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The Art and Science of Assisted Reproductive Technique (ART)
Gautam N Allahbadia, Rubina Merchant, Rita Basuray Das
SECTION 1: INTRODUCTION
CHAPTER 1:
Advent of Medically Assisted Reproductive Technologies (Mart) in India
INTRODUCTION
INDIA'S FIRST TEST-TUBE BABY
Novel Techniques used by the Kolkata team based on the Report submitted by Mukherjee to the West Bengal Government (1978) and the Article published in the Journal of Cryogenics (1979)
Concluding Statement
CHAPTER 2:
The Endocrinology of ART
ACKNOWLEDGEMENT
CHAPTER 3:
Efficient Classification of Infertility
CLASSIFICATION OF INFERTILITY INTO SPECIFIC GROUPS
WHY IS A NEW APPROACH TO MANAGEMENT OF INFERTILITY NEEDED?
THE PROPOSED NEW CLASSIFICATION OF INFERTILITY
CHAPTER 4:
Modern Work-up of Infertility
INTRODUCTION
PRACTICAL WORK-UP: CURRENT SCENARIO
The Usual Work-up
History and Physical Examination
EVALUATION OF THE MALE
Semen Analysis
Sperm Function Tests
EVALUATION OF THE FEMALE
Assessment of Ovulatory Factor
Assessment of Tubal and Peritoneal Factor
Assessment of the Uterus
Evaluation of the Cervix and Vagina
Hormonal Evaluation
Clomifene Citrate Challenge Test
Counselling
CONCLUSIONS
SECTION 2: STIMULATION STRATEGIES
CHAPTER 5:
Ovulation Induction with Tamoxifen Citrate
CLINICAL PHARMACOLOGY
Pharmacokinetics and Metabolism
Mode of Action
PHYSIOLOGICAL EFFECTS
Endocrine Effects
Bones and Lipids
CLINICAL APPLICATIONS
Indications
Dose, Administration and Monitoring
Contraindications
Side Effects
Conclusion
CHAPTER 6:
Defining the Poor Ovarian Response before Controlled Ovarian Hyperstimulation
OVERVIEW
Methods of Assessing Ovarian Reserve
Chronological Age
Cycle Day 3 FSH Levels
Follicular Phase Inhibin Levels
Serum Estradiol Levels
Clomiphene Citrate Challenge Test
Other Dynamic Ovarian Reserve Tests
Sonographic Assessment
FUTURE DIRECTIONS
CONCLUSIONS
CHAPTER 7:
Aromatase Inhibitors—Their Role in the Treatment of Infertility
CHAPTER 8:
Urinary Human FSH Versus Recombinant Human FSH
INTRODUCTION
Recombinant Human FSH (r-hFSH) Preparations
r-hFSH Induces Follicular Development
Comparison of r-hFSH with u-hFSH in ART
Comparison of r-hFSH and Highly Purified u-hFSH
CONCLUSIONS
CHAPTER 9:
Stimulation Strategies for Complex IVF Patients
INTRODUCTION
POOR RESPONDER PATIENTS
Definition of Poor Responder
Prediction of Response
DIFFERENT GNRH ANALOGUE PROTOCOLS
ROLE OF LH IN MULTIPLE FOLLICULAR STIMULATION FOR IVF
HIGH RESPONDER PATIENTS
CHAPTER 10:
Programming the Cycle with Oral Contraceptives Antecedent to the use of Antagonists
INTRODUCTION
GNRH-ANTAGONIST
WHAT IS THE ORAL CONTRACEPTIVE?
Effect on Endometriosis
Effect on Bleeding Pattern
Effect on Polycystic Ovaries
Ovarian Cysts and COC
Poor Responders
Good Responders
Use of COC Prior to GnRH-Antagonist
Protocol
CHAPTER 11:
Agonists Versus Antagonists: Physiology to Clinical Success
INTRODUCTION
GNRH ANTAGONISTS
Protocols
Cycle Characteristics
Luteal Phase
IVF-ET
Potential Benefits of GnRH Antagonists
Side Effect Profile
CONCLUSIONS
CHAPTER 12:
Microdose GnRH for the Stimulation of Low Responders
OVERVIEW
Methods and Results
‘Microdose’ Protocols in IVF
The ‘Poor Responder’
Determination of Down Regulation
CONCLUSIONS
CHAPTER 13:
The Role of GnRH Antagonist in the Management of Poor Responders
INTRODUCTION
Definition of Poor Responders
Assessment of Ovarian Reserve
Stimulation Protocol
Synthetic GnRH and its Analogs
Use of GnRH Analogue
DISCUSSION
CHAPTER 14:
Alternative Approaches to Ovarian Stimulation and Triggering of Ovulation
OVARIAN STIMULATION
Introduction
Types and Characteristics of Different Protocols
Treatment Protocols with GnRH-a and Gonadotropins
Long protocol
Short Protocol
Preparatory Protocol
Ultrashort Regimen
Long Protocol Using a Monthly Depot Preparation
Results with Various Protocols
Why do We Need Alternative Approaches to Ovarian Stimulation Protocols?
Alternative Approaches to Ovarian Stimulation Protocols
OVULATION TRIGGERING
Introduction
The Spontaneous LH/FSH Surge
The GnRHa-Induced LH/FSH Surge
The Luteal Phase
Benefits and Limitations
Prevention of OHSS
Ovulation Triggering Using Choriogonadotropin Alfa
Ovulation Triggering Using recLH
Recent Advances
CHAPTER 15:
Role of LH in Stimulation Protocols for ART
INTRODUCTION
Measures Taken to Lower Circulating Levels of LH and Characteristics of Exogenous Administered Gonadotropins
Is the LH Content in hMG Preparations Detrimental to the Outcome of IVF?
