Table Of ContentPregnancy and Birth Afffter Assisted Reproductive Technologies
Springer-Verlag Berlin Heidelberg GmbH
Michael Ludwig
Pregnancy and Birth
After Assisted
Reproductive Technologies
Assisted by Constanze Banz,Georgine Huberrr,
Annika K.Schröder,Anna Sophie Seelig,
and Pia Wülfffing
With a Foreword by Robert G.Edwards
With 3 Figures and 37 Tables
123
Author:
Priv.-Doz. Dr. Michael Ludwig
Department of Gynecology and Obstetrics, University Clinic
Div. of Reproductive Medicine and Gynecologic Endocrinology
Ratzeburger Allee 160,23538 Llibeck, Germany
Contributors:
Dr. med. Constanze Banz Dr. med. Georgine Huber
Dr. med Annika K. Schroder Dr. med. Anna Sophie Seelig
Department of Gynecology and Obstetrics, University Clinic
Ratzeburger Allee 160,23538 Llibeck, Germany
Dr. med. Pia Wiilfing
Department of Gynecology and Obstetrics
Westfffălische Universităt Mlinster
Albert -Schweitzer-Strasse 33,48149, Mlinster, Germany
ISBN 978-3-540-43531-0
Library of Congress Cataloging-in-Publication Data
Ludwig, Michael, 1968-. Pregnancy and birth after assisted reproductive
technologies / Michael Ludwig; with contributions by Constanze Banz ... [et al.].
p. ; cm. Includes bibliographical references and index.
ff
ISBN 978-3-540-43531-0 ISBN 978-3-642-56187-0 (eBook)
DOI 10.1007/978-3-642-56187-0
1. Pregnancy -Complications. 2. Childbirth. 3. Human reproductive technology.
I. Title. [DNLM: 1. Pregnancy Complications. 2. Labor. 3. Reproductive Techniques,
Assisted-adverse effects. WQ 240 L948p 2002] RG526 .L835 2002 618.3-dc21
2002070466
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© Springer-Verlag Berlin Heidelberg 2002
Originally published by Springer-Verlag Berlin Heidelberg in 2002
The use of general descriptive names, registered names, trademarks, etc. in this
publication does not imply, even in the absence of a specific statement, that such
names are exempt from the relevant protective laws and regulations and therefore
fffree for general use.
Product liability: The publishers cannot guarantee the accuracy of any information
about dosage and application contained in this book. In every individual case the
user must check such information by consulting the relevant literature.
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Dedicated to my teacher
Profffessor Dr.Klaus Diedrich
Foreword
It is a pleasure to see this book in print.It represents work
on an immense importance to assisted human conception.
Numerous books have presented virtuallyy everyy aspect of
fffollicular growth,fffertilization,male and fffemale sterilityy and
implantation.This is among the rare books dedicated to preg-
nancyyy,birth and infantgrowth.
Since the introduction ofIVF,it has been clear that various
problems could be associated with pregnancy after assisted
human conception.The fffirst clinical IVF pregnancy afffter the
transfffer ofa 5-day blastocyst turned out to be ectopic,and this
subjecthas neverbeen fffarfffrom debates on the safffety ofassist-
ed human conception ever since. Ectopic and heterotopic
pregnancies were two fffactors stressed in earlydaaays ofworld-
wide IVF,and multiple pregnancies emerged as perhaps as an
even more serious problem as high degrees ofovarian stimu-
lation began to be practised in some clinics.These chapters
add the experience ofthe author,working in a large German
IVF team,todiscussions on these topics in thisbook.
It is signiffficant to note two chapters devoted to chromo-
somal analysis and preimplantation and prenataldiagnosis.A
deeper awareness of the immensefffrequency of monosomic,
trisomic and other chromosomallyyabnormal embryos must
be stressed, since our species seems to be unique in this
regard,and such pregnancies add to the stress ofIVF.Todaaay’s
methods promise to analyse these situations in immensely
fffine detail, almost to the molecular level, without chromo-
somes having to be analysed when in mitosis.New techniques
constantly beckon,such as comparative genomic hhhyybridiza-
tion,to set the scene at ever-moredetailed analyses of cleav-
ing embryos, blastocysts and fffetuses. Prenatal diagnosis is
also essential,especiallyy when more new methods involving
non-invasive procedures are steadilyy introduced into IVFFF.
