Male Infertility Sijo J

Male Infertility Sijo J. Parekattil • Sandro C. Esteves Ashok Agarwal Editors

Male Infertility

Contemporary Clinical Approaches, Andrology, ART and Antioxidants

Second Edition Editors Sijo J. Parekattil Sandro C. Esteves PUR Clinic ANDROFERT and State University of Campinas University of Central Florida (UCF) (UNICAMP) Clermont, FL Campinas USA Brazil

Ashok Agarwal Cleveland Clinic Lerner College of Medicine Cleveland, OH USA

ISBN 978-3-030-32299-1 ISBN 978-3-030-32300-4 (eBook) https://doi.org/10.1007/978-3-030-32300-4

© Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, 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 free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland This work is dedicated to my wife and sons, who have been ever patient and considerate in allowing me to pursue my academic interests. It is also dedicated to my mentors who believed in me and gave me the opportunity to grow. It is also dedicated to our patients who place their faith in our hands and who allow us the honor and privilege to continue to learn and better the art of medicine for a better tomorrow. –Sijo J. Parekattil

To my father Waldemar Esteves (late) for instilling the virtues of integrity, perseverance, and enthusiasm. To my wife, Fabiola, my sons, Alexandre and Catarina, for their devotion, love, and support. To Prof. Nelson Rodrigues Netto Jr. (late) (UNICAMP), Prof. Anthony Thomas (late) (Cleveland Clinic), Prof. Sidney Glina (ABC University), and Prof. Ashok Agarwal (Cleveland Clinic) for their guidance and support and for being giants who take their apprentices by their hands and teach them how to climb; once on their shoulders they show us what to see, helping us to see better and further. –Sandro C. Esteves

To my father Professor RC Agarwal (late) for instilling the virtues of honesty, dedication, and hard work. To my wonderful wife, Meenu, sons, Rishi and Neil-Yogi, for their unconditional love and support. To Prof. Kevin Loughlin (Harvard Medical School), Prof. Anthony Thomas (late) (Cleveland Clinic), and Prof. Edmund Sabanegh (Cleveland Clinic) for their friendship, guidance, and support and for making an indelible positive impression on my life. To my associates at work, large number of researchers and students, and most importantly the patients who placed their trust in our work. –Ashok Agarwal Foreword

I have been eagerly awaiting the release of the second edition of this text, Male Infertility: Contemporary Clinical Approaches, Andrology, ART and Antioxidants, which is edited by three luminaries in the field of reproduction, Sijo J. Parekattil, MD; Sandro C. Esteves, MD; and Ashok Agarwal, PhD. The first edition of this text served as an invaluable resource to those of us involved in the clinical care of couples encountering reproductive challenges and also to those of us investigating the pathophysiology underlying disordered fertility. In the same vein, this second edition builds upon the important principles shared in that first edition but also includes new and important insights that have been subsequently reported in both the basic science and clinical literature. The editors have done a masterful job of assembling a panel of expert authors who are also fantastic writers. Each chapter is rich with important information, yet at the same time very pleasant to read. Additionally, while each chapter is a “stand-alone” piece of academic work, collectively, the chapters build upon one another to provide the reader with a truly 360-degree, state-of-the-art understanding of andrology, ART, and antioxidants. In an era where the clinical and research focus in reproductive medicine often pivots solely to assisted reproductive techniques, this text does a wonderful job of comprehensively and holistically examining andrology, assisted reproductive techniques, and the role of antioxidants. The “winners” in all of this are the clinicians who will use this book to enhance the integrated and informed care that they are providing their patients, as well as the patients themselves, who are on the receiving end of this optimized care. The editors are to be congratu- lated for passionately assembling this important group of academic manuscripts. There is no doubt that countless couples will benefit from the collective knowledge and inspiration that this text imparts within reproductive clinicians and scientists alike.