Negative Effects of Decreased Circulating Levels of LH During Ovarian Stimulation
CONCLUSIONS
CHAPTER 16:
Role of hMG-HP in Stimulated Cycles for ART
INTRODUCTION
The Rationale of Introducing Highly Purified hMG
The Role of Luteinizing Hormone (LH) in Ovulation Induction For Assisted Reproduction Techniques (ART)
Clinical Studies
CONCLUSION
CHAPTER 17:
Luteal Phase Support
INTRODUCTION
Physiology and Morphology of the Endometrium and its Correlation in Different Phases of the Menstrual Cycle
Corpus Luteum and its Function
Assessment of the Endometrial Maturity
Medications for the Luteal Phase Support
CONCLUSIONS
CHAPTER 18:
Severe OHSS: A Critical Care Physician's Point of View
INTRODUCTION
Incidence
Pathogenesis
Clinical Features of Severe OHSS
Principles of Management
CONCLUSION
CHAPTER 19:
Ovulation Induction: Surgical Approach
INTRODUCTION
BILATERAL OVARIAN WEDGE RESECTION (BOWR): HISTORY OF AN OLD TECHNIQUE
Mechanisms of Action:Theory
Posterior Endocrine Alterations
Adverse Iatrogenic Events
To Minimize Adhesions
TECHNIQUES OF THE LAPAROSCOPIC APPROACH: LAPAROSCOPIC OVARIAN DRILLING (LOD)
We Tested the Effect of the Monopolar LOD on the Embryo Quality, on the Implantation Rate in PCOS Undergoing IVF
Materials and Methods
Results
Postoperative Endocrine Alterations
Intraabdominal Adhesion Formation and Ovarian Atrophy
Abortion Rates
Indications
Clomiphene Citrate Resistant PCOS
Laparoscopic Treatment Failure
Indications that are Not Recommended
Treatment of Clomiphene-Responsive PCOS
Treatment of the Hirsute Patient
A NEW SURGICAL TREATMENT: TRANSVAGINAL OVARIAN DRILLING (TVOD)
COMPARISONS WITH MEDICAL TREATMENT OPTIONS FOR PCOS
Conventional Gonadotropin Therapy
Pulsatile GnRH Therapy
Low-dose GnRH Agonist–Gonadotropin Therapy
FUTURE DEVELOPMENTS
CONCLUSIONS
SECTION 3: POLYCYSTIC OVARY SYNDROME (PCOS)
CHAPTER 20:
Polycystic Ovary Syndrome (PCOS): An Update
INTRODUCTION
HISTORICAL BACKGROUND
PCOS PHENOTYPE
PCOS Prevalence
PCOS: Pathophysiology
PCOS: Clinical Complex
PCOS: Cosmetic Disorders
PCOS Cosmetic Disorder Therapies
Hormonal Interventions
Physical Interventions
Surgical Intervention
Medical Interventions
PCOS: Reproductive Disorders
PCOS Reproductive Disorder Therapies
Physiological Interventions
Hormonal Interventions
Hormonal Interventions for IVF Patients
PCOS: Metabolic Disorders
PCOS Metabolic Disorder Therapies
Hormonal Interventions
CONCLUSION
CHAPTER 21:
In vitro Oocyte Maturation
CHAPTER 22:
Polycystic Ovary Syndrome: Genetics and Health Consequences
HISTORY AND BACKGROUND
DEFINITION
EPIDEMIOLOGY
MORPHOLOGY
ENDOCRINE FINDINGS
OBESITY, HYPERINSULINAEMIA AND HYPERANDROGENISM
INSULIN RESISTANCE, HYPERINSULINAEMIA AND HYPERANDROGENISM
GENETICS OF POLYCYSTIC OVARY SYNDROME
Genes Involved in Secretion and Action of Insulin
The Insulin Receptor Gene
The Insulin Gene
Calpain-10 Genotype
Genes Involved in Folliculogenesis-Follistatin Gene
LONG-TERM HEALTH CONSEQUENCES AND IMPLICATIONS OF GENETICS
Fertility Problems
Non-fertility Related Problems
Diabetes
Cardiovascular Problems
SUMMARY
SECTION 4: ART PROCEDURES
CHAPTER 23:
Vaginal Oocyte Retrieval
INTRODUCTION
TECHNIQUE
TIMING OF OOCYTE RETRIEVAL
Precautions
COMPLICATIONS
CONCLUSIONS
CHAPTER 24:
Gamete Intrafallopian Transfer (GIFT)
OVERVIEW
INDICATIONS
TECHNIQUE
RESULTS
Factors that may Influence the Results
Quality and Number of Oocytes
Age
Cause of Infertility
COMPLICATIONS
FUTURE DIRECTIONS AND CONTROVERSIES
CHAPTER 25:
Zygote Intrafallopian Tube Transfer (ZIFT): Patient Selection is the Key to Beneficial Utilization
INTRODUCTION
THE TECHNIQUE
OUTCOME DATA
PATIENT SELECTION
CONCLUSION
CHAPTER 26:
Fallopian Tube Sperm Perfusion
INTRODUCTION
Our Technique of FSP
DISCUSSION
CONCLUSIONS
CHAPTER 27:
Use of Lasers in ART: Clinical Applications and Potential Research Tools
INTRODUCTION
LASERS AND DELIVERY SYSTEMS AVAILABLE FOR MICROMANIPULATIONS
SPERM MANIPULATIONS
Oocyte Manipulations
Laser Zona Drilling (LZD)
Laser Assisted Hatching (LAH)
BLASTOMERE BIOPSY AND PREIMPLANTATION GENETIC DIAGNOSIS
CONCLUSIONS
CHAPTER 28:
Blastocyst Transfer: One Step Further in the Quest for the Magic Bullet
INTRODUCTION
OUR EXPERIENCE
THE PROS AND CONS OF BLASTOCYST TRANSFER
CONCLUSION
SECTION 5: LABORATORY ISSUES
CHAPTER 29:
Semen Analysis for Clinical Interpretation
INTRODUCTION
Inherent Ambiguities
Further Testing
Repeat Testing
Logical Framework
Interpretation through Question and Answer
Can Sperm Get to the Fertilization Site?
