Andrology (eBook)

Preface to the 3rd Edition 5
Preface to the 2rd Edition 6
Preface to the 1st Edition 8
Contents 10
Contributors 13
Chapter 1 16
Scope and Goals of Andrology 16
1.1 Definition of Andrology 16
1.2 Andrology, Gynecology, Reproductive Medicine: Reproductive Health 16
1.3 Infertility, Subfertility, Sterility, Fecundity: Definition of Terms 18
1.4 The Infertile Couple as Target Patients 18
1.5 Prevalence of Infertility 20
1.6 Evidence-Based Andrology 22
1.7 Male Contribution to Contraception 24
References 24
Chapter 2 26
Physiology of Testicular Function 26
2.1 Functional Organization of the Testis 26
2.1.1 Interstitial Compartment 26
2.1.1.1 Leydig Cells 27
2.1.1.2 Macrophages. Lymphocytes and Nerve Fibers 29
2.1.2 Tubular Compartment 29
2.1.2.1 Peritubular Cells 29
2.1.2.2 Sertoli Cells 30
2.1.2.3 Germinal Cells 31
2.1.2.4 Kinetics of Spermatogenesis 34
2.1.2.5 Apoptosis and Spermatogenesis 36
2.2 Hormonal Control of Testicular Function 36
2.2.1 Functional Organization of the Hypothalamo-Pituitary System 36
2.2.2 The Kisspeptin-GPR54 System 37
2.2.3 GnRH 39
2.2.3.1 Structure of GnRH 39
2.2.3.2 Secretion of GnRH 41
2.2.3.3 Mechanism of GnRH Action 42
2.2.4 Gonadotropins 43
2.2.4.1 Structure of Gonadotropins 43
2.2.4.2 Secretion of Gonadotropins 44
2.2.4.3 Mechanism of Action of Gonadotropins 45
2.2.5 Endocrine Regulation and Relative Importance of LH and FSH for Spermatogenesis 46
2.2.6 Local Regulation of Testicular Function 48
2.2.6.1 Steroid Hormones 48
2.2.6.2 Insulin-like Factor 3 49
2.2.6.3 Growth Factors 50
2.2.6.4 Immune System Factors 50
2.3 Testicular Descent 51
2.4 Vascularization, Temperature Regulation and Spermatogenesis 52
2.5 Immunology of the Testis 52
2.6 Testicular Androgens 54
2.6.1 Synthesis of Androgens 55
2.6.2 Testosterone Transport in Blood 57
2.6.3 Extratesticular Metabolism of Testosterone 58
2.6.4 Mechanism of Androgen Action 59
2.6.5 Biological Actions of Androgens 64
2.6.6 Androgen Secretion and Sexual Differentiation 67
References 69
Chapter 3 75
Physiology of Sperm Maturation and Fertilization 75
3.1 Introduction 75
3.2 Development of the Ability of Spermatozoa to Fertilize Eggs During Epididymal Maturation 76
3.2.1 Anatomy of the Human Epididymis and Sperm Transport Through It 76
3.2.2 Epididymal Secretion and Absorption 77
3.2.3 Sperm Maturation in the Human Epididymis: Fertilizing Capacity 78
3.2.3.1 Evidence for Sperm Maturation in Man from Surgical Anastomoses 78
3.2.3.2 Evidence for Sperm Maturation in Man from Assisted Reproduction Techniques 79
3.2.4 Sperm Maturation in the Human Epididymis: Morphology and Motility 79
3.2.4.1 Changes in Sperm Morphology 79
3.2.4.2 Initiation of Sperm Motility 79
3.2.4.3 Acquisition of Co-ordinated Sperm Motion 79
3.2.4.4 Regulation of Sperm Motility 81
3.2.4.5 Consequences of Increased Vigor of Mature Spermatozoa 81
3.2.5 Sperm Maturation in the Human Epididymis: Interaction with the Egg 81
3.2.5.1 Development of Sperm-Zona Binding Capacity 81
3.2.5.2 Development of the Sperm’s Ability to Undergo an Induced Acrosome Reaction 82
3.2.5.3 Development of the Sperm’s Potential to Fuse with the Vitellus 82
3.2.5.4 Condensation of Sperm Chromatin and Ability to Form Male Pronuclei 82
3.2.5.5 Development of the Sperm’s Ability to Contribute to a Healthy Embryo 82
3.2.6 Sperm Storage in the Epididymis 83
3.2.6.1 Storage Capacity 83
3.2.6.2 Sperm Quiescence and Protection 83
3.2.6.3 Immune Protection of Auto-antigenic Spermatozoa 83
3.3 Natural Fertilization 85
3.3.1 Erection and Ejaculation 85
3.3.2 The Ejaculate 85
3.3.3 The Basis of Sperm Motility 86
3.3.3.1 Structure of the Axoneme and Flagellar Motion 86
3.3.3.2 Energy for Flagellation 87
3.3.4 Movement of Spermatozoa Through the Female Tract 88
3.3.4.1 Passage of Uncapacitated Spermatozoa Through Cervical Mucus 88
3.3.4.2 Capacitation in the Female Tract and Ascent of Spermatozoa to the Oviducts 88
3.3.5 Penetration of Spermatozoa Through the Egg Investments 75
3.3.5.1 Penetration Through the Cumulus Oophorus 89
3.3.5.2 Consequences of Capacitation: Interaction of Spermatozoa with the Zona Pellucida 91
3.3.5.3 Interaction of Spermatozoa with the Zona Pellucida: the Acrosome Reaction 91
3.3.6 Fusion of Spermatozoa with the Vitelline Membrane (Oolemma) and Egg Activation 92
3.3.6.1 Pre-fusion Events and Membrane Fusion 92
3.3.6.2 Post-fusion Events and Activation of the Egg 93
3.3.7 Post-fusion Events 93
3.3.7.1 Block to Polyspermy 93
3.3.7.2 Formation of the Male Pronucleus 93
3.3.7.3 Early Embryonic Development 94
