Armand Zini · Ashok Agarwal Editors A Clinician’s Guide to Sperm DNA and Chromatin Damage A Clinician’s Guide to Sperm DNA and Chromatin Damage Armand Zini • Ashok Agarwal Editors A Clinician’s Guide to Sperm DNA and Chromatin Damage Editors Armand Zini, MD, FRCSC Ashok Agarwal, PhD Professor American Center for Reproductive Department of Surgery Medicine Division of Urology Glickman Urological and Kidney Institute McGill University Cleveland Clinic Montreal, QC, Canada Cleveland, OH, USA ISBN 978-3-319-71814-9 ISBN 978-3-319-71815-6 (eBook) https://doi.org/10.1007/978-3-319-71815-6 Library of Congress Control Number: 2017963632 © Springer International Publishing AG 2018 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, express 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. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Foreword One of the great challenges for assessing male fertility is that with the microscope we can see the outside of a sperm and generally how it swims but that arguably the most important aspects of how it works to fertilize the egg and ultimately make a baby are hidden from view inside its head. One of the earliest ways of trying to crack that puzzle was to assess how deoxyribonucleic acid is packaged within the sperm and whether alterations in that packaging cause problems with male repro- duction. Scientific and clinical studies abound, but the conclusions are varied and challenging to interpret. The editors and authors of this book have done a masterful job in assembling the most complete compendium to date on the subject of sperm DNA packaging and most importantly its clinical relevance. It’s a reference work that will mark the era of sperm DNA assessment in the evaluation of male fertility and guide the clinician in what to order and how to interpret the results. Craig Niederberger, MD, FACS Department of Urology, UIC College of Medicine Department of Bioengineering, UIC College of Engineering Fertility and Sterility Chicago, IL, USA v Preface The essential role and pathophysiology of sperm DNA integrity in human reproduc- tion has been increasingly recognized and extensively studied in the last few decades. Sperm DNA fragmentation (SDF) has emerged as a valuable tool for male infertility evaluation. Defects in sperm DNA integrity are associated with modifica- tions during spermatogenesis, inflammatory processes, varicocele, and elevated post-testicular oxidative stress. Consequently, it has great potential as a functional diagnostic test that could complement the conventional sperm analysis. Clinical evidence is accumulating to show that the integrity of sperm DNA may also be linked with suboptimal embryo development, implantation failure, and recurrent miscarriage. The focus on sperm DNA damage continues to generate enormous interest among reproductive health specialists and basic medical scientists, and this in part is fueled by the growing awareness that ICSI is not a panacea for all couples diag- nosed with male infertility. Moreover, with the success rates of ICSI capping at 50–60%, the pursuit for a reliable test of sperm function which can accurately pre- dict fertility in assisted reproduction has taken on a renewed sense of urgency. Our book A Clinician’s Guide to Sperm DNA and Chromatin Damage summa- rizes the role of SDF in male infertility. Firstly, the normal sperm chromatin struc- ture and causative mechanisms of SDF are briefly introduced. Currently available SDF assays are also described. Secondly, the etiology of SDF and its implications on natural pregnancy and ART outcomes are presented. Finally, treatment options for high SDF and the clinical application of SDF tests are proposed. The book is written by internationally recognized experts from 15 countries and is organized into five sections and 32 chapters. Part I contains three chapters on the basic aspects of sperm chromatin structure, whereas the various tests used to evalu- ate sperm DNA fragmentation are discussed in seven chapters under Part II. In Part III, the etiology of this enigmatic test is described within eight chapters, while the clinical usage of SDF tests, a must read, is well-elaborated in six chapters within the penultimate Part IV. The treatment options for men with clinically significant SDF are the subject of Part V which is highlighted in eight impressive chapters. vii viii Preface We are deeply grateful to our distinguished group of contributors for sharing their research and clinical knowledge and experience. Our book is an excellent and timely product of effective collaboration with members of the Springer Publishing House. The outstanding support of developmental editors Barbara Lopez-Lucio and Sarah Simeziane and editor Kristopher Spring was highly commendable. The edi- tors are tremendously grateful to their families for their unwavering love and support. Montreal, QC, Canada Armand Zini, MD, FRCSC Cleveland, OH, USA Ashok Agarwal, PhD Contents Part I Human Sperm Chromatin Structure 1 Sperm Chromatin: An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Rod Balhorn 2 Sperm Nucleoproteins (Histones and Protamines) . . . . . . . . . . . . . . . 