The fetal period of human growth and development has become an area of intense study in recent years, due in large part to the development of diagnostic ultrasound. More than 2,000 articles have been published in the last five years describing anatomy and pathology in utero, as reflected in sonographic images. Yet, no stan dard reference exists to correlate these images with fetal gross anatomy and at tempts to draw parallels from adult structure have often led to false assumptions. The dictum "the newborn is not a miniature adult" is all the more valid for the fetus. This text aims to provide a comprehensive reference for normal sectional anat omy correlated with in utero ultrasound images. In addition, magnetic resonance images of therapeutically aborted or stillborn fetuses are paired with similar gross sections to serve as a foundation upon which current in vivo studies may build. Lastly, a miscellaneous section illustrates several anatomic points useful in the understanding of fetal anatomy. These points include the changing anatomy of the fetal brain during gestation and the anatomy of the meninges, the fetal heart, and ductus venosus. It is our hope that this atlas will provide a clear picture of fetal anatomy, rectify some of the confusion which exists in antenatal diagnosis, and stimulate further interest in fetal development."

Dedication to Professor Dr. med. Dr. h. c. mult. Benno Runnebaum on his 65th Anniversary The name of Benno Runnebaum is closely tied to the status of gynaecological endocrinology and reproductive medicine. Therefore, we would like to dedicate this conference book entitled "Fertility Control" to him in recognition of his achieve- ments. Who is Benno Runnebaum? Benno Runnebaum was born on 22 July, 1933, in Ruschendorf, Germany. After taking his A-levels, he studied medicine in Munster, Bonn and Cologne. He graduated from Cologne University in 1961 and then prepared his doctoral thesis on the "Identificati- on and quantification of progesterone, 20a-dihydroprogesterone, 20~-dihydroproge- sterone and 17a-hydroxyprogesterone in the plasma of human placental blood". This Benno Runnebaum VI Preface publication was the first to describe the progestin cycle in the feto-placental unit. His thesis was supported by Professor Dr. med. Dr. h. c. Josef Zander. It was graded "sum- ma cum laude" and won him a scholarship from the National Institute of Health for training in steroid biochemistry at the Biochemical Institute in Salt Lake City (Profes- sor Samuels) in 1962 and 1963. After his return to Germany he worked at the Univer- sity Women's Hospital of Cologne. He received his further specialist training in 1964 at the Heidelberg Women's Hospital, under the chairmanship of his teacher, Professor Zander.

The chapters in this book represent presentations at the first meeting ever held on the regulation and actions of follicle stimulating hormone. The meeting took place on the campus of Northwestern University, Evanston, Illinois, from October 25 to 28, 1990. The idea for this meeting was conceived by Neena B. Schwartz, and the valuable advice of the organizing committee contributed greatly to its scientific success. We gratefully acknowledge the funding and coordination of this meeting by Serono Symposia, USA. We also wish to acknowledge the financial contributions made by Northwestern University. We especially thank the invited speakers, poster presenters, and discussion participants who pro vided the science, interest, and enthusiasm that made this meeting on FSH a success. MARY HUNZICKER-DUNN NEENA B. SCHWARTZ vii Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv 1. An Overview of FSH Regulation and Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ULRIKE LUDERER AND NEENA B. SCHWARTZ Part I. Neuroendocrinology of FSH Secretion 2. Modulation of Gonadotropin Secretion by Proteins of the Inhibin Family: Studies in the Female Rat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 CATHERINE RIVIER AND WYLIE V ALE 3. Control of Follicle Stimulating Hormone Secretion in the Male Rhesus Monkey (Macaca mulatta) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 TONY M. PLANT 4. The Physiology of Puberty in Seasonally Breeding Birds . . . . . . . . . . . 54 BRIAN K. FOLLETT 5. Hypothalamic Regulation of FSH Secretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 JON E. LEVINE, LISA A. CONAGHAN, ULRIKE LUDERER, AND FRANK J. STROBL 6. Photoperiodic Control of Reproduction in Male Hamsters: Role of FSH in Early Stages of Photo stimulation . . . . . . . . . . . . . . . . . . . . . . . 83 FRED W. TUREK AND NEENA B."

