Exercise and Human Reproduction Diana Vaamonde Stefan S

Exercise and Human Reproduction Diana Vaamonde Stefan S. du Plessis • Ashok Agarwal Editors

Exercise and Human Reproduction Induced Fertility Disorders and Possible Therapies Editors Diana Vaamonde, PhD Ashok Agarwal, PhD, HCLD (ABB), Department of Morphological Sciences ELD (ACE) School of Medicine American Center for Reproductive University of Cordoba Medicine International Network on Physical Cleveland Clinic Foundation Exercise and Fertility (INPEF) Cleveland, OH, USA Cordoba, Spain

Stefan S. du Plessis, MBA, PhD (Stell) Division of Medical Physiology Department of Biomedical Sciences Stellenbosch University Tygerberg, Cape Town, South Africa

ISBN 978-1-4939-3400-3 ISBN 978-1-4939-3402-7 (eBook) DOI 10.1007/978-1-4939-3402-7 Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2016932003

© Springer Science+Business Media New York 2016 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 illus- trations, 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 ex- empt 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.

Printed on acid-free paper

Springer Science+Business Media LLC New York is part of Springer Science+Business Media (www.springer.com) Foreword

When a female athlete asks you as her physician, or her science teacher, or her coach, or her pharmacist, or her trainer, a seemingly simple set of two questions, like: “Can I continue to compete on my club soccer team and my husband on his while we are trying to get, and how will that affect our odds of getting pregnant?” and “Will prenatal vitamins help for me or for him or for both so we do have a better chance of conceiving a healthy baby?” You might probe with a few more questions, like how often and how intensely your patient and her partner practice and play. You would then think there would be an easy “Googleable source” to find answers. You had most likely be disappointed, until now. Yes, you would probably know that as the frequency and intensity of exercise increases, greater concern and major reactions might cause deleterious effects on somatic growth, pubertal development, and biological maturation. But you would almost certainly lack definitive answers. This book clarifies the questions to ask so that answers to these and many other key questions are clear, and does the most important part of knowing about any field, letting you know where the data are not available and/or are not definitive. For example, the authors of Chap. 17 present the data clearly on the interactions between the various components of oral or transdermal contracep- tion and factors influencing exercise performance. But the authors also state clearly where more data are needed to define specifically and with conclu- siveness the impact of specific hormonal contraceptive use and exercise performance. Yes, while sports and sex stories and videos are the most read and watched, it is rarer than seeing a 1947 Mercedes two seat convertible with a Spanish license plate on an American highway that practitioners of medicine or of coaching, or even trainers or participants have critical and well-informed conversations about how sex and sport performance relate to fertility and pregnancy outcomes. You want experts in the field to describe the current state of the art and the science, and that is what this book gives you. Whether the most strenuous part of your day is shampooing your hair or galloping 1000 m repeats at dawn and at dusk, this book answers concerns that range from the effects of specific nutrition and meditationon pregnancy rates and outcomes of oral contraceptive and anabolic steroid use you should have

v vi Foreword for your own well-being, and for the practitioners ask casual or concentrated questions. No matter who you are (and whether you know definitively that “who” should be a “whom” or a “who”), your physical activities and nutritional patterns affect your sex hormones and physiology. And for those most at risk of disturbing their reproductive health—those who exercise the most, the least, or with abetting from steroids—mastering the distinctions between beneficial and harmful levels of activity and nutrient intake is critical. Making sure you or your patients mechanics are primed for healthy baby making is simply one aspect, if a significant one, of exercise for both fitness and health (these are not the same, as the book differentiates). Bone health, nutrient availability, endocrine function, metabolism, mental well-being, and physical exercise intensity all interact—and the key knowledge about and parts of those complex interactions are described with enviable clarity in this book. And by the way, for the practitioner or the coach, or player, it is indispensable in guiding answers about exercise and fertility in both men and women—if you would read the chapter on that very subject about chances of getting pregnant while competing in this book, you might know to ask a few more questions to help define your answers to the questions posed at the start of this foreword. Whether you want just more information to advise your patients, or even your daughter, son, or yourself, or are a major researcher in the field, this book lets you know how to advise based on the current state of that area of this field. Yes, now there is a complete guide coupled with Physiologic Reference Manual, and you are reading from it. This book is unparalleled, unequalled, and indispensable for all touching others in any of the areas that affect the mix of sex and sport.

