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

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

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

Why Efforts to Expand the Meaning of "Teratogen" Are Unacceptable Disagreement about nomenclature in teratology is not new. Dissent even about the very fabric of the discipline-what congenital malformations consist of-has often been voiced. Time, instead of resolving such diffi culties, has sometimes worsened them. For example, in the past it was agreed that congenital malforma tions are abnormalities of structure present at birth, but differences of opinion concerning where the line between normal and abnormal was to be drawn prevailed. It was obvious that, in order to discover the causes of congenital malformations and cast strategies for their prevention, it would be necessary to have knowledge of the baseline of their frequency, and that this required uniformity of definition of terms. Since malfor mations of primary social concern are those having grave outcomes (and are, paradoxically, also the commonest ones), it is logical that such condi tions were the first consideration of investigators and were the defects whose frequency was considered to comprise the required baseline.

Proceedings of the NATO Advanced Study Institute, San Miniato, Italy, September 2-13, 1985

Thoroughly illustrated, this second edition provides the primary care physician with detailed information on the most commonly encountered clinical situations and the most frequently asked questions. The chapters address everything the primary care physician will regularly face and will need to know about the breast, pregnancy, sexually transmitted diseases, contraception, infertility, gynecologic cancers, urogynecology and gynecology.

A little picture is worth a million words. Chinese proverb Prenatal human development is an extremely complicated process related to genetics, biochemistry, anatomy, and physiology. There are no developmental changes, either chemical or morphologic, without simultaneous changes in molecular organization. The astonishing buildup ofbiostructures always precedes their proper function. The development of an embryo is genetically coded and is based on interactions related to the selective switching on and off of genes. Interactions are cell-to-cell mediated, mediated by extracellular fluids, or mediated by special pathways. Every substance involved in developmental is to be recognized by its target. interactions, before triggering a metabolic or a morphogenic event, Complex physical and immunologic recognitions are involved in the process of differentiation. Small pieces of evidence are collected to create a mosaic picture elucidating the development. This picture is fascinating and represents the biggest biological puzzle: the puzzle of development. There is no doubt that analysis of human prenatal development is a basis for understanding normal and pathologic relationships between structure and function. Today, there are approximately 2000 different inborn congenital anomalies and syndromes. This book attempts to present a complete realistic account of human morphogenesis, the differentiation of structures, using direct photographs of normal specimens obtained from legal medical abortions of unwanted pregnancies. Emphasis has been placed on contemporary techniques: histochemistry and scanning electron microscopy. The text is as simple as possible; meticulous detailed anatomic descriptions have been omitted.

This volume contains the papers on family planning research which were presented at the XIth World Congress on Fertility and Sterility held in Dublin, Ireland in June, 1983 under the auspices of the International Federation of Fertility Societies. These papers were presented during the related communi cations sessions of the Congress and have been brought together into a special volume which will be of major interest to those concerned with family planning. Section 1, deals with the area of natural family planning, determination of the fertile period and effects of lactation. Steroid contraception, vaginal and intrauterine contraception, abortion and sterilization are included in Sections 2-4. Social aspects of fertility control are covered in Section 5 and the final section contains studies of the effects of gossypol as a male contraceptive. This volume brings together important new knowledge in the area of family planning, clarifies some of the problems and should stimulate research on the many unresolved issues in this vitally important area."

practitioner up to date on the various aspects of conditions and diseases considered to be sexually transmitted. REFERENCES 1. Crissey JT, Denenholz DA: Development of the modern forms and concepts of syphilis. Clin Dermatol, 2(1):1-10, 1984. 2. Panconesi E, Mazzi M: The day syphilis came. Int 1 Dermatol, 23:284-286, 1984. 3. Washington AE, Johnson RE, Sanders LL: Chlamydia trachomatis infections in the United States: What are they costing us? lAMA, 257:2070-2074, 1987. 4. Bulkley LD: Syphilis in the Innocent. New York: Bailey and Fairchild, 1894. 5. Syphilis: Major perinatal killer. Med World Trib, 28(16):2, 1987. 6. Renshaw DC: Management of impotence. I. Psychological considerations. Clin Therap, 9:142-148,1987. Acknowledgments. We are very grateful to our teachers for the stimulation they provided in our studies of dermatology and sexually transmitted diseases. We partic ularly acknowledge the impetus given by Herman Beerman, M.D., Emeritus Professor of Dermatology, University of Pennsylvania School of Medicine, Philadel phia. Our office staffs have been particularly helpful, and we would like to recognize the contributions of Mrs. Carmela Ciferni. Lastly, this book was conceived through the inspiration of Dr. Jerry Stone, late Senior Medical Editor of Springer-Verlag, New York. Philadelphia, Pennsylvania LAWRENCE CHARLES PARISH Vienna, Austria FRIEDRICH GSCHNAIT Contents Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl . . . . . . . . . . . . . . . What are Sexually Transmitted Diseases? Chapter 1 History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 . . . . . . . . . . . . . LOIS Y. MATSUOKA Chapter 2 Definition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 . . . . . . . . . . . . HARRY L. ARNOLD, JR. Diseases Chapter 3 Syphilis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 . . . . . . . . . . . . . JOHN THORNE CRISSEY Chapter 4 Endemic Treponematoses . . . . . . . . . . .. . . . . . . . . . . . . . . . 32 . . ."