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 state of health care is reflected by perinatal and neonatal morbidity and mortality as well as by the frequencies of long-term neurological and developmental disorders. Many factors, some without immediately recognizable significance to childbearing and many still unknown, undoubtedly contribute beneficially or adversely to the outcome of pregnancy. Knowledge concerning the impact of such factors on the fetus and surviving infant is critical. Confounding analyses of pregnancy outcome, especially these past 2 or 3 decades, are the effects of newly undertaken invasive or inactive therapeutic approaches coupled with the advent of high technology. Many innovations have been introduced without serious efforts to evaluate their impact prospectively and objectively. The consequences of therapeutic misadventures character ized the past; it seems they have been replaced to a degree by some of the complications of applied technology. Examples abound: after overuse of oxygen was recognized to cause retrolental fibroplasia, its restriction led to an increase in both neonatal death rates and neurologic damage in surviving infants. Administration of vitamin K to prevent neonatal hemorrhagic disease, particularly when given in what we now know as excessive dosage, occasionally resulted in kernicterus. Prophy lactic sulfonamide use had a similar end result. More recent is the observation of bronchopulmonary dysplasia as a complication of re spirator therapy for hyaline membrane disease. The decade of the eighties opened with the all-time highest rate of cesarean section in the United States."

The peri-menopause is emerging more and more as a subject for study by the doctor, the psychologist, the social worker, the gerontologist, the clinical chemist, the public health specialist, the sociologist, the psychiatrist and the experimental pathologist. The results of studies are gradually becoming known to the public, particularly to the prospective clients, ageing women. Women have begun to ask for treatment and they will most likely determine whether oestrogen replacement therapy comes into vogue. Psychosomatics in peri-menopause is an important sub ject, since the life-span of the woman has extended to nearly twice that of her fertile period. The life-expectancy for women in industralized countries is now some 70-75 years. This means that most can now expect to spend one third of their lives in the post-menopause. Consequently, there is now much more time than before in which to notice, experience and be bothered by peri menopausal changes. Moreover modern medicine has much more to oner than mere moral support to sufferers from ailments connected with progressing ovarian failure during peri-menopause. Although we cannot promise eternal youth - as Wilson does -there are more possibilities for treatment than 10 years ago."

The Helene Harris Memorial Trust has become recognized as providing one of the most important international fora for the presentation of research in ovarian cancer. Four biennial meetings have taken place, the most recent of which was held between May 11-14, 1993, in Toronto, Canada. This forum has grown in stature from its inception in 1987 and has brought together interdisciplinary clinical and scientific researchers from around the world who are endeavouring to perform 'cutting edge' studies in the field. The assembled group of presti gious investigators met on this occasion to present their data, to exchange ideas, and to arrange collaborations with the goal of developing new means of detection, treatment and cure of ovarian cancer. The incentive for the establishment of the Trust and its international forum was the prema ture loss through ovarian cancer of Helene Harris, the wife of Mr John Harris. Mr Harris and the Trustees looked for a meaningful way to honour the memory of Helene and to advance the noble cause of gaining an increase in the scientific knowledge of the subject. For those of us who spend most of our waking hours assisting patients and their families who are devastated by this disease, the Trust's generosity provides inspiration, hope and the opportunity for their practical application in a unique professional forum.

The International Women's Health Coalition was pleased to be the convenor and host of the first Christopher Tietze International Symposium, held in Berlin in September 1985. The papers in this volume represent a wide range of international views and experience with the prevention and treatment of contraceptive failure. We believe the issues discussed at the Tietze Symposium to be of interest and concern to women throughout the world and to those who would serve them. The Coalition intends to l1'ive broad distribution to this volume and encourages those interested in these issues to be in touch with the Coalition in New York City (see address below). We would like to thank The Ford Foundation, Stewart Mott, The David and Lucile Packard Foundation, the Population Crisis Committee, and The Uockefeller Foundation for their support of this Symposium. In particular we would like to express our appreciation to Sarah Lewit Tietze and Uta Landy for the devotion ann dedication which made this Symposium possible and a worthy memorial to Christopher Tietze.

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 treatment of menopausal and postmenopausal symptoms is a focus of considerable debate, on account of both the medical and social factors involved. And perhaps the cause of the greatest current interest and concern is not so much the effectiveness of present-day treatment but its safety. Opinions on the subject vary; and to resolve the arguments we must turn to the results of scientific experiment, both the clinical and biological. It is only by comparing experimental results that it is possible to move forward, albeit slowly, towards a generally agreed consensus based upon objective scientific data. It is for this reason that we are particularly grateful to Ayerst Laboratories whose support and help have enabled us to turn our original proposal for an International Symposium into a reality. We are also grateful to the publishers for the efficiency with which they have organized the publication of the Proceedings. It is our hope and that of all the distinguished participants that all readers of this volume will be able to find something in it which will stimulate further thought and discussion - even though they may not necessarily agree with all the conclusions expressed - for the success of a Symposium turns not only on the subject under examination but also on the quality of debate and discussion it encourages.