Chief Wellness Officer, The Cleveland Clinic Gorman Family Chair Holder and Chair of the Wellness Institute at the Cleveland Clinic

Author of Four #1 NY Times Best Sellers, including RealAge: Are You As Young As You Can Be? and YOU: The Owner’s Manual.

Michael F. Roizen MD Preface

The etiologies of human reproductive disorders are fairly well known; yet, there are still many instances in which infertility is classified as idiopathic. This simply means that the cause behind the problem is unknown. There is growing evidence that physical exercise and sports practice may affect reproduction which may be the unknown factor in certain infertility cases. With this first-of-a-kind textbook, we aim to provide a comprehensive review of the interaction between exercise and human reproduction, how exercise can have a positive or negative impact on male and female fertility with specific emphasis on the mechanisms that may lead to such effects. This textbook, which consists of 20 different yet interrelated themed topics, is intended to provide the reader with a meaningful and comprehensive review of the biological processes related to sports practice and how they interact with the reproductive function. The content covers the fundamental principles of human reproductive potential, sports physiology, the interaction between physical exercise and the endocrine and reproductive systems, associated nutritional aspects and possible strategies to avoid the potential harm of exercise on human reproduction. Each chapter was written by inter- nationally recognized scientists and clinicians, making the text ideal for those seeking to increase their general knowledge in the field. We trust that this book will have a broad and global appeal and be used not only as a reference for basic scientists, in the fields of sports medicine and reproductive medicine; but may also act as a guideline for physicians, physiologists, coaches, and professionals in the sports-human reproduction fields. Moreover, we anticipate that it may be an invaluable tool for multidis- ciplinary research teams since it brings together knowledge from a multitude of fields desiring that future research gaps and flaws will be diminished. We want to thank all of the contributing authors for their inputs and are especially grateful to Michael D. Sova (developmental editor) and Kristopher Spring (executive editor) for their tireless efforts in reviewing and editing each manuscript. We would also like to acknowledge the University of Cor- doba (Spain), the Division of Medical Physiology at Stellenbosch University (South Africa) and the American Center for Reproductive Medicine at the Cleveland Clinic (USA) for their institutional support. Finally, we want to express our gratitude toward our families for their support and patience in allowing us to complete this book.

vii viii Preface

Cordoba, Spain Diana Vaamonde

Tygerberg, Cape Town, South Africa Stefan S. du Plessis

Cleveland, OH, USA Ashok Agarwal The original version of the book was revised. An erratum can be found at DOI 10.1007/978-1-4939-3402-7_21 Contents

1 Overview of the Male Reproductive System �� 1 Luis Jiménez-Reina, Pieter Johann Maartens, Ignacio Jimena-Medina, Ashok Agarwal and Stefan S. du Plessis

2 Overview of the Female Reproductive System �� 19 Juan Andrés Ramírez-González, Ricardo Vaamonde-Lemos, Joao Sabino Cunha-Filho, Alex C. Varghese and R. James Swanson

3 Overview of Fertilization, Gestation, and Parturition �� 47 Sergio Oehninger, R. James Swanson and Roberto Matorras

4 Conceptual and Terminological Foundations for the Sciences of Physical Exercise: New Perspectives �� 69 Marzo Edir Da Silva-Grigoletto and Juan Ramón Heredia Elvar

5 Sports Physiology and Endocrinology (Endurance vs. Resistance Exercise) �� 75 Anthony C. Hackney and Mehis Viru

6 General Adaptations to Exercise: Acute Versus Chronic and Strength Versus Endurance Training �� 93 Michael I. Lambert

7 Impact of Physical Activity and Exercise on Male Reproductive Potential: Semen Alterations �� 101 Diana Vaamonde, Ashok Agarwal, Stefan S. du Plessis, Carolina Algar-Santacruz and Thinus Frans Kruger

8 Hormonal Changes Associated with Physical Activity and Exercise Training �� 125 Anthony C. Hackney, William J. Kraemer and David R. Hooper

9 Common Male Reproductive Tract Pathologies Associated with Physical Activity, Exercise, and Sport �� 145 Amy R. Lane, Alberto Da Costa Stein and Vanessa Krebs Genro

ix x Contents

10 Consequences of the Use of Anabolic-Androgenic Steroids for Male Athletes’ Fertility ...... 153 Juan Manuel García-Manso and Teresa Valverde Esteve 11 Impact of Physical Activity and Exercise on Female Reproductive Potential ...... 167 Rebecca J. Mallinson, Jenna C. Gibbs and Mary Jane De Souza 12 Hormonal and Reproductive Changes Associated with Physical Activity and Exercise ...... 187 Jenna C. Gibbs, Rebecca J. Mallinson and Mary Jane De Souza

