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Beischer &
MacKay’s
OB
STETRIC
S, GY
NA
ECO
LOG
Y
AN
D TH
E NEW
BO
RN
FOU
RTH ED
ITION
Michael Perm
ezel Susan W
alker &
Kypros Kyprianou
spine 31.5mm confirmed
Michael Permezel, Susan Walker& Kypros Kyprianou
Beischer & MacKay’sOBSTETRICS, GYNAECOLOGY AND THE NEWBORNFOURTH EDITION
ISBN 978-0-7295-4074-2
9
780729 540742
Michael Permezel MD, MRCP(UK), MRCOG, FRANZCOG Professor of Obstetrics and Gynaecology, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia
Susan Walker MD, DDU, CMFM, FRANZCOGProfessor of Maternal Fetal Medicine, Director of Perinatal Medicine, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia
Kypros Kyprianou MBBS, FRACPPaediatrician, Royal Children’s Hospital, Werribee Mercy Hospital, Epworth Freemasons Hospital and University of Melbourne, Melbourne, Victoria, Australia
Beischer & MacKay’s Obstetrics, Gynaecology and the Newborn is a highly illustrated, evidence-based resource on the theory and practice of caring for women and their newborn babies.
Drawing on the clinical experience and research base of the specialist authors, Beischer & MacKay’s Obstetrics, Gynaecology and the Newborn provides a solid foundation of knowledge across obstetrics, gynaecology and neonatal paediatrics to ensure expert care.
“The image of delivery of a healthy infant remains the greatest experience patients will enjoy in their journey through life”Norman Beischer AO, MD, MGO, FRCS(Ed), FRCOG, FRACS, FRACOG, D Med. Science (Hon)
Beischer & MacKay’sOBSTETRICS, GYNAECOLOGY AND THE NEWBORNFOURTH EDITION
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Beischer & MacKay’s OBSTETRICS,
GYNAECOLOGY
AND THE
NEWBORN
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Beischer & MacKay ’ s OBSTETRICS,
GYNAECOLOGY
AND THE
NEWBORN FOURTH EDITION
Michael Permezel, Susan Walker
& Kypros Kyprianou
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Elsevier Australia. ACN 001 002 357 (a division of Reed International Books Australia Pty Ltd) Tower 1, 475 Victoria Avenue, Chatswood, NSW 2067
Copyright © 2015 Elsevier Australia. 3rd edition © 1997; 2nd edition © 1986 Elsevier Australia.
All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher ’ s permissions policies and our arrangements with organisations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions .
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).
Knowledge and best practice in this fi eld are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identifi ed, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of product liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
National Library of Australia Cataloguing-in-Publication Data
Permezel, Michael, author.
Beischer & MacKay ’ s obstetrics, gynaecology and the newborn / Michael Permezel, Susan Walker & Kypros Kyprianou.
9780729540742 (paperback)
Obstetrics–Textbooks. Gynecology–Textbooks. Newborn infants–Care–Textbooks.
Walker, Susan, author.
Kyprianou, Kypros, author.
613.0432
Content Strategist: Larissa Norrie Content Development Specialist: Neli Bryant Project Manager: Devendran Kannan Edited by Leanne Poll Proofread by Julie Ganner Design by Georgette Hall Permissions by Karen Forsythe & Anita Mercy Vethakkan Index by Robert Swanson Typeset by Toppan Best-set Premedia Limited Printed in China by China Translation and Printing Services
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CONTENTS
Foreword ................................................................................................................................................................................................................... X
Preface ........................................................................................................................................................................................................................XI
Acknowledgements ..............................................................................................................................................................................XII
List of Editors .............................................................................................................................................................................................. XIII
List of Contributors ..........................................................................................................................................................................XIV
List of Reviewers ....................................................................................................................................................................................XVI
Section 1 Anatomy and PhysiologyCHAPTER 1 Reproductive Anatomy and Physiology .............................................................................................................................................2
Peter Wein and Michael Permezel
CHAPTER 2 Anatomy and Physiology of Pregnancy ........................................................................................................................................... 14Michael Permezel and Peter Wein
Section 2 ObstetricsSection 2.1 Normal PregnancyCHAPTER 3 The Prepregnancy Consultation ..........................................................................................................................................................29
Michael Permezel
CHAPTER 4 The First Antenatal Visit .......................................................................................................................................................................32Michael Permezel
CHAPTER 5 Antenatal Care Beyond the First Antenatal Visit ......................................................................................................................... 39Michael Permezel
CHAPTER 6 Obesity and Nutrition in Pregnancy ................................................................................................................................................ 46Alexis Shub
Section 2.2 Problems of Early PregnancyCHAPTER 7 Hyperemesis Gravidarum .....................................................................................................................................................................52
Neil Israelsohn
CHAPTER 8 Bleeding in Early Pregnancy ................................................................................................................................................................55Neil Israelsohn
Section 2.3 Prenatal DiagnosisCHAPTER 9 Screening, Diagnosis and Management of Genetic and Structural Abnormalities in the Fetus ................................... 70
Susan Walker
Section 2.4 Obstetric ComplicationsCHAPTER 10 Antepartum Haemorrhage ................................................................................................................................................................... 85
Neil Israelsohn
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CHAPTER 11 Fetal Growth Restriction and Assessment of Fetal Wellbeing .................................................................................................. 91Alexis Shub
CHAPTER 12 Preterm Labour, Including Cervical Insuffi ciency ....................................................................................................................... 98Alison Fung
CHAPTER 13 The Postdates Pregnancy and Rupture of the Membranes Before Labour at Term ........................................................ 106Michael Permezel and Megan Di Quinzio
CHAPTER 14 Multiple Pregnancy .................................................................................................................................................................................111Susan Walker
CHAPTER 15 Malpresentation .....................................................................................................................................................................................120Michael Permezel
