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Fertility Preservation: Advances and Controversies
Botros RMB Rizk, Mohamed A Bedaiwy
SECTION 1: FERTILITY PRESERVATION APPROACHES IN THE FEMALE
1:
Fertility Preservation in Female Patients: An Overview
INTRODUCTION
EVOLUTION OF HUMAN OOGENESIS
ANTICANCER THERAPY-INDUCED PREMATURE OVARIAN FAILURE (POF)
POF Induced by Chemotherapy
POF Induced by Radiotherapy
CHEMOTHERAPY/RADIOTHERAPY-INDUCED POF: DIAGNOSIS AND PREDICTION
WHEN IS FERTILITY PRESERVATION INDICATED IN WOMEN?
STRATEGIES FOR FERTILITY PRESERVATION
Pharmacologically-Based Protection
Transposition of the Ovaries (Oophoropexy)
Assisted Reproductive Technologies
Oocyte Cryopreservation
Embryo Cryopreservation
Cryopreservation and Ovarian Tissue Transplantation
INTRODUCTION OF VASCULAR GRAFTS IN ANIMAL MODELS
THE USE OF VASCULARIZED GRAFTS IN HUMAN TRIALS
HETEROLOGOUS OVARIAN TRANSPLANTATION
IN VITRO MATURATION OF OOCYTES
CONCLUSION
2:
Fertility Preservation in Cancer and Noncancer Patients
INTRODUCTION
WHO IS A CANDIDATE FOR FERTILITY PRESERVATION?
Cancer Patients
Children and Teenagers
Adults
Noncancer Patients
OPTION TO PRESERVE FERTILITY
Women and Girls
Men and Boys
CONCLUSION
3:
Reproductive Implications of Chemotherapy and Radiotherapy
INTRODUCTION
CHEMOTHERAPY
Chemotherapeutic Agents
Doxorubicin
Cyclophosphamide
Cisplatin
Irinotecan and Etoposide
Chemotherapy Protocols
RADIOTHERAPY
Radiation Dose
Radiation Dose
Patient Age
PROTECTIVE AND PREVENTIVE MEASURES
4:
Ovarian Reserve Testing for Cancer Patients
INTRODUCTION
EFFECT OF CHEMOTHERAPY ON THE OVARY
EFFECT OF RADIOTHERAPY ON THE OVARY
ROLE OF OVARIAN RESERVE TESTS (ORT) IN CANCER PATIENTS
OVARIAN RESERVE TESTS
Follicle Stimulating Hormone
Anti-Müllerian Hormone
Antral Follicle Count
Inhibin B
Ovarian Volume
Estradiol (E2)
Dynamic Ovarian Reserve Tests
FERTILITY PRESERVATION
Hormonal Suppression
Transposition of the Ovaries (also known as Oophoropexy)
Cryopreservation of Oocytes
Cryopreservation of Embryos
Cryopreservation of Ovarian Tissue
CONCLUSION
5:
Medical Approaches for Fertility Preservation in Female Cancer Patients
THE NEED FOR FERTILITY PRESERVATION
DEVELOPMENT OF GONADAL DYSFUNCTION FOLLOWING CYTOTOXIC TREATMENT
Normal Physiological Considerations
The Impact of Cytotoxic Treatment on Ovarian Function
Factors Affecting for the Development of Gonadal Dysfunction
THE HYPOTHESIS BEHIND MEDICAL APPROACHES
PRESERVATION OF OVARIAN FUNCTION WITH THE USE OF GnRH ANALOGS
GnRH and GnRH Analogs
Proposed Mechanisms for the Use of GnRH Analogs in Ovarian Protection and their Controversy
Induction of a Temporary, Pre-pubertal Hormonal Milieu
Decrease in Utero-ovarian Perfusion
Activation of GnRH Receptors and Direct Effects on Ovarian Follicles
Studies Using GnRH Agonists for Ovarian Protection
GnRH AGONIST: HUMAN RANDOMIZED CONTROLLED TRIALS
GnRH AGONIST FOR GONADAL PROTECTION: CURRENT EVIDENCE
STUDIES USING GnRH ANTAGONISTS FOR OVARIAN PROTECTION
Use of Antagonist in Combination with the Agonist for Gonadal Protection
Use of Antagonist Only for Gonadal Protection
THE USE OF ORAL CONTRACEPTIVES FOR OVARIAN PROTECTION
ETHICAL ISSUES CONCERNING FERTILITY PRESERVATION IN CANCER PATIENTS
