Foreword

‘Children are the anchors that hold a mother to life’

Sophocles, Phaedra

In almost all traditions, the importance of procreation is inherent in man’s very creation; both Old and New Testaments of the Bible refer to the tragic plight of barren women, eloquently describing the pain and agony of childlessness. However, records dated far earlier than the Bible confirm that fertility has been a constant fundamental priority and preoccupation, in all societies, throughout the ages of man. Fertility symbols are clearly identified in the relics of prehistoric times, of ancient civilizations in all parts of the world, a recognition of the concept that man’s existence depends upon the renewal of fertility. The above quotation was written by Sophocles 2500 years ago. The ancient Canaanites and Greeks had gods of fertility – Ashtarte and Hermes. Today, infertility is recognized as a disease by the World Health Organization and by numerous healthcare providers throughout the world. Recurrent pregnancy loss represents one aspect of disordered fertility. Recurrent pregnancy loss has been described as the ‘orphan’ of infertility, as this condition is often overlooked in the larger process of research and management of fertility. Recurrent pregnancy loss is a heterogeneous condition, with numerous causes and numerous treatment options. It is multidisciplinary, involving gynecology, genetics, endocrinology, immunology, pediatrics, and internal medicine. Whatever the cause and possible treatment, the psychological implications are enormous. Both partners may feel that they have failed in their parenting role. Couples have divorced with mutual recriminations, each blaming the other. Even when pregnancy does succeed, it may be fraught with the fear of another loss. This anxiety is multipled when the diagnosis remains unexplained.

This book will be welcomed by many investigators and clinicians working in the field of recurrent pregnancy loss. There are chapters governing basic scientific topics such as cytokines, mechanisms of action of antiphospholipid antibodies, and signaling between mother and fetus. The major advances in genetics, including pregestational diagnosis, immunology, endocrinology, and thrombotic mechanisms, have been described in depth. The methodology of clinical research and the application of evidence-based medicine to clinical practice have been explained comprehensively. The problems of midtrimester loss and late obstetric complications are aired, including the problems associated with extreme prematurity and possible resulting handicaps, and recent views on the role of cerclage in prevention. However, as is inevitable in clinical practice, there are many controversies, leaving the clinician in a quandary, as how to help the patient. Hence, there are six debates, and one opinion article, that try to bring the relevant points before the clinician, to aid in deciding the most appropriate management. However, we must never forget that at the end of the line is a patient. Therefore, the chapter on psychological mechanisms and the connection between psychological mechanisms and the immune and other systems is welcome. The story told by the patient in Chapter 22 is most touching, and reminds us of the real problem at hand.

It is hoped that this book will be read by specialists working in recurrent pregnancy loss clinics and associated disciplines who wish to keep up to date, and generalists who wish to gain a comprehensive view of developments in the field. The ‘half-life’ of scientific knowledge has been said to be ten years. However, many advances are occurring so quickly that a ‘half-life’ of ten years seems to be out of date. It is to be hoped that the advances in scientific and

FOREWORD

clinical knowledge will continue at this pace, in order to improve the management of the patients

and to allow those still unable to have children to fulfil this most basic of human desires.

Professor Bruno Lunenfeld MD PhD FRCOG

FACOG (Hon) P.O.G.S. (Hon)

Professor Emeritus at Faculty of Life Sciences Bar-Ilan University President of the International Society for the Study of the Aging Male (ISSAM)

General Secretary of The Asian–Pacific Initiative on Reproductive Endocrinology (ASPIRE)

Member of the Israel Government National Council for Obstetrics, Genetics and Neonatology

Recurrent pregnancy loss is a vexing clinical problem as the cause often remains unexplained despite the major advances in genetics and immunology. Treatment is often controversial and ranges from “masterly inactivity”, to an approach which could be considered as “over aggressive”. The problem is distressing to couples, who understandably expect answers and solutions, and frustrating for the physician who often does not have these answers, particularly in the face of ever-changing and conflicting recommendations. This book tries to summarize those controversies, and discuss the scientific basis for various causes of pregnancy loss in depth, and to debate the various treatment modalities which have been used in recent years. Hence, it is hoped that this book describes the accumulating data in a way which is both scientifically sound and

also clinically useful, and which may improve the care of these couples.

The book is planned for general gynecologists, and specialists working in the field. Each contributing author is an authority on a specific area of recurrent pregnancy loss. I would like to thank each author for the time and effort taken in preparing the manuscripts to make publication of this book possible. I would also like to thank those responsible in a more indirect way for the publication of this book; my teachers over the years, particularly Prof. Shlomo Mashiach for his constant help and encouragement in my work in recurrent pregnancy loss. Thanks go to my collaborators, Prof ’s Yehuda Shoenfeld, Aida Inbal, Ephraim Gazit, and Vladimir Toder, and special recognition goes to the greatest teachers of all, the patients.