Dr. Heide Schatten is Professor at the University of Missouri, Columbia. Her research is focused on cytoskeletal regulation and on cytoskeletal dysfunctions of the centrosome-microtubule complex in reproductive disorders and in cancers of the reproductive system. Her publications include advanced imaging methods, cellular and molecular biology, cancer biology, reproductive biology, microbiology and space biology which included collaborations with NASA scientists and experiments aboard the Space Shuttle Endeavour to examine the effects of spaceflight on cytoskeletal organization during fertilization and development.? She entertains active collaborations with colleagues in the USA, Europe, China, and Latin America and has given numerous presentations in these and other countries. She is a member of the American Society for Cell Biology, American Association for the Advancement of Science, Microscopy Society of America. She has received numerous awards including grant awards from NASA, NIH, and NSF. She has published over 200 papers, 14 book chapters and edited several special topics journal issues and 10 books (completed; editor or co-editor), with 3 more books currently in progress. She is editor of several journals.

• List of Contributors xv1 Sperm Selection Techniques and their Relevance to ART 1Luke Simon, Monis B. Shamsi, and Douglas T. Carrell1.1 Introduction 11.2 Need of Sperm Selection in ART 21.3 Methodology of Sperm Selection 31.4 Electrophoretic Sperm Separation 141.5 Zeta Test 181.6 Microelectrophoresis Sperm Selection 211.7 Raman Spectroscopy 241.8 Hyaluronic Acid Binding Assay 271.9 Future Perspective 30References 312 In Vitro Maturation of Human Oocytes: Current Practices and Future Promises 45Catherine M.H. Combelles2.1 Introduction 452.2 Clinical Indications for IVM 462.3 Ovarian Stimulation Approaches for the Retrieval of Immature Oocytes 512.4 Maternal Conditions that may Influence IVM 542.5 Follicular Origins of Immature Oocytes for IVM 552.6 Clinical Safety of IVM 572.7 Concluding Remarks towards the Optimization of IVM 58References 613 Molecular Biology of Endometriosis 71Jayasree Sengupta, G. Anupa, Muzaffer Ahmed Bhat, and Debabrata Ghosh3.1 Introduction 713.2 Brief Background 713.3 Genetic Basis of Endometriosis 763.4 Molecular Mechanisms of Endometriosis 773.5 Molecular Etiopathological Basis of Endometriosis: Leads in Genomics Era 833.6 Molecular Etiopathological Basis of Endometriosis: Leads in the Post-Genomics Era 993.7 Future Targets 113Acknowledgments 115Conflicts of Interest 116References 1164 Novel Immunological Aspects for the Treatment of Age-induced Ovarian and Testicular Infertility, Other Functional Diseases, and Early and Advanced Cancer Immunotherapy 143Antonin Bukovsky4.1 Introduction 1434.2 Ovarian Infertility 1454.3 Novel In Vitro Proposals for Ovarian Infertility Treatment 1634.4 Novel In Vivo Proposal for Ovarian and Testicular Infertility Treatment 1704.5 Systemic Treatment of Other Functional Diseases by Tissue Rejuvenation 1744.6 Advantages of Local and Systemic Use of Honey Bee Propolis and Cayenne Pepper 1754.7 The Promise of Pyramid Healing Systems 1804.8 Raw Shiitake Causes Early Neoplasia Regression and Malignancy Recurrence Prevention 1804.9 Immune Modulation for the Treatment of an Advanced Cancer 1824.10 Advanced Ovarian Cancer Regression Case Report 1844.11 Discussion 1874.12 Conclusions 192Abbreviations 193Competing Interests 193Author Contribution 193References 1945 Mitochondrial Manipulation for Infertility Treatment and Disease Prevention 205Tetsuya Ishii5.1 Introduction 2055.2 The Roles of Mitochondria in Fertilization, Embryonic Development, and Disease 2065.3 The Genetics of Mitochondria