Infertility in Practice

I am pleased to present the fifth edition of Infertility in Practice, which has been updated every 5 years or so since it was first published in 1997. Throughout this time, our understanding of infertility and its management has continued to expand rapidly. Infertility in Practice has been written as a practical guide and is based on my experience over the last 40 years of daily clinical practice. The aim of the book is to place the modern approach to the management of infertility in the context of sound theory and evidence-based therapy. I have striven to provide the reader with a comprehensive classification of the causes of infertility, their investigation and their management. In this edition, I have thoroughly revised and updated the text and completely rewritten most of the chapters.This fifth edition of Infertility in Practice has been written during the global Covid-19 pandemic, caused by the SARS-CoV-2 coronavirus (discussed in Chapter 1). This is still evolving and there are many unknowns about the long-term effects of the virus, not only on population dynamics but also on fertility and pregnancy. We have all experienced the effects of the pandemic on our health services and also on our ability to provide fertility treatments when clinical resources, and personnel, have been so stretched. A global vaccination programme is the way forward, and I can only hope that we will be through these dark times by the time the sixth edition is being published. Cover Half Title Series Title Copyright Dedication Contents Foreword Preface About the Author 1. Epidemiology of Infertility, 21st-Century Considerations and the Covid-19 Pandemic 1.1 Introduction 1.2 Ovarian Ageing 1.3 At What Age Should Couples Start Trying for a Family? 1.4 Fertility Education 1.5 Measuring Infertility and Response to Treatment 1.6 Definition of Infertility 1.7 Is Infertility Becoming More Common? 1.8 Is Infertility on the Rise? 1.9 Principles of Infertility Treatment 1.10 Covid-19 and Fertility 2. Prevention of Infertility 2.1 Introduction 2.2 Impact of Age on Male and Female Fertility 2.3 Can Women Protect Fertility against Ageing? 2.4 Contraception 2.5 Environmental Pollutants 2.6 Are Sperm Counts Falling? 2.7 Hypospadias, Cryptorchidism and Testicular Cancer 2.8 Conclusion 3. Planning a Pregnancy and Preconception Care 3.1 Introduction 3.2 A Preconception Healthcare Programme 3.3 Body Weight 3.4 Dietary Advice for Women Wishing to Conceive 3.5 Folic Acid (Folate) 3.6 Exercise 3.7 Supplements for Male Fertility 3.8 Special Diets for Sex Selection 3.9 The Microbiome 3.10 Oral Health 3.11 Smoking, Alcohol and Recreational Drugs 3.12 Anabolic Androgenic Steroids 3.13 Acquired Infections 3.14 Medical Conditions and Drugs 3.15 Endocrine Disorders 3.16 Diabetes 3.17 Psychiatric Disorders 3.18 Neurological Disorders 3.19 Gastrointestinal Disease 3.20 Renal Disease 3.21 Cardiovascular Disease 3.22 Respiratory Disease 3.23 Antibiotics and Anti-Infective Agents 3.24 Haematological Problems 3.25 Connective Tissue Disorders 3.26 Chemotherapy 4. Obesity and Reproduction 4.1 Introduction 4.2 Defining Obesity and the Extent of the Problem 4.3 Influence of Obesity on Natural Fertility 4.4 Obesity and Polycystic Ovary Syndrome 4.5 Effect of Obesity on Treatment of Anovulatory Infertility 4.6 Effect of Obesity on IVF and Related Treatments 4.7 Effect of Obesity on Pregnancy 4.8 Provision of Support in Achieving Weight Loss 4.9 Guidelines for Accessing Treatment 5 Investigating Infertility 5.1 Introduction 5.2 General Investigations 5.3 Investigating the Female Partner 5.4 Diagnosis of Anovulatory Infertility 5.5 Endocrine Profile 5.6 Progesterone 5.7 Follicle-Stimulating Hormone 5.8 Ovarian Reserve Tests 5.9 Luteinising Hormone 5.10 Androgens 5.11 Thyroid Function 5.12 Prolactin 5.13 Oestrogen 5.14 Glucose Tolerance 5.15 Other Investigations 5.16 Pelvic Ultrasound 5.17 Ovarian Morphology 5.18 Differentiating between PCOM and PCOS 5.19 Ovarian Cysts 5.20 Endometrial Assessment 5.21 Doppler Ultrasound in Assisted Conception 5.22 Assessment of Tubal Patency and the Uterine Cavity 5.23 Ultrasound Contrast Hysterosalpingography or Hysterosalpingo Contrast Sonography 5.24 Selective Salpingography and Falloposcopy 5.25 Laparoscopy and Hysteroscopy 5.26 Transvaginal