Third Edition
Pankaj Desai MD FICOG FICMCH
Consultant and Specialist Obstetrics and Gynecology Janani Maternity HospitalVadodara, Gujarat, India
Formerly
Dean of Students Medical College Vadodara, Gujarat, India
Associate Professor and Unit Chief Department of Obstetrics and Gynecology Medical College and SSG Hospital Vadodara, Gujarat, India
President Federation of Obstetric and Gynaecological Societies of India (FOGSI), 2007
Headquarters
Jaypee Brothers Medical Publishers (P) Ltd.
4838/24, Ansari Road, Daryaganj
New Delhi 110 002, India
Phone: +91-11-43574357
Fax: +91-11-43574314
E-mail: jaypee@jaypeebrothers.com
Overseas Offices
JP Medical Ltd.
83, Victoria Street, London
SW1H 0HW (UK)
Phone: +44-20 3170 8910
Fax: +44(0)20 3008 6180
E-mail: info@jpmedpub.com
Jaypee Brothers Medical Publishers (P) Ltd.
17/1-B, Babar Road, Block-B, Shyamoli
Mohammadpur, Dhaka-1207
Bangladesh
Mobile: +08801912003485
E-mail: jaypeedhaka@gmail.com
Jaypee-Highlights Medical Publishers Inc.
City of Knowledge, Bld. 235, 2nd Floor, Clayton
Panama City, Panama
Phone: +1 507-301-0496
Fax: +1 507-301-0499
E-mail: cservice@jphmedical.com
Jaypee Brothers Medical Publishers (P) Ltd.
Bhotahity, Kathmandu, Nepal
Phone: +977-9741283608
E-mail: kathmandu@jaypeebrothers.com
Website: www.jaypeebrothers.com
Website: www.jaypeedigital.com
© 2018, Jaypee Brothers Medical Publishers
The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book.
All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers.
All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book.
Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book.
This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought.
Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. The CD/DVD-ROM (if any) provided in the sealed envelope with this book is complimentary and free of cost. Not meant for sale .
Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com
Recurrent Spontaneous Miscarriages
First Edition: 2009
Second Edition: 2014
Third Edition: 2018
9789352702763
Printed at:
fm5Preface to the Third Edition
I never expected that in less than 5 years, 4 to be precise, this book would warrant one more edition. It shows the popularity and usefulness this book enjoys. Before I started writing this edition, I sent nearly 25,000 emails to its potential readers all over inviting their suggestions. Many of them sent very valuable inputs. I have tried to incorporate nearly all, which has fortified this edition and has made it more reader-relevant.
As I had mentioned in the previous edition, this book is a part of my study of the subject of immunology in obstetrics of last three decades. I have always felt that as a teacher and as a scientist it is the responsibility of our community to share what all we learn and gain. Writing such books is a part of that sharing process. Paulo Coelho has said “Writing means sharing. It is part of the human condition to want to share things-thoughts, ideas, and opinions”. Though this is the third edition with the current publisher, I had also published a book titled “Recurrent Miscarriage more than a decade ago, as the first in this series. One can therefore, take the liberty of calling this as the fourth edition. Incessant advances in the field, necessitated a periodic overhaul and so editions after editions followed.
In the present edition, I have incorporated many nuances. The most prominent of these is the importance of color Doppler in the management of subjects with recurrent spontaneous miscarriages. One of the commonest causes of recurrent miscarriages is immunological vasculopathy. Vasculopathies have a vascular basis and so it is pertinent to view what is happening within the vessels. Color Doppler does precisely this. Once, I started going into the depth of the vascular basis of recurrent miscarriages, I found an entire new world opening up. Though it is intriguing, it also gave many solutions. It can reveal that the process of vasculopathy is active in any indexed pregnancy. At the same time, it can also predict a possible outcome. I have included this in great details in the book.fm6
Charged with the information provided by color Doppler, we as obstetricians are able to take decisive steps of preventive measures. As one of the earliest proponent of the use of heparin in recurrent spontaneous miscarriages of immunological origin, I always wanted a tool to help me in deciding in which subjects I can discontinue using heparin, earlier. Previously, before using color Doppler so extensively, we used to continue using heparin till 36 weeks of pregnancy and after stopping for a week induce labor at 37 weeks. Thanks to this new technology I am now able to discontinue Heparin much earlier. This aspect gets a detailed discussion in the pages to follow.