31 Ferran Barrachina, Ada Soler-Ventura, Rafael Oliva, and Meritxell Jodar 3 Sperm Nuclear Architecture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 W. Steven Ward Part II Laboratory Evaluation of Sperm Chromatin and DNA Damage 4 Sperm Chromatin Structure Assay (SCSA®): Evolution from Origin to Clinical Utility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Donald P. Evenson 5 TUNEL Assay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 Monica Muratori and Elisabetta Baldi 6 TUNEL Assay by Benchtop Flow Cytometer in Clinical Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 Rakesh Sharma, Zeynep Cakar, and Ashok Agarwal 7 The Comet Assay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Elva I. Cortés-Gutiérrez, Martha I. Dávila-Rodríguez, and Carmen López-Fernández 8 Sperm Chromatin Dispersion (SCD) Assay . . . . . . . . . . . . . . . . . . . . . 137 José Luis Fernández, Stephen Johnston, and Jaime Gosálvez 9 Cytochemical Tests of Sperm Chromatin Maturity . . . . . . . . . . . . . . . 153 Juris Erenpreiss and Ksenija Zubkova ix x Contents 10 Is There an Optimal Sperm DNA Test? . . . . . . . . . . . . . . . . . . . . . . . . 163 Michelle M. Kim and Cigdem Tanrikut Part III Etiology of Sperm DNA Damage: Biological and Clinical Factors 11 Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 Ralf Henkel and Michael Solomon 12 Apoptosis in Ejaculated Spermatozoa and in the Normal and Pathological Testes: Abortive Apoptosis and Sperm Chromatin Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197 Denny Sakkas and Hasan M. El-Fakahany 13 Defective DNA Repair in Spermiogenesis . . . . . . . . . . . . . . . . . . . . . . . 219 Tiphanie Cavé, Olivier Simard, Marie-Chantal Grégoire, and Guylain Boissonneault 14 Defective Spermatogenesis and Sperm DNA Damage . . . . . . . . . . . . . 229 Rakesh Sharma and Ashok Agarwal 15 Sperm Chromatin and Lifestyle Factors . . . . . . . . . . . . . . . . . . . . . . . 263 Sarah K. Fatool and Avi Harlev 16 Cancer and Sperm DNA Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 Peter T.K. Chan and Bernard Robaire 17 Sperm Chromatin and Environmental Factors . . . . . . . . . . . . . . . . . . 301 Aleksander Giwercman and Marcello Spanó 18 Sperm DNA Damage and Oocyte Repair Capability . . . . . . . . . . . . . 321 Sezgin Gunes and Semra Sertyel Part IV Clinical Studies on Utility of Sperm DNA Damage Tests 19 Experimental Studies on Sperm DNA Fragmentation and Reproductive Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 Serafín Perez-Cerezales, Priscila Ramos-Ibeas, Eva Pericuesta Camacho, Raul Fernández-González, Angela Patricia López-Cardona, Ricardo Laguna- Barraza, Noelia Fonseca Balvís, Alejandro Chacón de Castro, Benjamin Planells, and Alfonso Gutiérrez-Adan 20 Sperm DNA and Natural Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 Marcello Spanò and Aleksander Giwercman 21 Sperm DNA and ART (IUI, IVF, ICSI) Pregnancy . . . . . . . . . . . . . . . 393 Mona Bungum and Krzysztof Oleszczuk Contents xi 22 Sperm DNA and Pregnancy Loss After IVF and ICSI . . . . . . . . . . . . 411 Nirlipta Swain, Gayatri Mohanty, and Luna Samanta 23 Sperm DNA Tests Are Clinically Useful: Pro . . . . . . . . . . . . . . . . . . . . 431 Luke Simon, Douglas T. Carrell, and Armand Zini 24 Sperm DNA Tests Are Clinically Useful: CON. . . . . . . . . . . . . . . . . . . 469 Katherine Rotker and Mark Sigman Part V Treatment Options for Men with Sperm DNA Damage 25 Antioxidant Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 Ahmad Majzoub and Ashok Agarwal 26 Varicocelectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495 Matheus Roque and Sandro C. Esteves 27 Physiological Intracytoplasmic Sperm Insemination Based on Hyaluronic Acid- Binding Ability . . . . . . . . . . . . . . . . . . . . . . . . . . . 513 Mohammad Hossein Nasr-Esfahani, Shaghayegh Foroozan-Boroojeni, and Marziyeh Tavalaee 28 Advanced Sperm Processing/Selection Techniques . . . . . . . . . . . . . . . 529 Ashok Agarwal and Manesh Kumar Panner Selvam 29 Use of Testicular Sperm for ICSI: Pro . . . . . . . . . . . . . . . . . . . . . . . . . 545 Sandro C. Esteves and Matheus Roque 30 Debate on the Use of Testicular Sperm for ICSI: Con . . . . . . . . . . . . 559 Peter T.K. Chan 31 S trategies to Diminish DNA Damage in Sperm Samples Used for ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571 Jaime Gosálvez, Ashok Agarwal, and Sandro C. Esteves 32 S perm DNA Testing: Where Do We Go from Here? . . . . . . . . . . . . . . 589 Ahmad H. Al-Malki and Armand Zini Epilogue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 597