Recurrent Spontaneous Miscarriages Pankaj Desai
Page numbers followed by b refer to box, f refer to figure, and t refer to table.
primary 55
secondary 55
Abortion, threatened 54
Acquired uterine anomalies 28
Activated partial thromboplastin time 70
Adverse pregnancy outcomes 116
AES See Androgen excess society
AFI See Amniotic fluid index
Allograft inflammatory factor-1 46
American Fertility Society 21, 23b
Amniotic fluid index 8f
Androgen Excess Society 107
Anembryonic pregnancy 16
Anemia 152
Antibiotic treatment 142
Anticardiolipin 57
antibody 68, 143
Antinuclear antibodies, test for 150
Antiphospholipid antibody 56, 61, 126, 144, 150
originating in infections 126
prevalence of 58
syndrome 56, 86
APA syndrome, treatment of 69
APL syndrome See Antiphospholipid syndrome
APLA See Antiphospholipid antibody
APTT See Activated partial thromboplastin time
Arcuate uterus 27
Asherman's syndrome 31
Aspirin plus heparin therapy 72
Aspirin/heparin 71
Assisted reproductive technology 31
program 81
Autopsy 87
virtual 87
Bacterial vaginosis 122, 124
Beta human chorionic gonadotropin 10
Bicornuate uterus 25
complete 26
pregnancy in 38f
USG of 26f
Blighted ovum 81
BMI See Body mass index
Body mass index 143
Body's immune response 117
Cadherins 62
Calcium-dependent adhesion 62
Cardiac activity 12f
absent 13f
positive 6
Cardiac motion, detecting 9
Cardiotocography 7, 9f
Central nervous system 83
Cerebral artery, middle 7, 8f
cerclage 34, 102
incompetence 31
diagnosis of 32
weakness 139
Cesarean section, lower segment 36, 37f, 38f
Chimerism 80
Chinese herbal medicine 143
Chlamydia trachomatis 122, 124
Chromosomal abnormalities 84
high risk for 85
in abortuses 82t
Chromosomal anomalies 84
in abortuses 82t
in parents 78
in perinatal deaths, frequency of 83t
Chromosomal rearrangements, types of 83t
CNS See Central nervous system
Collin's knife 24
Conceptus alive 149
Congenital abnormalities 102
Congenital syphilis 142, 150
Congenital uterine anomalies 17, 22
diagnosis of 21
Corpus luteum flow 16
Coxiella burnetii 125
Cushing's syndrome 107
Cystathionine beta-synthase 43
Cystic fibrosis transmembrane conductance regulator 78
Cytochrome 105
Cytokines 116
protective 6
types of 6
Cytomegalovirus 121, 122, 150
DES See Diethylstilbestrol
Destructive cytokines 6
Diabetes 95
Didelphys 23
Diethylstilbestrol 18t
exposure-related anomalies 28
Doppler findings 16
Doppler in early pregnancy loss, qualitative observations on 16t
Dydrogesterone 102
Dysmenorrhea 17
Early fetal loss and malformation 86b
Early pregnancy failure, diagnosing 4
Ectopic pregnancy 26
Efficient syncytiotrophoblasts system 66
Embryo 45
Embryonic demise 16
radiographic assessment of 10b
Embryonic heart rate 10
Embryonic tissues 80
Endocrinal factors 139
Endometrial cavities, separate 24f
Endometriosis 115
causes of 117
Endometrium, benign growths from 28
Endoscopy 20
European Society for Gynecological Endoscopy Consensus on Diagnosis 18
European Society of Human Reproduction and Embryology 18
Female genital anomalies 18
autopsy 87
cardiac activity 9
at miscarriage 149
ultrasonographic features of 4
growth restriction 26
heart rate 11t
loss, etiological causes of 88
malformations 84
medicine expert 90
microchimerism, phenomenon of 48
pathology workups 87
pole, absent 109f
tissue 88
sampling for genetic evaluation 88
sampling techniques 89b
trophoblasts 49
as allograft 44
as unique allograft 47
Fluorescent polymerase chain reaction, quantitative 89
Folic acid 43, 144
Follicle-stimulating hormone 103, 150
G protein-coupled estrogen receptor 117f
Genetic causes, investigative workup for 85
Genetic counseling 90
Genetic factors 137