CONCLUSION
6:
Ovarian Transposition as a Fertility Preservation Strategy
OVARIAN AND REPRODUCTIVE PHYSIOLOGY
RADIATION-INDUCED OVARIAN FAILURE
TERMINOLOGY AND HISTORIC OVERVIEW
INDICATIONS AND SURGICAL TECHNIQUES
LAPAROTOMY VERSUS LAPAROSCOPY
SURGICAL PROCEDURE
COMPLICATIONS
OVARIAN FUNCTION AFTER TRANSPOSITION
FERTILITY OUTCOME
EFFECT OF RADIATION ON ENDOMETRIUM AND FERTILITY OUTCOME
CONCLUSION
7:
Surgical Strategies for Fertility Preservation in Women with Cancer
INTRODUCTION
GYNECOLOGIC CANCERS: SURGICAL TREATMENTS THAT PRESERVE FERTILITY
Cervical Cancer
Standard Treatment Approach
Fertility-Sparing Approach
Cone Biopsy
Radical Trachelectomy
Ovarian Cancer
Ovarian Cancer Subtypes
Standard Treatment Approach
Fertility-Sparing Approach
Endometrial Cancer
Standard Treatment Approach
Fertility-Sparing Approach
Pre-Treatment Studies
Progestin Therapy
Follow-Up
Outcomes
Subsequent Fertility
PROTECTING OVARIES AND OOCYTES DURING CANCER TREATMENT
Non-Surgical Approaches
Controlled Ovarian Stimulation and Cryotechnology
Gonadotropin Releasing Hormone Agonists During Chemotherapy
Surgical Approaches for Preserving Ovarian Function
Ovarian Transposition
Technique
Ovarian Function Preservation
Fertility Preservation
OVARIAN TISSUE TRANSPLANTATION
Ovarian Tissue Transplant with Vascular Pedicles
Ovarian Cortex Transplant
Orthotopic Transplantation
Fertility Preservation
Heterotopic Transplantation
CONCLUSION
8:
Basics of Cryobiology
INTRODUCTION
HISTORICAL OVERVIEW OF CRYOBIOLOGY IN PARTICULAR REFERENCE TO REPRODUCTIVE MEDICINE
RELEVANT CRYOBIOLOGICAL FACTS IMPORTANT TO REPRODUCTIVE BIOLOGISTS
Phenomena Behind Ice Formation
Mathematical Models Explaining Biophysics of Extracellular and Intracellular Water Movement, Cell Dehydration, Ice Nucleation and Crystal Growth
Cryoprotective Agents (CPAs)/ Cryoprotectants
Discovery of Cryoprotective Agents (CPAs)
Beneficial and Harmful Effects of Cryoprotectants
Osmotic Limits of Cells and Osmotic Effects of Cryoprotectants
Phenomena Occurring During Introduction and Removal of Cryoprotectant
CRYOPRESERVATION METHODOLOGIES
PHYSICS OF FREEZING BIOLOGICAL MATERIALS
PHYSICOCHEMICAL AND BIOLOGICAL EVENTS OCCURRING DURING FREEZING
PHYSICOCHEMICAL AND BIOLOGICAL EVENTS OCCURRING DURING THAWING
SAFETY ISSUES IN CRYOPRESERVATION
PRESERVATION OF CELLS AND TISSUES
CONCLUSION
9:
Oocyte Cryopreservation
INTRODUCTION
DETERMINANTS OF OOCYTE CRYOPRESERVATION OUTCOME
Intrinsic Factors
Extrinsic Factors
CLINICAL APPLICATION OF FROZEN OOCYTES
CLINICAL OUTCOME OF OOCYTE CRYOPRESERVATION
DISCUSSION
CONCLUSION
KEY ISSUES
10:
Embryo Cryopreservation
INTRODUCTION
HISTORY
INDICATIONS
Oncologic Indications
Non-oncological Indications
EMBRYO CRYOPRESERVATION
Controlled Ovarian Stimulation
Protocols
Protocols for Breast Cancer Patients
Tamoxifen
Aromatase Inhibitors
Combined Stimulation Protocols
CRYOPRESERVATION
SUCCESS RATES
ETHICAL AND LEGAL ISSUES
CONCLUSION
11:
The Challenges and Promises of Whole Human Ovary Cryopreservation
INTRODUCTION
SUCCESSES
Successes in Animals
Promising Human Results
Solving the Problem of Freezing
CHALLENGES
Removal of the Ovary
To Freeze or not to Freeze?
