Fertility Preservation in Male Cancer Patients

Contents
Contributors
Section 1 – Anatomy and physiology
1 Functional anatomy of the hypothalamic-pituitary-gonadal axis and the male reproductive tract
Anatomy of reproductive function
Hypothalamus and anterior pituitary gland
Gonadotropin-releasing hormone (GnRH)
Gonadotropic hormones: LH and FSH
Testosterone and LH
Negative feedback of testosterone
Testosterone and FSH
Inhibin
Testis
Arterial and venous supply
Testicular organization
Spermatogenesis
Epididymis
Innervation
Arterial and venous supply
Epididymal function
Storage of sperm
Maturation of sperm
Transport of sperm
Vas deferens and ejaculatory duct
Seminal vesicles
Prostate
Bulbourethral glands
Penis
Arterial and venous supply
Neuroanatomy
Erection and detumescence: cavernosal smooth muscle physiology
References
2 Spermatogenesis
Introduction
Macroscopic testicular anatomy
The epididymis
The vas deferens
Microscopic anatomy
The Leydig cell
The Sertoli cell
The blood-testis barrier
Spermatogenesis
Meiosis
Regulation of spermatogensis: the hypothalamic-pituitary-gonadal (HPG) axis
Conclusion
Acknowledgments
References
3 The semen analysis
Introduction
Technical considerations
Macroscopic characteristics
Gross appearance
Semen volume
pH
Liquefaction
Microscopic characteristics
Viscosity
Count and concentration
Motility
Computer-assisted sperm assessment (CASA)
Morphology
Viability
Anti-sperm antibodies (ASA)
Other cell types
Biochemical analysis
Semen analysis in cancer patients
Predictive parameters for successful fertility
Conclusion
Acknowledgments
References
4 Physiology of ejaculation
Emission and ejaculation
Neuroanatomy
Peripheral anatomy
Spinal and central anatomy
Physiological control of ejaculation
Summary
References
Section 2 – Disorders of male fertility
5 History and physical examination
Introduction
History
Reproductive history
Childhood illnesses and conditions
Systemic diseases
Past surgical history
Family history
Medications
Lifestyle exposures and occupational history
Cancer and cancer therapies
Testicular cancer
Hodgkins disease (HD)
Cancer therapies
Physical examination
Penis
Scrotum
Digital rectal examination
Summary
References
6 Abnormalities of semen parameters
Introduction
Low-volume ejaculate
Oligospermia
Asthenospermia
Teratospermia
Leukocytospermia
Tests of sperm function
Tests of sperm DNA integrity
Impact of cancer and cancer therapies on semen parameters
Summary
References
7 Azoospermia
Introduction
Classification of azoospermia into diagnostic categories
Initial evaluation of the azoospermic male
Indications for treatment of men with azoospermia
Treatment of non-obstructive azoospermia
Treatment of obstructive azoospermia
Conclusion
References
8 Varicocele
Introduction
Pathophysiology of varicocele
Clinical features of varicocele
Evaluation of men with suspected varicoceles
Indications for varicocele treatment
Special considerations in men with cancer
Summary
References
9 Disorders of ejaculation
Introduction
Reproductive anatomy
Ejaculatory physiology
Anejaculation
Retrograde ejaculation
Medical treatment for ejaculatory dysfunction
Pharmacotherapy
Assisted ejaculation procedures
Penile vibratory stimulation
Bladder sperm harvesting
Conclusion
References
10 Androgen deficiency in the male
Introduction
Physiology of the hypothalamic-pituitary-gonadal axis
Causes of hypogonadism
Effects of hypogonadism
Metabolic effects
Cardiovascular effects
Bone
Body composition
Cognition and mood
Sexual function
Diagnosis of hypogonadism
Treatment
Conclusion
References
11 Infertility and male sexual dysfunction
Introduction
Epidemiology of combined morbidity: MSD and infertility
Etiology of combined morbidity: MSD and infertility
Psychogenic MSD and male infertility
Hormonal disorders associated with MSD and male infertility
Cancer, MSD, and male infertility
MSD pharmacotherapy and infertility
Phosphodiesterase-5 inhibitors and infertility
