Manual of Obstetrics and Gynecology

for the Postgraduates

(Previously known as Master Pass in Obstetrics and Gynaecology)

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 Special Features
 Information provided, format of presentation and the method of learning, are consistent
with the current system of education and evaluation
 Case-based rather than disease-based approach has been made. This is for the integration
of knowledge with the clinical issues of diagnosis, investigations and management
Unmatched content with complete coverage of the latest results from clinical trials

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
 Simple answers even for complex questions
 Discussion with the most advanced treatment modalities

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 Adequate references at the end of each chapter for further study and clarification
 A number of relevant clinical images, drawings, illustrations, tables and summary lists, for
easy understanding and reproducibility
 Targeted answers to more than 4,500 clinical questions
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 Answers with explanations—more than 900 SBA and MCQs covering both the Obstetrics
and Gynecology
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 Wide coverage of 84 topics, with exciting new approach
 Model questions and answers with explanations for University Examination as well as
MRCOG, MRCPI and MICOG Examinations
 Most trusted resource in Obstetrics and Gynecology.
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Other Books by Author

„„ DC Dutta’s Textbook of Obstetrics (8th Edition), Edited by Dr Konar
„„ DC Dutta’s Textbook of Gynecology (7th Edition), Edited by Dr Konar
„„ Bedside Clinics and Viva-Voce in Obstetrics and Gynecology (4th Edition)
„„ A Guide to Clinical Obstetrics and Gynecology (4th Edition)
„„ Emergencies in Manipulative and Operative Obstetrics (4th Edition)
„„ Medical Disorders in Pregnancy—An Update (4th Edition)

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 Manual of Obstetrics and Gynecology
for the Postgraduates
(Previously known as Master Pass in Obstetrics and Gynaecology)

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Second Edition

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Hiralal Konar  (Hons; Gold Medalist)
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mbbs (Cal), md (pgi), dnb (India)
mnams, facs (usa), frcog (London)
Chairman, Indian College of Obstetricians and Gynecologists (2013)
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Professor, Department of Obstetrics and Gynecology
Calcutta National Medical College and Hospital, Kolkata, West Bengal, India
One-time Professor and Head, Department of Obstetrics and Gynecology
Midnapore Medical College and Hospital, West Bengal University of Health Sciences, Kolkata, India
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Rotation Registrar in Obstetrics, Gynecology and Oncology

Northern and Yorkshire Region, Newcastle-upon-Tyne, UK
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Examiner of MBBS, DGO, MD and PhD of different Indian Universities and National Board of
Examination, New Delhi, India and other International Colleges (MRCPI) and Universities
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Foreword
BN Chakravorty

The Health Sciences Publisher

New Delhi | London | Philadelphia | Panama

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 Jaypee Brothers Medical Publishers (P) Ltd
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
Email: [email protected]

Overseas Offices
J.P. Medical Ltd. Jaypee-Highlights Medical Publishers Inc.
83, Victoria Street, London City of Knowledge, Bld. 237, Clayton

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SW1H 0HW (UK) Panama City, Panama
Phone: +44-20 3170 8910 Phone: +1 507-301-0496
Fax: +44-(0)20 3008 6180 Fax: +1 507-301-0499
Email: [email protected] Email: [email protected]

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JP Medical Inc. Jaypee Brothers Medical Publishers (P) Ltd.
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Philadelphia, PA 19106 Mohammadpur, Dhaka-1207, Bangladesh
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Jaypee Brothers Medical Publishers (P) Ltd.

Bhotahity, Kathmandu, Nepal
Phone: +977-9741283608
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Email: [email protected]

Website: www.jaypeebrothers.com
Website: www.jaypeedigital.com

© 2017, Mrs Madhusri Konar

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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.
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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
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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
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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.
Inquiries for bulk sales may be solicited at: [email protected]
Manual of Obstetrics and Gynecology for the Postgraduates
First Edition: 2013
Second Edition: 2017
ISBN: 978-93-86056-28-3
Printed at

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 rs
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Dedicated
to
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those who strive relentlessly
to develop quality care
for
women’s health
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 Foreword
There are many objectives with which a book in medical discipline is
written or compiled. The first and foremost is to propagate contemporary
and currently available new information and discoveries in the topic on
which a chapter has been written. The second objective is to suggest
some new ideas or concepts, based on which further improvement in
our knowledge about pathogenesis, diagnosis and management can be
achieved. The last and most important objective is to outline the materials

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in each chapter in such a manner which is easily understandable and
reproducible even by a new entrant in medical discipline.

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The first two objectives will help those who are already in profession or proactive for quite
sometime and the last one will benefit immensely the fresh candidates who are aspiring for medical
graduation or if they are already graduates, to acquire higher postgraduate diplomas or degrees.
It gives me immense pleasure to write about Manual of Obstetrics and Gynecology for the
Postgraduates. Examination system all over the world is under constant refinement. Progressive
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advancement in technology and science, virtually has changed every area of obstetrics and
gynecology substantially. Simultaneously the examination system has changed to produce quality
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medical graduates and specialists in the discipline.
The earlier pattern of essay questions and long clinical case, have been proved unreliable
methods of assessing candidates’ knowledge, clinical as well as communication skills. Essay
questions have been replaced by more reliable methods like—Short Review Questions, Multiple
Choice Questions (MCQs), Single Best Answer (SBA) and Extended Matching Questions (EMQs).
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Clinical skills are assessed by Objective Structured Clinical Examinations (OSCEs).

Manual of Obstetrics and Gynecology for the Postgraduates is primarily aimed to help a
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candidate to qualify and to pass the examination for obtaining the postgraduate degree. This
book is designed to provide new format of testing knowledge and clinical skills. This book, to my
knowledge, is the first of its kind to have all the component of new assessment system.
I am proud to say that Professor Hiralal Konar, is one of my brilliant students. He has proved
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his excellency through dedication in the profession and also in the largest national organization of
the country, The Federation of Obstetric and Gynaecological Societies of India (FOGSI) and as the
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Chairman of Indian College of Obstetricians and Gynaecologists (ICOG). He is well known for his
two other books that are widely read in India as well as abroad, DC Dutta’s Textbook of Obstetrics
and DC Dutta’s Textbook of Gynecology.
I believe, this book would be of immense help to the students, residents and all the specialists
in this discipline of Obstetrics and Gynecology.
I congratulate him and wish his endeavor a huge success.

Professor (Dr) BN Chakravorty

MO, FRCOG, DSc
Director, Institute of Reproductive Medicine
HB-36/A/3, Sector – III
Salt Lake City
Kolkata 700106

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 Preface to the Second Edition
Manual of Obstetrics and Gynecology for the Postgraduates is designed to provide a synoptic
review of management issues covering the key areas in obstetrics and gynecology. The textbook
with its classic presentation provides knowledge that has no alternative. But failure of clinical
application of the same, makes a difference in examination performance. This book is focussed
to polish examination performance to improve the chance of passing the theory, clinical as well
as the table viva-voce part of the examination.

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Case-based rather than disease-based discussions have been made to provide the updated
and evidence-based information to the candidate.
This book addresses the new format of examination system currently pursued all over the

he
world. Extensive discussions have been made with Objective Structured Clinical Examinations
(OSCEs), Single Best Answer (SBA), Multiple Choice Questions (MCQs) and Extended Matching
Questions (EMQs). Model questions with answers in all the above-mentioned areas have been
provided and these are of distinct values. This book aims to help candidates to test and assess
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their knowledge and to find out the areas of weakness.
The current examination system explores the candidates’ analytical power rather than simple
factual recall. Manual of Obstetrics and Gynecology for the Postgraduates helps appropriate
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application of textbook knowledge in respect of an individual clinical scenario.
Commonly discussed topics are selected. A broad range of themes have been incorporated
in different sections (84 chapters) of this book with graded difficulty. I am ever grateful to my
teacher Professor (Dr) BN Chakravorty for his contribution of the topic ‘Infertility and Assisted
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Reproductive Technology (ART)’ (Section 5) in this book. History in medicine and eponyms have
been presented (Section 12). I personally feel, one should know about the ideals, whose footsteps
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we follow while working in the discipline.