13 Risk Biotypes and the Female Athlete Triad ...... 209 Kathryn E. Ackerman, Maria de Lourdes Eguiguren and Michelle Barrack

14 Consequences of the Use of Anabolic-Androgenic Steroids on Female Athletes’ Fertility ...... 229 Juan Manuel García-Manso and Teresa Valverde Esteve

15 Impact of Intense Physical Activity on Puberty and Reproductive Potential of Young Athletes ...... 239 Neoklis A. Georgopoulos and Nikolaos D. Roupas

16 Physical Activity and Pregnancy ...... 253 Sarah J. Moss, Andries Fourie van Oort and Yves Schutz

17 Impact of Combined Oral Contraceptive Use on Exercise and Health in Female Athletes ...... 287 Heather C. M. Allaway, Rebecca J. Mallinson and Mary Jane De Souza

18 Oxidative Stress and Infertility: A Possible Link to Exercise .... 303 Pieter Johann Maartens, Jason Peng, Ashok Agarwal, Diana Vaamonde and Stefan S. du Plessis

19 Nutritional Deficiencies and Impairment of Fertility in Athletes ...... 317 Juan Marcelo Fernández

20 Nutritional Strategies to Reduce Potential Fertility Problems Induced by Exercise. Nutritional and Exercise Strategies to Improve Fertility Disorders ...... 331 Diana Vaamonde, Juan Marcelo Fernández, Carolina Algar-Santacruz and Juan Manuel García-Manso

Erratum ...... E1

Index ...... 349 Contributors

Kathryn E. Ackerman, MD, MPH Division of Sports Medicine, Boston Children’s Hospital, Sports Endocrine Research Lab, Neuroendocrine Unit, Massachusetts General Hospital Boston, Boston, MA, USA Ashok Agarwal, PhD, HCLD (ABB), ELD (ACE) American Center for Reproductive Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA Carolina Algar-Santacruz, BSN Scientific Sport Association, Nutrir, Nutrición Médica y Ejercicio, Córdoba, Spain Heather C. M. Allaway, MS Department of Kinesiology, Pennsylvania State University, University Park, PA, USA Michelle Barrack, PhD, RD Department of Family and Consumer Sci- ences, California State University, Long Beach, CA, USA Joao Sabino Cunha-Filho, MD, PhD Department of Obstetrics and Gyne- cology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Marzo Edir Da Silva-Grigoletto, PhD Department of Physical Education, Universidade Federal de Sergipe, Aracaju, SE, Brazil Mary Jane De Souza, PhD Department of Kinesiology, Pennsylvania State University, University Park, PA, USA Stefan S. du Plessis, MBA, PhD (Stell) Division of Medical Physiology, Department of Biomedical Sciences, Stellenbosch University, Cape Town, Tygerberg, South Africa Maria de Lourdes Eguiguren, MD Department of Pediatric and Adoles- cent Medicine, Mayo Clinic, Rochester, MN, USA Juan Marcelo Fernández, MSc, PhD Sport and Clinical Nutrition, Nutri- tion Group, Nutrir Medical Nutrition and Exercise Clinic, Andalusian Soci- ety of Sports Medicine (S.A.M.E.D.E.), Cordoba, Spain Juan Manuel García-Manso, BS, MS, PhD Department of Physical Edu- cation, Universidad de Las Palmas de GranCanaria, Islas Canarias, Spain Vanessa Krebs Genro, PhD Department of Obstetrics and Gynecology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grand do Sul, Brazil

