Table Of ContentFertility Preservation
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Editors
Fertility Preservation
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Editors
Emre Seli, MD Ashok Agarwal, PhD,
Department of Obstetrics, HCLD (ABB), EMB (ACE)
Gynecology, and Reproductive Sciences Director
Yale University School of Medicine Center for Reproductive Medicine
New Haven, CT, USA Cleveland Clinic
[email protected] Cleveland, OH, USA
[email protected]
ISBN 978-1-4419-1782-9 e-ISBN 978-1-4419-1783-6
DOI 10.1007/978-1-4419-1783-6
Springer New York Dordrecht Heidelberg London
Library of Congress Control Number: 2011936522
© Springer Science+Business Media, LLC 2012
All rights reserved. This work may not be translated or copied in whole or in part without the
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Foreword
Women diagnosed with cancer prior to or during their reproductive period
often face both the uncertainty of long-term survival, and the risk of treat-
ment-induced infertility. Treatments for common cancers occurring in
younger women often necessitate extirpation of their reproductive organs,
radiation therapy, and/or chemotherapy, each of which may partially or com-
pletely impair reproductive (and endocrine) function. Fortunately, during the
last two decades, cancer survival in the USA has improved. This has resulted
in an increased focus on maximizing the quality of life for cancer survivors.
Preserving future fertility is a crucial component of the quality of life in pre-
pubertal and reproductive age women. Similarly, cancer can also strike young
men, the treatments for which pose comparable risks to future fertility. Thus,
clinicians caring for such patients will find this textbook valuable in both
counseling and caring for younger women and men with newly diagnosed
cancers.
However, there is a third group of patients in whom fertility preservation
is of increasing relevance, interest, and importance. Women in much of the
industrial world have been progressively delaying initiation/completion of
childbearing to later in life. More women in their late 30s and early 40s are
attempting to conceive for the first time than ever before. Since the incidence
of most cancers in the reproductive age group is comparatively low, inten-
tionally postponing childbearing presents a far more common indication for
fertility preservation than cancer.
The editors are well suited to the purposes of this text. Both are gifted
fertility practitioners and physician scientists. Dr. Ashok Agarwal is the
Director of the Center for Reproductive Medicine at Cleveland Clinic. He has
authored over 150 peer reviewed publications, garnered multiple research
grants, and is internationally recognized for his outstanding contributions in
scientific and clinical aspects of reproductive medicine. Dr. Emre Seli is an
accomplished reproductive scientist and physician at the Yale School of
Medicine. Dr. Seli has conducted novel and potentially landmark research
regarding basic oocyte mRNA processing, a process relevant to maternal age-
associated infertility. Dr. Seli has also pioneered the development of novel
technologies for assessing embryo quality in vitro. Meanwhile, Dr. Seli
directs a highly successful oocyte donation program at his home institution.
Drs. Agarwal and Seli have assembled an “All Star” cast of authors, each
an expert in the topics about which they write. The goal of the text is to pres-
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ent strategies for fertility preservation in women and men who require gonad-
otoxic and other fertility-impairing therapies. In addition, key epidemiologic,
ethical, medico-legal, psychologic and social aspects of fertility preservation
are discussed. A format that combines a concise scientific background with
practical methodological information, including detailed and straightforward
algorithms, is utilized. Step-by-step protocols for laboratory procedures are
presented. The result is a concise, readable, and highly practical reference
guide for reproductive endocrinologists, embryologists, reproductive scien-
tists, and oncologists. This text will also greatly aid the general ob/gyn in
counseling both the relatively uncommon younger patient facing fertility-
compromising treatments and the increasingly common woman in her 30s or
early 40s who elects to delay fertility for a myriad of professional and per-
sonal reasons. For all these reasons, I can enthusiastically recommend this
textbook to you.
New Haven, CT Charles J. Lockwood, MD
Preface
Dum spiro, spero [As long as I breathe, I hope]
Marcus Tullius Cicero
Cancer is not uncommon in men and women of reproductive age. In the USA
alone, over 130,000 men and women below the age of 45 were afflicted with
cancer in 2008. The compromised fertility that will be faced by many of these
patients can result in significant psychosocial stress and in reduced quality of
life; even long after the cancer has been successfully treated.
Fortunately, the rapid pace of scientific and technological discovery has
increased the options available to men and women in need of fertility preser-
vation. More than 30 years after the birth of the first child conceived by
assisted reproductive technologies, we are now able to cryopreserve embryos,
spermatozoa, and oocytes as well as testicular and ovarian tissue. In addition,
the effect of gonadotoxic treatments on fertility is better defined and the use
of medical interventions for fertility preservation is within reach. With
increasingly complex modalities available for fertility preservation comes the
need for a clear, concise, readable, and practical text to serve as a resource for
healthcare providers.
