre- pareandrunIWDM2002:theScientificAdvisoryBoardforitsexcellentworkin guaranteeingscientificsignificance,theOrganizationalBoardforitshardworkto accomplishanappropriateframeworkfortheevent,andtheindustrialexhibitors andsponsorsfortheirgeneroussupport. Bremen,January2003 Heinz-Otto Peitgen ConferenceChair ProfessorofMathematicsand BiomedicalSciences VI Scientific Committee SusanAstley UniversityofManchester,UK UlrichBick CharitBerlin,Germany/UniversityofChicago,USA MichaelBrady OxfordUniversity,UK HiroshiFujita GifuUniversity,Japan MaryellenGiger UniversityofChicago,USA NicoKarssemeijer UniversityHospitalNijmegen,TheNetherlands Heinz-OttoPeitgenUniversityofBremen,Germany EttaD. Pisano UniversityofNorthCarolina,USA MartinYaffe UniversityofToronto,Canada IWDM 2002 was supported by (MeViS SIEMENS BreastCare medical I' General Electric ARC-0 Fllmle. . Perfection for DI I JMammography Table of Contents Imaging Systems and Detectors...1 DigitalMammographicApplicationofaSinglePhotonCountingPixel Detector...3 Amendolia SR, Bisogni MG, Delogu P, Fantacci ME, Novelli M, Quattrocchi M, Rosso V, Stefanini A, Zucca S BreastCancerScreeningUsingaDedicatedBreastCTScanner:A FeasibilityStudy...6 Boone JM, Lindfors KK, Seibert JA, Nelson TR PhysicalEvaluationofaPrototypefortheSectraMicrodose MammographySystem...12 Lundqvist M, Bergstrom D, Cederstrom B, Chmill V, Chuntonov A, Danielsson M, Aslund M DoseMeasurementsonaScanningMulti-slitDigitalMammography System...17 Hansson B, Cederstrom B, Danielsson M, Aslund M DigitalMammographyvs. toScreen-FilmMammography:aPhantom Study...20 Heid P, PagliuchiC, Seradour B, Motte N, Langlois L, Kurkdjian S, Piana L MammographyTaxonomyforImprovementofLesionDetectionRates...27 Howard D, Roberts SC, Tabar L AHighResolution(25 p. m)HybridSelenium/CCDSlotScanDetector forDigitalMammography...33 Hunter DM, De CrescenzoG, Mainprize JG, Mawdsley GE, SmithC, Kasap SO, Rowlands JAR, Tumer T, Yin S, Yaffe MJ Co-registeredBreastImagingwith3DX-Raysand3DUltrasound...38 Kapur A, Eberhard JW, Abdalmajeid AM, Thomenius K ImagingCharacteristicsofaDirectConversionFull-FieldDigital MammographyDetectorusingSelenium...4 3 Lee DL, Yorker lG, ling Z, leromin LS SimultaneousAcquisitionofDiffraction,ScatteringandPhase-Contrast ImagesbyMeansofaMulti-LayerEdge-OnMicrostripDetector 48 Olivo A, Arfelli P, Bergamaschi A, Dreossi D, Longo R, Menk RH, Montanari F, Pani S, Poropat P, Rigon L, Vallazza E, Castelli E VIII FullFieldDigitalMammographywithaCCDBasedSlot-Scanned Detector. PhysicalCharacteristicsMeasurements...

Cancer and Pregnancy covers the clinical challenges to diagnosing and treating malignancies in the pregnant patient; however, the book also shows how an understanding of the common features of both processes (rapid cell proliferation) may lead to novel anti-cancer treatment options. The book should be read by obstetricians and gynaecologists, clinical oncologists, reproduction specialists, and those involved in investigation of development, biology, toxicology, immunology, as well as cancer research.

"Duplex Sonography" is the first comprehensive text written about this modality. The book offers the reader detailed information about all major uses of duplex and is introduced by a brief chapter on the physical principles of doppler ultrasound as it relates to duplex scanning. "Duplex " "Sonography" is intended to provide relevant information on all aspects of the technique, ranging from the basics of performing the examination to the features of sometimes complex pathological states. The book is intended for anyone interested in non-invasive vascular diagnosis including radiologists, vascular surgeons and ultrasound/peripheral vascular technologists. Other groups may find individual chapters appealing: carotid/cardiac sonography for cardiologists, fetal sonography for obstetricians or carotid sonography for neurologists. Each chapter is not only a guide to duplex evaluation, but also provides valuable information about vascular dynamics of the organ system under discussion. Physicians or technologists reading this book should come away with a well-rounded background in state-of-the-art duplex sonography and will undoubtedly discover new possibilities for using this non-invasive vascular technique.

This volume includes the latest diagnostic criteria for PCOS and comprises the most up-to-date information about the genetic features and pathogenesis of PCOS. It critically reviews the methodological approaches and the evidence for various PCOS susceptibility genes. The book also discusses additional familial phenotypes of PCOS and their potential genetic basis. All four editors of this title are extremely prominent in the field of PCOS.

Years of involvement, firsthand experience and research at the Menopause Clinic of the Groote Schuur Hospital, Cape Town, exist as the background to this book. The Clinic itself, however, as one of the first in the world to be established, if not the first, has a story and a lesson of its own to offer, and is therefore deserving of a brief description as the preface to the book. In 1967, shortly after Christiaan Barnard had completed the historical first human heart transplant at the Groote Schuur Hospital, I happened to be in West Berlin and was invited to visit a major international pharmaceutical firm. A new female hormone was mentioned, and thereby started my interest in the subject. Upon my return to Cape Town, I spent many hours in the large medical school library and completely surveyed the menopause literature to 1967. I was stunned by its general inadequacy and was bitten by a challenge to clarify what menopause really was, and to define the proper place of hormone replacement therapy.