Chicago, IL, USA Robert E. Brannigan, MD

vii Preface

The practice of male infertility has dramatically evolved over the past few decades. This has been achieved after the realization of the important contribution the male counterpart holds in the couple’s infertility. It is also supported by a number of breakthroughs in the diagnosis and treatment of this medical condition. The field of male infertility truly illustrates the need for a multispecialty approach to the effective diagnosis and management of such conditions. From the initial referral possibly from a reproductive endocrinologist or gynecologist to the male infertility urologist or andrologist, a multidisciplinary team including doctors, nurses, embry- ologists, technicians, researchers, and alternative medicine specialists needs to work as a cohe- sive unit to provide our patients with the most effective and highest quality care. Due to the success of the first edition of this book in 2012, we decided to work on the second edition in 2018 with the goal to bring out a medical textbook that can serve as the most reliable source of accurate information on various aspects of the rapidly developing field of male infertility. This book was an attempt to gather experts from each of these fields and present an integrated management approach with detailed descriptions of topics ranging from the initial clinical diagnosis, management, new treatment options, and scientific rational for the various approaches. The book initially focuses on the clinical aspects of male infertility and then dives into the use of antioxidants as adjunctive therapy and the current state of affairs in antioxidant research. In this second edition, which includes 72 chapters in total across 7 parts, over 20 new chapters were added to enhance the book’s appeal by including the most recent advances brought to the male infertility arena. Additionally, this edition has new features including video clips illustrating some of the most fascinating male infertility treatment modalities and a dedicated new part on current guidelines on male infertility and antioxidants to enlighten readers on how to most optimally manage male infertility clinical scenarios. The 129 contributing authors hail from leading institutions in 18 countries across 6 continents in an attempt to capture a wide range of techniques and approaches. New to this edition are dedicated sections within each chapter covering key points and review criteria, carefully bookended by introductory and con- cluding content that sets the stage for and sums up the state of the art in male infertility. We are hoping that this text may serve as a reference guide for specialists across the male infertility team to further enhance dialogue, discussion, and refinement in our multidisciplinary approach. We would like to thank the authors for their contributions and our families for their patience in allowing us to put together this project. We wish to acknowledge the Glickman Urological & Kidney Institute at the Cleveland Clinic Foundation, the PUR Clinic with University of Central Florida, and Androfert Fertility Center for institutional support for this endeavor as well. We are grateful to Kristopher Spring, senior editor, for his support and advice, and to Michael D. Sova, developmental editor, for his tireless efforts in reviewing and editing each of the manuscripts. We hope that this book will provide a comprehensive, consolidated reference for a broad range of topics in male infertility.

Clermont, FL, USA Sijo J. Parekattil Campinas, Brazil Sandro C. Esteves Cleveland, OH, USA Ashok Agarwal

ix About the Editors

Sijo J. Parekattil, MD is Co-director of PUR Clinic (Personalized Urology & Robotics) at South Lake Hospital and Orlando Health and Associate Professor of Urology at the University of Central Florida (UCF). He was an Electrical Engineer (University of Michigan) prior to his medical training and thus has interests in surgical techniques incorporating technology, robotics, and microsurgery. He completed his urology residency training at Albany Medical Center and then went on to complete dual fellowship training from the Cleveland Clinic Foundation, Cleveland, in Laparoscopy/Robotic Surgery and Microsurgery/Male Infertility. Dr. Parekattil has received numerous awards and published several articles in the field of robotic microsurgery. He is an editor of a few textbooks on Male Infertility and a surgical textbook on Robotic Microsurgery. He is a pioneer in robotic microsurgery in urology. He has developed novel treatments for chronic groin and testicular pain. He is one of the founding board members of the Robotic Assisted Microsurgical and Endoscopic Society (RAMSES) and is on the foundation board for Florida Polytechnic University, Lakeland, FL.

Sandro C. Esteves is Medical and Scientific Director of ANDROFERT—Andrology and Human Reproduction Clinic—a referral Fertility Center for Male Reproduction in Brazil. He earned his MD in 1990 from the University of Campinas (UNICAMP), Brazil, where he did residency training in General Surgery and Urology. He completed his training in the United States (1995–1996) as a Research Fellow at the Cleveland Clinic’s Center for Reproductive Medicine. He was awarded a Master’s degree in Surgery in 1998, at UNICAMP, and a PhD in Medicine (Urology) in 2001, at the Federal University of São Paulo (UNIFESP). Dr. Esteves is a board- certified Urologist by the Brazilian Society of Urology, and a certified-ART Center Director and IVF Consultant by the Brazilian Society of Assisted Reproduction. Dr. Esteves is a Collaborating Professor in the Department of Surgery (Division of Urology) at the University of Campinas (Brazil) and Honorary Professor of Reproductive Endocrinology at the Faculty of Health, Aarhus University, Denmark. He is also Research Collaborator at the Cleveland Clinic’s Center for Reproductive Medicine (USA). His major contributions in the