Hydroculdoscopy/Hydrolaparoscopy/Salpingoscopy 5.27 Choosing between HSG and Laparoscopy 5.28 MRI/Computed Tomography Scans 5.29 Investigating the Male Partner 5.30 Semen Analysis 5.31 Reduced Sperm Concentration (Oligozoospermia) 5.32 Impaired Sperm Morphology (Teratozoospermia) 5.33 Reduced Sperm Motility (Asthenozoospermia) 5.34 Sperm Dysfunction and DNA Fragmentation 5.35 Leukospermia 5.36 Cervical Mucus Penetration and the Post-Coital Test 5.37 Antisperm Antibodies 5.38 Serum Endocrinology in the Male 5.39 Chromosomal Analysis 5.40 Imaging in Male Infertility 5.41 Testicular Exploration and Biopsy 6. Anovulatory Infertility and Ovulation Induction 6.1 Introduction 6.2 Primary and Secondary Amenorrhoea 6.3 Pituitary and Hypothalamic Causes of Anovulation 6.4 Hypogonadotrophic Hypogonadism 6.5 Weight-Related Amenorrhoea 6.6 Systemic Disorders Leading to Anovulation 6.7 Exercise-Related Amenorrhoea 6.8 Hyperprolactinaemia 6.9 Polycystic Ovary Syndrome 6.10 Summary 7. Polycystic Ovary Syndrome 7.1 Introduction 7.2 What Is PCOS? 7.3 Pathophysiology of PCOS 7.4 Ovarian Biochemistry 7.5 Hypothalamic-Pituitary-Ovarian Axis 7.6 Hyperinsulinaemia 7.7 Definitions and Heterogeneity of PCOS 7.8 Prevalence of PCOS and Ethnic Variations 7.9 PCOS in Adolescence 7.10 Management of Non-Fertility Aspects of PCOS 7.11 Psychological Support and Quality of Life 7.12 Obesity 7.13 Menstrual Irregularity 7.14 Hyperandrogenism and Hirsutism 7.15 Reproductive Health in PCOS 7.16 Health Consequences of PCOS 7.17 PCOS and Cancer 7.18 Conclusion 8. Premature Ovarian Insufficiency and Oocyte Donation 8.1 Introduction 8.2 Control of Ovarian Ageing 8.3 Incipient POI (“Resistant Ovary Syndrome”) 8.4 Diagnosis of POI 8.5 Causes of POI 8.6 Management of POI 8.7 Oocyte Donation 8.8 Experimental Approaches to Combatting POI 9. Endometriosis 9.1 Introduction 9.2 Diagnosis 9.3 Non-Invasive Testing for Biomarkers of Endometriosis 9.4 Classification of Endometriosis 9.5 Biopsy 9.6 Cysts 9.7 Management of Endometriosis 9.8 Medical Therapy for Fertility 9.9 Surgical Therapy 9.10 Endometriosis and IVF 9.11 Adenomyosis 9.12 Proposed Strategy for Management of Endometriosis 10. Tubal Infertility, Fibroids and Uterine Factors 10.1 Introduction 10.2 Uterine Problems: Congenital Anomalies, Septa, Fibroids, Polyps, Adhesions and Uterine Anomalies 11. Male Factor Infertility 11.1 Introduction 11.2 General Lifestyle Factors 11.3 Drugs 11.4 Chemotherapy and Radiotherapy 11.5 Occupational Factors 11.6 Anabolic Steroids 11.7 Cannabis and Other Recreational Drugs 11.8 Hypospadias, Cryptorchidism and Testicular Cancer 11.9 Orchitis and Prophylactic Mumps, Measles, Rubella Vaccination 11.10 Sexually Transmitted Infections 11.11 Testicular Trauma 11.12 Hypogonadism 11.13 Oligoasthenozoospermia 11.14 Frequency of Intercourse 11.15 Leukospermia 11.16 Oxidative Stress and ROS 11.17 Varicocele 11.18 Antisperm Antibodies 11.19 Obstructive Azoospermia 11.20 Congenital Bilateral Absence of the Vasa Deferentia 11.21 Young’s Syndrome 11.22 Kartagener’s Syndrome 11.23 Surgical Trauma and Vasectomy 11.24 Microsurgical Reconstruction of the Vasa 11.25 Idiopathic Male Factor Infertility 11.26 Paternal Ageing 11.27 Coital Dysfunction and Psychosexual Problems 11.28 Hypergonadotrophic Testicular Failure 11.29 IUI, IVF and ICSI 11.30 Androgen Insensitivity Syndrome 11.31 Donor Insemination 12. Unexplained Infertility 12.1 Introduction 12.2 Assessing the Cause of Infertility 12.3 Management of Unexplained Infertility 12.4 Clomifene Citrate 12.5 Letrozole 12.6 IUI 12.7 Gamete Intrafallopian Transfer 12.8 IVF 12.9 Strategy for Management of Unexplained Infertility 13. In Vitro Fertilisation 13.1 Introduction 13.2 Indications for IVF 13.3 Viral Screening before Assisted Conception Therapies 13.4 IVF 13.5 Regimens for IVF 13.6 Dosing of Stimulation for IVF 13.7 Monitoring the IVF Cycle and Ovarian Response to Stimulation 13.8 Ovarian Reserve and Prediction of Response to Stimulation 13.9 Poor Responders 13.10 Response of the Polycystic Ovary to Stimulation for IVF 13.11 Oocyte Retrieval 13.12 Embryo Culture and Embryo Transfer 13.13 Number of Embryos for Transfer 13.14 ICSI for Severe Male Factor Infertility 13.15 The Embryo Transfer Procedure 13.16 Endometrial Assessment 13.17 The Endometrial Scratch 13.18 Luteal-Phase Support