This textbook has been written with the aim of providing an update on
options for fertility preservation for both men and women. Within this con-
text, this text reviews current therapeutic modalities in great detail and
describes the biologic basis for available interventions. A key aspect of this
volume is the valuable contributions from oncologists, obstetricians, psy-
chologists, epidemiologists, and ethicists in addition to reproductive scien-
tists and infertility specialists. This thorough resource thus recapitulates the
multidisciplinary approach that is required to adequately provide patient care
with a view to fertility preservation.
Following introductory chapters on the epidemiology and ethics of fertil-
ity preservation, this book is divided into two main sections that share a simi-
lar overall format while reviewing fertility preservation in female and then
male patients. Each section starts with a chapter reviewing the gender-
specific biology of the reproductive system within the context of fertility
preservation. Then, the impact of gonadotoxic treatment on gonadal function
and on the offspring is reviewed. Additional chapters in each section sum-
marize established and experimental methodologies currently available for
fertility preservation in both sexes, providing detailed protocols for laboratory
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procedures. The resulting comprehensive text provides cutting edge science
and evidence-based suggestions regarding potential interventions directed at
fertility preservation.
This book is dedicated to our patients who, despite facing potentially lethal
diagnoses and compromised quality of life, continue to hope, to live, and to
pursue their dreams of parenthood.
New Haven, CT Emre Seli
Cleveland, OH Ashok Agarwal
Contents
Part I Overview of Fertility Preservation: Epidemiologic,
Social, Ethical, and Medicolegal Aspects
1 The Epidemiology of Fertility Preservation .............................. 3
William Murk and Emre Seli
2 Ethical Discussions in Approaching Fertility
Preservation .................................................................................. 19
Pasquale Patrizio
Part II Fertility Preservation in Women
3 Ovarian Follicle Development and Fertility
Preservation .................................................................................. 29
Yuichi Niikura and Joshua Johnson
4 Impact of Chemotherapy and Radiotherapy
on the Ovary ................................................................................. 45
Maya L. Kriseman and Ertug Kovanci
5 Impact of Chemotherapy and Radiotherapy
on the Uterus ................................................................................ 57
Abbie L. Fields, Deleep Kumar Gudipudi,
and Giuseppe Del Priore
6 Ovarian Transposition ................................................................. 71
Elena S. Ratner, Dan-Arin Silasi, and Masoud Azodi
7 Embryo Cryopreservation and Alternative Controlled
Ovarian Hyperstimulation Strategies for Fertility
Preservation .................................................................................. 77
Bulent Urman, Ozgur Oktem, and Basak Balaban
8 Oocyte Cryopreservation ............................................................. 89
Andrea Borini and Veronica Bianchi
9 Ovarian Tissue Cryopreservation
and Autotransplantation ............................................................. 107
Mohamed A. Bedaiwy, Gihan M. Bareh,
Katherine J. Rodewald, and William W. Hurd
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10 Oocyte In Vitro Maturation: Formidable Obstacles
on the Road to Fertility Preservation ......................................... 121
David F. Albertini
11 Whole Ovary Cryopreservation .................................................. 129
Hulusi Bulent Zeyneloglu, Gogsen Onalan,
and Cengiz Karakaya
12 Risk of Transplanting Cryopreserved Ovarian Tissue
in Women with Malignancies ...................................................... 135
Javier Domingo del Pozo, María Sánchez-Serrano,
and Antonio Pellicer
13 Gonadotropin-Releasing Hormone Agonists
in Fertility Preservation ............................................................... 145
Hakan Cakmak and Emre Seli
14 Fertility Preservation in Gynecologic Malignancies ................. 159
Christine E. Richter and Peter E. Schwartz
15 Third-Party Reproduction and Adoption After
Cancer: Practical and Emotional Considerations .................... 199
Dorothy A. Greenfeld
16 Pregnancy and Cancer Treatment .............................................. 209
Christine Laky and Mert Ozan Bahtiyar
17 Fertility Preservation Strategies in Healthy Women ................ 225
Enrique Soto and Alan B. Copperman
18 Approach to Fertility Preservation in Adult
and Prepubertal Females ............................................................. 233
Kenny A. Rodriguez-Wallberg and Kutluk Oktay
Part III Fertility Preservation in Men
19 Spermatogenesis and Testicular Function ................................. 245
Ciler Celik-Ozenci
20 Impact of Radiotherapy and Chemotherapy
on the Testis .................................................................................. 261
Carolina Ortega and Herman Tournaye
21 Impact of Paternal Exposure to Gonadotoxins on Embryo
and Offspring and the Male Evaluation .................................... 271
Kathleen Hwang, Paul Gittens, Desiderio Avila Jr.,
and Larry I. Lipshultz
22 Update on Sperm Banking .......................................................... 289
Pankaj Talwar
23 Preservation of Sperm Isolates or Testicular
Biopsy Samples ............................................................................. 303
Bhushan K. Gangrade