xi xii Contributors

Neoklis A. Georgopoulos, MD, PhD Department of Obstetrics and Gyne- cology, Division of Reproductive Endocrinology, University of Patras, Medi- cal School, University Hospital, Patras, Greece Jenna C. Gibbs, PhD Department of Kinesiology, Pennsylvania State Uni- versity, University Park, PA, USA Anthony C. Hackney, PhD, DSc Department of Exercise & Sport Science, Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA Juan Ramón Heredia Elvar, MSc Department of Fitness and Health, Inter- national Institute for Exercise Science and Health, Alfàs del Pi, Spain David R. Hooper, MA Department of Kinesiology, University of Connecti- cut, Storrs, CT, USA Ignacio Jimena-Medina, MD, PhD Department of Morphological Sciences, School of Medicine, University of Cordoba, Cordoba, Spain Luis Jiménez-Reina, MD, PhD Department of Morphological Sciences, School of Medicine, University of Cordoba, Cordoba, Spain William J. Kraemer, PhD Department of Kinesiology, Physiology, Neuro- biology, Medicine, University of Connecticut, Storrs, CT, USA Thinus Frans Kruger, MBChB, MPharMed, MMed, MD, DSc Depart- ment of Obstetrics and Gynecology, Tygerberg Hospital, Stellenbosch Uni- versity, Cape Town, Western Cape, South Africa Michael I. Lambert, PhD Division of Exercise Science and Sports Medi- cine Department of Human Biology, University of Cape Town, Cape Town, Western Cape, South Africa Amy R. Lane, BS, MA Department of Allied Health Sciences, University of North Carolina, Chapel Hill, NC, USA Pieter Johann Maartens, BSc, HonBSc, MScMedSci Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch Univer- sity, Cape Town, Tygerberg, South Africa Rebecca J. Mallinson, PhD Department of Kinesiology, Pennsylvania State University, University Park, PA, USA Roberto Matorras, MD, PhD Department of Obstetrics and Gynecology, Human Reproductive Unit, Cruces Hospital, Basque Country University, IVI Bilbao, Baracaldo, Vizcaya, Spain Sarah J. Moss, PhD, MBA Physical activity, Sport and Recreation Research Focus Area, Faculty of Health Sciences, North-West University, Potchefst- room, South Africa Sergio Oehninger, MD, PhD Department of Obstetrics and Gynecology, The Jones Institute for Reproductive Medicine/EVMS, Norfolk, VA, USA Contributors xiii

Andries Fourie van Oort, MSc Physical activity, Sport and Recreation Research Focus Area, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa Jason Peng, BS Center for Reproductive Medicine, Cleveland Clinic Foun- dation, Cleveland, OH, USA Juan Andrés Ramírez-González, MD, PhD Department of Morphology, Health Sciences Faculty, University of Las Palmas De Gran Canaria, Las Palmas De Gran Canaria, Spain Nikolaos D. Roupas, MD, PhD Department of Obstetrics and Gynecol- ogy, Division of Reproductive Endocrinology, University of Patras, Medical School, University Hospital, Patras, Greece Yves Schutz, PhD Department of Integrative Physiology, University of Fri- bourg, Fribourg, Switzerland Alberto Da Costa Stein, PhD Department of Urology and Reproduction, Insemine Human Reproduction Center, Porto Alegre, Rio Grande do Sul, Brazil R. James Swanson, BS, BSN, MS, HCLD, PhD Department of Biological Sciences, Old Dominion University, Norfolk, VA, USA Diana Vaamonde, MS, PhD Department of Morphological Sciences, School of Medicine, University of Cordoba, International Network on Physical Exer- cise and Fertility (INPEF), Cordoba, Spain Ricardo Vaamonde-Lemos, MD, PhD Department of Morphological Sci- ences, School of Medicine, University of Córdoba, Córdoba, Spain Teresa Valverde Esteve, PhD Laboratorio de Investigación de Ciencias del Deporte, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain Alex C. Varghese, PhD ASTRA Fertility Group, Mississauaga, Ontario, Canada Mehis Viru, PhD Faculty of Exercise and Sport Sciences, University of Tartu, Tartu, Estonia About the Authors