xi xii About the Editors

field of reproductive medicine have been in the area of male infertility and microsurgery, reproductive endocrinology, assisted reproductive technology, cleanroom technology, and quality management. His center, ANDROFERT, was one of the first centers, both in Brazil and worldwide, to introduce quality management and IVF cleanroom technology, and it is certified according to ISO 9001:2015 and ISO 14644-1 standards. Prof. Esteves has published approximately 300 peer-reviewed scientific papers, authored over 80 book chapters, and pre- sented over 150 papers at both national and international scientific meetings. His current Hirsch index is 46 (Google Scholar) while his citation count is more than 6000. Sandro is also a Faculty Member of F1000Prime in the area of reproductive endocrinology and infertility since 2016 and is a co-founder of Group POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) (www.groupposeidon.com). He is also a member of the Society for Translational Medicine’s male infertility cooperative group. Dr. Esteves has served as an editor of eight textbooks related to male infertility, reproductive medicine, and assisted reproductive technology. He is also the guest editor of six special issues in scientific journals on topics related to reproductive medicine. He currently serves on the editorial board of several journals and is Associate Editor of International Brazilian Journal of Urology and Frontiers in Endocrinology (Reproduction). Dr. Esteves is a much-requested international lecturer and gives approximately 50 lectures annually. He has been invited as guest speaker in over 40 countries. He is the recipient of the “Alumni of the Year” Award from the Cleveland Clinic Center for Reproductive Medicine, and consecutive Star Awards from the American Society for Reproductive Medicine for the last 6 years.

Ashok Agarwal, PhD, HCLD(ABB), ELD(ACE) is the Head of Andrology Center and Director of Research at the American Center for Reproductive Medicine since 1993. He holds these positions at The Cleveland Clinic Foundation, where he is Professor of Surgery (Urology) at the Lerner College of Medicine of Case Western Reserve University. Ashok was trained in Male Infertility and Andrology at the Brigham and Women’s Hospital and Harvard Medical School and later worked as Assistant Professor of Urology at Harvard from 1988 to 1992. Ashok has over 26 years of experience in directing busy male infertility diagnostic facilities and fertility preservation services. He is very well published with over 730 scientific papers and reviews in peer-reviewed scientific journals and is ranked in Scopus as the #1 author in the world in the fields of Male Infertility/Andrology and Human Assisted Reproduction, based on the number of peer-reviewed publica- tions, citation scores (Scopus: 32,001; Google Scholar: 67,039), and h-index (Scopus: 96; Google Scholar: 125). He is currently an editor of 39 medical text books/manuals related to male About the Editors xiii

infertility, ART, fertility preservation, DNA damage, and antioxidants and active in basic and clinical research. His laboratory has trained over 1,000 scientists, clinicians, graduate, and undergraduate students from the United States and more than 55 countries. His current research interests include proteomics of male infertility and the molecular markers of oxidative stress and DNA integrity in the pathophysiology of male reproduction. Contents

Part I Male Infertility Diagnosis and Management

1 Causes of Male Infertility �� 3 Graham Luke Machen and Jay I. Sandlow 2 Epidemiologic Considerations in Male Infertility �� 15 Samuel J. Ohlander, Whitney R. Halgrimson, and Mark A. Faasse 3 Laboratory Evidence for Male Infertility �� 27 Neel Parekh and Ashok Agarwal 4 Imaging Modalities in the Management of Male Infertility �� 39 Marcello Cocuzza, Joao Paulo Cardoso, and Sijo J. Parekattil 5 Endocrinopathies �� 49 Sam Haywood, Isaac Lam, Eric L. Laborde, and Robert Brannigan 6 Oxidative Stress and Its Association with Male Infertility �� 57 Ashok Agarwal and Pallav Sengupta 7 Oxidative Stress Measurement in Semen and Seminal Plasma �� 69 Rakesh Sharma and Ashok Agarwal 8 Sperm Chromatin Integrity Tests and Indications �� 99 Rakesh Sharma, Marlon P. Martinez, and Ashok Agarwal 9 Proteomic and Metabolomic Fingerprinting in Male Infertility �� 123 Manesh Kumar Panner Selvam, Damayanthi Durairajanayagam, and Ashok Agarwal 10 Epigenetics and Male Infertility �� 139 Timothy G. Jenkins and Paul J. Turek 11 Genetic Aspects of Male Infertility �� 147 David Prokai and Orhan Bukulmez 12 Surgical Treatment for Male Infertility �� 165 Ricardo Miyaoka and Sandro C. Esteves 13 Microsurgery for Male Infertility �� 187 Rajeev Kumar and Manoj Kumar 14 Advanced Techniques of Vasoepididymostomy �� 197 Wayland Hsiao and Marc Goldstein 15 Grafting Techniques for Vasectomy Reversal �� 207 Henry M. Rosevear and Moshe Wald