Section 2.5 Medical and Surgical Disorders in PregnancyCHAPTER 16 Hypertensive Disorders of Pregnancy Eclampsia ..................................................................................................................... 130
Michael Permezel
CHAPTER 17 Thromboembolism, Cardiac Disorders and Respiratory Disease .......................................................................................... 140Michael Permezel and Lisa Hui
CHAPTER 18 Bacterial Infections in Pregnancy .....................................................................................................................................................145Peter Wein
CHAPTER 19 Viral and Protozoan Infections in Pregnancy .............................................................................................................................. 152Susan Walker
CHAPTER 20 The Blood: Anaemia, Thrombocytopenia and Coagulopathy ..................................................................................................163Lisa Hui and Michael Permezel
CHAPTER 21 Gastrointestinal, Hepatobiliary, Gynaecological and Renal Problems ...................................................................................168Michael Permezel
CHAPTER 22 Autoimmune and Isoimmune Disease in Pregnancy ................................................................................................................. 176Michael Permezel and Gillian Paulsen
CHAPTER 23 Diabetes Mellitus ...................................................................................................................................................................................185Peter Wein
CHAPTER 24 Neurological Disease ..............................................................................................................................................................................191Susan Walker
CHAPTER 25 Mental Health Disorders during the Perinatal Period ................................................................................................................196Megan Galbally and Martien Snellen
Section 2.6 Common Clinical Scenarios and Presenting Problems in Pregnancy
CHAPTER 26 Common Problems in Pregnancy ....................................................................................................................................................203Michael Permezel and Megan Di Quinzio
Section 2.7 Labour and BirthSection 2.7.1 Normal Labour and BirthCHAPTER 27 The Physiology of Parturition ............................................................................................................................................................216
Michael Permezel and Megan Di Quinzio
CHAPTER 28 Management of Normal Labour ...................................................................................................................................................... 226Michael Permezel
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Section 2.7.2 Induction of Labour, Instrumental Delivery and Casearean Section
CHAPTER 29 Induction of Labour, Including Cervical Ripening ....................................................................................................................243Michael Permezel and Gillian Paulsen
CHAPTER 30 Episiotomy and Vaginal Outlet Tears .............................................................................................................................................249Michael Permezel and Gillian Paulsen
CHAPTER 31 Instrumental Delivery ......................................................................................................................................................................... 257Michael Permezel and Gillian Paulsen
CHAPTER 32 Caesarean Section and Trial of Labour after Caesarean ........................................................................................................... 267Michael Permezel
Section 2.7.3 Intrapartum Clinical ProblemsCHAPTER 33 Intrapartum Fetal Compromise........................................................................................................................................................ 277
Michael Permezel and Julia Francis
CHAPTER 34 Failure to Progress in Labour............................................................................................................................................................ 285Michael Permezel and Julia Francis
CHAPTER 35 Malpresentation and Malposition ................................................................................................................................................... 294Julia Francis and Michael Permezel
CHAPTER 36 Postpartum Haemorrhage ..................................................................................................................................................................302Michael Permezel
CHAPTER 37 Maternal Collapse ................................................................................................................................................................................. 310Michael Permezel
CHAPTER 38 Obstetric Analgesia and Anaesthesia ..............................................................................................................................................315Richard Hiscock
Section 2.7.4 The Puerperium and LactationCHAPTER 39 The Physiology of the Puerperium and Lactation ..................................................................................................................... 323
Elizabeth Anne McCarthy
CHAPTER 40 Normal Postpartum Care .................................................................................................................................................................... 329Elizabeth Anne McCarthy
CHAPTER 41 Puerperal Disorders ..............................................................................................................................................................................335Elizabeth Anne McCarthy
Section 2.7.5 Global Women’s Health and Indigenous Women’s HealthCHAPTER 42 Maternal and Perinatal Mortality and Morbidity and Global Reproductive Health ...................................................... 340
Laurel Bennett
CHAPTER 43 Australian Indigenous Women’s Health in Pregnancy .............................................................................................................345Jacqueline Boyle and Marilyn Clarke
Section 3 GynaecologySection 3.1 Gynaecological AssessmentCHAPTER 44 Gynaecological History and Examination .....................................................................................................................................353
Emma Readman and Kate McIlwaine
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CHAPTER 45 Gynaecological Investigations ...........................................................................................................................................................358Kate McIlwaine and Emma Readman
Section 3.2 Menstrual DisordersCHAPTER 46 Paediatric and Adolescent Gynaecology ........................................................................................................................................ 372
Sonia Grover
CHAPTER 47 The Menstrual Cycle and Menstrual Disorders .......................................................................................................................... 377Carol Vance
Section 3.3 Reproductive Endocrinology and InfertilityCHAPTER 48 Infertility ................................................................................................................................................................................................. 401
Sameer Jatkar
CHAPTER 49 Amenorrhoea, Hyperprolactinaemia and Ovulation Induction ..............................................................................................414Sameer Jatkar