Selective serotonin reuptake inhibitors and infertility
Testosterone replacement therapy and infertility
Conclusion
References
Section 3 – Impact of cancers and treatment on male fertility
12 Radiation effects on spermatogenesis
Introduction
Cancer and radiation therapy
Studies in animals
Studies in humans
Gonadal shielding
Conclusions
References
13 Chemotherapy effects on spermatogenesis
Introduction
Overview of spermatogenesis
Effect of cancer on spermatogenesis
Gonadotoxicity of chemotherapy versus radiation
Mechanism of action of chemotherapeutic agents
Toxicity of chemotherapeutic regimens
DNA damage
Summary
References
14 Effects of therapy for solid tumors
Introduction
Alkylating agents
Platinum analogs
Antimetabolites
Cytotoxic antibiotics
Mitotic inhibitors
Topoisomerase inhibitors
Immunomodulators and hormonal agents
Monoclonal antibodies, tyrosine kinase inhibitors, and other new agents
Overview of childhood solid tumors
Central nervous system tumors
Neuroblastoma
Wilms’ tumor
Soft tissue sarcomas
Rhabdomyosarcoma (RMS)
Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS)
Bone sarcomas
Osteosarcoma
Ewing sarcoma
Summary
References
15 Lymphoma and leukemia
Introduction
Hodgkin's lymphoma
Non-Hodgkin's lymphomas
Leukemia
Stem cell transplantation
Conclusion
References
16 Stem cell transplantation
Introduction
The process of HSCT
HSCT and fertility
Summary
References
17 Fertility preservation in men with germ cell tumors
Introduction
Fertility preservation in patients with testicular cancer
Sperm banking prior to cancer therapy
Utilization of sperm banking by men with testicular cancer
Use of cryopreserved sperm
Partial orchiectomy: fertility-sparing approaches
Sperm retrieval at the time of orchiectomy
Fertility preservation following radical orchiectomy
Surveillance
Radiation
Chemotherapy
Retroperitoneal lymph node dissection
Re-establishing fertility following cytotoxic treatment
Conclusion
References
18 Effects of therapy for brain cancer
Introduction
Supportive treatment for patients with brain tumors
Antiepileptic drugs
Corticosteroids
Primary brain tumors
Gliomas
Temozolomide chemotherapy
Bevacizumab
Effects of cranial radiotherapy on pituitary function
Effect of systemic therapy for erectile dysfunction on glioma growth rate
Meningiomas
Pituitary tumors
Primary central nervous system lymphoma
Methotrexate
Vincristine
Procarbazine
Rituximab
Cytarabine
Tumors of the spinal cord and associated structures
Central nervous system metastases
Conclusion
Acknowledgments
References
19 Male infertility following childhood cancer: special considerations for fertility preservation in children
Introduction
Gonadal toxicity following childhood cancer treatment
The effects of chemotherapy
The effects of radiotherapy
The effects of disease
The potential for fertility following childhood cancer treatment
Options for fertility preservation
Established methods: semen cryopreservation
Experimental techniques
Testicular tissue harvesting
Germ cell transplantation
In-vitro maturation
Hormonal manipulation
Ethical and legal issues
Conclusion
References
Section 4 – Preservation strategies
20 Facilitating discussion about fertility preservation
Introduction
Interest in fertility preservation among men
Barriers to discussing fertility preservation with men
Patient barriers
Facilitating provider discussion
Conclusion
References
21 Development of a program to address fertility preservation and parenthood after cancer treatment
Introduction
The Memorial Sloan-Kettering Cancer Center program
Developing a program based on the MSKCC infrastructure
Assessment
Resources for patients
Resources for clinicians
Education of clinicians
Clinical expertise
Implementation and evaluation
Clinical research
Developing a program based on Fertile Hope's Centers of Excellence program
Conclusion
References
22 Psychological consultation and assessment