xv xvi Contents

16 Mini-incision Vasectomy Reversal Using the No-Scalpel Vasectomy Instruments and Principles �� 215 Judith Dockray, Keith Jarvi, Ethan D. Grober, and Kirk C. Lo 17 Office-Based Microsurgery Under Local Anesthesia for Male Infertility �� 223 Amir Toussi and Landon W. Trost 18 Robotic Microsurgery for Male Infertility and Chronic Orchialgia �� 231 Jamin V. Brahmbhatt and Sijo J. Parekattil 19 Robotic Vasectomy Reversal: An American Perspective �� 237 Parviz Keikhosrow Kavoussi 20 Robot-Assisted Vasectomy Reversal (Vasovasostomy) �� 251 George A. de Boccard 21 Robotic-Assisted Varicocelectomy �� 255 Tung Shu and Run Wang 22 Management of Fertility Preservation in Male Cancer Patients �� 261 Rakesh Sharma, Marlon P. Martinez, and Ashok Agarwal 23 Clinical Management of Men with Nonobstructive Azoospermia due to Spermatogenic Failure �� 283 Arnold P. P. Achermann and Sandro C. Esteves 24 Novel Approaches in the Management of Klinefelter Syndrome �� 297 Muhammad Asharib Arshad, Mohamed Mostafa Arafa Omar Yamani, Haitham Tharwat Elbardisi, and Ahmad Majzoub 25 Assisted Reproductive Technology and Its Impact on Male Infertility Management �� 309 Alice Rhoton-Vlasak, Joseph M. Kramer, and Elizabeth Plasencia

Part II Sperm Physiology and Metabolism

26 Fuel/Energy Sources of Spermatozoa �� 323 Pallav Sengupta, Damayanthi Durairajanayagam, and Ashok Agarwal 27 Physiological Role of ROS in Sperm Function �� 337 Sulagna Dutta, Ralf Henkel, Pallav Sengupta, and Ashok Agarwal 28 Sperm Physiology and Assessment of Spermatogenesis Kinetics In Vivo �� 347 Matheus Roque, Giuliano Bedoschi, and Sandro C. Esteves 29 Origins of Sperm DNA Damage �� 361 Ralf Henkel and Kristian Leisegang 30 Seminal Oxidation-Reduction Potential �� 377 Mohit Rana and Ashok Agarwal

Part III Common Conditions and Factors Affecting Male Reproductive Health

31 Varicocele �� 391 Daniel Suslik Zylbersztejn and Sandro C. Esteves 32 Infection in Infertility �� 409 Ralf Henkel 33 Ejaculatory Dysfunction and Vasodynamics �� 425 Paul J. Turek Contents xvii

34 Environmental Factors �� 437 Kristian Leisegang and Ralf Henkel 35 Effect of Exogenous Medications and Anabolic Steroids on Male Reproductive and Sexual Health �� 455 Jorge Hallak, Thiago Afonso Teixeira, and Guilherme Leme de Souza 36 Male Age and Andropause �� 469 Marwan Ali and Neel Parekh 37 Apoptosis and Male Infertility �� 479 C. Latchoumycandane, S. Vaithinathan, S. C. D’Cruz, and Premendu Prakash Mathur 38 Impact of Spinal Cord Injury �� 487 Nancy L. Brackett, Emad Ibrahim, and Charles M. Lynne 39 Obesity �� 497 Ashok Agarwal and Sulagna Dutta 40 Smoking Effects on Male Fertility �� 509 Jenna Meyer and Avi Harlev 41 Recreational Drugs �� 519 Neel Parekh and Edmund Sabanegh Jr.

Part IV Nutrition, Life-Style and Antioxidants Role for Male Reproductive Health

42 Nutritional Pathways to Protect Male Reproductive Health �� 529 Tung-Chin Hsieh, Jessica Marinaro, and Paul R. Shin 43 Antioxidants and Male Infertility �� 535 Melissa Cutini, Carmine Bruno, Antonio Mancini, and Giancarlo Balercia 44 Synthetic Antioxidants �� 543 Phillip Stokes, Ruth E. Belay, and Edmund Y. Ko 45 New Developments for the Enhancement of Male Reproductive Health Using Antioxidant Therapy: A Critical Review of the Literature �� 553 Kelton Tremellen 46 In Vitro Studies of Antioxidants for Male Reproductive Health �� 569 Armand Zini, Mohannad Alharbi, and Maria C. San Gabriel 47 Antioxidants Use and Sperm DNA Damage �� 577 Marlon P. Martinez, Ahmad Majzoub, and Ashok Agarwal 48 Yoga, Meditation, and Acupuncture for Male Reproductive Health �� 593 Vidhu Dhawan and Rima Dada