All these results had to pass through a rigorous statistical scrutiny. Many of these results have been published in peer-reviewed journals. I did not confine it only to the Chi-square test but also used other statistical tests to fortify the validity of these results. Only when more than one statistical tool indicated that one particular result was scientifically valid, would then I take a stand on its efficacy. Some results were statistically untenable and therefore mercilessly rejected. It was an exercise of revelation and development.
It is with a great sense of satisfaction that I have to report to the readers that results corroborating ours, regarding the use of low-dose aspirin, have started trickling in from around the world, of late. However, Indian obstetricians (on the basis of very solid scientific results published) are using low-dose aspirin for more than two decades. The world just follows!
Ultrasound, in general, is the most important aid for an obstetrician when one has to handle subjects with recurrent spontaneous miscarriages. I have covered this aspect in details. Also, there is a continuous support taken of this technology in specific chapters like “Anatomical causes of Recurrent Spontaneous Miscarriages.”
Genetics is a maze, more so when it comes to recurrent miscarriages. As in the previous edition, we have renowned geneticist Dr. Sharad Gogate to pen this chapter. He is the only contributing author in this book. He has thoroughly revised his chapter, making it updated.fm7
Evidence-based practice is a wonderful lamp which decisively breaks down the darkness of unscientific approaches including recurrent spontaneous miscarriages. When I was updating this chapter, I was delighted as any scientist should be. There were many aspects which may have been held valid previously, now not found to be valid anymore. There were others that were reinforced and evidence for some new aspects seeped in into the scene. Updating this chapter, therefore, was a greatly illuminating exercise.
Reproduction has a strong endocrinal basis. Some of the reproductive hormones have been found to have an immunological face. While updating the chapter on the endocrinology of recurrent spontaneous miscarriages I thoroughly examined the latest evidence to take a stand. Progesterone and human chorionic gonadotropin (hCG) were always eyed with suspicion for their efficacy in preventing recurrent miscarriages. There was such a wide gap between the clinical use of these hormones as supplements and their efficacy. Thankfully some evidence has appeared showing that they may, after all, be effective. However to what extent is this efficacy valid, remains a mystery. Maybe in subsequent editions, I may get evidence to bridge the yawning chasm between evidence and the mighty use of these agents in clinical practice.
Many interesting developments are now on the horizon spelling out the importance of sonographic imaging of the cervix in pregnancy. This has made the use of cervical cerclage much more accurate and scientific. It has reduced the need for this invasive procedure remarkably in practice. This aspect also has been dealt with in detail in this new edition. Cervical cerclage versus progesterone supplementation is a new debate on the horizon. As a scientist, I have always felt that cervical cerclage may be an overused procedure. Now with progesterone walking down the hall holding the banner that it can completely replace cerclage, it became necessary for me to visit this controversy. Have I found the answer?—well not a complete one! The truth lies midway.
Why do I retain endometriosis and infections in this book, editions after editions? The answer is plain and simple—many clinicians still continue to pay obeisance to these two as important fm8causes of recurrent spontaneous miscarriages. Ten years down the line and more, science has found no credible evidence to associate any of these with recurrent miscarriages. Until that time the requesting investigations for TORCH in particular and infections, in general, continues to be scribbled by practitioners of our subject and I will be including these in the book.
So as to make this edition free of grammatical mistakes and free of spelling errors, I have purchased the use of two softwares, besides getting the manuscript checked by a competent copy-editor. I assure you, I have done the best for this. However, if some errors may have still crept passed the scrutinizing eyes of the checking systems please ignore them.
