This series of volumes dealing with reproductive health care has as its primary objective the improvement of the quality of human reproduction. The of knowledge and new technology give us opportunities as never explosion before to accomplish this end. The Editor has brought together contributors who are outstanding scientists from around the world. A number of the authors have personally made significant contributions to our body of knowledge in reproductive medicine. Bringing all this information together in an easily readable format is a great service. This is essential reading for all concerned with the control and improvement of human reproduction and the correction of its many deficits. xv P'art I Physio-anatom-ical Parameters 1 Uterine microvasculature and spontaneous abortion M. TAKADA In the implantation and subsequent development of a fertilized ovum, its integrity is most significant. However, with maternal local factors, i.e., unsatisfactory uterine conditions, implantation may not succeed even if the integrity of the fertilized ovum is excellent; if implantation is made, the maturation of the fetoplacental unit following implantation is disturbed, which leads to abnormalities in fetal development or to miscarriage. Thus, the uteroplacental unit, as well as the fetoplacental unit, plays an important role in the establishment and maintenance of pregnancy. Among the mechanisms of the utero placental unit, most significant is the physiological mechanism of the uterine microvasculature and its correspon dence to gestation. In particular, homeostasis of simultaneous cooperative development of the uterine wall and the placenta is most important."

In the last decade substantial progress has been scientists and clinicians to intensify their research made in the understanding of prostatic physio- for better diagnostic techniques. Thanks are due to pathology by the application of modern techniques the contributors who prepared their chapters me- and instrumentation in microanatomy, immunol- ticulously. Thanks also are due to Ms. Lori Rust ogy, neurophysiology, pathology, genetics, endo- for her editorial skills, and to Mr. Jeffrey Smith of Martinus Nijhoff for his fine cooperation during crinology, biochemistry, biophysics and surgery. An attempt is made in this volume to coordinate the production of this volume. anatomical, physiological, biochemical, endocri- nological, pharmacological and immunological as- pects of human prostatic carcinoma. It is hoped E.S.E. HAFEZ that this volume will serve as a stimulus to basic Detroit, Michigan PROSTATIC CARCINOMA: BIOLOG Y AND DIAGNOSIS 1. BIOLOGICAL ASPECTS 1. FUNCTIONAL ANATOMY OF THE PROSTATE E. SPRING-M ILLS and A. KRALL I. EMBRYOLOGY into smooth muscle cells and collagen secreting fibroblasts. These cells form the stroma which ensheaths the branching glands and ejaculatory The prostate gland develops from solid. endo- ducts as they pass from the junction of the vas dermal outgrowths of urogenital sinus epithelium deferens and seminal vesicles to the urethra.

Extensive reviews have been published on the mor aspects, anatomy, ultrastructure, physiology, bio phology, anatomy, and physiology of the mam chemistry, endocrinology, pharmacology, and physiopathology of the mammalian ovary. The malian ovary. However, little attention has been given to the gaps between the physiological, endo contributors, who prepared their chapters metic ulously, are recognized experts in their respective crine and histochemical parameters of the ovary as disciplines and their writings reflect extensive per it relates to clinical aspects. There is a wealth of sonal experience and unpublished data of both publications concerning the biology of the ovary: basic and clinical sciences. Without the assistance of the purpose of this volume is to integrate this information with emphasis on modern concepts in good friends and permission to draw extensively microanatomy, physiology, methodology, clinical from investigations, this volume would not have complications, and therapeutic approaches. An been possible. attempt is made to place fundamental research in Thanks are due to G. F. Franchitto, F. Barberini, clear perspectives. P. Stoops. Lori Rust and J. Squiers for their editorial It is hoped that this volume will fulfil a long skills and for checking the references to the original standing need and serve as an important source for sources. Thanks are particularly due to 1. K. Smith investigators and clinicians concerned with the of Martinus Nijhoff Publishers BV for his excellent physiopathology of the ovaries for years to come. It cooperation during the production of the book."