in pregnancy loss, etiologies of 78b
Genital mycoplasma 125
Gestational age 11t, 13f, 14f
Gestational sac 4
irregular 14f
Glucocorticoids 141
GnRH See Gonadotropin-releasing hormone
Gonadotropin-releasing hormone 63
GPER See G protein-coupled estrogen receptor
Graft-versus-host diseases 48
Granulocyte-macrophage colony-stimulating factor 46
hCG See Human chorionic gonadotropin
activity, absent 111f
rate, slow 110f
Hematoxylin 87
Hemochorial pregnancy 45
Heparin 70
earlier, discontinue 71
side effect of 71
HER See Embryonic heart rate
Herpes simplex 122
virus 121
infections 150
Histocompatibility complex 45
HIV See Human immunodeficiency virus
Homocysteine 43
Human chorionic gonadotropin 15, 81, 98, 140, 149
immunological basis of 99
supplementation 140
Human immunodeficiency virus 121, 122
Human leukocyte antigen 47
Human menopausal gonadotropin 104
Human T-lymphotropic virus 121
Hydatidiform mole, partial 79
Hyperhomocysteinemia 43
Hyperprolactinemia 94
Hypersensitivity cells, delayed-type 55
Hypertension, chronic 66
Hypoimmunogenic embryo 47
Hysterosalpingo-contrast sonography 19
Hysterosalpingography 18
Hysteroscopy 20
Immune factors 141
Immunology 130
Immunomodulatory effects 73
Implantation failure 81
In vitro fertilization 69, 104, 137
embryo transfer 92
failures 78
Incompetent gonadotropin-releasing hormone activity 63
Infection 121, 142
specific 124
Infertility 3
Insulin resistance 106
severe 107
Interleukin 46
adhesions 31
growth restriction 12, 42, 148
synechia 31
Intravenous immunoglobulin 72, 141
IUGRs See Intrauterine growth retardations
IVF See In vitro fertilization
LAC See Lupus anticoagulant
Laparoscopic encerclage 35
Leukocyte transfusions 72
LH-releasing hormone 105
Listeria monocytogenes 122
Living organism 1
Lupus anticoagulant 143
Luteal phase defect 97, 139
and recurrent miscarriages 97
Luteinizing hormone 2, 139
endocrinopathy 103
hypersecretion of 94
suppression of 105
Male hormones 103
Maternal lymphatic systems 45
Maternal lymphomyeloid cells 47
Maternal protector systems and pregnancy, paralysis of 46
MCA See Middle cerebral artery
Medicine, evidence-based 135
Messenger ribonucleic acid 46
Methionine synthase 43
Methylenetetrahydrofolate 43
Methyltetrahydrofolate 144
Micro ribonucleic acid 117
Miracle of paradox 67
Miscarriage 3, 26, 77, 102
early 81
increased risk of 27
medical treatments for 145
partner specificity in 54
post-treatment 25
Missed abortion 1, 81, 149
Müllerian abnormalities 17
Müllerian anomalies 23
Müllerian duct 23, 27
anomalies 25
malformations 22
Müllerian fusion 25
Mycoplasma hominis 122, 125
Myometrium, benign growths from 28
National Institute for Health and Care Excellence Guidelines 138
Natural killer cell 53, 118, 130, 143
Neodymium-doped yttrium aluminum garnet 24
Neonatal intensive care unit 37
Neural tube defect 79
NICU See Neonatal intensive care unit
Nitric oxide synthase 2 46
NK cell See Natural killer cell
Nonfertile menstrual cycle 97
Nonimmunological basis 55
Obstetric vasculopathy 2, 42, 44
manifestation of 42
Oocytes, abnormalities in 78
Oogenesis, abnormal 78
Organisms associated with spontaneous miscarriages 122t
Ovarian hyperstimulation syndrome 99
Oxygen species, reactive 80
Parental chromosomal rearrangements 138
Parental karyotyping 90
PCOS See Polycystic ovarian syndrome
PIH See Pregnancy-induced hypertension
Placenta 53, 80
and cord, normal 12f
protective mechanisms in 53
Placental abruption 43
Platelets 59
Polycystic ovary 111f
syndrome 94, 106, 107, 107t, 149
Polymerase chain reaction 124
Poor prognostic indicators 10
abnormalities 79
mitotic divisions 79
Preeclampsia 42
abnormal 16
eight weeks 110f