While writing this book, I have deviated from the traditional approach of a textbook, with
expectation that core knowledge to be covered by a textbook. Attempts have been made to
incorporate much of the available evidences upon which our practice in obstetrics and gynecology
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should base.
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Manual of Obstetrics and Gynecology for the Postgraduates is intended to help medical
students, residents aspiring as well appearing for the postgraduate examinations MS, MD, DGO
(University), DNB, FNB, Fellowship Exit Examination (National Board), RCPI, MICOG, MRCOG
(membership examination of international colleges), American Board (USMLE), specialized nurses
(BSc, MSc), midwives as well as specialists in the discipline of obstetrics and gynecology.
I do hope this comprehensive book will be of immense educational resource to the readers.
I do welcome the views of students/teachers for their suggestions, comments through our
website: www.hiralalkonar.com.

Hiralal Konar

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 Preface to the First Edition
‘Master Pass’ is designed to provide comprehensive review of management issues covering the
key areas in Obstetrics and Gynaecology. Textbook knowledge has got no alternative. But failure
of clinical application of the same, makes the examination performance poor. ‘Master Pass’ focuses
polishing examination performances to improve the chance of passing the theory, clinical, as well
as the table viva-voce part of the examination.
Case-based and topic-based discussions have been made to provide the updated and

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evidence-based information to the candidate.
‘Master Pass’ addresses the new format of examination system currently persued all over the
world. Extensive discussions have been made with Objective Structured Clinical Examinations

he
(OSCEs), Multiple Choice Questions (MCQs), Extended Matching Questions (EMQs) and Short
Answer Questions (SAQs). Model approach with questions and answers in all the above-mentioned
areas have been made and these are of distinct value. This book aims to help the candidate to test
and assess their knowledge and to find out the areas of weakness.
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The current examination system explores the candidates’ analytical power rather than simple
factual recall. ‘Master Pass’ helps appropriate application of textbook knowledge in respect of an
individual clinical scenario.
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Commonly discussed topics are selected. A broad range of themes have been incorporated
in different sections (total 6) of this book with graded difficulty. I am so grateful to my teacher
Prof BN Chakravorty for his contribution of the topic ‘Infertility’ (Section III) in the book.
History in medicine and eponyms have been presented (Section VI). I personally feel, one
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should know the characters in whose steps we follow while working in the discipline.
While writing ‘Master Pass’, I have moved away from the traditional approach of a textbook,
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with expectation that core knowledge to be covered by a textbook. Attempts have been made
to incorporate much of the available evidences upon which our practice in Obstetrics and
Gynaecology should base.
Master Pass is intended to help medical students, residents aspiring for, as well appearing the
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master examination [MS, MD, DGO (University), DNB, FNB, Fellowship Exit Examination (National
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Board)], MICOG, MRCOG, specialized nurses (BSc, MSc), midwives as well as specialists in the
discipline of Obstetrics and Gynaecology.
I do hope this comprehensive book will be of immense educational resource to the readers.
I do welcome the views of the students/teachers for their suggestions, comments through
our website: www.hiralalkonar.com.
This book is dedicated to all who work relentlessly in Obstetrics and Gynaecology to develop
quality care for women’s health.

Hiralal Konar

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 Acknowledgments
I have consulted many of my esteemed colleagues in the country and abroad, a multitude of
eminent authors, many current evidence-based studies, guidelines and recommendations
particularly RCOG, London; ACOG; WHO; RANZCOG; SOGC. I do sincerely acknowledge my legacy
to all of them including the related authors and publishers.
I am deeply indebted to my esteemed teachers Professor KM Gun, MO, FRCOG, FRCS, FACS;
Professor BN Chakravorty, MO, FRCOG, DSc, Director, Institute of Reproductive Medicine (IRM),

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Kolkata; Prof DC Dutta, MO (Late), author of Textbook of Obstetrics and Textbook of Gynecology.
I sincerely acknowledge the following teachers across the country and abroad for their valuable
feedback to enrich our books. Their comments, suggestions have helped to shape this new

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edition. I hope, I have listed all those who have contributed and apologize if any names have
been missed inadvertently.
Professor Sabaratnam Arulkumaran, St George’s, University of London, President FIGO
(Past); Paul Fogarty, Senior Vice President, RCOG, London; Mr Michael O’Connel, Royal College
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of Physicians, Dublin; Mr. Tony Hollingworth, Queen Mary, University of London; Professor PS
Chakraborty, IPGMER, Kolkata; Professor P Mukherjee, Kolkata Medical College; Professor C Das,
NRSMCH; Professor A Biswas, CNMC, Kolkata; Professor Habibullah, Professor P Desari, JIPMER,
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Puducherry; Professor A Pedicaile, CMC Vellore; Professor A Kriplani, Professor KK Ray, AIIMS, New
Delhi; Professor V Das, KGMU, Lucknow; Professor RL Singh, RIMS, Imphal; Professor Ng Indra
Kumar, Imphal; Professor Santa Singh, NEGRIMS, Shillong; Professor R Chauhan NSCB, Jabalpur;
Prof V Das, PGIMER, Chandigarh; Professor (Mrs) L Das, Professor PC Mahapatra, Professor Maya
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Padhi, Professor S Kanungo, SCBMC, Cuttack; Professor NR Agarwal, Professor LK Pandey, Banaras
Hindu University, Banaras; Professor Ava Rani Sinha, Patna; Professor Hemali Sinha, AIIMS.
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Patna; Professor A Bhaniwad, JSS MCH, Mysore; Professor A Huria GMCH, Chandigarh; Professor
RShrivastava BRDMCH, Gorakhpur; Professor S Murthy Davangare, Karnataka; Professor K Pandey,
GSVMMC, Kanpur; Professor S Minhans, IGMC, Shimla, Himachal Pradesh; Professor R Bulusu,
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MVJMCH, Bengaluru; Professor Jayanthi, Kempegowda Medical College, Bengaluru; Professor S

Rani, Thanjavur MCH, Tamil Nadu. Professor Hemant Deshpande, Professor Himadri Bal, Pune;
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Professor R Ahmed, Dibrugarh; Professor A Goswami, Guwahati; Professor S Dutta, NBMCH,

Siliguri; Professor M Sarkar MMCH, Malda; Professor J Mukherjee, NBMCH, Siliguri; Professor BK
Kanungo, Gangtok; Professor M Pradhan, Tripura; Professor DK Bhowmik, JNMCH, Maharashtra;
Professor Renu Rohatgi, Patna; Professor Gita B Banerjee, Bankura; Professor Farhana Dewan,
Professor Kohinoor Begum, Dhaka; Professor Rokeya Begum, Chittagong; Professor Rowshan Ara
Begum, Professor Sabera Khatun, Dhaka; Professor S Nurjahan Bhuiyan, Chittagong; Professor Jyoti
Bindal, GRMC, Gwalior; Professor Seema Hakim, AMU, Aligarh; Professor RP Wadhwa, GMC, Mewat,
Haryana; Professor Beena Bhatnagar, NIMS, Jaipur; Professor Manpreet Kaur, DMC, Ludhiana;
Professor MG Hiremath, Hubli; Professor MB Bellad, Belgium; Professor Ajith, Kannur; Professor
Malik Goonewardene, University of Ruhuna, Sri Lanka; Professor HR Seneviratne, Colombo, Sri
Lanka; Professor Jyandip Nath, Guwahati; Professor Murali Pai, KMC, Manipal; Professor Nilesh
Dalal, MGMC, Indore; Professor Sudesh Agarwal, SPMC, Bikaner; Professor Pushpa Dahiya, Rohtak,
PIMS; Professor Sumangala, GMC, Calicut; Professor Mary Daniel, PIMS, Puducherry; Professor