A. CORBIN Investigations on LHRH and its analogs have just completed their first decade. We have witnessed a veritable explosion of chemical, physiologic and pharmacologic data on this hypothalamic peptide and the approximately 1500 agonist and antagonist analogs that have been synthesized. In order to track this expanding field, I was asked to organize an international symposium on basic and clinical aspects of LHRH analogs as part of the Reproductive Health Care: CDS Symposium held in Maui, Hawaii, in October 1982. This meeting brought together a number of the leading investigators in the field. Much new state-of-the-art information was presented which I and my colleagues felt deserved a wider audience. Drs Vickery, Nestor, and Hafez consented to undertake this task. Upon review of the literature, it was apparent that there was no recent text which fully covered the breadth of developments in the field. Accordingly, the editors decided to use the symposium as a nucleus on which to build a singular, comprehensive state-of-the-art analysis of this rapidly growing discipline, and the application of such knowledge to reproductive medicine. As exemplified by the various areas of expertise provided by the individual contributors, it becomes obvious that the scope of the subject matter, while relating solely to a well-defined chemical class (LHRH analogs) and a circumscribed physiologic and pharmacologic entity (reproduction), has expanded enormously.

In the last decade, physicians have witnessed a publication will serve as a stimulus to surgeons growing awareness of and concern with diseases of concerned with male reproductive disorders to in the male reproductive tract. Stimulated by this tensify their personal research attempts to develop interest, a refinement and re-evaluation of existing better therapy for diseases referable to the male reproductive system. It is finally hoped that this surgical techniques for treatment of male repro ductive disorders has been concurrently appreci publication will stimulate critical analysis of what ated. Rapid progress in this area has resulted we feel are currently accepted surgical modes of primarily from a cooperative effort from those therapy and to better promote a general inter specialists in the areas of microsurgery, medical change of clinical information referable to these and surgical oncology, endocrinology and neuro disorders. physiology, pathology, immunology, genetics and Those who have provided the text and illustra biochemistry. tions for this volume have contributed a significant As the surgical treatment of diseases and ab amount of work, and we hope that they feel their normalities of the male reproductive system has material has been well used. The editors also wish to expanded, so have the articles describing these often thank Mr."

Many of the studies discussed in this book were addition to discussions of a variety of hormonal, presented at the First Pan American Congress of biochemical, immunological, physical, and me Andrology, which was held in Caracas, Venezuela, chanical approaches. It is our hope that the efforts in March 1979. An international group of in of the contributors will help to intensify research vestigators have contributed reviews designed to and development of improved methods for safely be informative to medical, graduate, and post regulating male fertility. graduate students, as well as clinicians and in vestigators working in the area of male reproduc G. R. CUNNINGHAM tion. Current physiological concepts that may W. B. SCHILL provide insight for new initiatives are examined in E. S. E. HAFEZ TABLE OF CONTENTS Preface v Contributors IX Foreword by C. SCHIRREN XI 1. PHYSIOLOGY OF MALE REPRODUCTION 1. Hormonal regulation of testicular function 5 P. FRANCHIMONT 2. Inhibin: new gonadal hormone 15 P. FRANCHIMONT, A. DEMOULIN, J. VERSTRAELEN-PROYARD, M. T. HAZEE-HAGELSTEIN, and J. P. BOURGUIGNON 3. Morphological features of the epididymis: possible significance in male contraception 25 T. D. GLOVER 4. Regulatory physiology of male accessory organs 35 E. S. E. HAFEZ and G. R. CUNNINGHAM 5. Methods for evaluating contraceptive techniques 41 T. Z. HOMONNAI and F. G. PAZ II. HORMONAL CONTRACEPTION 6. Inhibition of male reproductive processes with an LH-RH agonist 55 A. CORBIN and F. J. BEX 7."

The role of prostaglandins in physiological events and pathological disorders related to human reproduction has been most actively investigated in the past decade. Their clinical use for fertility regulation, extensively evaluated, represents the most common clinical indication for the administration of these remarkable compounds. Thus, it is most appropriate to update the available information related to the use of prostaglandins in the regulation of human fertility to provide a background document for the benefit of clinicians and scientists. Invited experts of international reputation from various parts of the world have contributed, each in his own area of interest, to offer this book, which we hope will fill an existing gap. M. T. M. B. E. S. E. H. ix 1 Potential for prostaglandin use in controlling human reproduction K. T. KIRTON and F. A. KIMBALL BACKGROUND It was observed in 1930 that seminal plasma of a number of species contained very large amounts of substance(s) capable of altering uterine motility. These substances were subsequently demonstrated to be prostaglandins (PGs); this began the early and continued association of this group of compounds with reproduction. The activity was found to be associated with a fraction containing lipid-soluble acids, derived from prostanoic acid. Restrictions imposed by obscure sources and small amounts of material available for testing were initially impediments to their study.