CHAPTER 50 Androgen Excess, Including PCOS, Hirsutism and Acne ........................................................................................................425Chris Russell
Section 3.4 The MenopauseCHAPTER 51 The Menopause, Climacteric and Hormone Replacement Therapy .....................................................................................434
Michael Rasmussen, Samantha Mooney and Michael Permezel
Section 3.5 SexualityCHAPTER 52 Normal Sexuality, Sexual and Relationship Dysfunction, and Sexual Assault ..................................................................441
Patricia Moore
Section 3.6 Contraception, Sterilisation and AbortionCHAPTER 53 Contraception, Sterilisation and Abortion .....................................................................................................................................451
Patricia Moore
CHAPTER 54 Genital Tract Infections ......................................................................................................................................................................466Kathryn Anne Cook
Section 3.7 UrogynaecologyCHAPTER 55 Pelvic Organ Prolapse ..........................................................................................................................................................................483
Julio Alvarez and Peter Dwyer
CHAPTER 56 Urinary Incontinence ..........................................................................................................................................................................492Kristina Cvach and Peter Dwyer
Section 3.8 Pelvic Pain and EndometriosisCHAPTER 57 Pelvic Pain ...............................................................................................................................................................................................505
Lenore Ellett and Peter Maher
CHAPTER 58 Endometriosis .........................................................................................................................................................................................513Peter Maher and Lenore Ellett
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Section 3.9 The BreastCHAPTER 59 Breast Disorders ..................................................................................................................................................................................... 521
Antonia McLaren Jones
Section 3.10 Neoplasia and Other LumpsCHAPTER 60 Benign and Malignant Disorders of the Vulva and Vagina .....................................................................................................536
Ross Pagano
CHAPTER 61 Benign and Malignant Disorders of the Cervix ..........................................................................................................................545Jeffrey Tan
CHAPTER 62 Benign and Malignant Disorders of the Uterus, and the Pelvic Mass ................................................................................. 563Michael Quinn and Adam Pendlebury
CHAPTER 63 Benign and Malignant Disorders of the Ovary and the Fallopian Tube ..............................................................................572Vivek Arora
Section 4 NeonatologyCHAPTER 64 Neonatal Physiology: Adaptation and Resuscitation .................................................................................................................584
Kypros Kyprianou
CHAPTER 65 Routine Neonatal Care ........................................................................................................................................................................ 592Kypros Kyprianou
CHAPTER 66 Assessment of the Neonate ............................................................................................................................................................... 597Kypros Kyprianou
CHAPTER 67 Neonatal Feeding and Nutrition ....................................................................................................................................................... 617Kypros Kyprianou
CHAPTER 68 Neonatal Jaundice ................................................................................................................................................................................. 628Kypros Kyprianou
CHAPTER 69 Neonatal Neurological Presentations ..............................................................................................................................................636Kypros Kyprianou
CHAPTER 70 Neonatal Respiratory Distress ..........................................................................................................................................................643Kypros Kyprianou
CHAPTER 71 The Small for Gestational Age and Large for Gestational Age Neonate ..............................................................................651Kypros Kyprianou
CHAPTER 72 Neonatal Infection ................................................................................................................................................................................ 655Kypros Kyprianou
CHAPTER 73 Congenital Malformations ................................................................................................................................................................. 662Kypros Kyprianou
CHAPTER 74 Neonatal Haematology .........................................................................................................................................................................675Kypros Kyprianou
CHAPTER 75 The Preterm Neonate and Perinatal Transport .......................................................................................................................... 680Kypros Kyprianou
Index ..............................................................................................................................................................................................................................693
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FOREWORD
Since the third edition of Obstetrics and the Newborn was published in 1997, there have been enormous changes in the practice of care before, during and after pregnancy, and in gynaecological management of both pre- and postmenopausal women. Routine investigations are more numerous and sophisticated. Caesarean section rates have doubled, but the image of delivery of a healthy infant remains the greatest experience patients will enjoy in their journey through life. Cooperation between carers, midwives, medical offi cers, and both clinical and laboratory scientists remains an important requirement.
Likewise, in gynaecology the number of subspecialties has increased and marvellous new technology and investigative procedures have altered the techniques of surgical procedures. A new range of drugs have given respite from infertility, and improved chemotherapy has signifi cantly advanced the treatment of gynaecological cancers.
Unusually, this volume combines the disciplines of obstetrics, neonatal medicine and gynaecology into a single source that facilitates learning for medical students, midwives and postgraduates. This creates harmony, from adolescent gynaecology through to reproductive life and the management of pregnancy, and fi nally the gynaecological problems of the postmenopausal woman.
This volume contains a unique collection of photographs taken many years before restrictions in teaching hospitals, which have now made collecting clinical photographs more diffi cult.
In my view there are no more appealing medical occupations available than the practice of obstetrics, neonatal care and all aspects of gynaecology.
It should not be overlooked that in spite of modern changes in practice, the vast majority of women—with conventional methods of support—continue to have a normal labour with spontaneous delivery of a normal, healthy infant.
We practitioners should aim to be the custodians of normality.