and Mitochondrial Diseases 2095.4 Ooplasmic Transfer to Treat Infertility 2105.5 Pronuclear Transfer to Achieve Pregnancy 2145.6 Germinal Vesicle Transfer to Restore the Viability of Oocytes 2165.7 Mitochondrial Diseases and Prevention of their Inheritance 2175.8 Mitochondrial Replacement by Transferring Pronuclei and MII Spindle 2185.9 Discussion 220Acknowledgments 222References 2236 Novel Imaging Techniques to Assess Gametes and Preimplantation Embryos 231Jason E. Swain6.1 Introduction 2316.2 Light and Impact on Mammalian Gametes and Embryos 2326.3 Novel Imaging Approaches for Gametes and Embryos 2336.4 Conclusion 255References 2567 Clinical Application of Methods to Select In Vitro Fertilized Embryos 267Kirstine Kirkegaard, Thomas F. Dyrlund, and Hans Jakob Ingerslev7.1 Introduction 2677.2 Morphological Assessment 2687.3 Genomic and Transcriptomic Analysis 2797.4 Analysis of Conditioned Culture Medium 2857.5 Summary 294References 2958 New Horizons/Developments in Time-Lapse Morphokinetic Analysis of Mammalian Embryos 313Munevver Serdarogullari, Necati Findikli, and Mustafa Bahcecî8.1 Introduction 3138.2 Utilization of Time-Lapse Morphokinetics in Mammalian Embryos: A Historical Perspective 3148.3 What is TLM? 3158.4 What are the Benefits of TLM? 3168.5 Application of TLM in Human ART Practice 3188.6 The Possible Utilization of TLM Analysis in Aneuploidy Detection 3248.7 Expected Contributions of TLM Technology in the Future of Mammalian Embryology 327References 3289 The Non-Human Primate Model for Early Human Development 339Stuart Meyers and Renee Riejo-Pera9.1 Introduction 3399.2 Why Primate Models Are Critical to Understanding Human Development and Subfertility 3409.3 NHP Model of Assisted Reproductive Technology (ART) 3429.4 NHP Model of Early Embryo Development 3439.5 Research Perspective on NHP Embryo Development 3459.6 Summary 347References 34810 Cytoskeletal Functions, Defects, and Dysfunctions Affecting Human Fertilization and Embryo Development 355Heide Schatten and Qing-Yuan Sun10.1 Introduction 35510.2 Components of the Cytoskeleton and their Important Functions in Reproductive Biology 35610.3 The Role of the Cytoskeleton in Oocyte Maturation 36010.4 Maturation Failures and Oocyte Aging 36910.5 Fertilization and First Mitosis/Cell Division 37110.6 Cellular Differentiation/Polarization During Pre-Implantation Embryo Development/Compaction Stage 37410.7 Perspectives and Future Directions 380References 381Index 399

Dr. Heide Schatten is Professor at the University of Missouri, Columbia. Her research is focused on cytoskeletal regulation and on cytoskeletal dysfunctions of the centrosome-microtubule complex in reproductive disorders and in cancers of the reproductive system. Her publications include advanced imaging methods, cellular and molecular biology, cancer biology, reproductive biology, microbiology and space biology which included collaborations with NASA scientists and experiments aboard the Space Shuttle Endeavour to examine the effects of spaceflight on cytoskeletal organization during fertilization and development.? She entertains active collaborations with colleagues in the USA, Europe, China, and Latin America and has given numerous presentations in these and other countries. She is a member of the American Society for Cell Biology, American Association for the Advancement of Science, Microscopy Society of America. She has received numerous awards including grant awards from NASA, NIH, and NSF. She has published over 200 papers, 14 book chapters and edited several special topics journal issues and 10 books (completed; editor or co-editor), with 3 more books currently in progress. She is editor of several journals.