Can the Sperm Fertilize the Egg?
Are Immunological Factors Suspected?
Do Chemical Components Need to be Assessed?
Routine Semen Analysis
Macroscopic Analysis
Appearance
Coagulation and Liquefaction
Color and Odor
Viscosity
Volume
Microscopic Analysis
Sperm Agglutination
Non-Sperm Cellular Elements
Leukocytes
Erythrocytes
Epithelial Cells
Microorganisms
Cells of Spermatogenic Origin
Sperm Concentration and Sperm Count
Sperm Motility
Sperm Viability
Sperm Morphology
Sperm Movement Through The Cervical Mucus
Sperm Mucus Penetration Test
Specialized Semen Analysis
Hypoosmotic Swelling Assay
Sperm Acrosome Reaction Assay
Zona Binding Assay
Sperm Penetration Assay
Anti-Sperm Antibody Test
Anti-Sperm Antibody Assays
Semen Chemistry
Prostatic Contribution Analysis
Seminal Vesicular Contribution Analysis
Epididymal Contribution Analysis
Seminal Plasma pH Analysis
CONCLUSION
ACKNOWLEDGMENT
CHAPTER 30:
Fundamentals of Sperm Processing Techniques
INTRODUCTION
NATURE'S OWN SPERM PROCESSING CLINIC
Mimicry and Improvement
Evolution of Laboratory Sperm Processing
SPERM PROCESSING
Centrifugation
Viscosity Reduction
Sperm Migration Method
Swim-Up Procedure
Sperm Swim-Up Procedure (Without Centrifugation)
Swim-Down Procedure
Density Gradient Centrifugation Method
Colloidal Silica Based Density Gradient
Iodixanol-Based Density Gradient
Column Adherence Procedure
Sephadex Column Filtration Procedure
Glass Wool Column Filter Procedure (“GWCF”)
CONCLUSION
ACKNOWLEDGMENT
CHAPTER 31:
Sperm Separation Techniques: Comparison and Evaluation of Gradient Products
INTRODUCTION
Separation Techniques: General
Separation Techniques: Density Gradient Separation (Percoll) vs Swim-up
Sperm Separation Techniques: Percoll, Glass Wool and Sephadex Columns
Sperm Separation Techniques: Optipref, Ixaprep and Accudenz
Sperm Separation Techniques: Silane-Coated Silica-Based Gradients
SPERM SEPARATION TECHNIQUES: SUMMARY AND CONCLUSIONS
CHAPTER 32:
Prediction of ART Outcome in Male Factor Infertility Patients by a New Semen Quality Score
INTRODUCTION
DEVELOPING AN OVERALL SEMEN SCORE
Patient Selection in the Evaluation of Semen Scores
Assessment of Semen Variables
Measurement of Sperm Morphology
STATISTICAL MODEL FOR CALCULATING THE SEMEN SCORES
Calculation of the IUI-Semen Pregnancy Score
Semen Quality (SQ) and Relative Quality (RQ) as Measures of Semen Score
RELATIONSHIP OF SQ AND RQ SCORES WITH IUI PREGNANCY RATES
Relationship of IUI-SPS with IUI Pregnancy Rates
Relationship between Female Characteristics and Pregnancy Rate
SIGNIFICANCE OF SQ AND RQ AS NOVEL SEMEN SCORES
Computer Assisted Semen Analyzer Derived Versus Conventional Semen Scores
Information Provided by SQ and RQ Scores
CONTROVERSY OVER SEMEN QUALITY AND ART OUTCOME
The Role of SQ and RQ Scores and the IUI-Semen Pregnancy Score
Information Provided by IUI-SPS and Relationship with Pregnancy
CONCLUSION
SUMMARY
CHAPTER 33:
Why Should We Assess Oocyte and Embryo Morphology?
INTRODUCTION
Morphology Assessment: How and When?
Morphology Assessment
The Follicle
The Oocyte
The Pronuclear Embryo (Zygote)
The Cleaving/Compacting Embryo
The Blastocyst
MORPHOLOGY ASSESSMENT: SUMMARY AND CONCLUSIONS
CHAPTER 34:
Benefits and Drawbacks of Extended Embryo Culture
OVERVIEW
HISTORY OF BLASTOCYST TRANSFER
RATIONALE OF BLASTOCYST CULTURE
Methods and Results
Complications
Monozygotic Twinning
Blastocyst Registry
CONCLUSION
CHAPTER 35:
Really, Just How Important is the Level of Room Lighting in the IVF Laboratory on Embryo Development?
INTRODUCTION
Effect of Light: Early Studies
THe Effect of Light: Lessons from Cell Culture
The Effect of Light: Recent Studies
The Effect of Light: Toxic Effect of Oxygen
Protection against ROS
THE EFFECT OF LIGHT: SUMMARY AND CONCLUSIONS
CHAPTER 36:
The Mouse Embryo Bioassay: Is It the “Gold Standard” for Quality Control Testing in the IVF Laboratory?