3.3.7.4 Embryo Implantation 94
References 94
Chapter 4 100
Classifi cation of Andrological Disorders 100
4.1 Classification Based on Localizationand Cause 100
4.2 Classification According to Therapeutic Possibilities 104
References 105
Chapter 5 106
Anamnesis and Physical Examination 106
5.1 Anamnesis 106
5.2 Physical Examination 107
5.2.1 Body Proportions, SkeletalStructure, Fat Distribution 107
5.2.2 Voice 108
5.2.3 Skin and Hair 108
5.2.4 Olfactory Sense 109
5.2.5 Mammary Gland 110
5.2.6 Testis 110
5.2.7 Epididymis 112
5.2.8 Pampiniform Plexus 112
5.2.9 Deferent Ducts 112
5.2.10 Penis 113
5.2.11 Prostate and Seminal Vesicles 113
References 113
Chapter 6 114
Imaging Diagnostics 114
6.1 Scrotal Ultrasonography 114
6.2 Doppler Sonography of the Plexus Pampiniformis 116
6.3 Transrectal Ultrasonography of the Prostate Gland and the Seminal Vesicles 118
6.4 Further Imaging Techniques 118
References 120
Chapter 7 121
Endocrine Laboratory Diagnosis 121
7.1 Gonadotropins 121
7.2 GnRH, GnRH Test, GnRH Receptor 123
7.3 Prolactin, TRH Stimulation Test 123
7.4 Testosterone, Free Testosterone,Salivary Testosterone, SHBG 124
7.5 hCG Test 127
7.6 Anti-Mullerian Hormone, Insulin-Like Factor 3 127
7.7 Inhibin B 128
7.8 Further Diagnosis 128
References 128
Chapter 8 131
Cytogenetic and Molecular Genetic Investigations 131
8.1 Introduction 131
8.2 Cytogenetic Investigations 131
8.2.1 Conventional Cytogenetic Methods 132
8.2.2 Fluorescence In-Situ Hybridization 133
8.2.3 Indications for Chromosome Analysis in Andrology 134
8.3 Molecular Genetic Investigations 135
8.3.1 Microdeletionsof the Y Chromosome 135
8.3.2 Sequencing 135
8.3.3 Indications for Genetic Testing 135
8.4 Genetic Counselling 136
References 136
Chapter 9 137
Semen Analysis 137
9.1 Introduction 137
9.2 Semen Collection 137
9.3 Semen Analysis 138
9.3.1 Macroscopic Appearance of the Ejaculate 138
9.3.2 Initial Microscopical Examination 139
9.3.2.1 Sperm Aggregation and Agglutination 139
9.3.2.2 Non-sperm Cells 139
9.3.3 Further Microscopical Analysis 139
9.3.3.1 Sperm Motility 139
9.3.3.2 Total Sperm Numbers 140
9.3.3.3 Sperm Morphology 142
9.3.4 Additional Analyses 143
9.3.4.1 Sperm Vitality 143
9.3.4.2 Round Cells 143
9.3.4.3 Immunological Tests 143
9.4 Biochemical Analyses of Seminal Fluid 144
9.5 Microbiological Tests 144
9.6 Objective Semen Analysis 145
9.6.1 Sperm Concentration 145
9.6.2 Sperm Motility 145
9.6.3 Sperm Morphology 146
9.7 Quality Control in the Andrology Laboratory 146
9.7.1 Internal Quality Control 146
9.7.2 External Quality Control 146
9.8 Documentation, References Values, Nomenclature and Classifi cation of Semen Parameters 147
References 149
Chapter 10 151
Sperm Quality and Function Tests 151
10.1 Introduction 152
10.1.1 Sperm Function in General 152
10.2 Sperm Survival 152
10.3 Flagellar Function 152
10.3.1 Assessment of Sperm Motility 152
10.3.2 Motility in Semen 153
10.3.3 Motility After Sperm Washing 153
10.3.4 Motility Within Mucus 153
10.3.5 Passage Through the Cumulus 153
10.4 Mitochondrial Function 154
10.5 The Cytoplasmic Component 154
10.5.1 Cytoplasmic Droplets as a NormalStructure 154
10.5.2 Excess Residual Cytoplasm 154
10.5.3 Reactive Oxygen Speciesand Lipid Peroxidation 154
10.6 Capacitation 155
10.7 Interaction with the OviductalEpithelium 155
10.8 Interaction with the Zona Pellucida 155
10.8.1 Zona Binding Tests 155
10.8.2 Hyaluronic Acid as Zona Surrogate 156
10.8.3 Zona Penetration Test 156
10.9 Acrosome Reaction 156
10.9.1 Zona-Induced Acrosome Reactions 157
10.9.2 Recombinant Zona Proteins 157
10.10 Sperm–Egg Fusion 157
10.10.1 The Hamster Oocyte Penetration (HOP) Test/Sperm Penetration Assay (SPA) 157
10.10.2 Liposome Markers 157
10.11 Sperm Centrosome 158
10.12 Chromosomal Complement 159
10.13 DNA Degradation 159
10.13.1 Mitochondrial DNA (mtDNA) 159
10.13.2 Nuclear DNA (nDNA) 159
10.14 Assays of Chromatin Compaction 159
10.14.1 Staining Propertiesof Nucleoproteins 160
10.14.2 Staining Properties of NucleicAcids 160
10.14.3 Physical Dispersion of DNA 160
10.14.3.1 Sperm Chromatin Dispersion Assay (SCD)/Sperm Dispersion Assay (SDA) 160
10.14.3.2 Comet Assay 160
10.15 Assays of DNA Fragmentation 161
10.15.1 Detection of DNA Fragmentation 161
10.15.1.1 In Situ Nick Translation Assays 161
10.15.1.2 In Situ Hybridization Assays 161
10.15.2 Biochemical Assays 161
10.15.2.1 HPLC of DNA Oxidation Products 161
10.15.2.2 Alkaline Gel Electrophoresis 161
10.15.2.3 Q-PCR 161
10.16 DNA Methylation 161
10.17 Clinical Prognostic Value of DNAStatus Tests 161
10.18 Assays of Sperm RNA 162