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 xiv Manual of Obstetrics and Gynecology for the Postgraduates

Sasikala, SMVMCH, Puducherry; Professor Atiya Sayed, AIMS, J&K; Professor N Chaudhury, HIMS,
Dehradun; Professor Shehnaz Taing, GMC, Srinagar; Professor Abha Singh, LHMC, Delhi; Professor
S Nanda, PGI, Rohtak; Professor N Chutani, SMC and Professor SS Gulati, SMC, Greater Noida;
Professor Raksha Arora, SMC, Ghaziabad; Professor Jaya Chaturvedi, AIIMS, Rishikesh; Professor
Abha Singh, JNMCH, Raipur; Professor Rehana Nazam, TMU, Moradabad; Professor Bharati Misra,
MKCG, Brahmapur; Professor Neelam Pradhan, Professor Meeta Singh, Tribhuvan University and
Teaching Hospital (TU and TH), Kathmandu; Professor S Mishra, VMC, Nepal; Professor Sujatha
Sharma, GMC, Amritsar; Professor Madhu Nagpal, SGRDMC, Amritsar; Professor Promila Jindal;
PIMS, Jalandhar.
I would like to extend my thanks to many of the readers including the residents and students,

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who have contacted me with suggestions and seeking clarifications through e-mails. Their inputs
have been valuable and are much appreciated. I wish I could mention their names individually.
I am extremely grateful to Mrs Madhusri Konar, MA, BEd for all her insightful secretarial

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accomplishment in support of the book. I thank Dr Dorothy Dessa for her assistance throughout.
I sincerely thank Md Jakir Hossain, MSc, BEd for his diligent and expert work to accomplish the
entire Second Edition of this book.
I sincerely thank Shri JP Vij (Group Chairman), Mr Ankit Vij (Group President), Ms Chetna
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Malhotra Vohra (Associate Director–Content Strategy), Mr PS Ghuman (AGM Production), Jaypee
Brothers Medical Publishers (P) Ltd and production staff to maintain the commitment for this
book.
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 Contents
Section 1:  Obstetrics

1. Objective Structured Clinical Examination in Obstetrics..........................................................3

Case 1:  Severe Pre-eclampsia  3
Case 2:  Counseling  6

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Case 3:  Ectopic Pregnancy  7
Case 4:  Abruptio Placentae; Placenta Previa  10
Case 5:  Unstable Lie  12

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Case 6: Nonprogress of Labor  13
Case 7:  Cardiotocography-I  15
Case 8:  Cardiotocography-II  18


Case 9:  Management of Labor (Partograph-I)  20
Case 10:  Management of Labor (Partograph-II)  22
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Case 11:  Primary Postpartum Hemorrhage  25
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Case 12:  Secondary Postpartum Hemorrhage  27
Case 13:  Surgical Management of Postpartum Hemorrhage (PPH)  29
Case 14:  Pregnancy and Labor in a Woman with Prior Cesarean Delivery  36
Case 15:  Puerperal Pyrexia  37
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Case 16:  Multiple Pregnancy  38

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Case 17: Neural Tube Defects  40

Case 18:  Anencephaly  41
Case 19:  Hydrocephalus  43
Case 20:  Cystic Hygroma  44
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2. Self-Assessment in Obstetrics............................................................................................................. 46
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Section 2:  Gynecology

3. Objective Structured Clinical Examination (OSCE) in Gynecology.................................107

Case 1:  Polycystic Ovarian Syndrome (PCOS)  107
Case 2:  Endometriosis  110
Case 3:  Primary Amenorrhea  115
Case 4:  Secondary Amenorrhea  118
Case 5:  Pelvic Pain  119
Case 6:  Infertility  120
Case 7:  Hematocolpos  123
Case 8:  Infertility  124

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 xvi Manual of Obstetrics and Gynecology for the Postgraduates

Case 9:  Hydatidiform Mole  126

Case 10:  Endometriosis  129
Case 11:  Cervical Fibroid  130
Case 12:  Carcinoma Cervix  131
Case 13:  Carcinoma Endometrium  135
Case 14:  Carcinoma of the Ovary  138
Case 15:  Carcinoma Cervix  141
Case 16:  Menopause and Hormone Replacement Therapy (HRT)  144
Case 17:  Carcinoma Cervix  146

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Case 18:  Hysterectomy and Oophorectomy  148
Case 19:  Postmenopausal Bleeding  149
Case 20:  Inherited Cancers and the Management  152

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4. Self-Assessment in Gynecology........................................................................................................154

Section 3:  Obstetric Discussion

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5. Preterm Birth and Management Issues........................................................................................225
6. Gestational Diabetes Mellitus...........................................................................................................230
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7. Obesity in Pregnancy.............................................................................................................................237
8. Monochorionic Twin Pregnancy......................................................................................................242
9. Prenatal Screening for Fetal Abnormalities...............................................................................250
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10. Severe Pre-eclampsia and Eclampsia.............................................................................................258

11. HELLP Syndrome......................................................................................................................................263
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12. Cesarean Section......................................................................................................................................266

13. Placenta Previa, Placenta Previa Accreta and Vasa Previa..................................................271
14. Perimortem Cesarean Section...........................................................................................................276
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15. Puerperal Sepsis.......................................................................................................................................279

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16. Maternal Near Miss.................................................................................................................................285

17. Cesarean Delivery on Maternal Request......................................................................................289
18. Classification of Evidence Levels and Grades of Recommendations.............................294

Section 4:  Gynecology Discussion

19. Recurrent Miscarriage (First and Second Trimesters)............................................................299

20. Tubal Ectopic Pregnancy......................................................................................................................307
21. Cervical Insufficiency (Incompetence)..........................................................................................310
22. Heavy Menstrual Bleeding..................................................................................................................314
23. Urinary Incontinence.............................................................................................................................319

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 Contents xvii

24. Polycystic Ovary Syndrome................................................................................................................323

25. Male and Female Sterilization...........................................................................................................327
26. Gestational Trophoblastic Disease.................................................................................................334
27. Carcinoma of the Endometrium (Early Stage Diseases).......................................................339
28. Pregnancy of Unknown Location.....................................................................................................343
29. Abnormal Uterine Bleeding................................................................................................................348
30. Endoscopy in Gynecology (Laparoscopic Surgery).................................................................352
31. Robotic Surgery in Gynecology........................................................................................................355

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Section 5:  Infertility and Assisted Reproductive Technology (ART)

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32. Current Concept in Physiology of Ovulation.............................................................................361
33. Infertility Evaluation and Management.......................................................................................367
34. Female Infertility.....................................................................................................................................370
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35. Male Infertility...........................................................................................................................................383
36. Assisted Reproductive Technology (ART)...................................................................................388
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37. Management Strategies for Low Responder Woman............................................................396
38. Third Party Reproduction....................................................................................................................400

Section 6:  Maternal Medicine (Short Obstetric Reviews)

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39. Obstetric Case Presentation...............................................................................................................405

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40. Anemia in Pregnancy.............................................................................................................................407

41. Hemoglobinopathy................................................................................................................................411
42. Sickle Cell Disease in Pregnancy......................................................................................................414
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43. Thyroid Dysfunction in Pregnancy.................................................................................................418

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44. Heart Disease in Pregnancy................................................................................................................425

45. Gestational Age and Cesarean Delivery.......................................................................................429
46. Place of Thromboprophylaxis during Pregnancy....................................................................432
47. External Cephalic Version...................................................................................................................434
48. Diminished Fetal Movements............................................................................................................436
49. Transfusion in Obstetrics.....................................................................................................................441
50. Obstetric Cholestasis.............................................................................................................................445
51. Diabetic Nephropathy...........................................................................................................................446
52. Renal Transplant......................................................................................................................................448
53. Non Hemorrhagic Shock in Obstetrics..........................................................................................450