In the last few years rapid advances have been made in reproductive medicine, making it necessary for those involved to regularly update their knowledge. The purpose of this book is to describe the state of the art in this field, making it possible for the reader to gain an orientation among all the diagnostic and therapeutic potentials of modern reproductive medicine in order to advise patients fully. Chapters from the fields of gynecology, and reproductive medicine in a specific sense provide knowledge about these subjects. Authors of international standing have contributed chapters on their specialties. These chapters together form a book describing the state of the art in the diagnosis and therapy of sterility in gynecology and andrology.

It is a genuine honor and a privilege of distinction to provide the foreword for the proceedings that follow. This marvelous symposium reflects the unique qualities of its two principal sponsors. Whenever the Oregon Regional Primate Research Center is involved in matters of science, we see a consistent record of exceptional quality in both the work is unequaled and the people who do it. Likewise, Serono Symposia, USA in assuring a world-class speakers' forum, utterly without taint of commercial influence. The proceedings published herein are a remarkable testimony, not only to the contributors, but to Drs. Brenner, Wolf, Stouffer, and Burnett, who have shepherded its conception, presentation, and publication. Readers will notice immediately one of the universal strengths of this total composition; that is, the diversity of investigational interests among attendees. Presentations on the core topic of primate in vitro fertilization and embryo transfer were joined by specialist presentations in related areas, including human-assisted reproductive technologies, reproductive physiology of the great apes, sperm biology, implantation mechanisms, cryobiology, coculture systems for embryogenesis, micromanipulation technologies, and genetic diagnosis of heritable diseases in the pre embryo. Even though pro-fertility issues understandably dominated this forum, there was significant attention given to fertility-control research, especially the role of primates in this endeavor (more on this subject below)."

Since its inception in 1976, the overall goal of the Ovarian Workshop has been to bring together biologists from various disciplines so that they may collectively achieve a better understanding of the latest developments and define important problems in ovarian physiology. The Ovarian Workshop, which was pioneered by Dr. A. Rees Midgley, has developed into a major biennial meeting for investigators in the ovarian field. Largely as a consequence of advances in technology, especially in mo- lecular biology, progress in the area of gene expression and signal transduc- tion has been rapid. The Eighth Ovarian Workshop focused on two major topics: (1) the expression of hormonally and nonhormonally controlled genes involved in the functional and morphological differentiation of the cells forming the ovary and (2) the signaling mechanisms by which endogenous and exogenous hormones and cytokines affect ovarian differentiation and steroidogenesis. The Eighth Ovarian Workshop, held on the campus of Maryville College in Maryville, Tennessee, July 12 to 14, 1990, was again generously funded and coordinated by Serono Symposia, USA. I would especially like to thank Dr. Lisa Kern of Serono for her expert help in organizing this meeting. The board of directors of the Eighth Ovarian Workshop consisted of Drs. Eli Adashi, JoAnne Fortune, Anne Hirshfield, Aaron Hsueh, Julia Lobotsky, Gordon Niswender, David W. Schomberg, Richard Stouffer, and Jerry Strauss. Their valuable advice and the important roles they played in the planning of the scientific program are gratefully acknowledged.

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

The critical role of growth factors in normal as well as abnormal cellular growth and function has become overwhelmingly apparent in recent years. The significant advances in reproductive biology within this rapidly expanding field were highlighted at the Serono Symposia, USA, symposium entitled Growth Factors in Reproduc tion. The conference focused on growth factors as polyfunctional regulators of growth and development in the reproductive system. The program was organized into five areas: (1) growth factors as polyfunctional regulators of growth and development, (2) growth factors and gonadal function, (3) regulation of normal and neoplastic mammary growth, (4) regulatory peptides in reproductive tract development and function, and (5) embryo-maternal signaling. This volume constitutes the contributions ofthe invited symposium speakers and is organized into sections representing the five topic areas of the sessions. Drs. Eli Y. Adashi, Robert B. Dickson, David C. Lee, James Hammond, John A. McLachlan, and R. Michael Roberts, who served as chairmen ofthese sessions, not only provided invaluable advice and assistance in organizing the symposium, but contributed significantly to its content. The enthusiasm and esprit de corps of the poster presenters and discussion participants also helped make this symposium succeed as the first of its kind. Finally, special thanks are due Drs. James Posillico and Lisa Kern ofSerono Symposia, USA, for their guidance and support in the conception and planning of the symposium and in the publication of this volume."