I have tried to make this monogram as comprehensive as possible. However, I know that this is not the final word on recurrent spontaneous miscarriages as yet. New knowledge will continue to flow in, new research with continue to be game-changers and new technology will continue to change our approach to the subject. I will continue working in this field inspired by one of the greatest Indian rishis of modern times, Dr. A. P. J. Kalam who said “Never stop fighting until you arrive at your destined place - that is, the unique you. Have an aim in life, continuously acquire knowledge, work hard, and have the perseverance to realize the great life.”
In all humility, I place this book in the hands of the keen students of our subject (as clinicians, postgraduate students or research scientists) hoping to get their blessings in my pursuit of academic excellence at the service of humanity and mankind.
17th January 2018
Pankaj Desai
Vadodara, India
fm9Preface to the First Edition
Recurrent Spontaneous Miscarriages, as they are popularly called, touch a vast canvas from immunology to psychology. No wonder, it will have many facets and bearings. At the same time, with the science of obstetrics making giant strides due to influx of modern technology, the face of this entity is bound to change. My forays to understand this clinical condition is now more than two decades old. It all began with an unassuming question on this problem that I tossed to a PG student once during a teaching session and her failure to answer, made me start studying this challenge in depth. It was after assiduously following subjects of recurrent spontaneous miscarriages that I realized its links with seemingly diverse conditions like PIH, accidental hemorrhage, IUGR and recurrent stillbirths.
Once, we had the facility for testing of antiphospholipid antibodies at Vadodara during which our search for the causes and treatment became more productive and much water has flown under the bridge since then. I studied many research papers and chapters in different books later, and I am now fascinated by the advent of Color Doppler and 4-D Imaging Techniques on this subject.
In this book, I have invited two meritorious and knowledgeable authors Dr Sharad Gogate (Chapter 5) and Dr Jayakrishnan (Chapter 3) to share their expertise in the fields of chromosomal and anatomical cause of recurrent spontaneous miscarriages. Like immunological causes these need very special skills and experience to handle them. I am very thankful to them for their contributions.
I would be failing in my duty if I do not thank my wife Dr Meera Desai and my children Ushma and Shlok for their support during the completion of this book project.
My typist and loyalist for nearly 20 years, Mr Ramesh Kadam needs a special pat on his back. Though a graduate in arts for whom medical jargon could be perplexing, he deftly typed the manuscript reasonably flawlessly and shared this load mightily with me.fm10
Before I place this book in the hands of the readers, I would like to pray to Goddess Aetheus (Maa Saraswati) of knowledge to make this book valid so that the knowledge that flows here may help the reader handle patients of recurrent spontaneous miscarriages scientifically. This will ultimately help us serve humanity and mankind better.
Pankaj Desai
fm11Acknowledgments
Brené Brown, a renowned research professor at the University of Houston, has beautifully said, “I don't have to chase extraordinary moments to find happiness—it is right in front of me, if I am paying attention and practicing gratitude.” As I place third edition of this book in your hands, I would like to express my heartfelt gratitude to all those who have directly or indirectly helped me.
First of all, I express my gratitude to all my readers who have given me so many blessings, support, and encouragement that this book has gone into its new edition in a short span of time. I feel overwhelmed by their kindness.
I would also like to offer my thanks to Dr Sharad Gogate. He has kindly authored chapter Genetics of Recurrent Miscarriages and Other Pregnancy Losses, in this edition as well. He is the Director, Surlata Hospital and Fetal Medicine Consultancy Services at Mumbai, Maharashtra, India. He is nationally renowned as one of the finest in this field. This edition, like the previous edition, has been greatly enriched by this master contribution from him. I am indeed greatly obliged to him for his kind gesture.
My wife, Dr Meera Desai, my daughter, Ushma, my son, Shlok, my daughter-in-law-to-be Prathana; and Dr Purvi Patel, my associate in many of my educational undertakings, need special thanks for their great support and backing they have given me in my entire academic career, in general, and in this project, in particular.
I am grateful to Shri Jitendar P Vij (Group Chairman), Mr Ankit Vij (Group President), Ms Chetna Malhotra Vohra (Associate Director–Content Strategy), Ms Ritika Chandna (Development Editor) and others at M/s Jaypee Brothers Medical Publishers, New Delhi, India, and their staff, for their help in preparation of this book.