Introduction
Background
Psychosocial and emotional factors
Psychological consultation and assessment
Psychosocial assessment for fertility preservation
Psychological consultation for fertility preservation
The treatment team: the collaborative role of the mental health professional
Countertransference issues in cancer and fertility preservation
Summary
References
23 Nutraceuticals in fertility preservation
Lifestyle changes
Nutraceuticals/dietary supplements
Coenzyme Q10 (CoQ10)
Folic acid
L-carnitine
Omega-3 fatty acids
Selenium and vitamin E
Vitamin C
Other supplements
Conclusion
References
24 Application of spermatogenesis suppression therapies for fertility preservation
Introduction
Gonadal toxicity
History of the suppression hypothesis
Experimental studies in the rat
Experimental studies in other species
Human clinical trials
Relationship of experimental to human studies
Spermatogonial transplantation
Conclusion
References
25 Semen cryobiology and sperm banking
Introduction
History of cryobiology and cryopreservation
The scientific foundation of cryobiology
Methodology of cryopreservation
Sperm and male gamete collection
Cryoprotective agents (CPA)
Semen extenders
Media used in cryopreservation
Cooling rates in cryopreservation
Protocols used for cryopreservation
Vitrification
Freeze drying
Semen screening
Tracking
Indications for sperm cryopreservation
Homologous and donor insemination
Preoperative cryopreservation
Intraoperative cryopreservation
Postoperative cryopreservation
Premortem and postmortem cryopreservation
Cryopreservation prior to treatment (for non-malignant diseases)
Cryopreservation prior to treatment (for malignancies)
Cryopreservation in the patient with cancer
References
26 Ethical and legal considerations of sperm and tissue cryopreservation
Introduction
A cancer patient's fertility options and oncologists’ responsibilities
Legal and ethical issues surrounding the fundamental procreative right of a minor male cancer patient
How a male cancer patient can effectively preserve his right to procreate
Rule number 1: Male cancer patients should strongly consider cryopreserving their sperm rather than embryos created from their sperm
Rule number 2: One's intentions should be clearly and unequivocally stated
Rule number 3: Recognize the patient's right not to reproduce
Rule number 4: Be aware of storage costs and time limitations
Conclusion
References
27 The use of ejaculation induction procedures in cancer patients
Introduction
Physiology of ejaculation
Etiologies of ejaculatory dysfunction and relationship to cancer
Procedures to induce ejaculation
Penile vibratory stimulation (PVS)
Electroejaculation (EEJ)
Ejaculation induction procedures for semen cryopreservation
Adults
Adolescents
Fertility restoration after RPLND
Medical management
Electroejaculation following RPLND
Cost-benefit analysis
Conclusion
References
28 Sperm extraction in the pre-therapy patient
Introduction
Percutaneous testicular and epididymal aspiration
Surgical retrieval of vasal or epididymal sperm
Surgical retrieval of testicular sperm
Testicular cancer patients: special considerations
Conclusion
Acknowledgments
References
29 Fertility preservation in the pediatric population: germ cell culture and transplantation
Childhood cancer
Cancer treatment: radiation and chemotherapy
Options for fertility preservation
Sperm acquisition
Stem cell autotransplantation
Stem cell culture
Future directions and ethical issues
Conclusion
Acknowledgments
References
30 Exogenous androgens: effect on spermatogenesis
Introduction
Testosterone production and secretion
Testosterone and male sexual development
Requirements for spermatogenesis
Hypogonadism and male infertility
Anabolic steroid use and infertility
Different types of testosterone supplementation
Rebound therapy for idiopathic oligo/asthenospermia
Recovery of spermatogenesis after exogenous testosterone use
