Handbook of New Genetic Diagnostic Technologies in Reproductive Medicine : Improving Patient Success Rates and Infant Health

194 Pages·2017·6.691 MB·English

by  Rubio, Carmen, Simón, Carlos

Handbook of New Genetic
Diagnostic Technologies in
Reproductive Medicine

Handbook of New Genetic
Diagnostic Technologies in
Reproductive Medicine
Improving Patient Success Rates and
Infant Health
Edited by
Carlos Simón and Carmen Rubio
CRC Press
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Library of Congress Cataloging-in-Publication Data
Names: Simón, Carlos, 1961- editor. | Rubio, Carmen, 1968- editor.
Title: Handbook of new genetic diagnostic technologies in reproductive medicine : improving patient
success rates and infant health / edited by Carlos Simón and Carmen Rubio.
Description: Boca Raton, FL : CRC Press, Taylor & Francis Group, 2018. | Includes bibliographical references
and index.
Identifiers: LCCN 2017035073| ISBN 9780815367932 (hardback : alk. paper) | ISBN 9781498763295 (pack-
pbk. and ebook : alk. paper) | ISBN 9781315119793 (ebook)
Subjects: | MESH: Genetic Testing | Reproductive Medicine | Infertility–diagnosis | Genetic Diseases,
Inborn–diagnosis | Prenatal Diagnosis | Diagnostic Techniques, Obstetrical and Gynecological
Classification: LCC RG627 | NLM QZ 52 | DDC 618.3/2042–dc23
LC record available at https://lccn.loc.gov/2017035073
Visit the Taylor & Francis Web site at
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and the CRC Press Web site at
http://www.crcpress.com
Contents
Foreword: Views from a Pioneer .............................................................................................................vii
Editors .......................................................................................................................................................ix
Contributors ..............................................................................................................................................xi
1. Carrier Screening for Single-Gene Disorders .............................................................................01
Julio Martin, Beatriz Rodriguez, Arantxa Hervas, Ana Bover, and Roberto Alonso
2. Meiotic Abnormalities in Infertile Males.....................................................................................07
Zaida Sarrate, Joan Blanco, and Francesca Vidal
3. Chromosomal Analysis of Sperm ..................................................................................................17
Lorena Rodrigo Vivó, Vanessa Peinado, Lucía Marín López, Rupali Chopra, and Rajni Khajuria
4. DNA Fragmentation in Sperm: Does It Matter? ........................................................................29
Nicolás Garrido, María Gil, and Rocío Rivera
5. Aneuploidy in Human Oocytes and Preimplantation Embryos .................................................41
Eva R. Hoffmann, Alan H. Handyside, and Antonio Capalbo
6. Preimplantation Genetic Testing for Aneuploidy: All You Need to Know ...............................63
Carmen Rubio, Maria Vera, Pilar López, Roser Navarro, Carmen Garcia-Pascual,
Maria Eugenia Poo, and Gary Harton
7. Mitochondria and Embryo Viability ............................................................................................79
Antonio Diez-Juan, Irene Corachan Garcia, Laura Iñiguez Quiles, Jorge Jimenez-Almazan,
and Monica Clemente
8. Preimplantation Genetic Testing for Monogenic/Single Gene Defects .....................................93
Ana Cervero, Jose Antonio Martínez-Conejero, Lucía Sanz-Salvador, Claudia Gil-Sanchís,
Maribel Sánchez-Piris, and Alan Thornhill
9. Molecular Diagnosis of Endometrial Receptivity .....................................................................103
María Ruiz-Alonso, Jose Miravet-Valenciano, Eva Gómez, Carlos Marin,
Sergio Cabanillas, Alejandro Rincon, Diana Valbuena, and Carlos Simón
10. Chromosome Abnormalities in Human Pregnancy Wastage: A Review of Cytogenetic
and Molecular Analyses................................................................................................................113
Kathy Hardy and Terry Hassold
11. Products of Conception: Current Methodologies and Clinical Applications ........................127
Nasser Al-Asmar, Sandra Garcia-Herrero, Inmaculada Campos-Galindo,
Cengiz Cinnioglu, and Marcia Riboldi
12. Non-Invasive Prenatal Testing for Aneuploidy and Beyond ....................................................139
Miguel Milán Sánchez, Emilia Mateu, Pere Mir Pardo, and David Blesa Jarque
v
vi Contents
13. Obstacles to Implementing New Technology ..............................................................................149
David Jimenez, Victor Llinares, Francisco Rodriguez, Cristina Iranzo, Luis Aznar, and
Andy Chang
14. Dynamics and Ethics of Reproductive Genetics ........................................................................161
Guido de Wert and Wybo Dondorp
Index .......................................................................................................................................................175
Foreword: Views from a Pioneer
Does anyone doubt that discoveries in genetics are changing reproductive medicine? Recent decades
have seen a plethora of technological and analytical advances. Combined with progress in sex steroid
biology, embryo tissue culture, and cryopreservation, transformative changes have occurred in assisted
reproductive technology and elsewhere in reproductive medicine.
Drs. Simon and Rubio are renowned for having contributed to this very transformation. At multiple
levels, they have not only performed the basic research that has enabled this volume to be written, but
also translated their work into improved clinical management. Their perspectives and experience have
led them to identify those areas in which investigators and clinicians alike wonder just what genetic tests
are available. And, when should genetic tests be ordered? What are their validities? How would results
alter clinical management?
In male infertility, a host of these new tests exist, all with ostensible plausibility. To what extent does
sperm aneuploidy matter? Is in vitro DNA fragmentation truly significant clinically? Is any given test
preferable? Given that meiotic abnormalities virtually assure untoward outcomes, how can one best iden-
tify these? When would one proceed with intracytoplasmic sperm injection or other treatment modali-
ties? In separate chapters, Garrido, Vidal and Rodrigo address these questions, providing salient details
on technologies required.
Genetic screening before conception is expanding. Once relevant to only a few disorders in selected
ethnic groups, genome-wide perturbations can now be sought. Martin places this potential wealth of
information in perspective. In another chapter, Cervero discusses preimplantation genetic testing for sin-
gle gene disorders and Rubio for aneuploidy. Selecting proper technology is crucial given so little DNA
exists (1 or 5–10 cells), requiring technological adaptation that is lucidly described. Various approaches
to 24 chromosome aneuploidy testing are discussed and compared. That preimplantation genetic testing-
aneuploidy should accompany preimplantation genetic testing for single gene has become clear, and a
protocol for accomplishing this is provided.
Cell free DNA in maternal plasma is increasingly interrogated to detect fetal aneuploidy and other
conditions. Milan provides details on this rapidly changing technology. At present, noninvasive screen-
ing (i.e., venipuncture only) is applied once pregnant is achieved.
Finally, not all pregnancies succeed. Studying miscarriages remains a pivotal component of counsel-
ling and management in reproductive medicine. Al-Asmar traces the success using array comparative
genomic hybridization or next generation sequencing to determine chromosomal status of miscarriages.
These technologies are of great clinical usefulness because neither requires successful culture of prod-
ucts of conception.
Overall, this handbook covers the most important laboratory technologies encountered by reproduc-
tive specialists, lab directors, and staff. The editors are to be congratulated on the scope and details of
this handbook, which belongs on the shelf (or computer screen) of all of us in the field.
Joe Leigh Simpson, MD, FACOG, FACMG, FRCOG
Senior Vice President, Research and Global Programs
March of Dimes, New York, USA
vii