Norman Beischer AO, MD, MGO, FRCS(Ed), FRCOG, FRACS, FRACOG, DMedSci(Hon)
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LIST�OF�EDITORS
Michael Permezel MD, MRCP(UK), MRCOG, FRANZCOG Professor of Obstetrics and Gynaecology, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia
Susan Walker MD, DDU, CMFM, FRANZCOG Professor of Maternal Fetal Medicine, Director of Perinatal Medicine, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia
Kypros Kyprianou MBBS, FRACP Paediatrician, Royal Children ’ s Hospital, Werribee Mercy Hospital, Epworth Freemasons Hospital and University of Melbourne, Melbourne, Victoria, Australia
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LIST�OF�CONTRIBUTORS
Julio Alvarez U MD Urogynaecolgy Consultant, Hospital Padre Hurtado, Santiago, Chile; Assistant Professor, Universidad del Desarrollo, Concepción, Chile
Vivek Arora MBBS, MD, DNB, FRANZCOG, CGO Consultant Gynaecologic Oncologist, Royal Women ’ s Hospital and Western Health, Melbourne, Victoria, Australia
Laurel Bennett MBBS, FRANZCOG Consultant Visiting Medical Offi cer, Northeast Health Wangaratta, Wangaratta, Victoria, Australia
Jacqueline Boyle MBBS, FRANZCOG, MPH&TM, PhD Senior Staff Specialist, Monash Health, Clayton, Victoria, Australia; Head of Indigenous and Refugee Women ’ s Health Research, Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia
Marilyn Clarke MBBS(Class II Hons), GradDipClinEpi, FRANZCOG Staff Specialist, Department of Obstetrics and Gynaecology, Grafton Base Hospital, Grafton, New South Wales, Australia
Kathryn Anne Cook MBBS, FRANZCOG, FACSHM Obstetrician and Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia; Sexual Health Physician, Melbourne Sexual Health Centre, Carlton, Victoria, Australia
Kristina Cvach MBBS, MPHTM, FRANZCOG, CU Consultant Urogynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia
Megan KW Di Quinzio MBBS, MD, FRANZCOG Obstetrician Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia
Peter L Dwyer FRANZCOG, FRCOG, CU Head of Urogynaecology Department, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia
Lenore Ellett MBBS(Hons), FRACGP, FRANZCOG Consultant Obststrician and Gynaecologist, Visiting Medical Offi cer, Mercy Hospital for Women, Melbourne, Victoria, Australia
Julia Francis MBBS(Hons) Obstetrics and Gynaecology Registrar, Mercy Hospital for Women, Melbourne, Victoria, Australia
Alison Fung MBBS, FRANZCOG, CMFM, DDU Specialist in Maternal Fetal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia
Megan Galbally MBBS, MPM, PhD, FRANZCP Head of Unit and Consultant Psychiatrist, Mercy Hospital for Women, Melbourne, Victoria, Australia
Sonia R Grover MBBS, FRANZCOG, MD Clinical Professor, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia; Director, Department of Paediatric and Adolescent Gynaecology, Royal Children ’ s Hospital, Melbourne, Victoria, Australia; Unit Head, Consultant Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia; Head of Family Planning Service, Consultant Gynaecologist, Austin Health, Melbourne, Victoria, Australia; Research Fellow, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
Richard Hiscock MBBS, FANZCA Senior Consultant Anaesthetist, Mercy Hospital for Women, Melbourne, Victoria, Australia
Lisa Hui MBBS, PhD, GradCertClinEpi, FRANZCOG, CMFM, DDU Specialist in Maternal Fetal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia; Senior Clinical Lecturer, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
Neil Israelsohn MBBS(Hons), FRANZCOG Consultant Obstetrician and Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia
Sameer Jatkar MBBS(Hons), BA, MSc, MRMed, FRANZCOG Fertility Specialist, Monash IVF, Clayton, Victoria, Australia; Visiting Medical Offi cer, Monash Health, Clayton, Victoria, Australia
Antonia McLaren Jones MBBS, BMedSci Fellow in Gynaecological Oncology, Mercy Hospital for Women, Melbourne, Victoria, Australia
Peter J Maher MBBS, FRCOG, FRACOG Director, Department of Endosurgery, Mercy Hospital for Women, Melbourne, Victoria, Australia; Clinical Professor, University of Melbourne, Melbourne, Victoria, Australia
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Chapter 8 BLEEDING�IN�EARLY�PREGNANCY Neil Israelsohn
EARLY�PREGNANCY�BLEEDING Early pregnancy assessment clinics (EPAC) are now common in hospitals managing pregnancy. They help to streamline the diagnosis and management of early preg-nancy bleeding and provide a point of contact for ongoing medical care and support. Table 8.1 gives a simple dif-ferential diagnosis for bleeding in early pregnancy.
In assessing the patient with early pregnancy bleed-ing, two important clinical questions need to be answered.
1. Is the pregnancy intrauterine?
2. Is the pregnancy viable?
IS�THE�PREGNANCY�INTRAUTERINE? All patients with bleeding and a non-localised pregnancy should be considered to have an ectopic pregnancy until proven otherwise. Ultrasound (usually transvaginal) and quantitative serum β -hCG form the basis for localising the pregnancy ( Fig 8.1 ). The key component of this algo-rithm is the use of transvaginal ultrasound irrespective of the serum β -hCG. While intrauterine pregnancy con-tents are not expected to be visualised if the β -hCG < 1500 IU/L, an ectopic pregnancy with an inappropriate β -hCG for gestation may still be seen.
KEY�POINTS Bleeding in early pregnancy should be considered to be an ectopic pregnancy until proven otherwise. Defi nitive management of miscarriage and ectopic pregnancy needs to be individualised depending on the
patient ’ s clinical and social circumstances. Young, healthy women may compensate so eff ectively for signifi cant blood loss as to have no/few signs of
haemodynamic instability prior to haemodynamic collapse. Gestational trophoblastic disease should be considered in those with signifi cant, persistent bleeding
postpartum.