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

This book is a compilation of edited papers which were presented at the XIth World Congress of Fertility and Sterility held in June 1983 in Dublin, Ireland. Although it has long been known that male factors are responsible in at least 30% of infertile couples only recently have concerted efforts been made on the part of urologists, gynaecologists and basic scientists to identify these factors more precisely. The nature of spermatogenesis is complex but application of various scientific methods have at last opened up new and promising approaches to our understanding of this subject. Clinical results however have been depressing; the majority of treatments lack realistic evaluation and are initiated in hope rather than with a sound scientific basis. We anticipate that this volume will in some small way correct these deficiencies. The papers have been grouped into related topics. The first section deals with the evaluation of the spermatozoa and includes a critical assessment of the recently introduced zona-free hamster egg test of sperm function. Further sections include the biochemistry of gonadal function and the immunology of male reproduction; most papers are concerned with studies in the human. The clinical sections cover medical and surgical approaches to treatment and the final section deals with various aspects of AID practice.

Different genetic diagnostic and treatment options are used worldwide to improve routine IVF procedures for the benefit of patients. This handbook updates the new genetic diagnostic technologies that have been translated to the clinic, aiming to improve outcomes in the clinic and result in a healthy baby in the home. Chapters cover the use of genetic technologies in a personalized manner to unravel the possible genetic risks for the couple wishing to conceive, in terms of sperm, the embryo, the endometrium, miscarriage, and finally the fetus. This expanded new edition covers the range of the latest genetic diagnostic technologies being translated into practice internationally to improve routine IVF procedures for the benefit of patients. Bringing together international experts to discuss their work, this text gives a context for the developments in this very fast-moving area of research and offers a comprehensive and rounded appraisal of hot topics.

For many years now, our understanding of the somatotrophic and reproduc tive axes has evolved essentially independently, both fields of study reaching a highly advanced, although far from complete, level of under standing. Along the way, however, it became apparent that in some circumstances the reproductive and somatotrophic axes may be inter dependent. Inklings to this effect were at times feeble and at other times more convincing. Among those inklings are the clinical recognition by pediatric endocrinologists of the apparent association between isolated GH deficiency and delayed puberty, as well as of the apparent permissive, pUberty-promoting property of GH. Equally important is a body of experi mental studies establishing the ovary of multiple species as a site of GH reception and action. Arguing against an essential role for GH in the reproductive process is the observation that individuals who have GH resistance of the Laron variety are fertile arid that isolated GH deficiency does not constitute an absolute barrier to the attainment of sexual maturation and fertility. The intraovarian insulin-like growth factor (IGF) hypothesis proposes that IGFs may serve as amplifiers of gonadotropin action. Although the dependence of intraovarian IGFs on systemic GH action has never been unequivocally demonstrated, that leap of faith has often been made. The intraovarian IGF hypothesis serves as the rationale for the adjunctive use of GH in the induction of ovulation."

Each year since 1961, the Rochester Trophoblast Conference has grown in the diversity of its approaches to trophoblast research. At the Ninth Conference, Professors Klopper, Villee and Winick molded the conference with their state of the art addresses on Endocrinology, Metabolism and Nutrition of the Trophoblast. The Conference was favored with a multitude of creative studies and with warm, sunny, autumn weather to discuss these results. In October of 1982, one hundred and five investigators from 12 countries and 21 states discussed 42 different presentations at the Holiday Inn in Rochester, New York. The Ninth Conference introduced workshops on Metabolism, Nutrition, Endocrinology and Trophoblastic Neoplasia. The chairmen of these workshops were: Metabolism -Villee and Miller; Nutrition - Winick and Maulik; Endocrinology - Klopper and Muechler; and Trophoblastic Neoplasia -Szulman and Helmkamp. These two-hour, intimate discussion groups were well-received by all who attended. As with the Eighth Conference, the University of Rochester will no longer produce a transcript of the Conference. Beginning with the Ninth Conference, Plenum Press in association with the University, will publish a peer-reviewed series entitled Trophoblast Research. An international editorial advisory board has been named to assure the direction of the series. The editorial board and the organizing committee will develop the future meetings of the Rochester Trophoblast Conference. Trophoblast Research will be published as single bound volumes with original contributions and editorial reports of presentations from the Conference.