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 xviii Manual of Obstetrics and Gynecology for the Postgraduates

Section 7:  Short Reviews in Gynecology

54. Place of Prophylactic Salpingectomy or Salpingo-oophorectomy

in Current Gynecologic Practice.......................................................................................................463
55. Endometrial Carcinoma........................................................................................................................466
56. Bariatric Surgery in Gynecology and Obstetrics......................................................................469
57. Fertility Conserving Options for Women with Gynecologic Malignancies.................473
58. Fertility Conserving Options for Women with Cervical Cancer........................................476

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59. Fertility Conserving Options for Women with Endometrial Cancer...............................478
60. Advances in Contraception................................................................................................................480

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61. Interventional Radiology in Obstetrics and Gynecology.....................................................487
62. Surgical Site Infection...........................................................................................................................489
63. Abnormal Uterine Bleeding: Investigations and Management Issues..........................491
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64. Subfertility and Pelvic Endometriosis...........................................................................................497
65. Medical Methods of Termination of Pregnancy.......................................................................499
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Section 8:  Intrapartum Electronic Fetal Monitoring

66. Fetal Response in Labor.......................................................................................................................503

67. Fetal Heart Rate Patterns.....................................................................................................................505
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68. Fetal ECG......................................................................................................................................................509

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69. Management of Nonreassuring Fetal Status (NRFS)..............................................................511

Section 9:  Perinatal Medicine

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70. Immunization during Pregnancy and Breastfeeding............................................................517

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71. Noninvasive Prenatal Testing for Fetal Chromosomal Abnormality.............................521

72. Congenital Perinatal and Neonatal Infections..........................................................................525
73. Congenital HIV Infection and AIDS.................................................................................................527
74. Varicella Zoster Virus (Chickenpox) Infection...........................................................................530
75. Rubella in Pregnancy.............................................................................................................................532
76. Cytomegalovirus Infection in Pregnancy....................................................................................534
77. Viral Hepatitis in Pregnancy...............................................................................................................536
78. Listeriosis in Pregnancy........................................................................................................................540
79. Toxoplasmosis in Pregnancy.............................................................................................................542
80. Group B Streptococci Infection in Pregnancy............................................................................545

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 Contents xix

Section 10:  MRCOG Examination

81. PART I MRCOG Examination...............................................................................................................549

82. PART II MRCOG Examination.............................................................................................................574

Section 11:  MRCOG (EMQs)

83. Extended Matching Questions (EMQs)..........................................................................................585

rs
Section 12:  In Whose Footsteps We Follow

84. History in Obstetrics and Gynecology...........................................................................................597

he
Index.........................................................................................................................................................................603

ot
Br
e
y pe
Ja

Prelims.indd 19 11-07-2016 14:30:35

 Abbreviations
AACE American Association of Clinical BPP Biophysical Profile
Endocrinology BPV Bioprosthetic Heart Valves
AC Abdominal Circumference BSO Bilateral Salpingo-oophorectomy
ACA Anticardiolipin Antibodies BTB Breakthrough Bleeding
ACE Angiotensin Converting Enzyme CBAVD Congenital Bilateral Absence of Vas
ACHOIS Australian Carbohydrate Intolerance Deferens
Study

rs
CC Clomiphene Citrate
ACOG American College of Obstetricians and CDC Centers for Disease Control and
Gynecologists Prevention
ACS Acute Chest Syndrome CDMR Cesarean Delivery on Maternal Request

he
ACTH Adrenocorticotropic Hormone CECT Contrast-enhanced Computed
ADA American Diabetes Association Tomography
AEDF Absent End-diastolic Flow CEMACH Confidential Enquiry into Maternal and
AEDs Antiepileptic Drugs Child Health
AFASS Affordable, Feasible, Accessible,
Sustainable and Safe
ot cff-DNA
CFTR
Cell-free Fetal DNA
Cystic Fibrosis Transmembrane
Regulator
AFC Antral Follicle Count
Br
CGH Comparative Genomic Hybridization
AFE Amniotic Fluid Embolism
CIN Cervical Intraepithelial
AFP Alpha-fetoprotein
CIS Carcinoma in situ
AFS American Fertility Society CMV Cytomegalovirus
AIDS Acquired Immune Deficiency CNS Central Nervous System
Syndrome
e

CO Combined Obesity
ALT Alanine Transaminase COCs Combine Oral Contraceptives
AMH Anti-Müllerian Hormone
pe

COS Controlled Ovarian Stimulation

APA Antiphospholipid Antibody COX Cycloxygenase
APAS Antiphospholipid Antibody CPD Cephalopelvic Disproportion
Syndrome CPR Cardiopulmonary Resuscitation
API Association of Physicians of India CPR Cumulative Pregnancy Rate
y

ARM Artificial Rupture of the Membranes CPT Complete Perineal Tear

ART Assisted Reproductive Technology CRH Corticotropin-releasing Hormone
Ja

ASRM American Society for Reproductive CRS Congenital Rubella Syndrome

Medicine CS Cesarean Section
AST Aspartate Transaminase CSF Cerebrospinal Fluid
CT Computed Tomography
ASTEC A Study in the Treatment of
CTG Cardiotocography
Endometrial Cancer
CTPA Computed Tomographic Pulmonary
ATA American Thyroid Association
Angiography
BBT Basal Body Temperature CVD Cardiovascular Disease
BMD Bone Mineral Density CVS Chorionic Villus Sampling
BMI Body Mass Index CZ Carbimazole
BP Blood Pressure D&C Dilatation and Curettage
BPAD Bipolar Affective Disorder DF Dominant Follicle
BPD Biparietal Diameter DFMC Daily Fetal Movement Count
BPM Beats per Minute DHEAS Dehydroepiandosterone Sulphate

Prelims.indd 21 11-07-2016 14:30:35

 xxii Manual of Obstetrics and Gynecology for the Postgraduates

DIC Disseminated Intravascular HC Head Circumference

Coagulation hCG Human Chorionic Gonadotropin
DIPSI Diabetes in Pregnancy Society of HCV Hepatitis C Virus
India HDFN Hemolytic Disease of the Fetus and
DMPA Depot Medroxyprogesterone Newborn
Acetate HDL High Density Lipoprotein
DPG Diphosphoglycerate HDR High Dose Radiation
HDU High Dependency Unit
DTIC Distal Tubal Intraepithelial
HFEA Human Fertilization and Embryology
Carcinoma
Authority
DVT Deep Vein Thrombosis HELLP Hemolysis, Elevated Liver Enzymes,
Low Platelet count

rs
E Eclampsia
E2 Estradiol hGH Human Growth Hormone
EC Endometrial Curettage HGSOC High-grade Serous Ovarian Cancer
ECG Electrocardiogram HIV Human Immunodeficiency Virus

he
ECV External Cephalic Version HLA Human Leukocyte Antigen
EGF Epidermal Growth Factor HMB Heavy Menstrual Bleeding
EOCs Epithelial Ovarian Cancers HMG Human Menopausal Gonadotropin
EPAU Early Pregnancy Assessment Unit HPL Human Placental Lactogen
ESHRE European Society of Human
Reproduction and Embryology 
ot HPV
HRT
HWY
Human Papilloma Virus
Hormone Replacement Therapy
Hundred Woman Years (Pregnancy)
FBC Full Blood Count
Br
FDP Fibrinogen Degradation Products IADPSG International Association of Diabetes
FET Frozen Embryo Transfer and Pregnancy Study Groups
FFP Fresh Frozen Plasma IAP Intrapartum Antibiotic Prophylaxis
FGR Fetal Growth Restriction ICD International Statistical Classification
FIGO International Federation of of Disease
e