INTRODUCTION
Why do Bioassay Testing? Because We Have to!
Types of Bioassays
Sperm Motility Assay
Cell Lines
The Mouse Embryo
The Two-Cell Embryo
The One-Cell Embryo
Mouse Embryo Bioassay: Directions for the Future
SUMMARY
CHAPTER 37:
Human Oocyte and Embryo Cryopreservation
SUMMARY OF SYLLABUS
Cryostorage of the Female Gamete
Cryopreservation of the Preimplantation Human Embryo
Selection Criteria for Human Blastocysts for Cryopreservation
Why Freeze Embryos at the Blastocyst Stage?
Routine Freezing of Blastocysts
The Future of Egg and Embryo Cryopreservation
APPENDIX 37.1
Human Egg Cryopreservation
Freeze
Thaw
APPENDIX 37.2
Blastocyst Cryopreservation: Shady Grove RSC Protocol
Freezing
Thawing
APPENDIX 37.3
Blastocyst Freeze/Thaw Media
Blastocyst Freezing Procedure
Blastocyst Thawing Procedure
CHAPTER 38:
In Vitro Maturation: Future Clinical Applications
OVERVIEW
METHODS AND TECHNIQUES
Patients
Oocyte Recovery
In Vitro Maturation
In vitro Fertilization (IVF), In vitro Development (IVD), and Embryo Transfer (ET)
Endometrial Preparation
Results
IVM in Patients with Various Infertility Factors
Effect of HCG-priming in IVM Cycles
The Experience of HCG-primed IVM Cycles
Application of IVM Program for the Prevention of OHSS in COH Cycles
COMPLICATIONS
CONCLUSIONS
CHAPTER 39:
Oxidative Stress and DNA Damage in Human Sperm: The Cleveland Clinic Story
INTRODUCTION
ROS AND SPERM PHYSIOLOGY
CELLULAR ORIGIN OF ROS IN HUMAN SEMEN
ROS Production by Spermatozoa
ROS Production by Leukocytes
ROS SCAVENGING STRATEGIES
Prevention
Interception
Repair
THE CONCEPT OF OXIDATIVE STRESS (OS)
MECHANISMS OF ROS TOXICITY
Lipid Peroxidation (LPO)
Initiation Stage
Propagation Stage
Impairment of Sperm Motility
Sperm Nuclear DNA Damage
ORIGIN OF DNA DAMAGE IN SPERMATOZOA
Defective Chromatin Packaging
Apoptosis
Oxidative Stress-induced DNA Damage
COMPLICATIONS OF SPERM NUCLEAR DNA DAMAGE
Failure of Fertilization
Embryo Death
Childhood Cancer
Infertility
CONTRIBUTIONS OF THE CLEVELAND CLINIC
Mechanism of Seminal OS
Role of Seminal Leukocytes
Role of Abnormal Spermatozoa
Assessment of OS Status
Measurement of ROS (Fig. 39.3)
Measurement of TAC (Fig. 39.4)
ROS-TAC Score: A New Development in Field of OS
Quality Control of OS indices (ROS and TAC)
Clinical Significance of Assessment of Seminal OS
ROS in Neat (Raw) Semen: An Accurate and Reliable Test for OS
STRATEGIES TO REDUCE SEMINAL OS
FUTURE DIRECTIONS
SUMMARY
CHAPTER 40:
Quality Management in an Assisted Reproductive Therapy Environment
INTRODUCTION
RISK ASSESSMENT WITHIN THE ART ENVIRONMENT
RISK CLASSIFICATION
Consent Form
Unique Patient Identification
Gene Pool Restriction
NON-SPECIFIC REQUIREMENTS OF A QUALITY MANAGEMENT SYSTEM
Policy
Training
Legal Issues
Internal Audit System
Management Review
Customer Satisfaction
DEVELOPMENT OF A QUALITY MANAGEMENT SYSTEM
SECTION 6: CONTEMPORARY THOUGHTS
CHAPTER 41:
How to Improve Success Rates in IVF?
INTRODUCTION
Patient Factor
Laboratory Factor
The Physician Factor
OVULATION INDUCTION
TECHNIQUES TO IMPROVE EMBRYO QUALITY
Micromanipulation
Assisted Hatching
Preimplantation Genetic Diagnosis
The Role of the Endometrium
Embryo Transfer Technique
CHAPTER 42:
Current Immunological Assays: Are they Enough to Uncover the Supposed Immune Causes for Assisted Reproduction Failure?
INTRODUCTION
Antiphospholipid Antibodies
Antithyroid Antibodies
Reproductive Peripheral Blood Immunophenotyping
Antinuclear Antibodies and Antiovarian Antibodies
Human Serum Embryo-toxicity
Antisperm Antibodies
CHAPTER 43:
Endometriosis and ART
INTRODUCTION
Endometriosis and Infertility
Endometriosis and ART
GnRH-analogue Therapy in ART Cycles in Women with Endometriosis
Folliculogenesis and Ovulation in Endometriosis
Embryo Quality and Uterine Receptivity in Endometriosis
CONCLUSION
CHAPTER 44:
Infertility: Is there Success after Forty?