Part V Assisted Reproductive Technology in Male Fertility

49 The Role of Interventions to Reduce Oxidative Stress and Improve Sperm DNA Integrity Before ICSI �� 605 Chak-Lam Cho 50 Sperm Retrieval Techniques �� 621 Ricardo Miyaoka and Sandro C. Esteves 51 Microdissection Testicular Sperm Extraction �� 637 Ahmad A. Aboukshaba and Peter N. Schlegel xviii Contents

52 Sperm Processing and Selection �� 647 Rakesh Sharma and Ashok Agarwal 53 Microfluidic Sperm Selection �� 661 Hamilton de Martin, Guilherme J. A. Wood, and Pedro Augusto A. Monteleone 54 Antioxidants in Sperm Cryopreservation �� 671 Ahmad Majzoub and Ashok Agarwal 55 Antioxidants in ICSI �� 679 Clara Palacio, Rocío Rivera, and Nicolás Garrido Puchalt 56 Role of Sperm-Hyaluronic Acid Binding in the Evaluation and Treatment of Subfertile Men with ROS-Affected Semen �� 695 Ciler Celik-Ozenci, Leyla Sati, and Gabor Huszar 57 Male Gametes In Vivo to In Vitro: Clinical and Laboratory Management of Nonobstructive Azoospermia �� 707 Dharmaraj Palanisamy, Simi Mohandas, Mohamed C. Ashraf, and Alex C. Varghese 58 Sperm DNA Damage, ART Outcomes, and Laboratory Methods for Selecting DNA Intact Sperm for ICSI �� 717 Joanna Picó, Rocío Rivera, and Nicolás Garrido Puchalt 59 Testicular Sperm in Non-azoospermic Infertile Men with Oxidatively Induced High Sperm DNA Damage �� 735 Leonardo Seligra Lopes and Sandro C. Esteves 60 Development of Artificial Gametes �� 747 Marcela Santos Procópio, Samyra Maria dos Santos Nassif Lacerda, Guilherme M. J. Costa, and Luiz Renato de França 61 ICSI and Male Infertility: Consequences to Offspring �� 767 Giuliano Bedoschi, Matheus Roque, and Sandro C. Esteves

Part VI Guidelines and Best Practices in Male Infertility and Antioxidants

62 Best Practice Guidelines for Male Infertility Diagnosis and Management �� 779 Edward D. Kim and Oliver Benton IV 63 Best Practice Guidelines for Sperm DNA Fragmentation Testing �� 793 Ahmad Majzoub, Ashok Agarwal, Chak-Lam Cho, and Sandro C. Esteves 64 Antioxidants in the Medical and Surgical Management of Male Infertility �� 805 Rossella Cannarella, Francesco Lanzafame, Rosita Condorelli, Aldo E. Calogero, and Sandro La Vignera

Part VII Special Topics

65 Fertility Preservation for Boys and Adolescents �� 819 Mohamed Mostafa Arafa and Haitham Tharwat Elbardisi 66 Novel Home-Based Devices for Male Infertility Screening �� 831 Neel Parekh, Sarah C. Vij, and Ashok Agarwal 67 Ethical Dimensions of Male Infertility �� 839 Denise A. Asafu-Adjei and Lawrence C. Jenkins Contents xix

68 Harmful Effects of Antioxidant Therapy �� 845 Ralf Henkel and Ashok Agarwal 69 Male Infertility from the Developing Nation Perspective �� 855 Kasonde Bowa, John S. Kachimba, Victor Mapulanga, Mumba Chalwe, and Elaikim Manda 70 Diabetes and Male Infertility �� 865 Denise A. Asafu-Adjei and Paul R. Gittens 71 Empiric Medical Therapy for Idiopathic Male Infertility �� 873 Tejash Shah and David Shin 72 Testosterone Therapy in Male Infertility �� 883 Ranjith Ramasamy and John M. Masterson