loss 17, 77, 115
causes of 117
nine weeks 111f
seven weeks of 7f
six weeks 109f
test, false-positive 149
with gestational sac, abnormal 4
Pregnancy-induced hypertension 12, 50
Preimplantation genetic diagnosis 89, 92
Premature rupture of membranes 122
Preterm births, prevent 102
Preterm delivery 17
Preterm labor 17, 26
symptoms of 33
Progesterone 72, 101
and human chorionic gonadotropins supplementation 98
and recurrent spontaneous miscarriages 96
levels, low 96
receptor modulator 30
supplementation 140
Protects fetus 45
Protein 116
C activation 60
Proximal cervix, funneling of 33f
Psychology 130
Psychotherapist 133
Pyridoxine 43
Randomized controlled trials 135, 144
RCTs See Randomized controlled trials
Recurrent early pregnancy loss 96
Recurrent miscarriage 43, 96
corticosteroids in 69
genetic of 77
psychological bearings of 129
Recurrent pregnancy loss 81, 85, 106, 121, 122, 124, 130, 131
autoimmunity in 56
specific organism and 123
women with 22
Recurrent pregnancy miscarriage, immunology of 42
Recurrent spontaneous abortion 44, 104, 142
causes of 44
Recurrent spontaneous miscarriage 1, 2, 65, 95, 103, 115, 121, 143b, 148
anatomical causes of 17
endocrinal causes of 94
evidence-based practice in 135
management of 132
treatment of 98, 144b
Robotic encerclage 35
RPL See Recurrent pregnancy loss
Rubella 121, 122
Saline infusion sonography 143
Segmental müllerian agenesis-hypoplasia 23
Septate uterus 23
Sildenafil 73
Singleton versus twins 33
SIS See Saline infusion sonography
SLE See Systemic lupus erythematosus
Spermatogenesis, abnormal 79
Spontaneous resolution 65
Stillbirth 83
and neonatal deaths 81
Strassman metroplasty 26
Subchorionic hemorrhage 6, 109
absence of 153
diffuse areas of 14f, 109f
presence of 153
Subclinical hyperthyroidism 96
Submucous fibroids 29f
Superoxide anion radical 80
defective generation of 62
privileged status of 63
Syndromes 84
Systemic lupus erythematosus 44
TAS See Transabdominal sonography
Tender loving care 131, 143
Teratogens and environmental factors 80
Testosterone 103
Three-dimensional ultrasonography 19
Thrombomodulin 60
Thromboxane prostacyclin mechanism, disruption of 60
abnormalities 95
function 95
TORCH 121, 142
Toxoplasmosis 121
Transabdominal sonography 5
Transforming growth factor-beta 52
Transvaginal sonography 5
Trophoblastic flow 16
Tumor necrosis factor-alpha 46
Two well-formed cervices 36f
Two-dimensional ultrasonography 19
Unicornuate 23
uterus 26
infection 125
urealyticum 122, 125
classification of 18f
screening test for 138
embolization 30
pulsatility index 61
corpus 27
fibroids 28
malformation, classification of 138
septa 23
wall thickness 21
Uterus 53
anatomical defects in 3
coronal section of 24f
didelphys 27
ultrasonography of 36f
intraoperative appearance of 38f
left 36f
right 36f
Vaginal progesterone 102
Viruses 142, 150
Vitamin 43
B6 43
supplements 143
Waddlia chondrophila 126
White blood cell 122, 130
Yolk sac 14
double 15f
Zona pellucida 46
Chapter Notes

Save Clear

fm1Recurrent Spontaneous Miscarriagesfm2
fm3Recurrent Spontaneous Miscarriages
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
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Recurrent Spontaneous Miscarriages
First Edition: 2009
Second Edition: 2014
Third Edition: 2018
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
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.
Last but not least, I bow down in prayer to the presiding deities of learning and wisdom Maa Saraswati and Lord Ganesh for their immeasurable blessings and approval. I place this new edition of this book at their feet with complete adoration and in total devotion.fm12