Various scientific evaluations taken from these chapters were presented during the international symposium, 'Carcinoma of the Cervix, ' which was held from September 4-7, 1980 in Kiawah Island, Charleston, South Carolina, U.S.A. An international selection of research investigators have contributed reviews designed to be informative to medical, graduate and post-graduate students, as well as clinicians, oncologists and investigators working in the area of female carcinoma. An attempt has been made to provide a total coverage of current progress in carcinoma of the cervix. In particular, the following major areas are included: Epidemiology, Histology & Histochemistry, Ultra structure, Physiology & Biochemistry, Genetics & Cytogenetics, Immunology, Diagnosis, and Patho physiology & Complications. Major changes have occurred in incidence and mortality rates for carcinoma of the cervix in the past decade. Mass screening programs and their ability to detect earlier stage diseases have attributed to a reduction in invasive diseases. Most cervical cancers could be prevented by an extension of cytologic screening programs in high risk areas. Greater resources must be provided to reach high risk areas in order to prevent the occurrence of cervical cancer."

This volume represents the Proceedings of the World Conference on Embryo Transfer, In Vitro Fertilization and Instrumental Insemination held on September 24-27, 1980 in Kiel, West Germany. Professor Dr. L. Mettler and Dr. H. H. Riedel of Frauenklinik der UniversiUit in Kiel were the local co chairpersons, who contributed very richly to the program. Basic research, clinical trials, preparation of manuscripts, editorial assistance and presentation of results were generously supported by the following institutions and organizations: Kulturministerium des Landes Schleswig-Holstein Medizinische FakuItat der Christian-Albrechts-UniversiUit, Kiel Wayne State University School of Medicine; Detroit, Michigan, USA C. S. Mott Center for Human Growth and Development; Detroit, Michigan, USA Universitats-Frauenklinik und Hebammenlehranstalt; Kiel, West Germany Serono GmbH; Freiburg, West Germany Hutzel Hospital; Detroit Medical Center; Detroit, Michigan, USA Deutsche Gesellschaft fUr Gynaekologie und Geburtshilfe; West Germany Deutsche Gessellschaft zum Studium der Fertilitat und Sterilitat; Sektion Andrologie Thanks are also due to Aponti GmbH (5000 Koln 21), Bayropharm GmbH (5000 Koln 80), Deutsche Lufthansa (5000 Koln), Organon GmbH (8024 Oberschleissheim), Winthrop GmbH (6080 New Isenburg), and Wisap GmbH (8029 Sauerlach), for financial assistance. Sincere appreciation and gratitude are due to the contributors who meticulously prepared their chapters; to Ms Jackie Mucci for editorial skills and assistance, and Ms. Jackie Smieska for editorial help. Thanks are also due to Dr. H. D. Brackebusch for his assistance during the conference; to Ms. E. Seiss for her secretarial assistance; and to Mr."

During the past decade extensive investigations have been done on the testis. Since the observations have been published in many different journals. it seemed appropriate to bring together and summarize some of the pertinent findings in a single volume. Twenty-eight scientists and clinicians from nine countries have contributed to this book. They have reviewed the literature and presented their own, new observations on the developmentaL anatomicaL physiologicaL biochemical and pathological aspects of the descended and cryptorchid testis. In addition, several contributors have evaluated the usefulness of certain animals as models for systematically studying specific aspects of cryptorchidism. It is hoped that this volume will serve as a useful summary and reference for those working in this area and that it will encourage further research in testicular physiopathology. The editor thanks the contributors for their enthusiasm, cooperation and meticulous writing of the chapters. The support of the Departments of GynecologyjObstetrics and the Department of Physiology of Wayne State University School of Medicine. Detroit and the assistance from the staff of Martinus Nijhoff are gratefully acknowledged. The cheerful cooperation of Miss Lori Rust and Miss Penny Stoops who helped to type and assemble the volume is most deeply appreciated.