INTRODUCTION
OVARIAN RESERVE TESTING
Basal FSH/Estradiol (E2)
Clomiphene Citrate Challenge Test (CCCT)
OTHER TESTS FOR OVARIAN RESERVE
Gonadotropin Releasing Hormone Agonist Stimulation Test
ULTRASOUND EVALUATION OF OVARIAN RESERVE
TREATMENT OF THE OLDER PATIENT
Clomiphene Citrate with Intrauterine Insemination (CC-IUI)
Gonadotropins with IUI (INJ-IUI)
ASSISTED REPRODUCTIVE TECHNOLOGIES (IVF, GIFT)
WHAT IS THE OPTIMAL TREATMENT
CONCLUSION
CHAPTER 45:
Inheritance of Infertility
INTRODUCTION
Genetic Abnormalities in Female Infertile Population
X– Chromosome Abnormalities
XX-gonadal Dysgenesis
Familial Premature Ovarian Failure (POF)
Mullerian Aplasia
Hand Foot Genital Syndrome
Leiomyomata
Endometriosis
Polycystic Ovarian Syndrome
Genetic Abnormalities in Male Infertile Population
Genes Involved in Sex Determination
DSS: X-Linked Switch Between Female and Male Development
Autosomal Gene Involved in Sex Determination
Deletions of Y-Chromosome
Genes in the AZFa, b and c Families
Genes Involved in Spermatogenic Disruption
DAZ Gene Family
RBM Gene Family
Cystic Fibrosis: (CFTR Gene)
CHAPTER 46:
Sperm Separation
INTRODUCTION
In Vivo Methods
Dietary Methods
IN VITRO SEPARATION OF X AND Y BEARING SPERMS
Separation by Density or Motility
Sperm Separation by Cell Sorting
Principle of Cell Sorting
Development of Sperm Sorting Technology
Method as described by Johnson et al47
Preparation of Sperm Nuclei
Fluorescent Staining of Spermatozoa
Flow Cytometric analysis and Sorting
Collection of Sorted Spermatozoa
Change to High Speed Sorting (HiSON)
Mammalian Studies
Human Applications
ETHICAL ISSUES OF SEX SELECTION
Recommendations of Ethics Committee (2001)69
CONCLUSION
CHAPTER 47:
Ovarian Tissue Cryopreservation in Cancerous Patients: State of the Art
INTRODUCTION
CHEMOTHERAPY-ASSOCIATED GONADOTOXICITY
Effect of Dose-intensity, Cumulative Dose and Route of Administration on Incidence of POF
Other Alternatives for Fertility Preservation
FERTILITY CONSERVATION OPTIONS
Autotransplantation
Xenotransplantation
In Vitro Maturation
CHEMOTHERAPY and GnRH-a CO-TREATMENT
What are the Reasons for Discrepancy between Various Studies?
INHIBIN MEASUREMENTS
Future Endeavors
Acknowledgement
CHAPTER 48:
Molecular Biology Applied to ART
BACKGROUND
INTRODUCTION
The Genetic Material
The Human Genome Project
DNA based Systemic Diagnosis
DNA Hybridization (Southern)
Polymerase Chain Reaction (PCR)
The Use of PCR for PGD in Embryos
Fluorescent in-situ Hybridization (FISH)
The use of FISH for Genetic Screening in Spermatozoa
DNA Sequencing
Microarrays (Microchips)
Perspectives
CHAPTER 49:
Assisted Reproductive Technologies in Human Immunodeficiency Virus (HIV) Sero-discordant Couples: Practice, Prognosis and Future Prospects
INTRODUCTION
HIV, Gametes and Fertility
Assisted Reproductive Techniques for Serodiscordant Fertile Couples
Assisted Reproduction for Infertile Serodiscordant Couples
Procedure for Handling Gametes from HIV Serodiscordant Couples
ART, Pregnancy and HIV
Future Possibilities
SECTION 7: THIRD PARTY REPRODUCTION
CHAPTER 50:
Gestational Surrogacy
INTRODUCTION
LEGAL AND ETHICAL ISSSUES SURROUNDING SURROGACY
PSYCHODYNAMIC ISSUES
PSYCHOLOGICAL SCREENING
SCREENING THE PROSPECTIVE PARENTS
SELECTING THE SURROGATE
THE TEAM APPROACH
PREGNANCY
DELIVERY AND POSTPARTUM
COUNSELING
SUMMARY
CHAPTER 51:
Oocyte Donation
INTRODUCTION
PRE-TREATMENT COUNSELLING
RECIPIENTS OF OOCYTES—INDICATIONS
Broad Categorisation
Detailed Categorisation
Source of Oocyte Donors
Ideal Oocyte Donors
Counselling of Unsuitable Donors
Investigations for Donors
Benefits to the Donors
Investigations and Prerequisites for Oocyte Recipients
Medication for Recipients
Medication for Oocyte Donors
Success of IVF with Oocyte Donation
CONCLUSION
CHAPTER 52:
Oocyte-Sharing Programs
INTRODUCTION
The Non-patient Egg Sharer between two Egg Recipients
Patients Undergoing IVF Treatment and Agreeing to Share Oocytes
Technical Minutiae
CONCLUSIONS
CHAPTER 53:
Germinal Stem Cells: Culture and Replication
INTRODUCTION
TISSUE—CULTURE MATERIALS AND ROUTINE PROCEDURES
Equipment
Tissue Culture Media and Solutions
Medium
Serum
Preparation of Feeder Cells
Derivation and Culture of Human Embryonic Germ Cells
Expansion of Pluripotent Stem Cells into Permanent Cell Lines
Maintenance of Pluripotent Cell Lines
Subculture of PS Cells
Freezing and Thawing of Pluripotent Cells
Freezing Cells
Thawing Cells
In Vitro Differentiation in Pluripotent Cells
Formation of Simple Embryoid Bodies
Stem Cell Markers
Identification of Stem Cell Markers
Karyotype Analysis
Collection of Mitotic Cells
Preparation of Mitotic Spreads
G-banding Analysis
DISCUSSION
CHAPTER 54:
Cytoplasmic and Nuclear Transfer: New Life for an Old Egg?