Index �� 891 Contributors

Arnold P. P. Achermann, MD Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, SP, Brazil Ashok Agarwal, PhD American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA Ahmad A. Aboukshaba, MD Department of Urology, Weill Cornell Medical Center, New York, NY, USA Mohannad Alharbi, MD, FRCSC Division of Urology, Department of Surgery, Royal Victoria Hospital, McGill University, Montreal, QC, Canada Department of Urology, College of Medicine, Qassim University, Qassim, Saudi Arabia Marwan Ali, MD Department of Urology, Cleveland Clinic Akron General, Akron, OH, USA Muhammad Asharib Arshad, MD Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan Denise A. Asafu-Adjei, MD, MPH Department of Urology, Columbia University Medical Center, New York, NY, USA Mohamed C. Ashraf, MD, DGO Department of IVF, Craft Hospital and Research Centre, Kodungallor, Kerala, India Giancarlo Balercia, MD Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy Giuliano Bedoschi, MD Instituto Ideia Fertil, Faculdade de Medicina do ABC, Sao Paulo, Brazil Ruth E. Belay, MD Department of Urology, Loma Linda University Health, Loma Linda, CA, USA Oliver Benton IV, MD Department of Urology, University of Tennessee Medical Center, Knoxville, TN, USA Kasonde Bowa, FRCS, FACS, MPH Department of Surgery, University Teaching Hospital Lusaka, Lusaka, Zambia Nancy L. Brackett, PhD, HCLD The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA Jamin V. Brahmbhatt, MD PUR Clinic, University of Central Florida (UCF), Clermont, FL, USA Robert Brannigan, MD Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

xxi xxii Contributors

Carmine Bruno, MD Operative Unit of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy Orhan Bukulmez, MD Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA Aldo E. Calogero, MD Department of Clinical and Experimental Medicine, University of Catania, Catania, Sicily, Italy Rossella Cannarella, MD Department of Clinical and Experimental Medicine, University of Catania, Catania, Sicily, Italy Joao Paulo Cardoso, MD Department of Urology, University of Sao Paulo (USP), Sao Paulo, Brazil Ciler Celik-Ozenci, DDS, PhD Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey Mumba Chalwe, M.Med, FCS(Uro) Ndola Central Hospital, Ndola, Zambia Chak-Lam Cho, FRCSED (Urol), FHKAM (Surgery) Department of Surgery, Union Hospital, Tai Wai, Hong Kong Marcello Cocuzza, MD, PhD Departmento de Urologia, Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil Rosita Condorelli, MD, PhD Department of Clinical and Experimental Medicine, University of Catania, Catania, Sicily, Italy Guilherme M. J. Costa, PhD Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Melissa Cutini, MD Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy S. C. D’Cruz, PhD Department of Biochemistry & Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, India Rima Dada, MD, PhD Department of Anatomy, Lab for Molecular Reproduction and Genetics, All India Institute of Medical Sciences, New Delhi, India George A. de Boccard, MD Robot-Assisted Laparoscopy Surgery Center, Clinique Generale Beaulieu, Geneva, Switzerland Luiz Renato de França, PhD, DVM Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Hamilton de Martin, MSC Assisted Reproduction Laboratory, Hospital Das Clínicas Da Universidade De São Paulo/Clínica Monteleone, São Paulo, São Paulo, Brazil Guilherme Leme de Souza, MD Androscience – Science and Innovation Center and High- Complexity Clinical and Research Andrology Laboratory, Sao Paulo, Brazil Samyra Maria dos Santos Nassif Lacerda, PhD Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Vidhu Dhawan, MD, PhD, Scholar Department of Anatomy, Lab for Molecular Reproduction and Genetics, All India Institute of Medical Sciences, New Delhi, India Judith Dockray, MBBChir, MA, MSc, FRCS Murray Koffler Urologic Wellness Centre, Mount Sinai Hospital, Toronto, ON, Canada Contributors xxiii

Damayanthi Durairajanayagam, PhD Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia Sulagna Dutta, PhD Faculty of Dentistry, MAHSA University, Jenjarom, Selangor, Malaysia Haitham Tharwat Elbardisi, MD Department of Urology, Hamad Medical Corporation, Weill Cornell Medicine Qatar, Doha, Qatar Sandro C. Esteves, MD, PhD ANDROFERT and State University of Campinas (UNICAMP), Campinas, Brazil Mark A. Faasse, MD, MPH Department of Pediatric Urology, Advocate Medical Group, Oak Lawn, IL, USA Paul R. Gittens, MD Centers for Sexual Medicine, Philadelphia, PA, USA Centers for Sexual Medicine, New York, NY, USA Urology and Obstetrics & Gynecology, Drexel University, Philadelphia, PA, USA Marc Goldstein, MD, DSc (hon), FACS Center for Male Reproductive Medicine and Microsurgery, and Department of Urology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA Ethan D. Grober, MD, Med Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada Whitney R. Halgrimson, MD Department of Urology, University of Illinois at Chicago, Chicago, IL, USA Jorge Hallak, MD, PhD Androscience – Science and Innovation Center and High-Complexity Clinical and Research Andrology Laboratory, Sao Paulo, Brazil Men’s Health Study Group, Institute for Advanced Studies, Division of Urology, Reproductive Toxicology Unit, Department of Pathology, University of São Paulo, Sao Paulo, Brazil Avi Harlev, MD Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer- Sheva, Israel Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer-Sheva, Israel Sam Haywood, MD Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA Ralf Henkel, PhD, Habil American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic, Cleveland, OH, USA Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa Wayland Hsiao, MD Department of Urology, Kaiser Permanente, Oakland Medical Center, Oakland, CA, USA Tung-Chin Hsieh, MD Department of Urology, UCSD, La Jolla, CA, USA Gabor Huszar, MD Sperm Physiology Laboratory, Yale University School of Medicine, New Haven, CT, USA Emad Ibrahim, MD Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA Keith Jarvi, MD Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada Lawrence C. Jenkins, MD, MBA Department of Urology, The Ohio State University, Columbus, OH, USA xxiv Contributors