Extensive basic research and clinical trials have in some aspect of reproductive physiology, gyne been conducted on inert and medicated intrauterine cology, or family planning. There is in this volume devices. In the last decade, substantial progress has an attempt to provide a total coverage of current been made in understanding the modes of action progress in medicated intrauterine devices. The and the physiological mechanisms of IUDs - pro volume is intended for a broad readership, includ gress resulting from modern techniques and in ing physicians, medical workers, medical personnel, strumentation in microanatomy, immunology, pa and administrators in family planning. It is hoped thology, endocrinology, biochemistry and biophy that this volume will serve as a stimulus to basic sics. Such studies, however, are scattered in such a scientists and clinicians concerned with intrauterine wide spectrum of journals that the clinician and devices to intensify their research toward better family planner can hardly keep up to date with the contraceptive techniques. advances. An attempt is made in this volume to coordinate physiological and clinical parameters. Little is September 1980 known about the possible role of diet, diseases and environmental factors. E. S. E."

Extensive reviews have been published on the mor aspects, anatomy, ultrastructure, physiology, bio phology, anatomy, and physiology of the mam chemistry, endocrinology, pharmacology, and physiopathology of the mammalian ovary. The malian ovary. However, little attention has been given to the gaps between the physiological, endo contributors, who prepared their chapters metic ulously, are recognized experts in their respective crine and histochemical parameters of the ovary as disciplines and their writings reflect extensive per it relates to clinical aspects. There is a wealth of sonal experience and unpublished data of both publications concerning the biology of the ovary: basic and clinical sciences. Without the assistance of the purpose of this volume is to integrate this information with emphasis on modern concepts in good friends and permission to draw extensively microanatomy, physiology, methodology, clinical from investigations, this volume would not have complications, and therapeutic approaches. An been possible. attempt is made to place fundamental research in Thanks are due to G. F. Franchitto, F. Barberini, clear perspectives. P. Stoops. Lori Rust and J. Squiers for their editorial It is hoped that this volume will fulfil a long skills and for checking the references to the original standing need and serve as an important source for sources. Thanks are particularly due to 1. K. Smith investigators and clinicians concerned with the of Martinus Nijhoff Publishers BV for his excellent physiopathology of the ovaries for years to come. It cooperation during the production of the book."

The suggestion of Max Knoll that an electron fascinated by the numerous SEM photographs, the wealth of information and the enthusiasm of the microscope could be developed using a fine scanning researchers covering a variety of disciplines. All aspects beam of electrons on a specimen surface and recording the emitted current as a function of the position of the of the female and male genital tract have been covered, beam was launched in 1935. Since then several culminating in the prizewinning award showing the in investigators and clinicians have used this concept to vitro fertilized human egg. develop techniques now known as scanning electron In clinical diagnostics SEM also proved to be a microscopy (SEM) and scanning transmission electron valuable complementary technique, shedding new light microscopy (STEM). The choice to study the female on oncology, the pathogenesis of tubal disease and the reproductive organs was a logical one because cells and maturation process of the placenta. Future research has tissue samples can be sampled relatively easily; still to be accomplished; e.g. quantification of SEM furthermore, these cells and organs are influenced photographs for meaningful and sound biological, continuously by the cyclic production of hormones. scientific and statistical evaluation in diagnostic This atlas demonstrates the state of the art in 1983. gynecology, obstetrics, andrology and oncology.

Uncontrolled population growth, a significant problem for many countries, depresses real living standards in all developing areas. As a corollary, un controlled population growth also stresses the ability to deliver adequate reproductive health care on both national and individual levels. To focus on this and related problems an International Congress to examine many aspects of male and female Reproductive Health Center Care was held on 10-15 October 1982 in Maui, Hawaii, USA. This volume is a result of the proceedings from the 'Symposium on Male Fertility and its Regulation' which was a part of the Reproductive Health Care Congress. The organizers of this symposium recognized the need to focus male reproductive understanding on contraceptive development. The ultimate objective was and still is to produce a variety of safe and effective male contraceptives similar to that accomplished in the female. Speakers were invited to review the state of the art in several areas related to male contra ception, reproductive toxicity and reproductive biology. The abstracts of these sessions were published as a special issue of Archives of Andrology (Vol. 9, No.1, August, 1982). Subsequently, this volume was assembled from key papers presented at the Symposium. Additionally, invited man uscripts from leaders in specific areas were solicited to provide additional range to the topics covered."