INTRODUCTION
SEXUAL REPRODUCTION
Safety Mechanism
Mitochondria and Development
Mitochondrial DNA
Mitochondrial Genetics
Disorders of Mitochondrial Metabolism
Role of Mitochondria in Atresia
Mitochondria and Aging
Clinical use of Cytoplasmic Transfer
Nuclear Transfer
DISCUSSION
CONCLUSIONS
SECTION 8: IMPLANTATION
CHAPTER 55:
The Endometrium and Implantation
INTRODUCTION
MOLECULAR MARKERS OF ENDOMETRIAL RECEPTIVITY
Steroid Hormone
MUC 1
Cytokines
Cadherins
Adhesion Molecules
Heat Shock Proteins
Calcitonin
Hox Genes
EMBRYONIC REGULATION OF ENDOMETRIAL RECEPTIVITY HUMANS
EMBRYONIC REGULATION OF HUMAN ENDOMETRIAL EPITHELIAL CELL CYTOSKELETON
EMBRYONIC REGULATION OF CHEMOKINES IN HUMAN ENDOMETRIAL EPITHELIAL CELLS
EMBRYONIC REGULATION ADHESION AND ANTI-ADHESION MOLECULES IN HUMAN ENDOMETRIAL AND EPITHELIAL CELLS
THE BLASTOCYST REGULATES APOPTOSIS OF ENDOMETRIAL EPITHELIAL CELLS
CLINICAL IMPLICATIONS
SUMMARY
CHAPTER 56:
Modulators of Endometrial Receptivity: A Molecular Symphony
SUMMARY
THE BROAD PERSPECTIVE
Setting the Stage—the Overture
Act I – Apposition
Act II – Adhesion
Act III - Penetration
Act IV – Invasion
Act V – Vascular Breaching
Act VI – Placental Formation
The Players – at the Molecular Level
Calcitonin
Chemokines
Epidermal Growth Factor (EGF)
Ezrin, Radixin, and Moesin (ERM)
Integrins
Interleukin-1 (IL-1)
Leukemia Inhibitory Factor (LIF)
Mucins
Prostaglandins (PGs) and COX Enzymes
Proteinases
Improving the Outcome
Embryo Culture
Timing of the Embryo Transfer
pH and Gas Phase
Dilution Factor
CONCLUSION
CHAPTER 57:
Endometrial Preparation for Patients Undergoing Frozen- Thawed Embryo Transfer Cycles
INTRODUCTION
SYNCHRONIZATION
Endometrial Preparation Protocols
Natural Cycle
Hormone Replacement using Estrogen and Progesterone
Hormone Replacement using GnRHa followed by Estrogen and Progesterone
Ovulation Induction
CONCLUSIONS
CHAPTER 58:
Pathophysiology of Implantation Failure in IVF
INTRODUCTION
APPOSITION AND ATTACHMENT: ROLE OF ENDOMETRIUM
Role of Pinopodes
Adhesion Molecules in the Uterine Epithelium
Mucins
Integrins
Role of Growth factors and Cytokines
Leukemia Inhibitory Factor
Interleukin-1
Placental Invasion: Role of the Endometrium
Broad-spectrum Protease Inhibitors
Insulin-like Growth Factor Binding Protein-1
Role of Macrophages, T Cells and Natural Killer Cells in the Endometrium
Effect of Ovarian Stimulation and Embryo Development on Implantation
Significance of Embryo Replacement Technique
SUMMARY
CHAPTER 59:
Recurrent Implantation Failures: The Preferred Therapeutic Approach
PROTOCOL FOR ENHANCING ENDOMETRIAL RECEPTIVITY
Treatment
Luteal Support
Immune Modulation
CONCLUSION
Aknowledgements
CHAPTER 60:
Repeated Pregnancy Loss (RPL): Is Investigation Important?
INTRODUCTION
Parental Karyotyping
Pelvic Ultrasound
Hypersecretion of Luteinizing Hormone
Antiphospholipid Antibodies (APL)
Infection
Autoimmune Cause
CHAPTER 61:
Antiphospholipid Antibodies in ART
INTRODUCTION
Antiphospholipid Syndrome
Pathophysiology in the Clinical Context
Rationale of Heparin-Aspirin (H-A) Therapy
DISCUSSION
CONCLUSION
SECTION 9: CRYOPRESERVATION
CHAPTER 62:
Cryopreservation of Oocytes and Embryos
INTRODUCTION
HISTORY
INDICATIONS FOR EMBRYO AND OOCYTE CRYOPRESERVATION
Biological and Technical Aspects
Embryo Survival
Clinical Outcome
Our Experience
RELIGIOUS AND ETHICAL ISSUES
CHAPTER 63:
Cryopreservation of Human Spermatozoa
SUMMARY
INTRODUCTION
Indications for Human Sperm Cryopreservation
Sperm Preparation Techniques Before Cryopreservation
Effects of Freezing on Sperm Quality
Fertilization Rates with Cryopreserved Spermatozoa
Cryobanking of Semen for Fertility Protection from Cytotoxic Treatment
Use of Cryopreserved Epididymal and Testicular Spermatozoa for Intracytoplasmic Sperm Injection
SECTION 10: ENDOSCOPY AND ART
CHAPTER 64:
Fertility Following Laparoscopic Surgery and Hysteroscopic Surgery
INTRODUCTION
ADVANTAGES OF ENDOSCOPIC SURGERY IN AN INFERTILE PATIENT
Laparoscopic Surgical Treatment of Infertility Related to PCOD
Our Experience
Complications of Drilling
Laser Drilling
CONCLUSIONS
LAPAROSCOPIC SURGERY FOR ENDOMETRIOSIS IN AN INFERTILE PATIENT
Laparoscopy Versus Laparotomy
Conservative Laparoscopic Surgery
Lysis of Bowel Adhesions
Peritoneal Implants
Ovarian Endometriosis
Restoration of Tubo-Ovarian Anatomy
Fertility following Laparoscopic Surgery for Endometriosis
Laparoscopic Reconstructive Tubal Surgery
Laparoscopic Survey
Salpingoovariolysis
Fimbrioplasty
Laparoscopic Salpingostomy
Fertility following Salpingostomy
Laparoscopic Myometomy
Technique of Laparoscopic Myomectomy
Fertility following Laparoscopic Myomectomy
HYSTEROSCOPIC SURGERIES IN INFERTILE PATIENTS
Instrumentation
Operative Hysteroscopy
Distension Medium
Energy Sources
Resection of Submucous Myomas and Polyps
Transection of Uterine Septum
Lysis of Uterine Adhesions
Canulation of Fallopian Tube
CHAPTER 65:
The Role of Hysteroscopy in the Management of Infertility
INTRODUCTION
HYSTEROSALPINGOGRAPHY (HSG)
PELVIC ULTRASOUND
SONOHYSTEROGRAPHY (SHG)
HYSTEROSCOPY AND ASSISTED REPRODUCTIVE TECHNIQUES
CONCLUSIONS
CHAPTER 66:
Modern Management of the Ischemic Black-Blue Twisted Adenexa
INTRODUCTION
Extirpative Therapy
Conservative Management
Can the Ischemic Tissue Recover?