IS�THE�PREGNANCY�VIABLE? Once an intrauterine pregnancy is confi rmed, its viability should be determined. Serum β -hCG has little to offer in the management of an intrauterine pregnancy and the presence of fetal heart activity confi rms viability. Any one of the following criteria is indicative of a failed pregnancy according to the guidelines of the Australian Society of Ultrasound in Medicine (ASUM):
• mean gestational sac diameter > 25 mm with no fetal pole
• fetal pole > 7 mm and no fetal heart activity
• inadequate growth of the gestational sac or fetal pole over the course of a week (i.e. < 1 mm per day).
Poor prognostic features include a bradycardia ( < 85 bpm) and signifi cant subchorionic haematoma for-mation ( Fig 8.2 ).
MISCARRIAGE A miscarriage is the presence of a non-viable intrauterine pregnancy before 20 weeks ’ . It is not necessary for there to be an embryo or fetus present. Clinically recognised miscarriage occurs in approximately 15% of pregnancies.
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TABLE 8.1 DIFFERENTIAL DIAGNOSIS OF EARLY PREGNANCY BLEEDING.
Diagnosis Cause
Not pregnant In rare cases, a woman will have a false positive pregnancy test or for some other reason believe she is pregnant; bleeding may therefore be a menstrual period
Intrauterine pregnancy Viable intrauterine pregnancy Non-viable (miscarriage, gestational trophoblastic disease)
Ectopic pregnancy Most commonly tubal but may be ovarian, cervical or abdominal
Incidental cause for bleeding Cervical polyp/cancer, ectropion, other genitourinary tract cause
FIGURE 8.1 Management of bleeding in early pregnancy.
Early pregnancy bleeding +/– pain
Transvaginal ultrasound Intrauterine pregnancy Extrauterine pregnancy
Unlocalised pregnancy
B-hCG < 1500 IU/L B-hCG > 1500 IU/L
Highly suspicious of ectopic pregnancy
Senior obstetric review
?Early intrauterine versus extrauterine pregnancy
Consider admission
Repeat B-hCG in 48 hours
Appropriate rise in B-hCG Inadequate rise in B-hCG
Repeat ultrasound in 1 week
Manage accordingly Viable Non-viable
If unrecognised biochemical pregnancies are included, the fi gure is much higher.
AETIOLOGY The aetiology of miscarriage is as follows.
• Chromosomal abnormalities. These are the most common cause of miscarriage and are responsible for approximately 50% of spontaneous miscarriages. Most of these abnormalities are non-recurring and include trisomies (e.g. trisomy 13), monosomy X (Turner syndrome) and polyploidies (triploidy and tetraploidy). The incidence of autosomal trisomies increases with advancing age.
• Endocrine. Poorly controlled endocrine disorders are risk factors for both infertility and miscarriage.
Preexisting diabetes, thyroid disease and hyperan-drogenism (e.g. polycystic ovary syndrome [PCOS]) are associated with miscarriage. Obesity is also an independent risk factor for miscarriage. Although progesterone is essential for successful implantation and continuation of pregnancy, studies have shown neither a consistent correlation between progester-one levels and risk of subsequent miscarriage nor a benefi t in reducing miscarriage with the use of exog-enous progesterone.
• Thrombophilia. Antiphospholipid syndrome is a cause of recurrent miscarriage. The association of other hypercoagulable states and miscarriage is less certain as there are confl icting reports. It may be that thrombophilia has a greater association with late ( > 10 weeks ’ ) fi rst trimester miscarriage.
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Bleeding The amount of bleeding with a miscarriage is variable. In complete miscarriage, the loss is variable during the process but thereafter usually ceases entirely. In the major-ity of women with threatened miscarriage, the pregnancy continues uneventfully. The risk of loss is usually propor-tional to the amount of bleeding; if the loss continues or recurs or if there is any associated pain, the prognosis is less favourable. First-trimester bleeding predisposes to later pregnancy complications including preterm birth and preterm prelabour rupture of the membranes.
Pain Pain is experienced as the uterus contracts or when the cervix is dilating and products of conception are being passed. The pain is felt in the lower abdomen or back, is usually cramp-like and follows the bleeding—in contrast to the sequence in ectopic pregnancy, discussed later in this chapter.
Passage of products of conception The passage of defi nite tissue defi nes incomplete or com-plete miscarriage. A confusing picture is presented when the decidual lining of the uterus is passed in ectopic pregnancy (decidual cast), since this simulates tropho-blastic tissue ( Fig 8.3 ). In many women, no fetus is passed at any time, since it is either absent (blighted ovum) or rudimentary and unnoticed.
CLASSIFICATION Miscarriages were traditionally classifi ed according to clinical criteria as listed in Table 8.2 ; that is, whether the cervix is open/closed, whether any products of concep-tion have been passed and the size of the uterus relative to dates. More recently, however, ultrasound has played a more important role in the diagnosis and classifi cation of miscarriage. The far greater availability of fi rst-trimester ultrasound has led to the diagnosis of signifi -cantly more missed miscarriages in asymptomatic women. Note that the term ‘missed miscarriage’ means a ‘non-viable pregnancy that has not yet had any vaginal bleeding’. It does not mean that the diagnosis has not been made.
INITIAL�MANAGEMENT Assessment Take the patient ’ s history to elicit details of the presenting complaint as outlined in the Clinical features section. Clinical examination should include vital signs, abdomi-nal palpation, speculum examination and bimanual pal-pation. The following investigations are useful: full blood examination (FBE), blood group and save serum, quanti-tative β -hCG and ultrasound.
• Uterine abnormalities. Uterine malformations (bicor-nuate or septate) or fi broids (especially submucous) are implicated in recurrent pregnancy loss. Endome-trial scarring (Asherman syndrome) also contributes to miscarriage risk.
