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Infertility in the Male
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Book description

The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.

Reviews

'More than any other book in the field, it presents the entire spectrum of clinical assessment, laboratory diagnosis, and treatment of the infertile male with an array of medical, surgical, and laboratory techniques.'

Source: Doody's Reviews

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Contents


Page 1 of 2


  • Chapter 8 - New concepts in the genetics of male reproduction and infertility
    pp 122-131
  • View abstract

    Summary

    The understanding of embryology provides a foundation for the mastery of anatomy. In the treatment of men with infertility, it is only appropriate that one deals with the basics of fetal development of the male reproductive tract. This chapter reviews the germ layers from which all tissues organize themselves and develop, and also reviews the ductal system and its critical role in reproduction. The cloaca, as incorporated yolk sac, is an endoderm-lined cavity, anchored at the caudal end by the cloacal membrane. The mesonephric ducts, which are mesodermal structures, are connected to the urogenital sinus bilaterally. The common excretory ducts eventually move into the prostatic part of the urethra and become known as the verumontanum. Testosterone stimulates numerous changes in the existing ductal system. In the presence of testosterone, the phallus lengthens and enlarges to form the penis.
  • Chapter 9 - Erection, emission, and ejaculation:
    pp 132-152
  • mechanisms of control
  • View abstract

    Summary

    The male hypothalamic-pituitary-gonadal (HPG) axis is a finely controlled system whose role is to promote spermatogenesis and androgen biosynthesis. Testosterone is thought to feed back to restrain activity of the gonadotropin-releasing hormone (GnRH)-gonadotrope secretory unit. GnRH is released from the hypothalamus in a pulsatile pattern, and the stimulation of gonadotropin biosynthesis and secretion by GnRH is dependent on the pulsatile nature of GnRH delivery to the anterior pituitary. Gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are glycoproteins consisting of a common a subunit and a hormone-specific β subunit that are associated through noncovalent interactions. GnRH stimulates in vitro the synthesis of gonadotropin subunits and increases a, LH-β, and FSH-β subunit mRNA levels as well as the transcriptional activity of corresponding gene promoters. Testosterone seems to exert a direct feedback control of LH secretion, while its action on FSH secretion is mostly indirect.
  • Chapter 10 - Office evaluation of the subfertile male
    pp 153-176
  • View abstract

    Summary

    This chapter discusses the development of the adult population of Leydig cells from the stem cell precursor through the progenitor and immature Leydig cell stages. The morphogenetic events of early testis differentiation are controlled by the Sry (sex-determining region on the Y chromosome) gene. Lack of luteinizing hormone (LH) stimulation results in reduced steroidogenic enzyme activities and in Leydig cell atrophy. As men age, progressive decreases in serum concentrations of testosterone occur. Associated with these decreases are significant health consequences, including reduced sexual function, energy, muscle function, and bone density, and increased frailty and cognitive impairment. A number of hypotheses have been put forward over the years to explain changes that occur in aging cells, including late-onset gene expression, telomere shortening, gene modifications, changes in the immune system, and accumulated reactive oxygen-induced damage to DNA, lipids, and/or proteins.
  • Chapter 11 - Evaluation of sperm function
    pp 177-198
  • View abstract

    Summary

    The Sertoli cell is implicated centrally in spermatogenesis, organogenesis, male phenotypic development, and the hypothalamic-pituitary-gonadal axis. The cytoskeletal architecture of the Sertoli cell, as in many other cells, consists of actin filaments, intermediate filaments, and microtubules. The interaction of adjoining Sertoli cells with each other and with the basement membrane is crucially important to the function of the Sertoli cell: tight junctions and adherens junctions between Sertoli cells allow for the creation of an immunologically privileged space within the seminiferous tubule. This barrier, created by Sertoli cells and the basement membrane, is known as the blood-testis barrier. This chapter provides a brief discussion spermiogenesis and spermiation. Sertoli cells in adult mammals exist as a terminally differentiated, postmitotic population. Regulation of the Sertoli cell in its function as "nurse cell" for developing spermatogenic cells is obviously multifaceted and complex.
  • Chapter 12 - Endocrine evaluation
    pp 199-214
  • View abstract