Timothy G. Jenkins, PhD Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA John S. Kachimba, M.Med, FCS, FCS (Urol) Department of Surgery, University Teaching Hospital, Ridgeway, Lusaka, Zambia Parviz Keikhosrow Kavoussi, MD, FACS Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA Edward D. Kim, MD The University of Tennessee Medical Center, Knoxville, TN, USA Edmund Y. Ko, MD Department of Urology, Loma Linda University Health, Loma Linda, CA, USA Joseph M. Kramer, PhD IVF and Andrology Laboratory, UF Health Reproductive Medicine, Gainesville, FL, USA Manoj Kumar, MCh Department of Urology, All India Institute of Medical Sciences, New Delhi, India Rajeev Kumar, MCh Department of Urology, All India Institute of Medical Sciences, New Delhi, India Sandro La Vignera, MD, PhD Department of Clinical and Experimental Medicine, University of Catania, Catania, Sicily, Italy Eric L. Laborde, MD Department of Urology, Ochsner Health Systems, New Orleans, LA, USA Isaac Lam, BA Department of Urology, Northwestern Memorial Hospital, Chicago, IL, USA Francesco Lanzafame, MD ASP, Responsabile del Centro Territoriale di Andrologia, Catania, Italy C. Latchoumycandane, PhD Department of Life Sciences, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India Kristian Leisegang, PhD School of Natural Medicine, University of the Western Cape, Bellville, South Africa Kirk C. Lo, MD, CM Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada Leonardo Seligra Lopes, MD Department of Urology, ABC Faculty of Medicine (UROABC/ FMABC), Santo André, São Paulo, Brazil Charles M. Lynne, MD Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA Graham Luke Machen, MD Department of Urology, Medical College of Wisconsin, Milwaukee, WI, USA Ahmad Majzoub, MD Department of Urology, Hamad Medical Corporation, Weill Cornell Medicine Qatar, Doha, Qatar Antonio Mancini, MD Operative Unit of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy Elaikim Manda, M.Med (Uro) Department of Surgery, Maina Soko Military Hospital, Lusaka, Zambia Victor Mapulanga, M.Med, FCS (Uro) Department of Surgery, University Teaching Hospital, Ridgeway, Lusaka, Zambia Contributors xxv

Jessica Marinaro, MD Department of Urology, MedStar Georgetown University Hospital, Washington, DC, USA Marlon P. Martinez, MD Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines John M. Masterson, BBA Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA Premendu Prakash Mathur, MSc, PhD Department of Biochemistry & Molecular Biology, Pondicherry University, Pondicherry, India Jenna Meyer, MS Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer- Sheva, Israel Ricardo Miyaoka, MD, PhD ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, São Paulo, Brazil ANDROFERT – Center For Male Reproduction, Campinas, Brazil Simi Mohandas, MS (OBG) Department of Reproductive Medicine, Craft Hospital and Research Centre, Kodungallur, Kerala, India Pedro Augusto A. Monteleone, PhD Department of Gynecology, Hospital das Clínicas da Universidade de São Paulo/Clínica Monteleone, São Paulo, São Paulo, Brazil Samuel J. Ohlander, MD Department of Urology, University of Illinois at Chicago, Chicago, IL, USA Clara Palacio, BSc Unversitat de València and IVI Global Educaiton, IVI Foundation, Valencia, Spain Dharmaraj Palanisamy, MBBS, DNB (Gen), DNB (Uro) Department of Andrology, Craft Hospital and Research Centre, Kodungallur, Kerala, India Sijo J. Parekattil, MD PUR Clinic, University of Central Florida (UCF), Clermont, FL, USA Neel Parekh, MD Department of Urology, Cleveland Clinic Foundation, Cleveland, OH, USA Joanna Picó, BSc IVI Foundation, Instituto de Investigación Sanitaria La Fe, Valencia, Spain Elizabeth Plasencia, MD Department of Obstetrics and Gynecology, University of Florida, College of Medicine, Gainesville, FL, USA Marcela Santos Procópio, PhD Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil David Prokai, MD Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA Nicolás Garrido Puchalt, PhD, MSc Fertility and Sterility, Hospital Universitario y Politécnico La Fe, Valencia, Spain Ranjith Ramasamy, MD Department of Urology, University of Miami, Miami, FL, USA Mohit Rana, BS American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA Alice Rhoton-Vlasak, MD Department of Obstetrics and Gynecology, University of Florida, College of Medicine, Gainesville, FL, USA Rocío Rivera, PhD, MSc Andrology Laboratory and Sperm Bank, Instituto Universitario IVI Valencia, Valencia, Spain xxvi Contributors