This fallback form of diagnosis has been extremelyy signifi-
cant since before the birth of Louise Brown, and is still
immensely relevant today when new forms ofovarian stimu-
lation,or ways of achieving conception,raise risks of more
VIII Foreword
and novelffforms ofchromosomal anomalies.Congenital mal-
ffformations must also be closely monitored,especially since
recent reports indicate a slightly higher degree of them afffter
IVF and ICSI.
Perinatal outcome is the consequence of ovarian,embry-
onic and uterine aspects of conception. To record the fre-
quencyy of congenital malformations at birth and one or two
years later is a veryy time-consuming and expensive task.Every
aspect of development could be influenced by disorders in
imprinting,uterine nutrition,and events at parturition in a
group ofpatients fffarbeyond the mean ages ofreproduction.
These effects could be transmitted to children and become
operative long afffter birth, as witnessed in reproductive
cloning in animal species.Even though a maajor task for annny
author,Michael Ludwig has taken it in his stride to comple-
ment the earlier events determining child health at birth.
Chapters on oocyte donation, lesbian families, family
structure and gender identity complete the make-up of this
book.It couldbe a classic,consultedby clinical and scientifffic
investigators,and perhaps by patients andby general readers.
The author must have spent an immense amount of time
attending to fffine detail in so mannyy areas of pregnancyyy,par-
turition and earlyy development. He is to be complimented
greatlyy on this vast effort.
August 2002 Robert G.Edwards
Preface
Assisted reproductive techniques have become more and
more widespread throughout the world.It is estimated that
about a million childrenhavebeenborn afffter an IVF proce-
dure – taking all techniques together,the total must be much
higher.
TTTogether with the number ofbirths,the number ofstudies
investigating the course of the pregnancies and the health of
the children has increased. Several predictions made even
befffore the possibility ofIVFbecame reality have not,howeverrr,
come true.
Within thisbook we have striven to bring together as manny
publications as possible – including,hopefullyyy,all ofthe most
important studies to date – and to combine them into a coher-
ent picture,notjust single parts without a common thread.In
doing this,we wanted to create a book which assists not only
the specialist in reproductive medicine,but also the general
obstetrician and everyone who has to counsel couples who
undergo an ART treatment.
This book provides possible answers to a lot of questions
that maaayy arise in adialogue with the infffertile couple,based on
establishedfacts.
I would like to thank all myy co-authors,who spent a great
deal of time collecting and collating all the data from the
different studies.I also thank Dr.Heilmann and Mrs.McHugh
ofSpringer-Verlag for the opportunity to create this book and
fffor theirhelp with the fffinalpreparation ofthe manuscript.
We sincerely hope that this book proves as helpffful as we
intended.