This volume contains papers presented at the Conference on the Demographic and Programmatic Consequences of Contraceptive In novations, which was sponsored by the Committee on Population and held at the National Academy of Sciences, October 6-7, 1988. The papers consider how new contraceptive methods currently being developed and changes in the use of already available contraceptives could affect contraceptive practice, levels and patterns of abortion use, and the health of women. In addition, several of the papers re view the probable consequences of introducing new technology into family planning programs in developing countries. The Committee on Population sponsored this conference in order to stimulate think ing and to provide a forum for scientists, family planning program managers, and donor agency personnel to exchange information and ideas about these important issues. The committee is publishing these papers to expand the discussion of consequences of contracep tive innovations and to give scientists, policy makers, and members of the public who could not attend the conference an opportunity to learn about new developments in fertility control and their likely consequences for individuals and the societies in which they live. NEED FOR NEW METHODS While a strong case can be made that the pill and the intrauterine device (IUD) have contributed to declines in the level of unintended pregnancies around the world, it is also clear that for many couples existing methods present problems.

About 21 years ago prenatal diagnosis became part of the physician's diagnostic armamentarium against genetic defects. My first monograph in 1973 (The Prenatal Diagnosis of Hereditary Disorders) critically assessed early progress and enunciated basic principles in the systematic approach to prenatal genetic diagnosis. Six years later and under the current title, a subsequent volume provided the first major reference source on this subject. The present second (effectively third) edition, which was urged in view of the excellent reception of the two earlier volumes, reflects the remarkable growth of this new discipline and points to significant and exciting future developments. Notwithstanding these advances, the use of the new tools and techniques for the benefit of at-risk parents has taken many more years than most anticipated. Key factors have been the lack of teaching of human genetics in medical schools in the preceding decades and the difficulty of educating practicing physicians in a new scientific disci pline. Even today the teaching of genetics in medical schools leaves much to be desired and this will further delay the introduction of newer genetic advances to the bedside."

Interest in sexuality and reproductive function does not cease when people begin to age. Instead, a new set of questions arises. Women want to know if it is safe to have babies in their late thirties and early forties. They want to know more about hot flashes and other symptoms of menopause-which ones are dangerous and which are merely uncomfortable. They are eager to learn about the relative risks and benefits of estrogen replacement therapy. Men, too, are concerned about age-related changes in their sexual function. Experts in reproductive physiology, gerontology, and genetics met at the National Institutes of Health in June of 1984 to discuss these and other concerns about aging and the reproductive system. The conference on Aging, Reproduc tion, and the Climacteric was sponsored by the American Fertility Society, The National Institute on Aging, and the National Institute of Child Health and Human Development. This volume is based on the proceedings of that confer ence."

This birefs examines mortality among young children in the period from the seventeenth to the nineteenth century. It does so using several types and sources of information from the census unit England and Wales, and from Ireland. The sources of information used in this study include memoirs, diaries, poems, church records and numerical accounts. They offer descriptions of the quality of life and child mortality over the three centuries under study. Additional sources for the nineteenth century are two census-derived numerical indexes of the quality of life. They are the VICQUAL index for England and Wales, and the QUALEIRE index for Ireland. Statistical procedures have been applied to the numbers provided by the sources with the aim to identify effects of and associations between such variables as gender, age, and social background. The briefs examines the results to consider the impact of children's deaths upon parents and families, and concludes that there are differences and continuities across the centuries.

The 15th International Symposium of the Japan Human Cell Society on Cell and Molecular Biology of Endometrial Carcinoma brought together leading researchers from Japan and around the world. The papers collected here are the work of twenty-two leaders in their field and are organized in ten major categories. The first section, in vitro experimental systems, takes up the pioneering work by Kuramoto in 1968 and Nishida in 1980 in establishing, respectively, the HEC-1 and hormone-responsive endometrial carcinoma cell lines. Other topics include apoptosis, proliferation, and growth factors; cell cycle regulators; signaling pathways; angiogenesis; carcinogenesis; hormones and hormone receptors; genes and gene expression; endometrial receptivity; and chemo-resistance and -sensitivity. Presenting the latest work in the cell and molecular biology of endometrial carcinoma, this volume is a valuable resource for gynecologists, pathologists, and molecular biologists.