Raising testosterone levels and preserving fertility
Testosterone as a male contraceptive
Conclusion
References
31 Fertility preservation in the female with cancer
Introduction
Early counseling to preserve fertility
Gonadal damage induced by cancer treatment
Chemotherapy
Radiotherapy
Fertility preservation options for local treatment of cancer
Shielding to reduce radiation damage and ovarian transposition
Fertility-sparing surgery
Fertility preservation methods for systemic gonadotoxic treatment
Cryopreservation of embryos or oocytes after controlled ovarian stimulation
Stimulation protocols for women with breast cancer
Cryopreservation of immature oocytes
Ovarian tissue freezing
Ovarian tissue transplantation
In-vitro culture of ovarian follicles
Gonadal protection by drugs
References
Section 5 – Post-therapy considerations
32 Psychosocial issues surrounding the use of sperm donation
Introduction
Background
Barriers to communication
How to discuss fertility preservation
A team approach
Finding sperm banks
Discussing sensitive topics
Psychological reactions to infertility
History of sperm donation
Medical screening
Cultural differences in sperm donation
Research on donor insemination
Adoption
Recipient counseling in preparation for donor insemination
Sperm donor selection
Conclusion
References
33 Medical therapy for male infertility
Introduction
Evaluation of the infertile male cancer patient
Medications
Clomiphene citrate
Tamoxifen
Aromatase inhibitors
Gonadotropin-releasing hormone (GnRH)
Human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG)
Recombinant FSH
Androgens
Nutraceuticals
Antioxidants
Treatment of hyperprolactinemia
Treatment of infectious and inflammatory infertility
Treatment of immunological infertility
Summary
References
34 Management of the varicocele in the treated patient
Introduction
Pathophysiology
Diagnosis
Management of varicocele
Surgery
Percutaneous embolization
Efficacy of varicocelectomy
Varicocelectomy and azoospermia
Varicocelectomy and hypogonadism
Varicocele treatment in the era of advanced reproductive technology
References
35 Sperm extraction in the treated patient
Introduction
Use of cryopreserved sperm
Use of spermatozoa from men who have received chemotherapy or radiation
Sperm retrieval in the patient who is anejaculate following retroperitoneal or pelvic surgery
Sperm retrieval in the patient who is azoospermic after chemotherapy
Sperm retrieval in the patient who is azoospermic after radiation therapy
Conclusion
Acknowledgments
References
36 Postmortem sperm extraction
Introduction
Background and context
Issues of consent
Ethical considerations
Logistical issues
Legal issues
Discussion
References
37 Fertility following antineoplastic therapy in the male: intrauterine insemination and the assisted reproductive technologies
Introduction
Assisted reproductive technologies (ART)
Etiologies of female infertility
Tubal factor
Endometriosis
Polycystic ovary syndrome (PCOS)
Unexplained infertility
Prognostic factors: female partner
Ovarian reserve testing
Ultrasonographic markers: antral follicle count
Hormonal assays
FSH
Anti-Müllerian hormone
Clomiphene citrate challenge test
Cryopreservation
IUI versus IVF
Intrauterine insemination (IUI)
Sperm preparation techniques for IUI and IVF
Ovarian stimulation
“Long” agonist protocols
“Short” antagonist protocols
Ovarian stimulation for the hyper-responding patient
Alternative ovarian stimulation for the poorly responding patient
Oocyte retrieval
Assessment of oocyte maturity
Preparation of the oocyte for fertilization and ICSI
Additional laboratory procedures
Assisted hatching (AH)
Autologous endometrial co-culture (AECC)
Pre-implantation genetic diagnosis (PGD) and screening (PGS)
Embryo transfer
IVF outcomes
Complications of ART
Ovarian hyperstimulation syndrome (OHSS)
Multiple gestations
Ectopic pregnancy
Perinatal outcomes from ART
Conclusion
References
Index