10.18.1 Gene Transcripts 162
10.18.2 Transcript Translation Products 162
10.19 Sperm Proteomics 162
10.20 Conclusion and FutureApproaches 163
References 163
Chapter 11 167
Testicular Biopsy and Histology 167
11.1 Indications for Testicular Biopsy 167
11.2 Surgical Procedures and Tissue Preparation 168
11.2.1 Surgical Techniques 168
11.2.2 Multiple Testicular Biopsy 169
11.2.3 Fixation of Testicular Biopsies 170
11.3 Histology 170
11.3.1 Defi nitions 170
11.3.2 Evaluation 171
11.3.3 Score Count Evaluation 174
References 177
Chapter 12 180
12.1 Isolated/Idiopathic Hypogonadotropic Hypogonadism (IHH) and Kallmann Syndrome 181
12.1.1 Defi nition and Prevalence 181
12.1.2 Etiology and Pathogenesis 181
12.1.3 Clinical Picture 183
12.1.4 Diagnosis 184
12.1.5 Therapy 185
12.2 Prader-(Labhart-)Willi Syndrome 187
12.2.1 Etiology and Pathogenesis 187
12.2.2 Clinical Picture and Diagnosis 187
12.2.3 Therapy 188
12.2.4 Bardet-Biedl and Laurence-Moon Syndromes 188
12.3 Cerebellar Ataxia and Hypogonadism 189
12.4 Congenital Adrenal Hypoplasia with Hypogonadotropic Hypogonadism 189
12.5 Constitutional Delay of Development 190
12.5.1 Normal Onset of Puberty and Definition of Delayed Puberty 190
12.5.2 Etiology and Pathogenesis of Constitutional Delay of Puberty 190
12.5.3 Clinical Picture 191
12.5.4 Diagnosis 191
12.5.5 Treatment 192
12.6 Secondary GnRH Defi ciency 192
12.6.1 Etiology and Pathogenesis 192
12.6.2 Clinical Picture 193
12.6.3 Diagnosis 193
12.6.4 Therapy 193
12.7 Hypopituitarism 193
12.7.1 Etiology and Pathogenesis 193
12.7.2 Clinical Picture 193
12.7.3 Diagnosis 193
12.7.4 Therapy 194
12.7.5 Hypopituitarism in Heritable Disorders of Pituitary Development 194
12.8 Isolated LH or FSH Defi ciency 194
12.9 Hyperprolactinemia 195
12.9.1 Etiology and Pathogenesis 195
12.9.2 Clinical Picture 196
12.9.3 Diagnosis 196
12.9.4 Therapy 196
12.10 Gonadotropin-Secreting Tumors 198
References 198
Chapter 13 204
Disorders at the Testicular Level 204
13.1 Anorchia 205
13.1.1 Congenital Anorchia 205
13.1.1.1 Diagnosis 206
13.1.1.2 Therapy 206
13.1.2 Acquired Anorchia 206
13.1.2.1 Accidental Castration 206
13.1.2.2 Medical and Legal Castration 207
13.1.2.3 Socio-cultural Castration 207
13.2 Polyorchidism 208
13.3 Maldescended Testes 208
13.3.1 Pathophysiology and Classifi cation 208
13.3.2 Infertility and Risk of Malignancy 209
13.3.3 Diagnosis 210
13.3.4 Therapy 210
13.4 Varicocele 211
13.4.1 Pathophysiology 211
13.4.2 Prevalence and Infl uence of Varicocele on Fertility 212
13.4.3 Clinical Picture 212
13.4.4 Diagnosis 213
13.4.5 Infl uence of Therapy on Fertility 213
13.4.6 Meta-analysis of Studies on Treatment 215
13.4.7 Treatment Modalities 215
13.4.7.1 Surgical Procedures 215
13.4.7.2 Angiographic Procedures 216
13.4.8 Varicocele in Adolescence 216
13.5 Orchitis 217
13.5.1 Clinical Picture and Diagnosis 217
13.5.2 Therapy 217
13.6 Germ Cell Aplasia (SCO Syndrome) 217
13.6.1 Pathophysiology 217
13.6.2 Clinical Picture and Diagnosis 218
13.6.3 Therapy 218
13.7 Spermatogenic Arrest 218
13.7.1 Pathophysiology 218
13.7.2 Clinical Picture 219
13.7.3 Diagnosis 219
13.7.4 Therapy 219
13.8 Specific Structural Sperm Defects 219
13.8.1 Globozoospermia 219
13.8.2 9 + 0 Syndrome 220
13.8.3 Syndrome of Immotile Cilia 220
13.8.4 Clinical Picture 220
13.8.5 Diagnosis 220
13.8.6 Therapy 220
13.9 Klinefelter Syndrome 221
13.9.1 Incidence and Etiology 221
13.9.2 Clinical Picture 222
13.9.3 Diagnosis 223
13.9.4 Therapy 224
13.10 XX Male Syndrome 225
13.11 XYY Syndrome 227
13.12 Noonan Syndrome 227
13.13 Structural Chromosome Abnormalities 227
13.13.1 Structural Abnormalities of SexChromosomes 228
13.13.2 Y Chromosome Microdeletions 229
13.13.3 Structural Abnormalities of the Autosomes 231
13.14 Oviduct Persistence 231
13.15 Gonadal Dysgenesis 232
13.15.1 Defi nition 232
13.15.2 Clinical Picture 232
13.15.3 Diagnosis 232
13.15.4 Therapy 233
13.16 46,XY Disorders of Sexual Development (DSD) due to Disturbed Testosterone Synthesis 233
13.16.1 Definition 233
13.16.2 Etiology 233
13.16.3 Clinical Picture 233
13.16.4 Diagnosis 234
13.16.5 Therapy 234
13.17 Mutations of Gonadotropin Receptors 235
13.17.1 Inactivating LH Receptor Mutations: Leydig Cell Hypoplasia 235
13.17.2 Activating LH Receptor Mutations 236
13.17.3 Inactivating FSH Receptor Mutations 236
13.17.4 Activating FSH ReceptorMutations 237
13.18 Ovotesticular Disturbances of Sexual Development (DSD) 237
13.18.1 Defi nition and Etiology 237
13.18.2 Clinical Picture 237
13.18.3 Diagnosis 237
13.18.4 Therapy 237
13.19 Testicular Tumors 238