This book will explore the childbirth process through globally diverse perspectives in order to offer a broader context with which to think about birth. We will address multiple rituals and management models surrounding the labor and birth process from communities across the globe.

Labor and birth are biocultural events that are managed in countless ways. We are particularly interested in the notion of power. Who controls the pregnancy and the birth? Is it the hospital, the doctor, or the in-laws, and in which cultures does the mother have the control? These decisions, regarding place of birth, position, who receives the baby and even how the mother may or may not behave during the actual delivery, are all part of the different ways that birth is conducted.

One chapter of the book will be devoted to midwives and other birth attendants. There will also be chapters on the Evolution of Birth, on Women s Birth Narratives, and on Child Spacing and Breastfeeding.

This book will bring together global research conducted by professional anthropologists, midwives and doctors who work closely with the individuals from the cultures they are writing about, offering a unique perspective direct from the cultural group."

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.

The no-man's-land between reproductive physiology and immunology is becoming crowded. The last 10 years have seen a revolution in our under standing of many reproductive processes, brought about by the application of ever more sophisticated immunological methods. The increasing precision of these techniques has given us specific ways of assaying, enhancing or blocking hormonal mechanisms to yield more critical and interpretable information. In this volume eleven authors have presented the current status and future prospects of some immunological aspects of reproduction and fertility con trol. These include the relationships between mother and fetus, the diagnosis of pregnancy, the immunological complications seen in clinical management of human reproduction and some novel approaches for immunological control of fertility. We hope that in these chapters we have achieved an up-to-date account of a fast-moving field that calls on several disciplines. We intend the book to provide an adequate background and a current review for research workers and clinicians who wish both to understand the complex mechanisms involved and to develop improved scientific and clinical methods. We hope too that the student and newcomer will find this a useful reference book."

Yury Verlinskyand Anver Kuliev Reproductive Genetics Institute, Illinois Masonic Medical Center, 836 W. Wellington chicago, IL 60657 Although introduction of a first trimester prenatal diagnosis by chorionic viIIus sampling (CVS) has considerably improved the possibility for prevention of genetic diseases, it requires a selective abortion in case of an affected fetus. Following the direction of an earlier prenatal diagnosis and to avoid the need for abortion, preimplantation genetic diagnosis has been initiated based on polar body removal and pre-embryo biopsy. The First International symposium on Preimplantation Genetics, Chicago, September 17-19, 1990, was organized to explore these important developments, to review the state of knowledge in the field, and to address existing problems to be solved for developing and improving current approaches for preimplantation diagnosis of genetic disorders. A growing interest in the subject was obvious from the wide attendance of the meeting: over 250 scientists from 19 countries participated. This was the first attempt to put together the advances in different areas of basic and applied research relevant to Preimplantation Genetic Diagnosis, with the multidisciplinary scientific program including the sessions on embryology, micromanipulation and biopsy, genetic analysis of gametes and pre-embryos, IVF, gene expression and gene therapy, and ethical and legal issues. The deliberations of the Symposium presented in the above mentioned sessions, which comprise the contents of correspond ing sections of the Proceedings, open a newarea in medical research based on the interaction of IVF and New Genetics."

It is clear today that several prostaglandins play an important role in the regulation of many of the physiological events of the reproductive organs in the human. Both naturally occurring prostaglandins and their analogues are used routinely in many countries to ripen the cervix and induce labour at term as well as to dilate the cervix and to terminate pregnancy. Prostaglandin biosynthesis inhibitors are widely used in the treatment of primary dysmenorrhoea. The editors have aimed at an accurate, thorough, yet easily under standable review of the status in 1986 of medical knowledge regarding both the physiological importance and the clinical use of prostaglan dins and their inhibitors in obstetrics and gynaecology. I believe this book will be of value for all clinicians concerned with reproductive health. The list of authors guarantees an authoritative and up-to-date review of this active field. SUNE BERGSTROM Karolinska Institutet, Stockholm, Sweden Table Examples of clinical use of natural prostaglandins and some prostaglandin analogues Indications Prostaglandin Route of administration Manufacturer Dilatation of the cervix prior 15-methyl-PGF * Intramuscular Upjohn, USA 2 to vacuum aspiration 16-phenoxy-PGE methyl sulphonylamide Intramuscular Schering AG, West Germany 2 16,16-dimethyl-PGE methyl ester 1 Vaginal ONO, Japan; May & Baker, UK Second trimester abortion Intra -amniotic Upjohn, USA; ONO, Japan PGF 20 Upjohn, USA PGE Vaginal 2 Upjohn, USA 15-methyl-PGF 2.