Matheus Roque, MD, PhD Center for Reproductive Medicine, MATER PRIME, São Paulo, Brazil Henry M. Rosevear, MD Colorado Springs Urological Associates, Colorado Springs, CO, USA Edmund Sabanegh Jr, MD Cleveland Clinic Health System, Cleveland, OH, USA Maria C. San Gabriel, MSc, PhD Surgery Department, Division of Urology and Research Institute- McGill University Health Centre (MUHC-RI), McGill University, Montreal, QC, Canada Jay I. Sandlow, MD Department of Urology, Medical College of Wisconsin, Milwaukee, WI, USA Leyla Sati, MSc, PhD Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey Peter N. Schlegel, MD Department of Urology, Weill Cornell Medical Center, New York, NY, USA Manesh Kumar Panner Selvam, PhD American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA Pallav Sengupta, MSc, PhD Department of Physiology, MAHSA University, Jenjarom, Selangor, Malaysia Tejash Shah, MD Department of Urology, Rutgers New Jersey Medical School, Newark, NJ, USA Rakesh Sharma, PhD American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA David Shin, MD Department of Urology, Hackensack University Medical Center, Hackensack, NJ, USA Hackensack Meridian School of Medicine at Seton Hall University, Nutley, NJ, USA Paul R. Shin, MD Shady Grove Fertility Center, Washington, DC, USA Tung Shu, MD Vanguard Urology Institute, Houston, TX, USA Phillip Stokes, MD Department of Urology, Loma Linda University Health, Loma Linda, CA, USA Thiago Afonso Teixeira, MD, MSc Androscience – Science and Innovation Center and High-Complexity Clinical and Research Andrology Laboratory, Sao Paulo, Brazil Men’s Health Study Group, Institute for Advanced Studies, Division of Urology, University of Sao Paulo, Sao Paulo, Brazil School of Medicine, Federal University of Amapa, Macapa, Brazil Amir Toussi, MD Department of Urology, Mayo Clinic, Rochester, MN, USA Kelton Tremellen, MB, BS(Hons), PhD Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, Dulwich, SA, Australia Landon W. Trost, MD Department of Urology, Mayo Clinic, Rochester, MN, USA Paul J. Turek, MD, FACS, FRSM The Turek Clinics, San Francisco, CA, USA S. Vaithinathan, PhD Department of Biochemistry & Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, India Alex C. Varghese, PhD Department of Embryology and IVF, Craft Hospital and Research Centre, Kodungalloor, Kerala, India Contributors xxvii

Sarah C. Vij, MD Department of Urology, Cleveland Clinic Foundation, Cleveland, OH, USA Moshe Wald, MD Department of Urology, University of Iowa, Iowa City, IA, USA Run Wang, MD Division of Urology, University of Texas Medical School at Houston, University of Texas MD Anderson Cancer Center, Houston, TX, USA Guilherme J. A. Wood, MD Department of Andrology, Hospital das Clínicas da Universidade de São Paulo/Huntington IVF, São Paulo, São Paulo, Brazil Mohamed Mostafa Arafa Omar Yamani, MD Department of Andrology, Cairo University, Cairo, Egypt Armand Zini, MD, FRCSC Division of Urology, Department of Surgery, Royal Victoria Hospital, McGill University, Montreal, QC, Canada Daniel Suslik Zylbersztejn, MD, PhD DSZ Medicina Reprodutiva, São Paulo, Brazil