• Chronic maternal disease. Signifi cant maternal medical disease (e.g. cardiac, renal, connective tissue) is another risk factor in miscarriage.
• Toxins. Heavy tobacco use and heavy alcohol con-sumption are associated with an increased risk of sporadic miscarriage. Other risk factors are medica-tions (e.g. methotrexate) and environmental toxins (e.g. arsenic, aniline dyes, benzene, ethylene oxide, formaldehyde, pesticides, lead, mercury and cadmium).
• Trauma. Invasive diagnostic procedures such as cho-rionic villus sampling (CVS) and amniocentesis are associated with small risks of miscarriage.
Aetiology of recurrent miscarriage The causes of recurrent miscarriage are similar to that for non-recurring miscarriage. With regards to chromosomal causes, parental balanced chromosomal translocations is a causative factor in approximately 4% of recurrent miscarriage.
CLINICAL�FEATURES Pregnancy symptoms Symptoms and signs of pregnancy are usually present; pregnancy failure may be refl ected by a diminution or cessation of typical pregnancy symptoms.
FIGURE 8.2 Perigestational haematoma (H). CRL indicates crown–rump length of the fetus equivalent to 7 weeks’ and 6 days’ gestation on this scan.
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evidence of cervical tissue and bleeding is heavy and ongoing, ergometrine 0.5 mg intravenously may be tri-alled while theatre is arranged for an urgent curette.
Usually, the bleeding is much less troublesome, and after the diagnosis has been made, ongoing management options are discussed, as detailed in the next section.
Missed miscarriage Ultrasound criteria for confi rming a non-viable preg-nancy are described earlier in this chapter. Where there is no suggestion of a septic miscarriage or haemodynamic instability, ongoing management may be expectant, medical or surgical. A Cochrane review has revealed that the rates of infection are similar for each management strategy. While the likelihood of success is a critical factor in determining ongoing management, other issues to con-sider include the patient ’ s:
• tolerance of potential ongoing bleeding and/or pain at home
• acceptance of having a complete miscarriage in a setting outside of the hospital
should be asked to present earlier if she experiences sig-nifi cant pain or bleeding.
Inevitable miscarriage While the patient will go on to pass the products of con-ception, this may occur after a variable amount of further bleeding and/or pain. Expectant or medical management is most appropriate. Occasionally patients will require a curette if there is sustained heavy bleeding.
Incomplete miscarriage This common presentation causes the most trouble from bleeding and shock; blood transfusion may be required in a few women.
Cervical shock may occur if products become trapped within the cervix. This presents as bleeding, signifi cant pain and often vagal/parasympathetic symptoms (brady-cardia, hypotension, sweatiness and nausea/vomiting). Speculum visualisation of the cervix and removal of the products with sponge forceps may be necessary ( Fig 8.4 ). It is often necessary to perform a curette to ensure com-plete removal of products of conception. If there is no
FIGURE 8.4 Incomplete miscarriage at 10 weeks ’ gestation in a 21-year-old primigravida who presented with heavy vaginal bleeding and abdominal pain. A Placental tissue is seen protruding through the cervical os. Sponge-holding forceps grasp and remove the placental tissue. B Products of conception visible at a partly dilated external os. Source: Courtesy of Prof. Norman Beischer.
A B
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FIGURE 8.11 Laparoscopic salpingectomy. A Shows the le� ampullary ectopic pregnancy (E), the le� ovary (LO) and the uterus (U). Free peritoneal blood is seen on the visceral and peritoneal surfaces. Evidence of parafi mbrial blood clot. B Post-salpingectomy showing the le� ovary (LO) and the uterus (U).
A B
< 5 IU/L. Patients should present if they experience signifi -cant abdominal pain and or bleeding. If the β -hCG level does not drop by 15%, consideration is given to either a second dose of methotrexate or surgical management.
The multi-dose regimen has a similar success rate to the single dose for tubal ectopics; however, side effects are more common. It is generally only considered in cases of cornual, scar and cervical ectopic pregnancy.
Surgical treatment Surgical management is indicated if medical treatment is contraindicated (as outlined earlier in Box 8.1 ) or if medical treatment fails or is declined by the patient.
Laparoscopy or laparotomy? Laparoscopy is appropriate for almost all ectopic preg-nancies (even those with haemoperitoneum) except those with signifi cant haemodynamic compromise. Ultimately the decision depends on the experience and skills of the attending gynaecologist and anaesthetic team.
Salpingectomy or salpingostomy? Laparoscopic salpingectomy ( Fig 8.11 ) is the standard surgical treatment for tubal ectopic pregnancy. Research has shown similar rates of future intrauterine pregnancy and recurrent ectopic rates compared with medical management.
Salpingostomy (incision of the affected tube with removal of the products of conception) is occasionally performed with a view to increasing future intrauterine pregnancy rates. Non-randomised studies suggest that
intrauterine pregnancy rates are greater after salpingos-tomy compared with salpingectomy ONLY in those with contralateral tubal disease. Against salpingostomy, there is increase in both persistent trophoblast requiring treatment and future ectopic pregnancy relative to salpingectomy.
Other treatment options Live cervical, scar and cornual ectopics may be managed with intra-gestational potassium ± methotrexate injection.
GESTATIONAL�TROPHOBLASTIC�DISEASE CLASSIFICATION Gestational trophoblastic disease (GTD) encompasses a range of conditions characterised by a proliferative disor-der of trophoblastic cells. These disorders can be broadly classifi ed into benign or invasive/malignant (see Box 8.2 ) and are largely distinguished on histopathology.