Gynaecology and Obstetrics ICSI Intracytoplasmic Sperm Injection

FISH Fluorescence in situ Hybridization ICU Intensive Care Unit
pe

FL Femur Length IDDM Insulin-dependent Diabetes Mellitus

FOGSI Federation of Obstetricians and IFA Immunofluorescence Assay
Gynaecologists of India IGF Insulin-like Growth Factor
FSH Follicle Stimulating Hormone IPV Inactivated Polio Vaccine
ITP
y

FVS Fetal Varicella Syndrome Idiopathic Thrombocytopenic

Purpura
GBS Group B Streptococci
Ja

ITS Indian Thyroid Society

GDM Gestational Diabetes Mellitus ITU Intensive Therapy Unit
GIFT Gamete Intrafallopian Transfer IUCD Intrauterine Contraceptive Device
GIT Gastrointestinal Tract IUD Intrauterine Device
GnRH Gonadotropin Releasing Hormone IUFD Intrauterine Fetal Demise
GO Generalized Obesity IUGR Intrauterine Growth Restriction
GSI Genuine Stress Incontinence IUI Intrauterine Insemination
GTD Gestational Trophoblastic Disease IVC Inferior Vena Cava
GTN Gestational Trophoblastic Neoplasia IVF-ET In vitro Fertilization and Embryo
HAART Highly Active Antiretroviral Therapy Transfer
HAPO Hyperglycemia and Adverse IVH Intraventricular Hemorrhage
Pregnancy Outcome IVIG Intravenous Immunoglobulin
HAV Hepatitis A Virus LAC Lupus Anticoagulant
HbF Fetal Hemoglobin LARVT Laparoscopic Assisted Radical
HBV Hepatitis B Virus Vaginal Trachelectomy

Prelims.indd 22 11-07-2016 14:30:35

 Abbreviations xxiii

LAVH Laparoscopic Assisted Vaginal MTX Methotrexate

Hysterectomy MVA Manual Vacuum Aspiration
LBC Liquid-based Cytology MVP Maximum Vertical Pocket
LDH Lactate Dehydrogenase
NEC Necrotizing Enterocolitis
LDL Low Density Lipoprotein
NICE National Institute for Health and
LFT Liver Function Test
Clinical Excellence
LGSOC Low-grade Serous Ovarian
NICHD National Institute of Child Health and
Cancer
Human Development
LH Luteinizing Hormone
NICU Neonatal Intensive Care Unit
LLETZ Large Loop Excision of the
NIPT Noninvasive Prenatal Testing
Transformation Zone
NSAIDs Nonsteroidal Antiinflammatory
LMP Last Menstrual Period

rs
Drugs
LMWH Low Molecular Weight Heparin
NTD Neural Tube Defects
LNG-IUD Levonorgestrel-intrauterine Device
LNG-IUS Levonorgestrel-intrauterine System OA Occiput Anterior

he
LOA Left Occiput Anterior OAB Overactive Bladder
LOD Laparoscopic Ovarian Drilling OAT Oligoasthenoteratozoospermia
LOS Laparoscopic Ovarian Surgery OGTT Oral Glucose Tolerance Test
LPD Luteal Phase Defect OHSS Ovarian Hyperstimulation Syndrome
LSCS
LUF
LVSI
Lower Segment Cesarean Section
Luteinized Unruptured Follicle
Lymphovascular Space Involvement
ot OP
OSCE
Occiput Posterior
Objective Structured Clinical
Examination
Br
OTA Oligoasthenoteratozoospermia
MAHA Microangiopathic Hemolytic Anemia
MAP Mean Arterial Pressure PAPP-A Pregnancy Associated Plasma
MC Monochorionic Protein-A
MCA Middle Cerebral Artery PCOS Polycystic Ovarian Syndrome
MCA-PSV Middle Cerebral Artery Peak Systolic PCR Polymerase Chain Reaction
e

Velocity PDA Patent Ductus Arteriosus

MCDA Monochorionic Diamniotic PE Pulmonary Embolism
pe

MCTP Monochorionic Twin Pregnancy PESA Percutaneous Epididymal Sperm

MDTA Multidisciplinary Team Approach Aspiration
MEA Microwave Endometrial Ablation PET Positron Emission Tomography
MFR Monthly Fecundity Rate PGD Prenatal Genetic Diagnosis
y

MgSO4 Magnesium Sulfate PID Pelvic Inflammatory Disease

MHV Mechanical Heart Valves PMB Postmenopausal Bleeding
Ja

MMK Marshall-Marchetti-Krantz PMS Premenstrual Syndrome

MMR Maternal Mortality Rate POD Pouch of Douglas
MNM Maternal Near Miss POF Premature Ovarian Failure
MOM Multiple of the Median POP Pelvic Organ Prolapse
MPGS Massively Parallel Genomic POP Progestin only Pill
Sequencing PORTEC Postoperative Radiation Therapy in
MRg FUS MR-guided Focused Ultrasound Endometrial Cancer
MRI Magnetic Resonance Imaging PPA Primary Peritoneal Adenocarcinoma
MRSA Methicillin-resistant Staphylococcus PPIUCD Postpartum Intrauterine
Aureus Contraceptive Devices
MSAFP Maternal Serum Alpha-fetoprotein PRBCs Packed Red Blood Cells
MTCT Mother-to-child Transmission PRES Posterior Reversible Encephalopathy
MTHFR Methylenetetrahydrofolate Syndrome
Reductase PROM Premature Rupture of Membranes
MTP Medical Termination of Pregnancy PSOC Papillary Serous Ovarian Cancer

Prelims.indd 23 11-07-2016 14:30:35

 xxiv Manual of Obstetrics and Gynecology for the Postgraduates

PSP1 Pregnancy Specific Protein 1 TIC Tubal Intraepithelial Carcinoma

PSTT Placental Site Trophoblastic Tumor TLH Total Laparoscopic Hysterectomy
PTD Postpartum Thyroid Dysfunction TNFs Tumor Necrosis Factors
PT Prothrombin Time TOT Transobturator Tape
PTT Partial Thromboplastin Time TPO Thyroid Peroxidase
PTU Propylthiouracil TPOAbs Thyroid Anti-TPO Antibodies
PUL Pregnancy of Unknown Location TRAP Twin Reverse Arterial Perfusion
PVD Peripheral Vascular Disease
TRH Thyrotropin Releasing Hormone
RALH Robotic Assisted Laparoscopic TSHRAbs Thyrotropin Receptor
Hysterectomy Autoantibodies
RCOG Royal College of Obstetrics and TTN Transient Tachypnea of the Newborn

rs
Gynecology TTTS Twin-twin Transfusion Syndrome
RCTs Randomized Controlled Trials TVS Transvaginal Sonography
RDS Respiratory Distress Syndrome TVT Tension-free Vaginal Tape

he
RFM Reduced Fetal Movements TZ Transformation Zone
RMI Risk of Malignancy Index
ROMA Risk of Ovarian Malignancy UAE Uterine Artery Embolization
Algorithm UE3 Unconjugated Estriol
RVT
SAMM
Radical Vaginal Trachelectomy
Severe Acute Maternal Morbidity
ot
UFH
UI
USG
Unfractionated Heparin
Urinary Incontinence
Ultrasonography
SCD Sickle Cell Disease
Br
SCJ Squamocolumnar Junction UTI Urinary Tract Infections
SGA Small for Gestational Age VaIN Vaginal Intraepithelial Neoplasia
SHBG Sex Hormone Binding Globulin VBAC Vaginal Birth After Cesarean
SI Shock Index VBAC-TOL Vaginal Birth After Cesarean-Trial of
SIL Squamous Intraepithelial Lesion
e

Labor
SIS Saline Infusion Sonography
VCB Vaginal Cuff Brachytherapy
SLE Systemic Lupus Erythematosus
pe