13.19.1 Incidence 238
13.19.2 Testicular Intraepithelial Neoplasia (TIN) 238
13.19.3 Germ Cell Tumors 239
13.19.4 Testicular Tumors with Endocrine Activity 242
References 243
Chapter 14 250
The Aging Male and Late-Onset Hypogonadism 250
14.1 Physiology of Aging 250
14.2 Theories of Aging 251
14.3 Sexuality in Senescence 251
14.4 General Endocrinological Changes in Advanced Age 252
14.5 Reproductive Functions of Older Men 253
14.5.1 Sex Hormones in Older Men 253
14.5.2 Testicular Morphology in Advanced Age 255
14.5.3 Semen Parameters in Older Men 255
14.5.4 Fertility of the Aging Male 257
14.5.5 Reproductive Risks Associated with Advanced Paternal Age 259
14.5.5.1 Miscarriage and Paternal Age 259
14.5.5.2 Chromosome Abnormalities and Advanced Paternal Age 259
14.5.5.3 Genetic Disturbances and Advanced Paternal Age 259
14.6 Late-Onset Hypogonadism 260
14.6.1 Definition 260
14.6.2 Mortality and Testosterone Defi ciency 260
14.6.3 Symptoms of Late-Onset Hypogonadism (LOH) 261
14.6.3.1 General Symptoms 261
14.6.3.2 Osteoporosis 261
14.6.3.3 Metabolic Syndrome 261
14.6.3.4 Psychosomatic Aspects 262
14.6.4 Hormone Substitution in Advanced Age 264
14.6.4.1 Testosterone Substitution 264
14.6.4.2 Other Hormone Substitution 266
14.7 Diseases of the Prostate in Older Men 267
14.7.1 Benign Prostate Hyperplasia (BPH) 267
14.7.2 Prostate Cancer 268
14.8 Outlook 268
References 269
Chapter 15 273
Diseases of the Seminal Ducts 273
15.1 Infections of the Seminal Ducts 274
15.1.1 Etiology and Pathogenesis 274
15.1.2 Clinical Picture and Diagnosis 274
15.1.3 Therapy 276
15.2 Obstructions 276
15.2.1 Etiology and Pathogenesis 276
15.2.2 Clinical Picture 277
15.2.3 Diagnosis 277
15.2.4 Therapy 278
15.3 Cystic Fibrosis 278
15.3.1 Etiology and Pathogenesis 278
15.3.2 Clinical Picture and Diagnosis 279
15.3.3 Therapy 279
15.4 Congenital Absence of the Vas Deferens 280
15.4.1 Etiology and Pathogenesis 280
15.4.2 Clinical Picture and Diagnosis 281
15.4.3 Therapy 281
15.4.4 Unilateral Absence of the Vas Deferens 281
15.4.5 Bilateral Obstruction of the Ejaculatory Ducts 282
15.5 Young Syndrome 282
15.5.1 Etiology and Pathogenesis 282
15.5.2 Clinical Picture and Diagnosis 282
15.5.2 Therapy 283
15.6 Disorders of Liquefaction 283
15.7 Immunological Infertility 283
15.7.1 Etiology and Pathogenesis 283
15.7.2 Clinical Picture 283
15.7.3 Diagnosis 284
15.7.4 Therapy 284
References 285
Chapter 16 289
Disorders of Erection, Cohabitation, and Ejaculation 289
16.1 Penile Alterations 289
16.1.1 Hypospadias and Epispadias 289
16.1.2 Phimosis 290
16.1.3 Penile Deviation 290
16.1.3.1 Congenital Penile Deviation 290
16.1.3.2 Acquired Penile Deviation 291
Peyronie’s Disease (Induratio Penis Plastica, IPP) 291
16.1.3.3 Therapy of Penile Deviations and IPP 292
Conservative Therapy of IPP 292
Surgical Therapy of Penis Deviations 292
16.2 Erectile Dysfunction (ED) 293
16.2.1 Epidemiology 293
16.2.2 Functional Anatomy 294
16.2.3 Physiology of Erection 295
16.2.3.1 Hemodynamics 295
16.2.3.2 Neurophysiology 296
16.2.3.3 Local Control of Erection 297
16.2.4 Pathophysiology of Erection 298
16.2.4.1 Psychogenic Erectile Dysfunction 298
16.2.4.2 Vasculogenic Erectile Dysfunction 298
16.2.4.3 Neurogenic Erectile Dysfunction 299
16.2.4.4 Endocrine Erectile Dysfunction 299
16.2.4.5 Drug-Induced Erectile Dysfunction 299
16.2.5 Diagnostic Workup in Erectile Dysfunction 300
16.2.5.1 History and Clinical Presentation 300
16.2.5.2 Clinical Examination 302
16.2.5.3 Laboratory Tests 302
16.2.5.4 Intracavernosal Testing with Vasoactive Substances 302
16.2.5.5 Doppler Sonography 305
16.2.5.6 Duplex Sonography 306
16.2.5.7 Penile Angiography 307
16.2.5.8 Evaluation of Venous Drainage 307
16.2.5.9 Neurophysiological Investigations 309
16.2.5.10 Nocturnal Penile Tumescence and Rigidity Measurements (NPT) 310
16.2.6 Therapy of Erectile Dysfunction 310
16.2.6.1 Psychological Treatment 310
16.2.6.2 Hormone Therapy 311
16.2.6.3 Topical Therapy 312
16.2.6.4 Oral Therapy 312
16.2.6.5 External Devices 318
16.2.6.6 Self-injection Therapy 320
16.2.6.7 Surgical Treatment 323
Venous Surgery 324
Revascularization Surgery 324
Prosthesis Surgery 325
16.3 Ejaculation Disorders 326
16.3.1 Anejaculation and Retrograde Ejaculation 327
16.3.2 Premature Ejaculation 327
References 328
Chapter 17 332
Disorders of Androgen Target Organs 332
17.1 Introduction 332
17.2 Androgen Insensitivity 332
17.2.1 Complete Androgen Insensitivity 334
17.2.2 Partial Androgen Insensitivity 336
17.2.3 Minimal Androgen Insensitivity 337