Editors
Carlos Simón is a Spanish reproductive endocrinologist and researcher. He is board
certified and full professor of obstetrics and gynecology at the University of Valencia,
Valencia, Spain; adjunct clinical professor, Department of Ob/Gyn, Stanford
University School of Medicine, Stanford, CA; adjunct professor, Department of Ob/
Gyn, Baylor College of Medicine, Houston, TX; and scientific director of Igenomix.
He has published 412 papers in peer-reviewed journals with an accumulated
impact factor of 1,827.122, cited 14,355 times with an average of 35 citations/paper.
His H-Index is 66.
He is the editor of 18 books in English, Spanish, and Portuguese, and the quality of
his work has been recognized with awards by the American Society of Reproductive
Medicine, the Society for Gynecological Investigation, the Spanish Society of Obstetrics & Gynecology,
and the Spanish Fertility Society. He received the Prize Jaime I in Medical Investigation in 2011, and the
ASRM Distinguished Research Award in 2016.
Carmen Rubio was trained in science and biochemistry at the University of
Valencia, Valencia, Spain, and has a background in human embryology. She
completed her PhD in 2004 in the field of reproductive genetics specializing in
cytogenetic studies in gametes and embryos.
Becoming interested in chromosomal abnormalities in human embryos, she
did her post-doctoral research in male and female meiosis and the mechanism
underlying human aneuploidy at the laboratory of Drs. Patricia Hunt and Terry
Hassold at the School of Molecular Biosciences (Washington State University,
Pullman, WA).
At present, she is focused on embryo genetics and preimplantation embryo test-
ing at Igenomix (Valencia, Spain). She has published more than 100 papers in
the main peer-reviewed specialist journals in the field, book chapters, as well as numerous lectures at
conferences worldwide. She is one of the most cited authors in the field, with more than 25 years profes-
sional experience.
ix