after IVF 13.19 The Frozen Embryo Replacement Cycle 13.20 Pregnancy Rates after IVF 13.21 Oocyte Donation 13.22 Surrogacy 13.23 The Human Fertilisation and Embryology Authority and Regulation in the United Kingdom 14. Fertility Preservation 14.1 Cryopreservation of Gametes and Embryos 14.2 In Vitro Growth of Follicles 14.3 Protection of the Ovaries against Chemotherapy 14.4 Testicular Tissue Freezing 14.5 Transgender Fertility Preservation 15. Pre-Implantation Genetic Testing and Emerging Technologies 15.1 Pre-Implantation Genetic Testing 15.2 Modes of Inheritance 15.3 The Process of PGT 15.4 PGT-A 15.5 Supernatant Testing 15.6 Emerging Technologies 16. Complications of Ovarian Stimulation 16.1 Introduction 16.2 Drug-Specific Side Effects 16.3 The Ovarian Hyperstimulation Syndrome 16.4 Multiple Pregnancy 16.5 The Risk of Cancers in Subfertile Populations and after Fertility Treatment 17. Counselling and Modern Families 17.1 Introduction 17.2 Infertility and Subfertility 17.3 Psychosexual Problems 17.4 How to Deal with Work 17.5 Special Needs of the Male Partner 17.6 Adjustment to Parenthood 17.7 How to Tell Children of Donated Gametes 17.8 Surrogacy 17.9 Modern Families 17.10 Transgender Pregnancies 17.11 Emotional Support for Clinic Staff 17.12 The Infertility Counsellor 17.13 Welfare of the Child 18. Ethical and Religious Issues 18.1 Introduction 18.2 Does Everyone Have a Right to Treatment? 18.3 Biological Considerations 18.4 Moral Status of the Embryo 18.5 Is IVF Ethical? 18.6 Experiments on Human Embryos, Cloning and Stem Cell Research 18.7 Donors and Donation 18.8 Sex Selection 18.9 Fetal Reduction 18.10 Should Older Women Be Offered IVF? 18.11 Religious Perspectives 18.12 Conclusion 19. Health Outcomes of Children Born after Assisted Conception 19.1 Introduction 19.2 Manipulated Gametes 19.3 IVF 19.4 ICSI 19.5 Imprinting Disorders 19.6 Cryopreserved Gametes or Embryos 20. Miscarriage and Ectopic Pregnancy 20.1 Introduction 20.2 Incidence of Miscarriage 20.3 Parental Age 20.4 Health Conditions, Lifestyle Factors and Risks of Miscarriage 20.5 Diagnosis of Pregnancy 20.6 Prevention of Miscarriage 20.7 Management of Miscarriage 20.8 Ectopic Pregnancy 20.9 Diagnosis of Ectopic Pregnancy 20.10 Management of Ectopic Pregnancy 20.11 Counselling and Support 21. Recurrent Miscarriage and Recurrent Implantation Failure 21.1 Introduction 21.2 Classification of Recurrent Miscarriage 21.3 Nutritional Causes 21.4 Environmental Factors 21.5 Genetic Causes 21.6 Anatomical Abnormalities 21.7 Infection and the Microbiome 21.8 Endocrine Abnormalities 21.9 Luteal-Phase Defects and Progesterone Therapy 21.10 Thrombophilias 21.11 Immunological Causes of Recurrent Miscarriage 21.12 Summary of the Investigation and Management of Couples with Recurrent Miscarriage 21.13 Recurrent Implantation Failure 22. Alternative Therapies and “Add-Ons” 23. When to Stop Treatment and Other Options 23.1 Introduction 23.2 Adoption 23.3 Adopting a Child from Overseas 23.4 Fostering 23.5 Respite Care Appendix: Daily Vitamin and Mineral Requirements (See Chapter 3) Books for Further Reading Index "This text has been written as a practical guide, based on the author's experience over the last 40 years of daily clinical practice and aiming to place the modern approach to the management of infertility in the context of sound theory and evidence-based therapy. It provides the reader with a comprehensive classification of the causes of infertility, their investigation, and their management. This new edition covers many advances in the understanding and management of infertility and other updates to practice - for example, a greater understanding of the pathophysiology of ovarian aging and ovarian reserve testing, the classification of disorders of ovulation and management of polycystic ovary syndrome, the refinement of regimens for superovulation, improved embryo culture systems and the use of artificial intelligence for the selection of embryos, assessments for endometrial receptivity and management of recurrent implantation failure, and pre-implantation genetic testing (PGT) as a therapeutic tool opening up the possibility for aneuploidy screening, as well as the latest thoughts on nutritional health, periconception care, and the exciting new world of the microbiome"-- Provided by publisher