17.2.4 X-linked Spinal and Bulbar Muscular Atrophy (SBMA) 337
17.3 Perineoscrotal Hypospadias with Pseudovagina (5alpha-Reductase 2-Deficiency) 337
17.4 Estrogen Resistance and Estrogen Deficiency 338
17.5 Gynecomastia 338
17.5.1 Clinical Examination 338
17.5.2 Laboratory Investigation 340
17.5.3 Pathophysiology 340
17.5.3.1 Physiologic Gynecomastia 340
17.5.3.2 Gynecomastia Caused by ReducedAndrogen Production or Availability 340
17.5.3.3 Gynecomastia Caused by Androgen Insensitivity 342
17.5.3.4 Gynecomastia Caused by Increased Estrogen Production 342
17.5.3.5 Gynecomatia Caused by Shiftin Estrogen/Androgen Availability 342
17.5.4 Male Breast Cancer 343
17.5.5 Therapy 343
17.6 Androgenetic Alopecia 344
17.6.1 Epidemiology and Pathophysiology 344
17.6.2 Diagnosis 344
17.6.3 Therapy 344
References 345
Chapter 18 347
Testicular Dysfunction in Systemic Diseases 347
18.1 Background 347
18.2 Mechanisms of Reproductive Disruption by Systemic Diseases 347
18.2.1 Onset of Hypogonadism 348
18.2.2 Level of Disruption in the Male Reproductive Axis 348
18.3 Specific Diseases and Disorders 349
18.3.1 Renal Disease 349
18.3.2 Liver Disease 350
18.3.3 Respiratory Diseases 352
18.3.4 Malignant Disease 353
18.3.4.1 Surgery 353
18.3.4.2 Chemo-/Radiotherapy 353
18.3.5 Neurological Diseases 354
18.3.5.1 Genetic Disorders 355
18.3.5.2 Acquired Disorders 356
18.3.6 Gastrointestinal Diseases 357
18.3.7 Hematological Diseases 357
18.3.8 Endocrine and Metabolic Diseases 358
18.3.9 Immune Diseases 359
18.3.10 Infectious Diseases 360
18.3.11 Cardiovascular Diseases 361
18.3.12 Dermatological Diseases 362
18.3.13 Other Chronic Diseases 362
18.4 Therapeutic Implications 363
References 364
Chapter 19 373
Environmental Influences on Male Reproductive Health 373
19.1 Potential Adverse Effects on Spermatogenesis 374
19.2 Targets for Toxicity 376
19.2.1 Pre-testicular Targets for Toxicity 376
19.2.2 Testicular Targets for Toxicity 377
19.2.3 Post-testicular Targets for Toxicity 378
19.3 Instances of Environmental or Occupational Toxicity of Possible Relevance to Humans 379
19.3.1 General 379
19.3.2 Ionizing Radiation 380
19.3.3 Anti-cancer Therapies 380
19.3.4 Dibromochloropropane 381
19.3.5 Metals 381
19.3.6 Complex Organochlorine Compounds 382
19.3.7 Smoking 383
19.3.8 Diet, Alcohol and Social Drugs 384
19.3.9 Electromagnetic Radiation 384
19.3.10 Heat 385
19.3.11 Unknown Factors 385
19.3.11.1 Testicular Dysgenesis Syndrome 387
19.4 Design and Interpretation of Toxicological Studies 387
19.4.1 Design of Non-human Studies 387
19.4.2 Design of Human Studies 387
19.4.3 Regulatory Testing for Reproductive Toxicity 388
19.4.3.1 Regulatory Reproductive Research Strategies 388
19.4.3.2 Experimental Methods in Male Reproductive Research 388
19.4.4 Criteria for the Evaluation of Human Toxicology Data 389
19.5 Future Perspectives 389
19.5.1 Experimental Studies 389
19.5.1.1 Non-human Studies 389
19.5.1.2 Human Studies 390
19.5.2 Clinical Implications 390
19.5.2.1 Historical Perspective 390
19.5.2.2 Clinical Practice 391
References 391
Chapter 20 398
Gynecology Relevant to Andrology 398
20.1 Medical History and Somatic Factors 399
20.1.1 Age 399
20.1.2 Coital Frequency 400
20.1.3 Length of Childlessness 400
20.1.4 Risk of Infection 400
20.1.5 Psychological Factors 401
20.1.5.1 Libido Dysfunction and Orgasmic Disturbances 401
20.1.5.2 Dyspareunia 401
20.1.6 Hormones and Female Sexuality 401
20.1.7 Stress 401
20.1.7.1 Immunological Modulation and Stress 402
20.1.8 Environmental Factors 402
20.1.8.1 Definitions 402
20.1.8.2 Epidemiology 402
20.1.8.3 Nicotine 403
20.1.8.4 X Rays and Radioactivity 403
20.1.8.5 Electromagnetic Fields 403
20.1.9 Pertinent Medical History 403
20.1.9.1 Physiology of Pregnancy 403
20.1.9.2 Pertinent Medical Disorders 404
20.2 Ovarian Cycle and Ovulation 405
20.2.1 Follicles 405
20.2.1.1 Early Oocyte Development 405
20.2.1.2 Meiosis 406
20.2.1.3 Follicle Development 406
20.2.1.4 Regulatory Mechanisms 406
20.2.2 Menstrual Cycle 409
20.2.2.1 Hormone Variations 409
20.2.2.2 Changes in the Uterine Cervix and in Cervical Mucus Production 410
20.2.2.3 Endometrium 411
20.2.2.4 Vaginal Epithelium 412
20.2.3 Diagnostic Evaluation of the Cycle 412
20.2.3.1 Ultrasound 412
20.2.3.2 Endometrial Biopsy 414
20.2.3.3 Progesterone Levels and Evaluation of Luteal Quality 414
20.2.4 Impairment of Follicle Maturation 415
20.2.4.1 Amenorrhea 415
20.2.4.2 Hyperprolactinemia 418
20.2.4.3 Polycystic Ovarian Disease 420
20.2.4.4 Causes and Risk Factors 423
20.2.4.5 Primary Ovarian Failure 425