The subject matter in this volume was derived from papers presented at the Pediatric Andrology session of the 1st Pan American Congress of Andrology held in Caracas, Venezuela in February 1979, as well as from selected additional manuscripts of interest in this field. Prior to this session, identification of a distinct discipline and specialty devoted to pediatric andrology had not occurred, nor had it been conceptualized. Pediatric andrology encompasses many different areas: disorders of sexual development, structural disease of the genital organs, normal and abnormal puberty, undescended testes, genital tumors, gonadal function and its relationship to growth, virilization, fertility and gender identity all represent areas of specific interest, to name but a few. Andrology itself is a unique field, bringing together clinicians and basic scientists with diverse back grounds. It should be noted that between one-half and three-quarters of the clinicians contributing to this issue conduct basic research as well. It has been this unique blend of basic research and clinical medicine which has done much to unravel many of these problems characteristic of this field."

This volume contains a collection of papers based on presentations made at the Reproductive Health Care International Symposium held in Maui, Hawaii, USA, October 1982. The papers evaluate biologic interactions be tween intrauterine contraceptive devices and the host, examine the risks associated with the use of these devices and describe aspects of technical progress in the field. The contributing authors bring their knowledge and expertise from four corners of the world to the readers. The editors wish to express their appreciation to the authors for their valuable contributions, to Carolyn K. Osborn for helpful assistance in editing the manuscripts and to MTP Press for accurate preparation and fine presentation of the material. It is hoped that this volume will serve to expand knowledge and generate further interest among its readers in the dynamic and fascinating field of intrauterine contraception. April, 1984 H.M. Hasson, MD Chicago, Illinois, USA ix 1 Ultrastructure of the decidual response to a progesterone releasing IUD U.M. SPORNITZ. K.S. LUDWIG and M. MALL-HAEFELI INTRODUCTION The ever-increasing world-wide use of the IUD has prompted intensive research into the physiology of its contraceptive action. From these studies it has become clear that the alterations in morphology as well as in the physiological milieu produced by the IUD are manifold and differ greatly with the type of IUD used."

Many of the studies discussed in this book were addition to discussions of a variety of hormonal, presented at the First Pan American Congress of biochemical, immunological, physical, and me Andrology, which was held in Caracas, Venezuela, chanical approaches. It is our hope that the efforts in March 1979. An international group of in of the contributors will help to intensify research vestigators have contributed reviews designed to and development of improved methods for safely be informative to medical, graduate, and post regulating male fertility. graduate students, as well as clinicians and in vestigators working in the area of male reproduc G. R. CUNNINGHAM tion. Current physiological concepts that may W. B. SCHILL provide insight for new initiatives are examined in E. S. E. HAFEZ TABLE OF CONTENTS Preface v Contributors IX Foreword by C. SCHIRREN XI 1. PHYSIOLOGY OF MALE REPRODUCTION 1. Hormonal regulation of testicular function 5 P. FRANCHIMONT 2. Inhibin: new gonadal hormone 15 P. FRANCHIMONT, A. DEMOULIN, J. VERSTRAELEN-PROYARD, M. T. HAZEE-HAGELSTEIN, and J. P. BOURGUIGNON 3. Morphological features of the epididymis: possible significance in male contraception 25 T. D. GLOVER 4. Regulatory physiology of male accessory organs 35 E. S. E. HAFEZ and G. R. CUNNINGHAM 5. Methods for evaluating contraceptive techniques 41 T. Z. HOMONNAI and F. G. PAZ II. HORMONAL CONTRACEPTION 6. Inhibition of male reproductive processes with an LH-RH agonist 55 A. CORBIN and F. J. BEX 7."

Despite the increasing number of andrological pub opment of basic and clinical research in andrology, lications, the diagnostic aspects of andrology have to analyze modern techniques for the evaluation of received relatively little attention. In the last decade male infertility, to stimulate the development of substantial progress has been made in the under guideliness for therapeutic procedures, to recom standing of the fundamentals of andrology, this ment common norms of measurement, to promote progress resulting from modern techniques and and interchange of information and to stimulate the instrumentation in microanatomy, immunology, interest of scientists and clinicians in andrological neurophysiology, pathology, genetics, endocrino problems. logy, biochemistry, biophysics, urology and sur We are grateful to the authors who have given so gery. These studies are scattered in such a wide much of their time and talents to produce chapters spectrum of journals that andrologists can hardly of depth and breadth and who have made such a keep abreast of the advances. There have been significant contribution to the andrological litera textbooks on the testes, male accessory organs and ture. We are also indebted to Morag M. Smith, Lori semen but none that have attempted to bring Rust and Penny Stoops for the time and patience together the various aspects of diagnosis."