Does Detorsion Increase the Risk of Thromboembolism?
Can Detorsion Postpone Treatment of Hidden Malignancy?
The Risk of Retorsion
CONCLUSION
CHAPTER 67:
Fertiloscopy: A New Technique and an Alternative to Conventional Laparoscopy in Infertility
OVERVIEW
INDICATIONS
TECHNIQUE
Pre-operative Workup and Patient Selection
Instrumentation (See Fig. 67.2)
COMPLICATIONS
FUTURE DIRECTIONS
CONCLUSION
CHAPTER 68:
Hysteroscopic Assessment of Selective Tubal Pressures and Tubal Cannulation by Air Bubble Stents
HYSTEROSCOPIC MARKERS FOR AN OPTIMAL SEPTOPLASTY
HYSTEROSCOPIC FIBROID RESECTION: AN ENDOMETRIAL AND MYOMETRIAL CONSERVING APPROACH
HYSTEROSCOPIC MARKERS FOR ENDOMETRITIS
CHAPTER 69:
Intrauterine Adhesions
INTRODUCTION
Aetiology and Pathogenesis
Diagnosis
Classification
Technique
Postoperative
Success Rate
CONCLUSION
SECTION 11: ULTRASONOGRAPHY
CHAPTER 70:
Update on Ultrasound Guided Embryo Transfer
INTRODUCTION
What Factors are Important for Successful ET?
Absence of Bleeding/blood on Catheter
Type of Catheter Used
Not Touching the Fundus
Avoiding the Use of a Tenaculum
Removal of all Mucus from Cervix
Ultrasound Details of Cavity Before Treatment
Leaving Catheter in Place for at Least 1 min
Thirty min rest After Transfer
Dummy Transfer Before Treatment
Ultrasound Monitoring of Transfer
SUMMARY
CHAPTER 71:
Cervical Mucus Evaluation by Transvaginal Ultrasonography: A Novel Approach
INTRODUCTION
MATERIALS AND METHODS
Phase I
Phase II
Amount of Mucus
Quality of Mucus
Spinnbarkeit
RESULTS
DISCUSSION
CHAPTER 72:
Multifetal Pregnancy Reduction
INTRODUCTION
RELIGIOUS, EMOTIONAL AND PRACTICAL CONSIDERATIONS
HISTORICAL AND TECHNICAL CONSIDERATIONS
ULTRASOUND GUIDANCE
Medication
Needling
Fetal Loss and Maternal Morbidity
Prematurity
CONCLUSION
SECTION 12: THE MALE FACTOR
CHAPTER 73:
Non-obstructive Azoospermia: Predictive Criteria for Sperm Retrieval
INTRODUCTION
Parameters Considered
Study of the Ejaculate
Genetic Considerations
Predictability for Repeat Procedure
Minimizing False Negative Sperm Retrieval
CONCLUSION
CHAPTER 74:
Epididymal and Testicular Sperm Retrieval
INTRODUCTION
INDICATIONS
SPERM RETRIEVAL METHODS
Epididymal Sperm Retrieval
Open Procedures
Percutaneous Procedures
Testicular Sperm Retrieval
Open Procedures
Percutaneous Procedures
OPEN EPIDIDYMAL SPERM RETRIEVAL
MESA (Microsurgical Epididymal Sperm Aspiration)
OFNA (Open Fine Needle Aspiration)
MESA Versus OFNA
PERCUTANEOUS EPIDIDYMAL SPERM RETRIEVAL
PESA (Percutaneous Epididymal Sperm Aspiration)
Open Versus Closed Epididymal Sperm Retrieval
PERCUTANEOUS TESTICULAR SPERM RETRIEVAL
TESA (Testicular Sperm Aspiration)
NAB (Needle Aspiration Biopsy)
TESA Versus NAB
Needle Biopsy
OPEN TESTICULAR SPERM RETRIEVAL
Conventional Biopsy
SST (Single Seminiferous Tubule) Biopsy
Microsurgical Selective Biopsy
Percutaneous Versus Open Biopsy
Open Conventional Biopsy Versus Microsurgical Biopsy Techniques
CHOICE OF PROCEDURE
CONCLUSION
CHAPTER 75:
Microdeletions in the Y-Chromosome and Male Infertility
INTRODUCTION
BACKGROUND
SIGNIFICANCE OF THE Y-CHROMOSOME
METHODOLOGY AND TESTING
TRANSFERENCE MECHANISM AND MUTATION ETIOLOGY
CONCLUSION
CHAPTER 76:
Isolated Teratozoospermia — ICSI or IUI
INTRODUCTION
WHO Criteria for Normal Sperm
Why Morphology has a Specific Role?