Michael Ludwig
Contents
1 A Follow-up ofPregnancies
in Assisted Reproduction:Necessityy and Problems
Michael Ludwig . . . . . . . . . . . . . . . . . . . . . 1
Whhhyy Is It Necessaryy to Perform a Follow-up
ofPregnancies After an ART Procedure? . . . . . . . 2
Whhhyy Do Not All Centres Perform a Follow-up
ofPregnancies After an ART Procedure? . . . . . . . 4
Conclusion . . . . . . . . . . . . . . . . . . . . . . . 5
2 Incidence ofEarlyy Abortions
and Ectopic Pregnancies in Assisted Reproduction
Annika K.Schröder,Michael Ludwig . . . . . . . . . 7
Introduction . . . . . . . . . . . . . . . . . . . . . . 7
Definitions . . . . . . . . . . . . . . . . . . . . . . . 7
Incidence ofSpontaneous Abortions . . . . . . . . . 8
IVF . . . . . . . . . . . . . . . . . . . . . . . . . . 8
GIFT . . . . . . . . . . . . . . . . . . . . . . . . . 12
ICSI . . . . . . . . . . . . . . . . . . . . . . . . . 12
Frozen/Thawed ET . . . . . . . . . . . . . . . . . 15
ArtiffficialInsemination with Donor Sperm (AID) 16
Incidence ofEctopic Pregnancies . . . . . . . . . . . 17
Incidence ofHeterotopic Pregnancies . . . . . . . . 20
Incidence ofDisappearing Gestational Sacs . . . . . 21
Is There a Higher Abortion Risk Following ART? . . 21
3 Incidence ofChromosomal Abnormalities
in Abortions After Assisted Reproduction
Annika K.Schröder,Michael Ludwig . . . . . . . . . 25
Monosomy . . . . . . . . . . . . . . . . . . . . . . . 26
TTTrisomy . . . . . . . . . . . . . . . . . . . . . . . . . 27
TTTriploidyy . . . . . . . . . . . . . . . . . . . . . . . . . 28
TTTetraploidy . . . . . . . . . . . . . . . . . . . . . . . 28
StructuralChromosomal Anomalies . . . . . . . . . 29
Mosaics . . . . . . . . . . . . . . . . . . . . . . . . . 29
XII Contents
Factors that Might Influence the Incidence
ofChromosomal Anomalies . . . . . . . . . . . . . . 29
Effffect ofOvarian Stimulation . . . . . . . . . . . 29
Effffect ofICSI . . . . . . . . . . . . . . . . . . . . 30
Effect ofParental Age . . . . . . . . . . . . . . . . 30
Conclusion . . . . . . . . . . . . . . . . . . . . . . . 31
4 Assisted Reproduction and Prenatal Diagnosis
Pia Wülfing,Michael Ludwig . . . . . . . . . . . . . 33
Invasive Prenatal Diagnosis . . . . . . . . . . . . . . 33
IVF and Prenatal Diagnosis . . . . . . . . . . . . 33
ICSI and Prenatal Diagnosis . . . . . . . . . . . . 42
Non-invasive Prenatal Diagnosis . . . . . . . . . . . 49
Ultrasound . . . . . . . . . . . . . . . . . . . . . 50
Serum Markersfffor Prenatal Diagnosis . . . . . . 51
Conclusion . . . . . . . . . . . . . . . . . . . . . . . 52
5 Obstetric Outcome ofPregnancies
Afffter Assisted Reproduction
Georgine Huber,Michael Ludwig . . . . . . . . . . . 55
Singletons Conceived by ART
Versus Spontaneously Conceived Pregnancies . . . . 55
Singleton Versus Multiple Pregnancies Afffter IVF
or IVF/ICSI . . . . . . . . . . . . . . . . . . . . . . . 59
Multiple Pregnancies Afffter ART Versus
Spontaneouslyy Conceived Multiple Pregnancies . . . 62
Higher Order Multiple Pregnancies Following ART . 64
Obstetric Outcome ofPregnancies
After Cryopreservation . . . . . . . . . . . . . . . . . 64
Descriptive Studies Without Control Groups . . . 65
ControlledStudies . . . . . . . . . . . . . . . . . 65
Conclusion . . . . . . . . . . . . . . . . . . . . . . . 68
6 Oocyte Donation
Anna Sophie Seelig,Michael Ludwig . . . . . . . . . 69
Introduction . . . . . . . . . . . . . . . . . . . . . . 69
Oocyte Recipients and Donors . . . . . . . . . . . . 70
Hormonal Substitution for Oocyte Recipients . . 70
Oocyte Donors . . . . . . . . . . . . . . . . . . . 71
Follow-up ofOocyte Donors . . . . . . . . . . . . 72
Effffects ofAnonymity and Secrecy . . . . . . . . . 74
Obstetric Outcome in Oocyte Donation Pregnancies 75
The Impact ofAge . . . . . . . . . . . . . . . . . . . 79
Conclusion . . . . . . . . . . . . . . . . . . . . . . . 83