Having received the invitation from Springer-Verlag to produce a volume on drug-induced birth defects for the Handbook of Experimental Pharmacology, we asked ourselves what new approach could we offer that would capture the state of the science and bring a new synthesis of the information on this topic to the world's literature. We chose a three-pronged approach, centered around those particular drugs for which we have a relatively well established basis for understanding how they exert their unwanted effects on the human embryo. We then supplemented this information with a series of reviews of critical biological processes involved in the established normal developmental patterns, with emphasis on what happens to the embryo when the processes are perturbed by experimental means. Knowing that the search for mechanisms in teratology has often been inhibited by the lack of understanding of how normal development proceeds, we also included chapters describing the amazing new discoveries related to the molecular control of normal morphogenesis for several organ systems in the hope that experimental toxicologists and molecular biologists will begin to better appreciate each others questions and progress. Several times during the last two years of developing outlines, issuing invitations, reviewing chapters, and cajoling belated contributors, we have wondered whether we made the correct decision to undertake this effort.

Lipids and Women's Health is an up-to-date critical review of pertinent scientific and clinical issues connected with lipid disorders in women. Topics discussed include the public health significance of cardiovascular disease in women, lipoprotein and lipid metabolism, effects of estrogens and progestins on lipid metabolism, metabolic changes of menopause, and the paradox of obesity, a curable disease that is rarely cured, as well as those conceptual advances in our understanding of diabetes mellitus that have clarified diagnosis and may have improved treatment. The relationship of diet and lipid intake to the development of breast and uterine cancer; dietary and drug treatment of lipid disorders; effects of exercise, smoking, and stress; and repercussions of lipid disorders on the family are explored. The volume should prove of use to gynecologists, internists, family practitioners, and pediatricians, as well as to all other professionals with a major concern for the health of female patients.

A central concept in the evolutionary theory of senescence is the idea that ageing results from life-history trade-offs. In particular, the disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. Comparative studies among mammalian species confirm that cells from long-lived species appear to have a greater intrinsic capacity to withstand stresses than cells from short-lived species. Childbearing at older ages has become increasingly common in modern societies because of demographic changes, medical progress and personal choice. While the detrimental effects of late reproduction on infant mortality and genetic diseases have been well documented, little is known about the possible postponed detrimental effects of late parenting.

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita tive change in GH secretion was the net result of pituitary stimulation and inhibition by the hypothalamic neurohormones, GH releasing hormone (GHRH), and somatostatin (somatotropin release inhibiting factor; SRIF), respectively. During the 1970s, another endocrine research pioneer, Dr. Cyril Bowers, discovered that structural modification of enkephalin re sulted in a family of peptides with GH releasing properties. These com pounds, simply called GH releasing peptide (GHRP), were originally thought to mimic GHRH. However, upon subsequent investigation they were found to supplement the activity of the natural hormone through a different mechanism. Nearly two decades after their discovery, the differ ences between GHRP and GHRH have been described by many different laboratories throughout the world. The complementary GH secretagogues have different binding sites, second messengers, and effects on gene expres sion. Based on these differences, it has been suggested that expansion of the original two hormone mechanisms for GH regulation to include a third molecule may be appropriate, even though the naturally occurring ana logue of GHRP has not yet been identified. Despite our lack of knowledge concerning the natural product mimicked by GHRP, clinical development of the new family of GH secretagogues for diagnostic and therapeutic purposes has begun in earnest."

The VIIIth Annual International Spring Symposium on Health Sciences held at the George Washington University School of Medicine in Washington, D.C., attracted over three hun dred fifty scientists from twenty-five countries. The leading scientific experts in the field reported on recent biomedical advances in aging. They provided an up-to-date account of the molecular, genetic, nutritional, and immunological mechanisms associated with the aging process and approaches to intervention and treatment of the major disorders associated with the aging process, including Alzheimer's disease. A unique aspect of this meeting was a concurrent one-day hearing of the U.S. Senate Sub-Committee on Aging, organized by the Alliance for Aging Research. The theme for the hearing was "Advances in Aging Research." Seven scientists attending our aging sym posium were asked to testify. They were Drs. Carl Cotman (University of California-Irvine), Trudy Bush (Johns Hopkins University), Takashi Makinodan (University of California-Los Angeles), William Ershler (University of Wisconsin-Madison), Gino Doria (ENEA, Rome), Mr. Dan Perry (Director of the Alliance for Aging Research), and myself."