Localised GTD Localised molar pregnancies are a result of aberrant fer-tilisation and as such are primary entities and cannot follow from a clinical pregnancy. Invasive GTD, on the other hand, may follow either a molar or clinical preg-nancy including term, preterm, miscarriage or ectopic pregnancy.
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CLINICAL�FEATURES�AND�PATHOLOGY Mole A hydatidiform mole is characterised by oedematous avascular villi with trophoblastic proliferation ( Fig 8.13 ). Typically, a mole is initially diagnosed following an ultra-sound performed because of vaginal bleeding (95%) in early pregnancy. Other clinical features may include hyperemesis gravidarum, theca lutein cysts ( Fig 8.14 ), preeclampsia (may be before 20 weeks ’ gestation), hyper-thyroidism and vaginal passage of hydropic vesicles. Symptoms from metastatic spread of molar tissue may also occur (e.g. haemoptysis and/or pleuritic pain from spread to the lung).
Choriocarcinoma The clinical presentation of choriocarcinoma is varied depending on the antecedent pregnancy. Following a complete molar pregnancy, it may be diagnosed in asymptomatic women with routine β -hCG monitoring.
Invasive GTN In the case of invasive moles, the degree of invasion may be local or may involve metastases, usually to the lungs or vagina. Invasive moles follow approximately 15% of complete moles and 3% of partial moles. The diagnosis is generally made clinically based on persistent β -hCG elevation after molar evacuation.
Choriocarcinoma is a malignant disease characterised by abnormal trophoblastic hyperplasia and anaplasia, absence of chorionic villi, haemorrhage and necrosis. This malignant tumour of the trophoblast follows a hyda-tidiform mole in 50% of cases, normal pregnancy in 25% and miscarriage or ectopic pregnancy in 25% (see Fig 8.12 ).
PREDISPOSING�FACTORS Rates vary signifi cantly based on geographic region, eth-nicity and maternal age. The condition is more common in Australasia (1 in 750 pregnancies) than in the United States, the United Kingdom and Europe (1 in 1500), but is most frequent in South-East Asia and Mexico (1 in 500). Choriocarcinoma is more common in older and younger women and there is a 1% recurrence risk if there is a past history of GTD.
HISTOPATHOLOGY�AND�CYTOGENETICS Complete and incomplete moles differ signifi cantly in certain characteristics ( Table 8.4 ). Complete molar preg-nancy occurs as a result of fertilisation of an empty ovum with either two sperm or one that divides. The karyotype is generally 46XX (occasionally 46XY) and all of paternal origin. Partial molar pregnancy results from the fertilisa-tion of an ovum with two sperm or one that divides resulting in triploidy 69XXY, 69XXX or, rarely, 69XYY. There is often a co-existing fetus that is prone to fetal death in utero and growth restriction. Partial moles have a much lower malignant potential.
FIGURE 8.12 Choriocarcinoma. The woman was aged 17 and presented with a haemoperitoneum. As in 50% of cases, there was no preceding hydatiform mole. Uterine perforation necessitated hysterectomy. There were multiple pulmonary metastases but recovery was complete a� er hysterectomy. Source: Reproduced with permission from the Royal Women ’ s Hospital, Parkville, Victoria.
BOX�8.2 Classifi cation of gestational
trophoblastic disease.
Localised (‘benign’) gestational trophoblastic disease (localised GTD) ✚ Partial hydatidiform mole ✚ Complete hydatidiform mole
Invasive gestational trophoblastic neoplasia (invasive GTN) ✚ Invasive mole ✚ Choriocarcinoma ✚ Placental site trophoblastic tumour (PSTT)
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TABLE 8.4 CHARACTERISTICS OF PARTIAL AND COMPLETE MOLES.
Characteristic Partial mole Complete mole
Karyotype 69XXY, 69XXX, 69XYY 46XX or 46XY
Embryonic fetal tissue Present Absent
Villi Focal hydropic villi Diff usely hydropic
Theca lutein cysts Uncommon Common
Malignant GTN 3% Almost exclusively invasive mole
15% (invasive mole 90%, choriocarcinoma 10%)
FIGURE 8.13 Section of a hydatidiform mole showing considerable trophoblastic proliferation. The chorionic villi show the typical enlargement (hydrops) and avascularity. Source: Courtesy of Norman Beischer.
FIGURE 8.14 Uterus and bilateral theca-lutein cysts seen a� er hysterectomy at 18 weeks ’ gestation in a woman with a hydatidiform mole. Suction cure� age is the usual treatment of a hydatidiform mole. Source: Courtesy of Monash Health.
Following a normal pregnancy, persistent vaginal bleed-ing is the most frequent symptom. Vaginal bleeding after 6 to 8 weeks ’ should prompt consideration of GTN along with the other more common conditions such as retained products of conception and endometritis. There may be evidence of metastatic tumour—vaginal metastases are present in 30% cases. These lesions are highly vascular and prone to bleeding. Patients may exhibit respiratory, gastrointestinal or neurological symptoms refl ecting sites of distant metastases.
DIAGNOSIS Ultrasound Ultrasound of a complete mole reveals a central hetero-geneous mass with numerous discrete anechoic spaces. There is no fetus or amniotic fl uid ( Fig 8.15 )— unless there is a co-existent twin (4 to 6%, Figs 8.16 and 8.17 ). A partial mole may also have a co-existent fetus. A
choriocarcinoma appears as a hypervascular heteroge-neous mass.