Reanastomosis and Avoidance of Ischemia and Thrombosis
Tumor Reseeding
CONCLUSION
12:
Ovary Transplantation for Fertility Preservation in Cancer Patients: Fresh and Frozen
SUBJECT RECRUITMENT AND CONSENT
CLINICAL PROFILE
GENETIC STUDIES
FRESH CORTICAL OVARIAN TISSUE TRANSPLANTATION
Whole-Ovary Transplantation
Postoperative Results
FROZEN CORTICAL OVARIAN TRANSPLANTATION
DISCUSSION
13:
In Vitro Maturation of Oocytes as a Fertility Preservation Strategy
INTRODUCTION
IN VITRO MATURATION OF HUMAN OOCYTES
Overview of an IVM cycle for fertility preservation
EMBRYOLOGY LABORATORY PROCEDURES
IVM TREATMENT OUTCOME
Chromosomal Constitution of IVM Embryos
Pregnancy Rates
Pregnancy Loss
Obstetric Outcome
Congenital Abnormalities, Physical and Neuromotor Development
IVM FOR FERTILITY PRESERVATION FOR WOMEN WITH MEDICAL CONDITIONS
IVM FOR SOCIAL FERTILITY PRESERVATION
CONCLUSION
14:
Fertility Preservation in Women with Breast Cancer
THE EPIDEMIOLOGY OF BREAST CANCER
BREAST CANCER TREATMENT
Surgery
Radiation
Chemotherapy
Hormonal Treatment
CHEMOTHERAPY AND OVARIAN RESERVE
Age and Amenorrhea
Effect of Chemotherapy and Tamoxifen on Amenorrhea
FERTILITY AFTER CHEMOTHERAPY
Pregnancy after Chemotherapy
Fertility Outcome with IVF/ICSI after Chemotherapy
Safety of Fertility Treatment
Timing of Fertility Preservation
FERTILITY PRESERVATION OPTIONS
Ovarian Stimulation Regimens— Letrozole/FSH Protocol
In Vitro Maturation
Random Start Cycle
Embryo Cryopreservation
Oocyte Cryopreservation
Ovarian Tissue Transplantation or Preservation
OVARIAN SUPPRESSION DURING CHEMOTHERAPY
ALTERNATIVES—DONOR EGG, GESTATIONAL CARRIER, AND ADOPTION
SPECIAL CONSIDERATIONS
Hereditary Breast and Ovarian Cancer Syndromes
SUMMARY
SECTION 2: FERTILITY PRESERVATION STRATEGIES IN THE MALE
15:
Pathology Affecting Male Fertility
INTRODUCTION
EVALUATION
History
Physical
Diagnostic Studies
PATHOLOGY
Genitourinary (GU) Anomalies
Cryptorchidism
Varicocele
Ductal Obstruction
Ejaculatory Disorders
Endocrinopathies
Hyperprolactinemia
Diabetes Mellitus
Thyroid Abnormalities
Genetic Anomalies
Kallmann Syndrome
Klinefelter Syndrome
Other Genetic Abnormalities
Malignancy
Testicular Cancer
Other Malignancies
SUMMARY
16:
Cryopreservation of Spermatozoa, Individual Sperm and Testicular Tissue
INTRODUCTION
EFFECT OF CRYOPRESERVATION ON HUMAN SPERMATOZOA
CLINICAL APPLICATIONS OF SPERM CRYOPRESERVATION
Donor banking: Sperm Cryopreservation to be Offered for Others
Autoconservation: Sperm Cryopreservation for one's Future use
Convenience Cryobanking
Freezing of Surgically Retrieved Spermatozoa
Fertility Preservation
SPERM CRYOPRESERVATION FOR CANCER PATIENTS
Available Options for Men and Postpubertal Boys
Options for Prepubertal Boys
Effect of Cancer Therapy on Gonadal Function
Offspring of Cancer Survivors
LABORATORY TECHNIQUES FOR SPERM CRYOPRESERVATION
To Wash or Not to Wash
Cytoprotective Agents
Different Sperm Cryopreservation Techniques
Vapor Freezing
Slow Programmable Freezing
Sperm Vitrification
Special Concerns of Sperm Cryopreservation
Cryopreservation of Surgically Retrieved Spermatozoa
Single Sperm Freezing
STORAGE AND TRANSPORTATION OF CRYOPRESERVED SPERM
CONCLUSION
17:
Strategies for Fertility Preservation in the Male Cancer Patient
INTRODUCTION
CRYOPRESERVATION OF EJACULATED SPERM
AZOOSPERMIA AT PRESENTATION
PERCUTANEOUS TESTICULAR AND EPIDIDYMAL ASPIRATION
SURGICAL RETRIEVAL OF VASAL OR EPIDIDYMAL SPERM
SURGICAL RETRIEVAL OF TESTICULAR SPERM
SPECIAL CONSIDERATIONS IN TESTICULAR CANCER PATIENTS
PERSISTENT AZOOSPERMIA AFTER SYSTEMIC TREATMENT
RETRIEVAL OF SPERM IN ANEJACULATE PATIENT
SPERM RETRIEVAL IN THE AZOOSPERMIC PATIENT AFTER CHEMOTHERAPY
SPERM RETRIEVAL IN THE AZOOSPERMIC PATIENT AFTER RADIATION THERAPY
USE OF SPERMATOZOA FROM MEN WHO HAVE RECEIVED CHEMOTHERAPY OR RADIATION
CONCLUSION
INDEX
TOC
Index
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