20.3 Infertility Due to Disturbances of Gamete Migration 426
20.3.1 Vagina and Cervix 427
20.3.2 Anomalies of the Female Genital Tract 428
20.3.2.1 Uterus 428
20.3.2.2 Fallopian Tubes 428
20.3.3 Physiology of Tubal Function 428
20.3.4 Diseases of the Fallopian Tubes 429
20.3.4.1 Salpingitis 429
20.3.5 Diagnostic Tests for Uterineand Tubal Patency 430
20.3.5.1 Tubal Insufflation 430
20.3.5.2 Hysterosalpingography 430
20.3.5.3 Hysteroscopy and Laparoscopy 431
20.3.6 Treatment 431
20.4 Endometriosis 432
20.4.1 Pathogenesis and Epidemiology 432
20.4.2 Symptoms 432
20.4.3 Pathophysiology 432
20.4.4 Staging of Endometriosis 433
20.4.5 Treatment 433
20.4.5.1 Danazol 433
20.4.5.2 GnRH Analogs 434
20.4.5.3 Aromatase Inhibitors 434
20.4.5.4 Surgical Treatment 435
20.4.5.5 IVF 435
20.5 Sperm Antibodies 435
20.5.1 Pathophysiology 435
20.5.2 Antibody Testing 435
20.5.3 Treatment 435
20.6 Early Pregnancy Abnormalities 436
20.6.1 Implantation 436
20.6.2 Pregnancy Loss 436
20.6.3 Epidemiology 436
20.6.4 Etiologic Factors 437
20.7 Idiopathic Infertility 438
20.8 Prospects and Conclusion 438
References 438
Chapter 21 444
Testosterone Therapy 444
21.1 Indications and Preparations: An Overview 444
21.2 Pharmacology of Testosterone Preparations 446
21.2.1 Oral Testosterone Preparations 446
21.2.1.1 Testosterone Undecanoate 446
21.2.1.2 Methyl Testosterone and Fluoxymesterone 448
21.1.2.3 Mesterolone 448
21.2.2 Buccal Administration 448
21.2.3 Intramuscular Testosterone Preparations 449
21.2.3.1 Testosterone Enanthate 449
21.2.3.2 Testosterone Propionate 449
21.2.3.3 Testosterone Undecanoate 450
21.2.4 Transdermal Testosterone Preparations 451
21.2.4.1 Testosterone Patches 451
21.2.4.2 Testosterone Gels 452
21.2.4.3 Transdermal Dihydrotestosterone 452
21.2.5 Testosterone Implants 452
21.3 Monitoring Testosterone Therapy in Hypogonadism 453
21.3.1 Psyche and Sexuality 453
21.3.2 Somatic Parameters 454
21.3.3 Laboratory Parameters 454
21.3.4 Prostate and Seminal Vesicles 456
21.3.5 Bone Mass and Muscles 457
21.4 Evaluation of Testosterone Substitution Therapy 458
21.5 Excessive Height 458
21.6 Misuse and Abuse of Anabolic Steroids 459
References 460
Chapter 22 463
Empirical Therapies for Idiopathic Male Infertility 463
22.1 Definition and Incidence of Male Idiopathic Infertility 463
22.2 Empirical Therapy 464
22.2.1 hCG/hMG 464
22.2.2 Pulsatile GnRH 465
22.2.3 Highly Purified and Recombinant FSH 465
22.2.4 Antiestrogens and Aromatase Inhibitory Agents 465
22.2.5 Androgens 466
22.2.6 Kallikrein 469
22.2.7 Pentoxyphylline 469
22.2.8 alpha-Receptor Blocking Agents 469
22.2.9 Antioxidants 469
22.2.10 Further Substances 470
22.2.11 Physical Procedures 470
22.3 Therapeutic Guidelines 470
References 471
Chapter 23 474
Assisted Reproduction 474
23.1 Assisted Reproduction as a Treatment of Infertility 475
23.2 Methods of Assisted Reproduction Available for Treatment of Male Infertility 475
23.3 Insemination 476
23.3.1 Spontaneous Conception Rate in the Infertile Couple 476
23.3.2 Intravaginal and Intracervical Insemination (ICI) 476
23.3.3 Intrauterine Insemination (IUI) 477
23.3.4 Intratubal Insemination (ITI) 478
23.3.5 Direct Intraperitoneal Insemination (DIPI) 478
23.3.6 Intrafollicular Insemination 478
23.4 In vitro Fertilization and Related Techniques 479
23.4.1 In vitro Fertilization (IVF) 479
23.4.2 Gamete Intra-Fallopian Transfer (GIFT) 481
23.4.3 Intra-Fallopian Transfer of Zygotes (ZIFT) or Pronucleate-Stage Oocyte Transfer (PROST) 482
23.4.4 Tubal Embryo Transfer (TET) 482
23.5 Micro-assisted Fertilization 482
23.5.1 Previously Used Techniques of Micro-assisted Fertilization 483
23.5.2 Intracytoplasmic Sperm Injection (ICSI) 483
23.6 Semen Donation 487
23.7 Collection and Preparation of Sperm for Assisted Reproduction 488
23.7.1 Collection of Semen for Assisted Reproduction 488
23.7.2 Preparation of Sperm for Assisted Reproduction 490
23.7.3 Filtration 490
23.7.4 Swim-up 490
23.7.5 Density Gradient Centrifugation 491
23.7.6 Sorting of Spermatozoa Based on Defined Characteristics 492
23.7.7 Removal of Contaminant Infectious Particles 492
23.7.8 Processing of Sperm for ICSI in Difficult Cases 493
23.7.9 Treatment of Spermatozoa In vitro 493
23.8 Ovarian Follicular Development, Ovarian Stimulation, Ovulation Induction and Oocyte Collection 493
23.8.1 Monitoring of Ovarian Follicular Development and Ovarian Stimulation for Insemination 493
23.8.2 Ovarian Stimulation for IVF and ICSI 494
23.9 Methods of Oocyte Collection 495
23.10 Assisted Hatching 496
23.11 Embryo Transfer 497