β -hCG β -hCG is universally elevated as compared with other intrauterine or ectopic pregnancies. Occasionally, the diagnosis of a partial mole may only be made on histol-ogy of curettings from a suspected incomplete abortion.
MANAGEMENT Localised GTD Initial management The initial treatment is similar to that outlined for the woman with suspected miscarriage. Heavy bleeding may complicate this process, so adequate blood must be cross-matched. Suction curette is fi rst-line management for complete and partial molar pregnancy. Hysterectomy
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would rarely be performed as fi rst line management ( Fig. 8.18 ). Tissue is sent in normal saline ( not formalin) for histological analysis and karyotyping if necessary.
If the diagnosis of a complete mole is established preoperatively, baseline investigations with a quantitative β -hCG and chest X-ray should be taken.
Follow-up Due to the possibility of persistent GTD (invasive molar pregnancy/choriocarcinoma), especially after complete
FIGURE 8.15 Complete mole. Enlarged uterus showing hypoechoic vesicles consistent with a molar pregnancy.
FIGURE 8.16 Partial mole in association with triploidy 69. The mother had severe preeclampsia and was delivered at 24 weeks ’ . The single placenta was diff usely molar and the triploidy fetus had multiple abnormalities. Source: Reproduced with permission from the Royal Women ’ s Hospital, Parkville, Victoria.
FIGURE 8.17 Twin molar and normal pregnancy. The mother had severe preeclampsia at 16 weeks ’ gestation. The fetus and a� ached placenta had a normal male karyotype but the separate molar tissue had a female karyotype and was thus a dizygotic twin. Source: Reproduced with permission from the Royal Women ’ s Hospital, Parkville, Victoria.
molar pregnancy, ongoing follow-up with serial β -hCG measurements for 6 months is important. Contraception should be commenced and if there is a trophoblast regis-try in the region, the case should be notifi ed. Use of the oral contraceptive pill does not increase rates of invasive disease. The theca lutein cysts are managed con-servatively although they may take months to resolve. Surgery may be necessary if torsion ensues.
Invasive GTN Initial management The preferred management of invasive GTN is with chemotherapy. Repeat curette is contraindicated due to the signifi cant risk of maternal haemorrhage and uterine perforation. Chemotherapy is the cornerstone of management. ‘Staging’ into low- and high-risk groups takes place to determine the most appropriate chemo-therapy. Low-risk women receive single-agent chemother-apy but the high-risk group are prescribed a multi-agent chemotherapeutic regimen (etoposide, methotrexate, acti-nomycin D, cyclophosphamide and vincristine [EMA/CO]). Cure rates approach 100% for those treated with single-agent chemotherapy. For high-risk disease neces-sitating a multi-drug regimen ± adjuvant radiotherapy or surgery, cure rates are approximately 90%.
Follow-up Once chemotherapy has been completed and β -hCG levels have returned to normal, the β -hCG levels should be mon-itored at monthly intervals for a further 12 months. The risk of relapse is 3% in the fi rst year and rare after that. Pregnancy should be avoided during the fi rst 12 months
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FURTHER READING Hajenius PJ , Mol F , Mol BW , et al. Interventions for
tubal ectopic pregnancy . Cochrane Database Syst Rev 2007 .
Luise C , Jermy K , May C , et al. Outcome of expectant management of spontaneous fi rst trimester miscarriage: observational study . BMJ 2002 ; 324 ( 7342 ): 873 .
Lurain JR . Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole . Am J Obstet Gynecol 2010 ; 203 ( 6 ): 531 – 9 .
Lurain JR . Gestational trophoblastic disease II: classifi cation and management of gestational trophoblastic neoplasia . Am J Obstet Gynecol 2011 ; 204 ( 1 ): 11 – 18 .
Mol BW , Matthijsse HC , Tinga DJ , et al. Fertility after conservative and radical surgery for tubal pregnancy . Hum Reprod 1998 ; 13 ( 7 ): 1804 – 9 .
Neilson JP , Gyte GML , Hickey M , et al. Medical treatments for incomplete miscarriage (less than 24 weeks) . Cochrane Database Syst Rev 2010 ; 1 .
Royal College of Obstetricians and Gynaecologists . The management of early pregnancy loss. Green-top Guideline No. 25 . London : RCOG ; 2006 .
Scott F , Meagher S . Media release. Australasian Society for Ultrasound in Medicine (ASUM) . Online. Available : < http://www.asum.com.au/newsite/Resources.php?p = Media > ; [ 24 October 2011 ].
Soto-Wright V , Bernstein MMHP , Goldstein DP , et al. The changing clinical presentation of complete molar pregnancy . Obstet Gynecol 1995 ; 86 : 775 – 9 .
Van Mello NM , Mol F , Opmeer BC , et al. Salpingotomy or salpingectomy in tubal ectopic pregnancy: what do women prefer? Reprod Biomed Online 2010 ; 21 ( 5 ): 687 – 93 .
Zhang J , Gilles JM , Barnhart K , et al. A comparison of medical management with misoprostol and surgical management for early pregnancy failure . N Engl J Med 2005 ; 353 ( 8 ): 761 – 9 . after β -hCG returns to normal in order to facilitate β -hCG
surveillance. An effective method of contraception should be used. The combined oral contraceptive pill is consid-ered safe. Due to the risk of recurrence in subsequent pregnancies, women should have an ultrasound in the fi rst trimester, placental histopathology and a serum β -hCG at 6 weeks ’ .
FIGURE 8.18 Classic hydatidiform mole appearance from a hysterectomy specimen of a 56-year-old woman. Source: Courtesy of Monash Health.
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