    Summary

    In mammals, spermatogenesis begins with diploid stem cells that resemble other somatic cells; it ends with highly specialized motile haploid cells that are remarkably unique in appearance and function. Continuous production of spermatozoa throughout life requires that spermatogonia replenish themselves. Type B spermatogonia undergo mitosis to give rise to diploid primary spermatocytes. The spermatocytes then cross the blood-testis barrier formed by the Sertoli tight junctions to the adluminal compartment. Spermiogenesis refers to the acquisition by the germ cell of several organelles and accessory structures such as the acrosome and the flagellum. Testosterone and follicle-stimulating hormone (FSH) are the two major regulatory hormones of spermatogenesis. FSH binding to its receptor activates adenylate cyclase, and the resultant rise in cAMP triggers binding of cAMP response element modulator (CREM) to ACT (activator of CREM). The complex then acts as a molecular master-switch for a number of genes involved in spermatogenesis.
  • Chapter 13 - Testicular biopsy in male infertility evaluation
    pp 215-225
  • View abstract

    Summary

    The mesonephric duct becomes the epididymis and vas deferens, and the residual mesonephric tubules form the efferent ducts. Non-pathological specimens of men within their reproductive years are understandably difficult to obtain, and even when such epididymides are made available, they often lack the proper preservation for good biological studies. It is well established that mammalian sperm, in general, mature in the epididymis, and the changes that occur in sperm during maturation have been recently reviewed. The propelling forces for sperm transport through the epididymis are: hydrostatic pressure from fluid secretion in the testis, and peristaltic contractions of the tubule. The bulbourethral glands are encased in the urogenital diaphragm. The bulbourethral gland secretion forms the first part of the ejaculate, or the pre-ejaculate, and serves to flush the tract with a buffered lubricant prior to the transport of sperm.
  • Chapter 14 - Adverse effects of environmental chemicals and drugs on the male reproductive system
    pp 226-250
  • View abstract

    Summary

    Human semen is ejaculated into the anterior vagina and, within minutes, spermatozoa enter the cervix by traversing the cervical mucus. Human sperm capacitation is initiated when the male gamete traverses the cervical mucus, with the removal of inhibitory factors from the seminal plasma. Studies performed in several mammalian species have shown that sperm cells that have completed capacitation first bind to the zona pellucida (ZP) and undergo acrosomal exocytosis (AE). Acrosome-reacted spermatozoa penetrate the ZP, reach the perivitelline space, and bind and fuse to the egg plasma membrane. Sperm-ZP binding involves the interaction of ZP components with sperm surface proteins of capacitated cells, known as primary binding. The evaluation of the subfertile male should include a basic semen analysis, followed by bioassays aimed at assessing sperm functional competence. Many of the molecular mechanisms underlying mammalian sperm capacitation, AE, and fusion with the egg modulate somatic cell functions.
  • Chapter 15 - Genetic aspects of infertility
    pp 251-276
  • View abstract

    Summary

    The X chromosome may be as important as the Y in determining male fertility potential. By refining the analysis of the particular recombination abnormalities in infertile men, this study confirmed that there may be decreased chromosomal pairing quality as well as recombination frequencies in men with non-obstructive azoospermia. Documentation of the normal variability in recombination is a prerequisite for the understanding of changes observed in abnormal situations, such as non-disjunction or a chromosome re-arrangement. It appears that G-group as well as sex chromosomes are most susceptible to having no recombination foci and thus are more susceptible to non-disjunction during spermatogenesis. The growing knowledge of the close relationship between germ cells and stem cells, and the successful manipulation of these cells in vitro, has tremendous implications not only for the treatment and cure of male infertility but also for a host of other medical diseases in the future.
  • Chapter 16 - Immunologic infertility
    pp 277-294
  • View abstract

    Summary

    The neurophysiological control of the erectile process is under the influence of central and peripheral processes. At least three kinds of erection can be distinguished in man: central, reflexogenic, and nocturnal types. Emission, as the first phase of ejaculation, is a sympathetic spinal cord reflex. The spermatozoa undergo final maturation in the epididymis and are stored there prior to ejaculation. The autonomic nervous system plays a key role in the efferent pathway of the ejaculatory reflex. The spinal network plays a significant role in processing and directing afferent and efferent information in the ejaculatory process. The ejaculatory-related cerebral network includes the medial preoptic area (MPOA), the paraventricular nucleus of the hypothalamus (PVN), the nucleus paragigantocellularis (nPGi), the posterodorsal medial amygdaloid nucleus (MeApd), and the parvocellular subparafascicular thalamic nucleus (SPFp). An improved understanding of the complex influences on ejaculation may open new therapeutic strategies for ejaculatory disorders.
  • Chapter 17 - The effect of genital tract infection and inflammation on male infertility
    pp 295-330
  • View abstract