VEGF Vascular Endothelial Growth Factor

SSI Surgical Site Infections
VIA Visual Inspection using Acetic Acid
STIs Sexually Transmitted Infections
SUI Stress Urinary Incontinence VKA Vitamin K Antagonist
SUZI Subzonal Insemination VTE Venous Thromboembolism
y

VVF Vesicovaginal Fistula

TAH Total Abdominal Hysterectomy VZIG Varicella Zoster Immunoglobulin
Ja

TBEA Thermal Balloon Endometrial VZV Varicella Zoster Virus

Ablation
TCRE Transcervical Resection of WHO World Health Organization 
Endometrium WLTC Women with Life-threatening
TEC Thromboembolic Complications Condition

Prelims.indd 24 11-07-2016 14:30:35

 36 Assisted Reproductive
Technology (ART)

r s
MCQs

he
Q.1 Regarding gonadotropin stimulation for controlled ovarian stimulation (COS):
a. Gonadotropin stimulation could be done either using follicle-stimulating hormone
(FSH) or human menopausal gonadotropin (HMG)
ot
b. Monitoring with serum estradiol levels with transvaginal ultrasound is essential in all
assisted reproductive technology (ART) cycles
c. Less aggressive stimulation increases cycle cancellation rates
Br
d. Pretreatment therapy with combined oral contraceptives (COCs) reduces pregnancy
rates
e. Supportive treatment in women with polycystic ovarian syndrome (PCOS) may prevent
ovarian hyperstimulation syndrome (OHSS)
ee

Ans. a. T b. F
c. F d. F
e. T
Q.2 Use of gonadotropin-releasing hormone (GnRH) analogs and ART cycles:
yp

a. GnRH agonists cause immediate down regulation

b. GnRH agonists long protocols have better pregnancy rates
c. GnRH antagonist use results of higher pregnancy rate
Ja

d. Daily dose GnRH agonists have higher pregnancy rate

e. GnRH analogs suppress premature luteinizing hormone (LH) surge
Ans. a. F b. T
c. F d. T
e. T
Q.3 In ART cycles:
a. Blastocyst transfer has lower implantation failure
b. Three embryo transfer is optimum in women age, < 35 years
c. Embryo cryopreservation facilitates the multiple transfer cycles from single oocyte
retrieval
d. Overall success rates of fertility treatment following in vitro fertilization (IVF) and
embryo transfer (ET) is 35%
e. Live birth rate per cycle from donor oocyte depends on recipient’s age

Chapter 36.indd 388 08-07-2016 12:45:59

 Assisted Reproductive Technology (ART) 389

Ans. a. T b. F
c. T d. T
e. F
ART encompasses all the procedures that involve manipulation of gametes outside the body for
the treatment of infertility. The procedures are exclusively carried out in tertiary care unit.

Most Frequently and Currently Practiced ARTs

„„ In vitro fertilization and embryo transfer (IVF-ET)
„„ Intracytoplasmic sperm injection (ICSI)
„„ Intrauterine insemination (IUI).
By strict criteria of definition, IUI is not included under the heading of ART, as the procedure

s
does not involve in direct retrieval of oocytes from the ovaries. However, extracorporeal male

r
gamete manipulation and superovulation of the female partner is involved in this procedure.
Considering these issues, majority of the IVF clinics consider IUI as one of the technologies of

he
assisted reproduction. Other procedures of ART are—gamete intrafallopian transfer (GIFT),
zygote intrafallopian transfer (ZIFT), subzonal insemination (SUZI) and peritoneal oocyte and
sperm transfer (POST).
Steps of Assisted Reproductive Technology
„„ Patient counseling and selection
ot
Pretreatment therapy with COCs to synchronize follicular growth and to prevent ovarian cysts
Br
„„
„„ Controlled ovarian stimulation
 GnRH analog down regulation followed by gonadotropin stimulation
„„ Ovulation triggering with human chorionic gonadotropin (hCG) or GnRH agonist
„„ Oocyte retrieval (see Figs 36.1 and 36.2)
ee

„„ Insemination (IVF or ICSI)

„„ In vitro embryo culture in nutrient media and incubation in CO2 incubator
 Embryo transfer (not more than 3) back into mother’s uterus between D2 and D5 at the
cleaving embryo (4–8 cell) stage or blastocyst stage
yp

 Cryopreservation of surplus embryos

„„ Luteal support mostly with micronized progesterone
„„ Serum βhCG estimation D14 postembryo transfer.
GnRH agonist: It has long half-life and increased receptor binding affinity. Initial 7 days of ad-
Ja

ministration, GnRH agonist exerts a flare effect due to upregulation of GnRH receptors. This is fol-
lowed by receptor desensitization resulting in fall in the level of gonadotropins (down regulation).
Ultimately with prolonged use, GnRH agonist induces menopause-like state (low estradiol levels).
GnRH agonist are available either depot or daily use. Intramuscular/subcutaneous (IM/SC) or
intranasal route can be used. The GnRH agonist protocols may be long or short. Long protocols
may again be long follicular or long luteal down regulation.
In long luteal down-regulation protocol, GnRH agonist is started in the luteal phase, D21 of the
previous cycle (See Dutta’s Textbook of Gynecology, 7th Edition, p. 205). After 10–14 days of GnRH
agonist therapy on D2 of subsequent menstrual cycle (whichever is earlier), a pelvic ultrasound
and serum estradiol levels are done to confirm suppression. Thereafter, gonadotropin stimulation
is begun. Use of single-dose depot GnRH agonist is associated with higher gonadotropin (dose
and duration) requirement and has lower pregnancy rates when compared with daily GnRH
agonist formulation.

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 390 Manual of Obstetrics and Gynecology for the Postgraduates

GnRH antagonist (Cetrorelix, ganirelix) (See Dutta’s Textbook of Gynecology, 7th Edition,
Ch 32, p. 435): GnRH antagonists have no agonist action. Suppression to GnRH receptor and
desensitization effect is immediate. There is immediate suppression of FSH and LH. GnRH
antagonist is started on D4–D7 of stimulation in ART cycles. This schedule reduces the risks of
premature LH surge. This also allows endogenous FSH-mediated follicular recruitments prior to
GnRH suppression.
GnRH antagonists: Protocols may be fixed or flexible.
„„ Fixed protocol uses the antagonist on D4, D5, D6 or D7 of stimulation irrespective of follicular
growth1
„„ Flexible protocol: Antagonist is used when the leading follicle has reached 12–16 mm or

s
when serum estradiol level has reached above 600 pg/mL.
Till date, there is no randomized control trial to establish the superiority of one protocol over

r
the other.2 However, most of the centers have shifted to the antagonist protocol. Advantages

he
are: (a) Shorter duration of therapy and (b) Simplicity of protocol.
Other protocols are flare, ultrashort, microdose and modified natural.