The commonest cause of blindness in young and middle-aged people in the Western world is diabetes mellitus. Although the mechanism underlying diabetic retinopathy is still not understood, the technology to reduce its progress exists, provided treatment is given at the appropriate time. Doctors caring for patients with diabetes should be familiar with all aspects of diabetic retinopathy as well as the other ocular complications of diabetes. They also need a basic knowledge of the special techniques used in the diagnosis and treatment of diabetic eye disease (fundus fluorescein angiography, retinal photocoagulation, vitrectomy) and to understand how these procedures affect the diabetic patient in terms of limitation of activities and time off work. To ensure the most efficient use of ophthalmic services a clear plan of referral to ophthalmologists is required. These are the concepts on which this guide is based, compiled by an ophthalmologist involved in the treatment of diabetic eye disease and a physician with a special interest in diabetes. In addition to doctors involved in the management of diabetic patients, this guide may be of value to ophthalmic opticians, medical students and nurses as a self-instruction manual. ' 7 1 Examination of the Eye Testing visual acuity Using the ophthalmoscope The normal fundus The abnormal fundus Recording the findings 9 TESTING VISUAL ACUITY Method Test one eye at a time. Test distant visual acuity. Correct the refractive error if the visual acuity is worse than 6/6.

In this book we have expert urologists and gynaecologists on the two sides of the Atlantic working together with a common interest, the inadequate female urethra. What makes this volume so valuable is that it is not restricted to one speciality or one cult, but bravely (and systematically) presents established principles and practice. Not only is the current knowledge of the anatomy and function of the continence mech anisms defined by experts carefully selected by the two authorities in the field, but this infor mation is directly applied to clinical problems for the reader to use in the care of patients. Because the basics are presented first, and followed by the methods of diagnosis, the sec tions describing each form of treatment, whether medical or surgical, are set on rational bases. These are not cookbook directions. This background is especially valuable because the incontinent female usually has a complicated disorder, each case being different, so that the responsible gynaecologists or urologists must apply as much understanding as technique if their efforts are to achieve dryness. The clear descriptions and illustrations in this book, then, act as guides as much as directives. This second edition builds on the success of the first. All of us trying to help these unfortu nate women will do more for them from having this new edition at hand."

This new SpringerBrief in Physiology explores the newest research findings on how exercise influences the fetus in utero and beyond. "Physiology of Prenatal Exercise and Fetal Development" reviews the current findings of how maternal exercise throughout gestation influences fetal development of key organ systems, and also encompasses the relationship between maternal activity level and fetal, birth, and neonatal effects. This information will help researchers and scientists better understand the physiological effects of exercise during pregnancy on offspring development."

Several papers dealing with the clinical relevance of steroid hormone receptors in breast cancer have already been published. However, no publication has overviewed studies currently being conducted in Europe, nor is there a register of the european centers performing receptor assays. It has been our purpose to fill these gaps. A large majority of authors who we contacted kindly agreed to con tribute to our book. Papers were grouped into six main parts according to their contents. The abundance of clinical data relevant to receptor assays led us to add critical summaries to help the reader to form his own opinions on the subject. We would like to thank Drs. R. J. B. King, G. Contesso, L. Santi, and E. Engelsman, who helped us in this regard. We hope that this book will enable the reader to become acquainted with the present state of European steroid hormone receptor studies devoted to breast cancer treatment. We also hope that it will promote cooperation between European oncologists involved in this field of research."

Pathobiology of Human Germ Cell Neoplasia is a state-of-the-art compendium on a very recent branch of tumor biology. It offers an awareness and understanding of germ cell tumors: from the earliest stages to their va- rious differentiations. Original data for this volume was supplied by experts in the fields of pathology, developmental biology, genetics, molecular biology and other related fields. This compilation of knowledge provides information necessary to persons working in clinical and preclinical areas.