    Summary

    Infertility is due to a significant male factor alone, whereas combined male and female factors are present in an additional 20%. Thus, a male factor is involved in approximately 50% of infertile relationships. The primary goals of the evaluation of the male presenting with infertility are to identify: etiologic conditions, irreversible conditions, irreversible conditions not amenable to assisted reproductive techniques, medically significant pathologies, and genetic etiologies. Bilateral cryptorchidism results in a significant decrease in spermatogenesis, while the effect of unilateral cryptorchidism appears to be much milder. Approximately 50% of testicular cancer patients have subnormal sperm densities prior to chemotherapy. Of note, of those with oligo- or azoospermia, 75% normalized during surveillance. Diethylstilbestrol (DES) was given to pregnant women in the 1950s, and reports of epididymal cysts and cryptorchidism in males with prenatal DES exposure have raised concerns about effects on fertility. Exogenous androgens are well known to induce hypogonadotropic hypogonadism.
  • Chapter 18 - Varicocele
    pp 331-361
  • View abstract

    Summary

    Tests of sperm DNA damage and sperm chromosome anomalies have also been developed. The advanced sperm tests yield information on the fertilizing capacity of human spermatozoa, as well as their ability to support normal embryonic development. The most common abnormalities involve the structure of the sperm tail, with defects in either the axoneme or outer dense fibers. Postcoital test (PCT) assesses the ability of sperm to traverse the cervical mucus, and is performed by examining the cervical mucus several hours after intercourse for the presence of sperm. The sperm penetration assay (SPA) utilizes hamster ova, which have had the zona pellucida enzymatically removed, allowing penetration by human spermatozoa. The hemizona assay uses zona pellucida from nonfertilizable, nonliving oocytes. Reactive oxygen species (ROS) are ubiquitous in aerobic biologic systems and are formed as a by-product of oxygen metabolism.
  • Chapter 19 - Evaluation of female infertility for the non-gynecologist
    pp 362-374
  • View abstract

    Summary

    An evaluation of the reproductive endocrine status is an essential component in the investigation of all male partners with either an abnormal physical examination suggestive of a disorder in testosterone production and action, an abnormal semen examination, or evidence of impaired sexual function. Initial laboratory assessment of the hypothalamic- pituitary-testicular axis includes the measurement of circulating levels of LH, FSH, and testosterone. The differential diagnosis and treatment of endocrine- dependent male-factor infertility is based on the history, physical examination, and reproductive hormone levels. Hypogonadotropic hypogonadism, also referred to as secondary hypogonadism, can occur as the congenital condition idiopathic hypogonadotropic hypogonadism (IHH). Androgen receptor abnormalities are rarely amenable to hormone therapy. Testosterone replacement therapy available in the United States includes oral, intramuscular, transdermal, and buccal preparations. A number of non-FDA-approved drugs and supplements are marketed as alternative therapies for declining androgens and decreasing libido and potency in older men.
  • Chapter 20 - The use of ultrasound and radiologic imaging in the diagnosis of male infertility
    pp 375-391
  • View abstract

    Summary

    Innovative techniques for testis biopsy interpretation continues to generate new and meaningful information regarding the pathophysiology in the infertile male. This chapter outlines the relevant histologic features of both abnormal and normal testis biopsies. It reviews existing, new, and promising technologies that are being applied to testis biopsy. A by-product of the refinement of needle biopsy techniques in the testis is fine-needle aspiration (FNA) for systematic mapping of sites of active spermatogenesis. Cytological assessment of biopsy or aspirate specimens can be performed in several ways. Basement membrane hyalinization refers to concentric thickening of the inner basement membrane, as evidenced by deposition of hyaline. The germinal epithelium of the seminiferous tubule is composed of germ cells in various stages of development and Sertoli cells. The therapeutic nature of the testis biopsy depends on the ability to identify mature spermatids that might be appropriate for IVF/intracytoplasmic sperm injection (ICSI).
  • Chapter 21 - Microsurgical treatment of male infertility
    pp 392-406
  • View abstract

    Summary

    Apoptosis is a highly regulated form of cell death, involving a cascade-like activation of a series of catabolic processes that progressively disassemble the cell. High levels of endogenous maternal estrogens are associated with increased risks of testicular cancer and cryptorchidism in male offspring. In males, smoking negatively affects sperm production, motility, and morphology. Enzymes involved in the steroid biosynthesis pathway are beginning to be recognized as targets for the action of a number of endocrine-disrupting chemicals (EDCs). The blood-testis barrier (BTB) serves to protect spermatogenesis from many potentially cytotoxic drugs and other chemicals. Drugs and medications may have an adverse impact on fertility through a variety of mechanisms including direct toxicity to the testicular germ cells and supporting cells, alterations of the hypothalamic-pituitary-gonadal (HPG) axis, or effects on sexual performance by impairment of libido, erections, or ejaculation.
  • Chapter 22 - Techniques of sperm retrieval
    pp 407-420
  • View abstract