• List of Contributors xv1 Sperm Selection Techniques and their Relevance to ART 1Luke Simon, Monis B. Shamsi, and Douglas T. Carrell1.1 Introduction 11.2 Need of Sperm Selection in ART 21.3 Methodology of Sperm Selection 31.4 Electrophoretic Sperm Separation 141.5 Zeta Test 181.6 Microelectrophoresis Sperm Selection 211.7 Raman Spectroscopy 241.8 Hyaluronic Acid Binding Assay 271.9 Future Perspective 30References 312 In Vitro Maturation of Human Oocytes: Current Practices and Future Promises 45Catherine M.H. Combelles2.1 Introduction 452.2 Clinical Indications for IVM 462.3 Ovarian Stimulation Approaches for the Retrieval of Immature Oocytes 512.4 Maternal Conditions that may Influence IVM 542.5 Follicular Origins of Immature Oocytes for IVM 552.6 Clinical Safety of IVM 572.7 Concluding Remarks towards the Optimization of IVM 58References 613 Molecular Biology of Endometriosis 71Jayasree Sengupta, G. Anupa, Muzaffer Ahmed Bhat, and Debabrata Ghosh3.1 Introduction 713.2 Brief Background 713.3 Genetic Basis of Endometriosis 763.4 Molecular Mechanisms of Endometriosis 773.5 Molecular Etiopathological Basis of Endometriosis: Leads in Genomics Era 833.6 Molecular Etiopathological Basis of Endometriosis: Leads in the Post-Genomics Era 993.7 Future Targets 113Acknowledgments 115Conflicts of Interest 116References 1164 Novel Immunological Aspects for the Treatment of Age-induced Ovarian and Testicular Infertility, Other Functional Diseases, and Early and Advanced Cancer Immunotherapy 143Antonin Bukovsky4.1 Introduction 1434.2 Ovarian Infertility 1454.3 Novel In Vitro Proposals for Ovarian Infertility Treatment 1634.4 Novel In Vivo Proposal for Ovarian and Testicular Infertility Treatment 1704.5 Systemic Treatment of Other Functional Diseases by Tissue Rejuvenation 1744.6 Advantages of Local and Systemic Use of Honey Bee Propolis and Cayenne Pepper 1754.7 The Promise of Pyramid Healing Systems 1804.8 Raw Shiitake Causes Early Neoplasia Regression and Malignancy Recurrence Prevention 1804.9 Immune Modulation for the Treatment of an Advanced Cancer 1824.10 Advanced Ovarian Cancer Regression Case Report 1844.11 Discussion 1874.12 Conclusions 192Abbreviations 193Competing Interests 193Author Contribution 193References 1945 Mitochondrial Manipulation for Infertility Treatment and Disease Prevention 205Tetsuya Ishii5.1 Introduction 2055.2 The Roles of Mitochondria in Fertilization, Embryonic Development, and Disease 2065.3 The Genetics of Mitochondria and Mitochondrial Diseases 2095.4 Ooplasmic Transfer to Treat Infertility 2105.5 Pronuclear Transfer to Achieve Pregnancy 2145.6 Germinal Vesicle Transfer to Restore the Viability of Oocytes 2165.7 Mitochondrial Diseases and Prevention of their Inheritance 2175.8 Mitochondrial Replacement by Transferring Pronuclei and MII Spindle 2185.9 Discussion 220Acknowledgments 222References 2236 Novel Imaging Techniques to Assess Gametes and Preimplantation Embryos 231Jason E. Swain6.1 Introduction 2316.2 Light and Impact on Mammalian Gametes and Embryos 2326.3 Novel Imaging Approaches for Gametes and Embryos 2336.4 Conclusion 255References 2567 Clinical Application of Methods to Select In Vitro Fertilized Embryos 267Kirstine Kirkegaard, Thomas F. Dyrlund, and Hans Jakob Ingerslev7.1 Introduction 2677.2 Morphological Assessment 2687.3 Genomic and Transcriptomic Analysis 2797.4 Analysis of Conditioned Culture Medium 2857.5 Summary 294References 2958 New Horizons/Developments in Time-Lapse Morphokinetic Analysis of Mammalian Embryos 313Munevver Serdarogullari, Necati Findikli, and Mustafa Bahcecî8.1 Introduction 3138.2 Utilization of Time-Lapse Morphokinetics in Mammalian Embryos: A Historical Perspective 3148.3 What is TLM? 3158.4 What are the Benefits of TLM? 3168.5 Application of TLM in Human ART Practice 3188.6 The Possible Utilization of TLM Analysis in Aneuploidy Detection 3248.7 Expected Contributions of TLM Technology in the Future of Mammalian Embryology 327References 3289 The Non-Human Primate Model for Early Human Development 339Stuart Meyers and Renee Riejo-Pera9.1 Introduction 3399.2 Why Primate Models Are Critical to Understanding Human Development and Subfertility 3409.3 NHP Model of Assisted Reproductive Technology (ART) 3429.4 NHP Model of Early Embryo Development 3439.5 Research Perspective on NHP Embryo Development 3459.6 Summary 347References 34810 Cytoskeletal Functions, Defects, and Dysfunctions Affecting Human Fertilization and Embryo Development 355Heide Schatten and Qing-Yuan Sun10.1 Introduction 35510.2 Components of the Cytoskeleton and their Important Functions in Reproductive Biology 35610.3 The Role of the Cytoskeleton in Oocyte Maturation 36010.4 Maturation Failures and Oocyte Aging 36910.5 Fertilization and First Mitosis/Cell Division 37110.6 Cellular Differentiation/Polarization During Pre-Implantation Embryo Development/Compaction Stage 37410.7 Perspectives and Future Directions 380References 381Index 399