23.12 Cryopreservation of Oocytes in the Pronucleate Stage 497
23.13 Complications of Assisted Reproduction 498
23.13.1 Ovarian Hyperstimulation Syndrome (OHSS) 498
23.13.2 Ovarian Torsion 499
23.13.3 The Risk of Multiple Pregnancies 499
23.13.4 Cancer Risk in the Mother After Assisted Reproduction 499
23.14 Genetic Counselling in Assisted Reproduction 500
23.15 Health of the Offspring After Assisted Fertilization 501
References 502
Chapter 24 510
Cryopreservation of Human Spermatozoa 510
24.1 Introduction 511
24.2 History of Cryopreservation of Human Semen 511
24.3 Indications for Cryopreservation of Semen 511
24.3.1 Fertility Preservation 511
24.3.1.1 Vasectomy and After Vasovasostomy 511
24.3.1.2 Oncological Diseases in Adults 512
24.3.1.3 Oncological Diseases in Childhood 513
24.3.2 Infertility Treatment 514
24.3.2.1 Assisted Fertilization 514
24.3.2.2 MESA and TESE Samples Including Onco-TESE 515
24.3.2.3 Patients with Anejaculation 515
24.3.3 Donor Semen 516
24.3.4 Quarantine of Potentially Infected Samples 516
24.3.5 Quality Control of Semen Analysis 516
24.4 Requirements and Risk Assessment for Cryoconservation of Human Semen 516
24.4.1 Required Resources 516
24.4.2 Risk of Cross-contamination 517
24.4.3 Staff Safety and Protection 517
24.4.4 Labelling of Straws and Records 517
24.5 Preparation of Semen Samples for Cryopreservation 517
24.5.1 Preparing the Sample 517
24.5.2 Routine Sample Freezing and Cryoprotectants 517
24.5.3 Relative Resistance of Spermatozoa to the Freezing Process 518
24.5.4 Standard Cryoprotectants 518
24.5.4.1 For Normal Samples 518
24.5.4.2 For Samples with Low Sperm Numbers 518
24.5.4.3 Improvements in Cryopreservation Techniques 519
24.5.5 Adding the Cryoprotectant 519
24.5.5.1 For Normal Samples 519
24.5.5.2 For Samples with Low Sperm Numbers 519
24.5.6 Closing the Straws 519
24.5.7 Freezing the Samples 519
24.5.8 Storing the Samples 520
24.5.9 Thawing the Samples 520
24.5.10 Frozen Semen Transport 520
24.6 Use and Quality of Stored Cryopreserved Semen Samples 520
24.6.1 Use of Cryopreserved Samples 520
24.6.2 Quality of Stored Cryopreserved Semen Samples 521
24.7 Problems and Limitations of Cryopreservation 522
24.7.1 Genetic Risks 522
24.7.2 Psychological Aspects 522
24.7.3 Methodological Considerations 522
References 523
Chapter 25 526
Psychology of Fertility Disorders 526
25.1 Introduction and Overview 526
25.2 Psychological Conditions of Unwanted Childlessness 527
25.3 Psychological Effects of Unwanted Childlessness 528
25.4 The Psychology of Male Fertility Disorders 529
25.5 Psychosocial Aspects of the Desire for Children 530
25.5.1 Acceptance of Multiple Pregnancies 531
25.6 The Role of Clinicaland Psychosocial Factors in the Indication and Contraindication of Therapeutic Procedures 531
25.6.1 Psychosocial Consultation Within an ART Team for Persons Seeking Parenthood 532
25.6.2 Aims of Psychotherapeutic Intervention 533
25.6.3 Effects of Psychotherapeutic Intervention 534
25.6.4 Further Psychosocial Developments Following InfertilityTreatment with Special Reference to Family Constellations 534
25.6.4.1 Twin and Multiple Birth Families 535
25.6.4.2 Family Bonding Through Donor Insemination 536
25.6.4.3 Starting a Family by Egg Donation 537
25.6.4.4 Starting a Family by Embryo Donation 537
25.6.4.5 Starting a Family by Adoption or Fostering 538
25.6.5 Outlook and Future Psychological Research 538
References 539
Chapter 26 543
Sexual Medicine and Andrology 543
26.1 Sexual Medicine in Clinical Practice 543
26.2 Interdisciplinary References in Sexual Medicine 544
26.3 Basic Understanding of Human Sexuality 544
26.4 The Spectrum of Sexual Disorders 545
26.4.1 Sexual Dysfunction 547
26.4.1.1 Disorders of Sexual Desire 547
26.4.1.2 Erectile Dysfunction 547
26.4.1.3 Premature Ejaculation 548
26.4.2 Disorders of Sexual Development 549
26.4.2.1 Disorders of Sexual Maturity 549
26.4.2.2 Disorders of Sexual Orientation 549
26.4.2.3 Sexual Identity Disorders 549
26.4.2.4 Disorder of Sexual Partnership 550
26.4.3 Disorders of Gender Identity 550
26.4.4 Disorders of Sexual Preference (Paraphilias) 551
26.5 Impact of Disorders of Sexual Preference, Sexual Behavior and Sexual Reproduction 551
26.5.1 Disorders of Sexual Behavior (Dissexuality) 552
26.5.2 Disorders of Sexual Reproduction 553
26.6 Principles of Diagnosis in Sexual Medicine 553
26.6.1 Exploration of a Sexual Disorder/Dysfunction 554
26.6.2 Exploration of the Three Dimensions of Sexuality 555
26.6.2.1 Dimension of Attachment 555
26.6.2.2 Dimension of Reproduction 555
26.6.2.3 Dimension of Desire 555