    Summary

    This chapter focuses on the genetic basis of male infertility. The male specific Y (MSY) is a chromosomal material that bridges the two polar pseudoautosomal regions and is unique in the human genome. A karyotype and Y-chromosomal microdeletion assay should be obtained as complementary tests in all non-obstructive azoospermia (NOA) and severely oligospermic men prior to intracytoplasmic sperm injection (ICSI) and the use of testicular sperm. Prognosis and planning are optimized with any informative result. Steroidogenic acute regulatory (StAR) protein is the rate-limiting step for androgen biosynthesis in particular and all steroids in general. The hypothalamic-pituitary-gonadal (HPG) axis controls human sexual maturation and spermatogenesis. The hypothalamus secretes gonadotropin- releasing hormone (GnRH) which regulates the production of Folliclestimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary gonadotropes. Kallmann syndrome results from the failure of the GnRH-releasing neurons to migrate to the olfactory lobe during development.
  • Chapter 23 - Management of ejaculatory duct obstruction
    pp 421-429
  • View abstract

    Summary

    This chapter summarizes normal immune function and its relationship to immunologic infertility. The normal immune system identifies and destroys antigen within the body. The humoral immune system is suited to the destruction of whole, extracellular antigens, including most bacteria, larger parasites, and viruses. Antispermatogenic autoantigens induce autoimmunity to the germinal epithelium, resulting in a specific decline in sperm production due to germ cell destruction. Tail-directed sperm antibodies are more likely to impair motility and cause agglutination, sperm head-directed antibodies may preferentially affect zona binding and fertilization, as suggested by immobilization and penetration assays. Corticosteroids prevent the chemotaxis of inflammatory cells, impede cytokine release, decrease antibody production, and even weaken antigen-antibody association. Intrauterine insemination (IUI) is suited for treatment of infertility when there is evidence of cervical mucus problem, whether it is due to antibodies or not, as demonstrated by the inability of sperm to penetrate the cervical mucus.
  • Chapter 24 - Nonsurgical treatment of male infertility:
    pp 430-437
  • specific therapy
  • View abstract

    Summary

    This chapter discusses the sites of genitourinary tract infections, infectious organisms, the numerous ways in which leukocytes may impair male reproduction, and the diagnosis and treatment of leukocytospermia and bacteriospermia. Infections of the urethra are most common due to sexually transmitted pathogens, and they are separated into two broad categories: gonococcal urethritis (due to Neisseria gonorrhoeae ) and nongonococcal urethritis (Chlamydia trachomatis, Mycoplasma species, Trichomonas vaginalis). Immunohistology employs monoclonal antibodies (mAb) targeted against white blood cell (WBC) surface markers. Flow cytometry, when used in conjunction with monoclonal antibodies, can provide rapid analysis of scant WBC subpopulations without purification procedures. Leukocytes, monocytes, and granulocytes are differentiated by using the light-scatter properties of the WBCs and the density of the leukocyte marker antibody, CD45. The chapter suggests that abnormal concentrations of leukocytes are a common finding in the semen of men with spinal cord injury (SCI).
  • Chapter 25 - Nonsurgical treatment of male infertility:
    pp 438-453
  • empiric therapy
  • View abstract

    Summary

    This chapter reviews the current concepts and ongoing controversies regarding the pathophysiology, diagnosis, significance, and treatment of the varicocele. Varicocele may also affect reactive oxygen species generation, rendering the testicle and the sperm unable to handle oxidative stress, and resulting in reactive oxygen species buildup. Toxic agents and heavy metals accumulate in tissues undergoing apoptosis, several investigators has examined testicular tissue heavy-metal content in men with varicocele. A pencil-probe Doppler stethoscope has been advocated as an adjunctive tool in the examination of the varicocele. Ultrasonography has become an increasingly useful modality in the diagnosis of varicocele. Surgical varicocelectomy is the cornerstone of varicocele therapy. Several surgical approaches are available to accomplish varicocelectomy. The approaches include the scrotal approach, the subinguinal approach, the inguinal approach, the retroperitoneal approach, and the laparoscopic approach. Azoospermia has generally been regarded as a contraindication to varicocelectomy.

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