Comparison of GnRH agonists to GnRH antagonists

ot
(See Dutta’s Textbook of Gynecology, 7th Edition, Ch 32, p. 434)
Use of GnRH antagonist is associated with lower duration of stimulation, lower dose of
gonadotropins and reduced rates of OHSS. According to 27 randomized controlled trials (RCTs),
Br
both the regimens have similar rates of production of good quality embryos.3 However, clinical
pregnancy rates are higher by 4.7% in agonist compared to antagonist cycles.4
What is early LH surge? How it causes premature follicular luteinization?
Due to high estradiol level in early follicular phase (as a consequence of gonadotropin stimulation),
ee

early LH surge occurs. GnRH agonist or antagonist is used to suppress it. Spontaneous ovulation
prior to oocyte retrieval is observed in about 16% of nonsuppressed cycles. Premature LH surge
occurs usually 5–7 days after starting follicular stimulation. Overall premature luteinization
has been observed in 7–35% of cases. The possible mechanism of premature luteinization are:
yp

(a) Incomplete pituitary desensitization, (b) increased receptor sensitivity of granulosa cells to LH,
(c) innate poor responder and (d) total amount of progesterone secreted from multiple follicles
equals to the late follicular phase.
Ja

The main disadvantage of premature luteinization is endometrial advancement. Adverse

effect on quality of oocyte or embryo has not been remarkably observed.
The different measures to overcome the problems of premature follicular luteinization are:
„„ Triggering ovulation at the appropriate time
„„ Using less aggressive stimulation protocols
„„ Cryopreservation of oocytes and embryos
„„ Use of antiprogesterone (mifepristone) at the time when hCG is given (less commonly used
procedure).
Follicular growth and maturation: Initial growth of preantral and small antral follicles is
independent of any hormone. Small antral follicles > 2 mm become responsive to FSH stimulation.
The follicles become recruitable in the late luteal phase of the cycle. Preceding ovulation, FSH
induces the receptors for LH on the granulosa cells once the antral follicle attains the size of
10 mm or more. At that state, LH can induce FSH-like actions on the granulosa cells (contrary to

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 Assisted Reproductive Technology (ART) 391

the 2-cell, 2-gonadotropin theory) and also stimulate the enzyme aromatase. Human menstrual
cycles have two waves of follicular development. The first wave is the minor wave that occurs
immediately after the ovulation in the preceding cycle. Once progesterone is available following
ovulation, all the follicles, except the dominant one, undergo atresia. The subsequent wave is
the major wave that occurs during the time of menstruation of the previous cycle. During this
time, the dominant follicle is selected and other follicles are deprived of their growth. The follicle
having the maximum number of FSH receptors and higher level of E2—androgen ratio in the
follicular microenvironment is recruited as the dominant one. The dominant follicle is recruited
by the cycle D6 or D7 which coincides with an estradiol rise that inhibits FSH.
Controlled ovarian stimulation (COS): Synchronous growth of dominant and codominant

s
follicle(s) is achieved by gonadotropin stimulation. The main hormone in this process is the FSH.

r
Most investigators suggest that the optimum number of retrieved oocytes in a given cycle is

he
between 5 and 15. The optimal level of estradiol at the time of hCG administration is between
70 and 140 pg/mL per follicle. Estradiol monitoring may not be that essential in the ART cycle.5
Ultrasound monitoring alone may be adequate to maximize pregnancy and live birth rates.6
Cycle cancellation in normal responders occurs in up to 6% of the cycles because of inadequate
ot
response. Cycle cancellation increases with advancing age and is decreased with ovarian reserve.
It can be minimized by increasing the dose of gonadotropins. However, maximum upper limit of
gonadotropin dose is 450 IU beyond which no benefit is observed.
Br
Gonadotropin stimulation could be done either using FSH or with HMG: A systematic
review of 14 RCTs found no significant differences between HMG and urinary FSH in rates per
cycle pregnancy, multiple pregnancy, miscarriage, ovulation or hyperstimulation.7 However, risk
of OHSS was less with FSH compared to HMG. Similarly, no significant difference in the outcome
ee

was observed when urinary FSH was compared with recombinant FSH.8
However, recent studies have shown that HMG use is associated with higher androgen and
lower progesterone levels on the day of hCG trigger for ovulation. This indicates a more favorable
endocrine profile with HMG compared to FSH.9
yp

Less aggressive stimulation reduces cycle cancellation rate: The problems of premature
luteinization and lower pregnancy rates are encountered when more aggressive FSH stimulation
protocols are used. COCs given for 28 days prior to GnRH analogs, can give some benefits. It helps
Ja

in cycle regularity, synchronizes follicular development, prevents premature LH surge, reduces

the incidence of ovarian cysts and hyperstimulation syndrome. More importantly, it reduces the
cycle cancellation.
Therapy schedule of COCs for antagonist cycles: COS is to begin 2–5 days after stopping
of COCs (irrespective of menses). For long agonist protocols, the agonist overlaps the last 5 days
of COC pills followed by start of COS on D2 or D3 of withdrawal bleeding. COCs pretreatment
during GnRH agonist cycles is associated with higher pregnancy rates.10
Supportive medications have been used with some benefits. Prophylactic antibiotics
(doxycycline or azithromycin) are of help when subclinical infection is thought of. Glucocorticoids
during peri-implantation period may improve pregnancy rates in women with autoimmune
disease, assisted hatching or with advanced age. Metformin has been shown to prevent ovarian
hyperstimulation (OHSS) in PCOS patients and is of benefit.

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 392 Manual of Obstetrics and Gynecology for the Postgraduates

Growth and maturation of oocyte and ovulation (Figs 36.1A and B): In natural cycle, meiosis-I
is completed just before ovulation. The oocyte will extrude the first polar body and the oocyte-
cumulus complex will detach from the ovarian wall and ovulation will occur.
Ovulation triggering in ART: It is done when at least two follicles are 17–18 mm or larger
in diameter (but <24 mm), with endometrial thickness 8 mm or more is observed. Recombinant
hCG 250 µg SC or urinary hCG 10,000 IU is given. When there is the risks of OHSS, GnRH agonist
can be given in place of hCG in antagonist protocol or recombinant LH can be given for hCG in
agonist protocol.
Oocyte retrieval is performed by transvaginal ultrasound-guided needle aspiration. Each
follicle is punctured and the follicular fluid is aspirated. In Kolkata, Institute of Reproductive
Medicine protocol, intravenous conscious sedation is used. Prophylactic antibiotic (augmentin

s
and metronidazole) is given. Oocyte retrieval is usually done 34–36 hours after the hCG injection.

r
Luteal support (See Manual of Obstetrics and Gynecology for the Postgraduates, p. 121, 389) is
started after embryo transfer.

he
In vitro fertilization insemination: 100,000–800,000 motile sperm/mL per oocyte is used.
Processed sperm are incubated in media for 3–4 hours for sperm capacitation and acrosome
reaction. Before insemination, retrieved oocytes are cultured in media.
ot
Embryo culture: Assessment of embryo development is done after 15–20 hours of insemination
or ICSI. Fertilization is characterized by the presence of two pronuclei and extrusion of second
polar body. After another 24–30 hours, embryos are examined for cleavage. First embryo cleavage
Br
occurs about 21 hours after the fertilization, subsequent divisions occur every 12–15 hours up
to the 8 cell stage on 3rd day of embryo development. Compaction to form the 16 cell morula
occurs on 4th day of embryo development. Blastocyst formation with differentiation of inner cell
mass and trophectoderm is completed on D5 or D6.
Blastocyst transfer is observed to have lower implantation failure, higher pregnancy rate
ee

and higher live birth rate (32–42%) than cleavage stage transfer.11

Embryo Morphology and Selection of Embryo for Transfer

Cleavage stage embryo with normal development is characterized by—early cleavage (2 cells)
yp

on D1, 4 cells on D2, and 8 cells on D3. About 10% or less number of blastomeres should have
fragmentation.
Ja

A B

Figs 36.1A and B:  A. Very immature oocyte: Tightly packed cumulus and corona, granular ooplasm, presence
of germinal vesicle and absence of first polar body (FPB); B. Mature oocyte: Well-expanded cumulus, sun
burst-like corona, clear ooplasm and FPB in perivitelline space (PVS)

Chapter 36.indd 392 08-07-2016 12:46:00

 Assisted Reproductive Technology (ART) 393

s
A

r
Figs 36.2A to D:  Embryos are divided into four

he
types depending upon the extent of fragmentation.
C
Type-A is the best and Type-D is the worst.
Type-A:  Minimal volume of fragmentation
associated with one blastomere.
Type-B:  Localized fragmentation mainlyot
occupying the periphery of the blastomeres.
Type-C:  Small fragmentation speckled in all the
Br
blastomeres over the embryo.
Type-D:  Large volume of fragmentation in all
the blastomeres. D