26.6.2.4 Individual and Partner-Related Interaction of these Three Dimensions 555
26.6.2.5 History of Diseases and Somatic Findings 555
26.7 Principles of Therapy in Sexual Medicine 556
26.7.1 Sexological Consultation 557
26.7.2 Sexual Therapy 557
26.7.3 Integration of Somatic Therapy Options 558
References 558
Chapter 27 560
Male Contribution to Contraception 560
27.1 Requirements and Perspectives 560
27.1.1 Contraception, Family Planning and World Population 560
27.1.2 Global Goal of WHO: Reproductive Health 563
27.1.3 Acceptability of Male Contraception 563
27.1.4 Possibilities 564
27.2 Existing Methods 565
27.2.1 Coitus Interruptus 565
27.2.2 Periodic Abstinence 565
27.2.3 Condoms 566
References 567
Chapter 28 568
Vasectomy and Refertilization 568
28.1 History of Vasectomy 568
28.2 Social and Demographic Relevance 569
28.3 Indications for Vasectomy 569
28.4 Informed Consent 570
28.5 Surgical Vasectomy Techniques 570
28.6 Technical Modifications 571
28.7 Effectiveness and Cost Efficiency 571
28.8 Complications 571
28.9 Vasectomy and Long-TermMorbidity 572
28.10 Psychosexual Effects 573
28.11 Refertilization 573
28.11.1 History of Refertilization Surgery 573
28.11.2 Current Demand and Frequency of Refertilization 573
28.11.3 Vasovasostomy 574
28.11.3.1 Indications, Counseling, Consent, Costs 574
28.11.3.2 Vasovasostomy Technique 574
28.11.3.3 Results of Vasovasostomy 575
28.11.3.4 Complications Following Vasovasostomy 576
28.11.4 Epididymovasostomy 576
28.11.5 Future Developments in Surgical Refertilization 576
28.12 Future Developmentof Vasectomy 577
References 578
Chapter 29 580
Approaches to Hormonal Male Contraception 580
29.1 Principle of Hormonal Male Contraception 580
29.2 Androgens Alone 581
29.2.1 Testosterone Enanthate 581
29.2.2 Testosterone Buciclate 582
29.2.3 Testosterone Undecanoate 582
29.2.4 Testosterone Pellets 584
29.2.5 19-Nortestosterone 584
29.2.6 7alpha-Methyl-19-Nortestosterone (MENT) 584
29.3 Androgens Combined with GnRH Analogues 584
29.3.1 GnRH Agonists 584
29.3.2 GnRH Antagonists 584
29.4 Androgens Plus Gestagens 585
29.4.1 Depot Medroxyprogesterone Acetate (DMPA) 586
29.4.2 Levonorgestrel 586
29.4.3 Norethisterone 586
29.4.4 Cyproterone Acetate 586
29.4.5 Desogestrel and Etonogestrel 587
29.5 Résumé and Outlook 587
References 588
Chapter 30 591
Pharmacological Approaches to Male Contraception 591
30.1 Introduction 591
30.2 Attacking Sperm Production in the Testis 592
30.2.1 Chemically Blocking Spermatogenesis 592
30.2.1.1 Targeting Drug Accumulation Within the Testis 592
30.2.1.2 Clinical Observations 592
30.2.2 Physically Blocking Spermatogenesis 592
30.3 Preventing Sperm Maturation and Survival in the Epididymis 593
30.3.1 Altering the Epididymal Transport of Spermatozoa 593
30.3.1.1 Effective Classes of Compounds in Animal Studies 593
30.3.2 Modifying the Composition of Epididymal Fluid 594
30.3.2.1 Compromising Epithelial Structure 594
30.3.2.2 Interfering with Transepithelial Transport and Fluid Secretion and Resorption 594
30.3.2.3 Interfering with Specific Epididymal Proteins 595
30.3.2.4 Inducing a Hostile Epididymal Environment 595
30.3.2.5 Clinical Observations 596
30.3.3 Attacking Epididymal Spermatozoa 596
30.3.3.1 Displacing Fertility-Related Sperm Proteins 596
30.3.3.2 Inhibiting Sperm Glycolysis 596
30.3.3.3 Preventing Sperm Volume Regulation 596
30.3.3.4 Targeting Drug Accumulation in the Epididymis 597
30.3.3.5 Clinical Observations 597
30.4 Preventing Seminal Emission 597
30.4.1 Surgical Approaches 597
30.4.1.1 Use of a Scalpel 597
30.4.1.2 No-scalpel Approaches 597
30.4.2 Pharmacological Blockade of Seminal Emission 598
30.4.2.1 Animal Studies 598
30.4.2.2 Clinical Observations 598
30.5 Sperm-Specifi c Targets 598
30.6 Overall Conclusion 598
References 599
Chapter 31 602
Ethical Aspects of Reproductive Medicine* 602
31.1 Social and Cultural Context 602
31.1.1 A Shared Intellectual Responsibility 602
31.1.2 The Structures of Interdisciplinary Dialogue 603
31.1.3 The Dilemma of the Theologian 603
31.2 Church Statements 604
31.2.1 Previous History: Artificial Insemination 604
31.2.2 In Vitro Fertilization 605
31.2.3 The Dignity of Man and the Right to Life 605
31.3 The Coordinates of Ethical Discussion 607
31.3.1 The Basic Understanding of Marriage 607
31.3.2 Concern for Psycho-Social Health 608
31.3.3 Rights and Certainties 609
31.4 The Context of In Vitro Fertilization (“Dignitas Personae” nn. 24–35) 610
31.5 Challenges to Tolerance 611
31.6 Conclusions 612
References 612
Church Documents 613
Index 614