Is Isolated Teratozoospermia Another Entity Than Teratozoospermia with Oligoasthenospermia?
What Therapy should be offered to the Isolated Teratozoospermia Cases?
Materials and Method
Results
Discussion
How is Sperm Function in Isolated Teratozoospermia?
CHAPTER 77:
Hormone Substitution in Male Infertility
SUMMARY
INTRODUCTION
Human Chorionic Gonadotropin (hCG)
Human Menopausal Gonadotropin (hMG)
Pure and Recombinant FSH
Gonadotropin Releasing Hormone (GnRH)
Androgens
Testosterone Undecanoate
Mesterolone
SECTION 13: PREIMPLANTATION GENETIC DIAGNOSIS (PGD)
CHAPTER 78:
Preimplantation Genetic Diagnosis in Cases with Abnormal Gamete Cell Morphology
OVERVIEW
Centrally Located Granular Oocytes
METHODS OF TECHNIQUE
Megalo-pinhead Spermatozoa
Blastomere Biopsy and FISH Analysis
Results
Centrally Located Granular Oocytes (CLGO)
Megalo-pinhead Spermatozoa
Future Directions and Controversies
CONCLUSION
CHAPTER 79:
Preimplantation Genetic Diagnosis (PGD) for Sex Selection
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
SECTION 14: PRESENT AND FUTURE OF INFERTILITY
CHAPTER 80:
Present and Future of Infertility Therapy
INTRODUCTION
Post-infectious Infertility
Basic Research
In vitro Maturation of Gametes
Early Follicular Development and Apoptosis
Drug Development
Recombinant Gonadotropins
Functional Proteino-mimetic Molecules
GnRH Analogs
Functional Peptido-mimetic Molecules
Applied Clinical Research
Implantation
Embryonic Development
Cryopreservation
Reduction of Multiple Pregnancy Rate
ETHICAL, SOCIAL AND POLITICAL CONSIDERATIONS
CHAPTER 81:
Patient Support in the ART Program
OVERVIEW
STRESS AND INFERTILITY
OBJECTIVES OF COUNSELLING
INDICATIONS FOR COUNSELLING
FUNDAMENTAL AREAS OF CONCERN/SITUATIONS DEMANDING COUNSELLING INCLUDE
Continued Treatment with Persistent Failure as is the Case in Patients Suffering from Idiopathic Infertility often leading to Advanced Maternal Age
Third Party Reproduction (TPR)
Donor Insemination (DI)
Oocyte Donation (OD)
Embryo Donation
Surrogacy
Adoption
Complications Associated with Pregnancy after Infertility such as Miscarriages, Multiple Pregnancies, Ectopics, and Genetic and Congenital Abnormalities
Threatened Sexuality
Gender Differences
Chronic H/O of Illness or Psychiatric Disease
TYPES OF COUNSELLING
Therapeutic Counselling
Implications Counselling
Support Counselling
Counselling Approach
Single Counselling
Couple Counselling
Group Counselling
Counselling Team Responsibilities
Media for Patient Support
Patient Support Booklets
Telephone Counselling
Self-Help Groups
Patient Support Organizations
CONCLUSION
CHAPTER 82:
Politics, Partnerships and IVF
OVERVIEW
INTRODUCTION
The Limited Recognition of Infertility as a Disease or Medical Condition
Early History
1996 Campaign
Equity of Access to ART
The Impact of Legislation on ART Treatment
Reproductive Technology Accreditation Committee (RTAC)
Real Costs of Infertility: Societal, Social, Emotional
CONCLUSION
CHAPTER 83:
IVF Success from a Clinician's Viewpoint: How to Get it, How to Keep it?
INTRODUCTION
Patient Selection
Stimulation Protocol
Normal Responders
Poor Responders
High Responders
Oocyte Retrieval
Embryo Transfer
Introduction
Trial Embryo Transfer (TrET)
Embryo Transfer (ET)
Other Issues Regarding ET
Ultrasound-guided ET
CONCLUSION
CHAPTER 84:
Bandwagon IVF: All for One and One for All
INTRODUCTION
BANDWAGONS IN IVF: WHAT ARE THEY?
Bandwagons in IVF: Assisted Hatching
General Considerations
Partial Zona Dissection (PZD)
Zona Drilling using Acid Tyrode's Solution
Zona Thinning/Removal using Acid Tyrode's Medium
Zona Drilling using Laser Assisted Methods
Assisted Hatching: Who Benefits?
Assisted Hatching: Summary and Conclusions
Bandwagons in IVF: Intracytoplasmic Sperm Injection (ICSI)
General Considerations
ICSI: Who and When?
ICSI: Risks from the Technique
ICSI: Risks of Chromosomal Abnormalities
ICSI: Summary and Conclusion
Bandwagons in IVF: Extended Embryo Culture/Blastocyst Transfer
General Considerations
Extended Culture/Blastocyst Transfer: Risks and Limitations
Blastocyst Transfer: Summary and Conclusions
BANDWAGONS IN IVF: CONCLUSIONS
INDEX
TOC
Index
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