Diana Vaamonde MS, PhD (Diana Maria Vaamonde Martin) is a professor at School of Medicine of the Uni- versity of Cordoba (Cordoba, Spain). Dr. Vaamonde cur- rently leads a PhD research group in the area of physical exercise and fertility, with several ongoing doctoral theses. She received her bachelors in biology from Wash- ington and Lee University in 1998 and her masters in biology with emphasis on human reproduction from Old Dominion University/Jones Institute for reproductive medicine in 2004. She later completed a PhD program in physical activity and sport sciences at the University of Cordoba (Spain) where she brought together knowledge from the reproductive medicine and the sports medicine fields. Her main expertise is in the area of male infertility and physical exercise. Most of her work has been on the effect of sports training, especially in elite athletes, on the male reproductive system. Her most recent work has included assessment of sperm DNA damage as a result of physical exercise as well as the use of antioxidant agents to revert exercise-associated damage in animal models. She has presented part of her work in prestigious international meetings (European Society for Human Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine, European College of Sport Sciences). She has been invited as a speaker on the andrology pre-congress course of the ESHRE and embryology as well as a speaker for a plenary session on the topic of physical exercise and male reproduction for the ESHRE meeting of 2012. She serves as a reviewer for a number of journals including Fertility and Sterility, Human Reproduction, Asian Journal of Andrology, etc. and she is part of the Scientific Committee and Editorial Board for several journals (Revista Andaluza de Medicina del Deporte, Histology Histopathology, etc). She has also been the project leader for Gynemed (Germany) and embryologist and head of research at Repro- ductive Care Center (USA) as well as scientific consultant for FIV Marbella (Spain). She has recently created the International Network on Physical Exercise and Fertility (INPEF) along with Profs. Drs. Juan Manuel Garcia-Manso and Anthony C Hackney, who have extensively studied the effect of physical exercise on the endocrine system and fertility. Dr. Vaamonde was funded by the Andalusian Government (Consejeria de Comercio, Turismo y Deporte) for studies on semen quality and endurance exercise.

xv xvi About the Authors

Stefan S. du Plessis MBA, PhD (Stell) is the head of Medical Physiology in the Faculty of Medicine and Health Sciences (Tygerberg) at Stellenbosch University (South Africa) where he is actively involved in undergraduate teaching and postgraduate training. He is also the head of the Stellenbosch University Reproductive Research Group (SURRG) and his research interests pre- dominantly include male infertility and sperm function with the focus on factors that can influence it (e.g., life- style and noncommunicable diseases). He graduated with a BSc (1989), BSc Hon (1990), MSc cum laude (1994), HonB, B&A (1997), MBA (1999), and PhD (2002) from Stellenbosch University and also received a certificate in human assisted reproduction from the CRM at the Cleveland Clinic (2014). Till date Dr. Du Plessis has published 2 books, 57 peer-reviewed scientific articles, and more than 20 book chapters. He serves on the editorial board of three leading international journals; act as an ad hoc reviewer for various scientific journals and funding agencies, as well as moderator and examiner to several national and international universities. He is regularly invited as a speaker, trainer, and mentor in semenology workshops; is an NRF rated researcher and has received numerous awards, the most notable of which include a Fulbright Research Scholarship (2015), Lasec Award for Excellence in Physiol- ogy Research (2013), and the Dr. Edmund Sabanegh Award for Excellence in Male Infertil- ity Research (2012).

Ashok Agarwal PhD, HCLD (ABB), ELD (ACE) is a professor at Lerner College of Medicine, Case Western Reserve University and the head of the Andrology Cen- ter. He is the director of research at the American Center for Reproductive Medicine, Cleveland Clinic, USA. He has over 525 scientific papers and review articles in peer reviewed scientific journals. He has authored over 150 book chapters, and presented over 750 papers at both national and international scientific meetings. His current Hirsch index (h-index) is 97 on Google Scholar, 74 on Scopus, and 63 on Web of Science, while his cita- tion count is 33,147 on Google Scholar. According to ResearchGate, Ashok has an RG score of 51.9 on 1516 publications. Ashok has served as an editor of over 26 medical text books/manuals related to male infertility, ART, fertility preservation, DNA damage, and antioxidants. He is the guest editor of four special journal issues. Ashok is a member or office bearer of several professional societies and he serves on the Editorial Board of a large number of journals in the area of reproductive medicine. Ashok is active in basic and clinical research and his laboratory has trained more than 500 basic scientists and clinical researchers from the USA and more than 50 countries. He has been invited as a guest speaker at important international meetings in over 25 countries, and is the program director of a unique and highly successful Summer Internship Course in Reproductive Medicine. In the past 8 years, over 180 pre-med and medical students from across the USA and overseas have graduated from this highly competitive program. His unique style of training and motivating young undergraduate and medical students into cutting edge original bench research and scientific writing of research articles for publication in medical journals has been recognized for the prestigious “Scholarship in Teaching Award” by the Case Western Reserve University School of Medicine every year since 2011. He serves on the editorial board of several key journals in human reproduction. His current research interests are identifying biological markers of oxidative stress, DNA damage and apoptosis using proteomic research tools and bioinformatics analysis as well as preserving fertility in patients with cancer. He is actively involved in laboratory and clinical studies assessing the efficacy of certain antioxidants in improving the male fertility.