The blastomere size should be regular and there should be no multinucleation. Scoring of
ee

blastocysts: Scale 1 (worst) to scale 6 (best), is done by Gardner and Schoolcraft. The trophectoderm
in a grade 6 blastocyst has completely escaped or hatched from the zona. Similarly, the inner cell
mass is graded from A to C depending upon tightness and cellularity (A is the best). Trophectoderm
is graded from A to C based on cohesiveness and cellularity (A is the best) (Figs 36.2A to D).
yp

Morphological Assessment of Embryo Quality

A good quality embryo is considered with the following morphological characters:
„„ All the blastomeres’ size and shape should be almost equal
Ja

„„ Blastomeres should occupy almost whole of the space within the zona pellucida
„„ There should be no multinucleation
„„ The blastomeres should appear transparent with clear cytoplasm (less fragmentation).
Table 36.1:  Number of embryo transfer [American Society for Reproductive Medicine
(ASRM-2013)]

Age (years) Embryo transfer

<35 1 (maximum 2)
35–37 2 (maximum 3)
38–40 3 (maximum 4)
41–42 5

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 394 Manual of Obstetrics and Gynecology for the Postgraduates

Number of embryos to be transferred: It is not a uniform one. Current guidelines indicate 1–3
embryos to be transferred depending on age of the patient. This is done to avoid risks of multiple
pregnancies and the complications thereof. Single embryo transfer should be considered for
younger patients (age <35 years). Usually, these women have large quantity of good quality
embryos. Otherwise, two embryo transfers may be optimum. For women with advanced age,
maximum number of cleavage stage embryo transfer could be three (age >35 years) (Table 36.1).
Embryo transfer procedure: It is aimed to deliver the embryos transcervically, safely in an
atraumatic manner, within the endometrial cavity for implantation. It is performed using a soft
catheter. It is done to deposit the embryos at a level of about 0.5–1.0 cm below the uterine fundus.
Transfer under ultrasound guidance may be helpful. Currently, multiple meta-analysis have shown

s
Ultrasonography (USG)-guided ET improves clinical pregnancy rates and implantation rates. Most
centers now do the ET under USG guidence.

r
Cryopreservation of Embryos/Oocytes

he
Embryo cryopreservation can be done at (a) pronuclear, (b) cleavage stage and also at (c) blastocyst
stage.
Benefits
„„
„„
ot
Multiple transfer cycles from single oocyte retrieval
Pregnancy rates following cryopreserved embryos are nearly similar or marginally less
„„ Fertility treatment can be optimized significantly
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„„ Reduces treatment cycle complications, OHSS, and failure rates.
Methods of cryopreservation: Slow freezing or rapid freezing (or victification) are two methods.
Slow freezing protocols take longer time and concentration of cryoprotectants is less. Victification
uses high concentration of cryoprotectants for rapid cooling. It is less expensive and has higher
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postthaw embryo survival. Embryo thawing is done by brief exposure to air and warm water
followed by rehydration. Pregnancy rates following frozen embryos are lower compared to
fresh transfer cycles.12 This again may be due to embryo selection as best embryos are selected
for fresh transfer.13
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Endometrial preparation for frozen embryo transfer (FET): In natural cycle, no exogenous
treatment is needed for the recipient. Transfer is timed to spontaneous ovulation.14 Otherwise
estradiol supplementation is started in early follicular phase and is continued for 13–15 days till
endometrial thickness of 8 mm is obtained. Endometrial thickness is measured with transvaginal
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ultrasound. Progesterone supplementation begins 48–72 hours prior to transfer of cleavage state
embryo. Blastocysts are thawed 5–6 days prior to transfer. GnRH agonists are sometimes used in
medicated cycles to prevent premature LH surge, which may affect the endometrial maturation
adversely.
Success rates of fertility treatment: Overall success rates are follows—clomiphene citrate (CC)
and timed intercourse (TI): 3–17%; IUI, CC and IUI: 10–14%; Gonadotropins and IUI: 15–20% and
IVF success: clinical pregnancy rate/cycle for age <35 years: 31–46%.15
Donor Oocyte
Indications of pregnancy from donor oocytes
„„ Woman with ovarian failure
„„ Poor ovarian response to stimulation
„„ Poor oocyte quality (as in advanced age)

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 Assisted Reproductive Technology (ART) 395

„„ Repeated failure of fertilization

„„ Failure of implantation after multiple ART
„„ Inherited genetic disorders.
Live birth rate per cycle of donor oocyte IVF are 50% regardless of the recipient’s age. Oocyte
recipient needs to undergo endometrial preparation (described above). At present, donor oocytes
must be used to create embryos during the retrieval cycle (as oocyte freezing is considered
experimental till date).

References

1. Devroey P, Aboulghar M, Garcia-Velasco J, et al. Improving the patient’s experience of IVF/ICSI: A proposal

s
for an ovarian stimulation protocol with GnRH antagonist co-treatment. Hum Reprod. 2009;24(4):
764-74.

r
2. Huirne JA, Homburg R, Lambalk CB. Are GnRH antagonists comparable to agonists for use in IVF? Hum

he
Reprod. 2007;22(11):2805-13.
3. Reh A, Krey L, Noyes N. Are gonadotropin-releasing hormone agonist losing popularity? Current trends
at a large fertility center. Fertil Steril. 2010;93(1):101-8.
4. Al-Inany HG, Abou-Setta AM, Aboulghar M, et al. Gonadotropin-releasing hormone antagonists for
ot
assisted conception: a Cochrane review. Reprod Biomed Online. 2007;14(5):640-9.
5. Lass A, UK Timing of hCG Group. Monitoring of IVF-ET cycles by ultrasound versus by ultrasound and
hormonal levels:A prospective, multicenter, randomized study. Fertil Steril. 2003;80(1):80-5.
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6. Kwan I, Bhattacharya S, McNeil A, et al. Monitoring of stimulated cycles in assisted reproduction (IVF
and ICSI). Cochrane Database Syst Rev. 2008;(2):CD005289.
7. Nugent D, Vandekerckhove P, Hughes E, et al. Gonadotropin therapy for ovulation induction in
subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev. 2000;4:CD000410.
8. Smitz J, Andersen AN, Devroey P, et al. Endocrine profile in serum and follicular fluid differs after ovarian
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stimulation with HP-hMG or recombinant FSH in IVF patients. Hum Reprod. 2007;22(3):676-87.
9. Daya S. Follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation
in assisted reproductive cycles. Cochrane database Syst Rev. 2009;1.
10. Biljan MM, Mahutte NG, Dean N, et al. Effects of pretreatment with an oral contraceptive on the
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time required to achieve pituitary suppression with gonadotropin-releasing hormone analogs and
subsequent implantation and pregnancy rates. Fertil Steril. 1998:70(6):1063-9.
11. Blake DA, Farquhar CM, Johnson N, et al. Cleavage stage versus blastocyst stage embryo transfer in
assisted conception. Cochrane Database Syst Rev. 2007;4:CD002118.
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12. Urman B, Balaban B, Yakin K. Impact of fresh-cycle variables on the implantation potential of
cryopreserved thawed human embryos. Fertil Steril. 2007;87(2):310-5.
13. Wennerholm UB, Söderström-Anttila V, Bergh C, et al. Children born after cryopreservation of embryos
of oocytes: a systematic review of outcome data. Hum Reprod. 2009;24(9):2158-72.
14. Glujovsky D, Pesce R, Fiszabjn G, et al. Endometrial preparation for women undergoing embryo
transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database Syst Rev.
2010;(1):CD006359.
15. Centers for disease controls and prevention (2016). 2007 assisted reproductive technology success rates
[online] CDC website. Available from http://www.cdc.gov/art/ART 2007/PDF/Complete.2007_ART.pdf.

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