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Male Factor Infertility

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Male Factor Infertility 2 Male Factor Infertility SECTION CONTENTS 3 Evaluation and Diagnosis of Male Infertility 4 Hormonal Management of Male Infertility 5 Immunology of Male Infertility 6 Surgical Management of Male Infertility 7 Genetics and Male Infertility 3 Evaluation and Diagnosis of Male Infertility Sandro C Esteves, Alaa Hamada, Ashok Agarwal to the andrological armamentarium. Today, it is possible CHAPTER CONTENTS to correctly classify some cases which were previously ♦ Definition and Epidemiology of Male Infertility believed to be idiopathic. The initial evaluation of com- ♦ Pathophysiology, Etiology and Classification of Male mon infertility complaint comprises the meticulous his- Infertility tory taking, as well as conducting a thorough physical ♦ Probabilities of Conception for Fertile and Infertile examination along with proper laboratory and imaging Couples studies as needed. ♦ Goals and the Proper Timing for Fertility Evaluation ♦ Approaching the Subfertile Male DEFINITION AND EPIDEMIOLOGY OF MALE INFERTILITY The infertility is defined as failure of the couples to INTRODUCTION conceive after 12 months of unprotected regular inter- course.2 Infertility is broadly classified into primary t is well known that the motivation to have children infertility, when the male partner has no previous history Iand the formation of a new family unit are essential of fertility, and secondary infertility, when there was components of the individual instinct for existence and previous man’s history of successful impregnation of well-being. Fertility problems may represent a stressful a woman. Subfertility refers to a reduced but not unat- situation to the individual’s life with important nega- tainable potential to achieve pregnancy, while sterility tive psychological consequences.1 The experienced cli- is denoted by permanent inability to induce or achieve nician should realize and comprehend the burdensome pregnancy.3 Fecundity, on the other hand, indicates the bearings and frustrated mood of the infertile individual. capability of a given male or female to produce live Most adults are prompted to discuss their sexual issues births. and behaviors if the interview is conducted in a respect- Epidemiology studies indicate that 13–15% of couples ful, confidential, professional and nonjudgmental way. face difficulties to conceive.4 Approximately 8% of men In the last decades, extraordinary advances have in reproductive age seek medical assistance for fertility- been achieved in the field of male infertility. Significant related problems.5 Isolated male factor infertility, and its progress has been made regarding both diagnostic and combination with female problems accounts for more treatment techniques. Novel tests have been incorporated than 50% of the couples’ inability to conceive.6 The male Section 2 Male Factor Infertility factor is purely responsible for 20% of infertile couples, PATHOPHYSIOLOGY, ETIOLOGY AND 6 while it is contributory in another 30–40% of infertility. CLASSIFICATION OF MALE INFERTILITY The World Health Organization defines male factor infertility as the presence of abnormalities in the semen The male reproductive system consists of the testes, analysis, or the presence of sexual or ejaculatory dys- accessory glands and the ductal system for sperm trans- function.7 However, modern andrology has revealed port. The seminal ducts constitute the pathways for sperm that normal semen testing does not guarantee fecundity, transport; and it includes the efferent ductules and rete and unraveled the predictive power of normal semen to testis, epididymis, vas deferens, ejaculatory ducts and induce natural pregnancy is about 60%.8 The introduc- urethra. The accessory sex glands include the seminal ves- tion of novel sperm function testing is revolutionizing icles, prostate and bulbourethral glands (Figures 1 and 2). the criteria of diagnosis and definitions of male infertility. The testes perform two important functions: sper- Recent reports indicate that sperm counts of men matogenesis and steroidogenesis. Daily sperm produc- from certain regions of the world have significantly tion is about 40 million and declines progressively with deteriorated. Remarkable differences in sperm pro- aging. Recent data suggests that the duration of sper- duction have been detected among men from different matogenesis is less than 60 days instead of 70 ± 4 days countries in Europe and the United States of America. as previously thought for over 40 years.21 As such, the Differences are also seen in individuals of different sperm production of an individual actually represents regions within the same country. Moreover, there is a the result of influencing biological, physical and occu- noticeable epidemiologic increase in the incidence of pational factors, which acted within the past 2 months testicular cancer and urogenital anomalies.9-12 These from ejaculation. Steroidogenesis and hormone produc- observations cause public concerns particularly with tion is another essential testicular function. The hormo- regard to the implication of environmental factors nal milieu that regulates spermatogenesis depends on and modern life habits.13-15 Some authors claim that complex coordinated interaction between the testes, the buildup in the prevalence of infertility among men pituitary gland and hypothalamus that form the hypo- may be attributed to increased prevalence of obesity.16-18 thalamic-pituitary-gonadal (HPG) axis (Figure 3). Others factors may also be implicated in the apparent The storage and maturation of spermatozoa occur rising prevalence of male infertility problems such as in the epididymis. However, the maturation process is exposure to cell phones radiation19 and certain endo- exclusively completed within the female reproductive crine disruptors.20 tract. Spermatozoa transit throughout the epididymis for Figure 1 Schematic illustration of the male reproductive organs 30 Chapter 3 Evaluation and Diagnosis of Male Infertility transport and sperm function constitute the essential causes of male infertility. The fourth category is represented by “infertility of unknown origin”, a condition in which male infertility has aroused spontaneously, or from an obscure or unknown cause. This category accounts for 37–58% of the cases, and it is divided into two major subtypes: idi- opathic and unexplained male infertility.22-24 Idiopathic male infertility is the cause of about 30% of male infer- tility, and it is characterized by unexplained reduction in semen quality with no previous history associated with fertility problems, and having normal findings on physi- cal examination and endocrine laboratory testing.23 The term “unexplained male infertility”, on the other hand, is reserved for infertile men with infertility of unknown ori- gin with normal semen profile, and in whom female infer- tility factors have been ruled out. This category accounts for 6–27% of male infertility, and it strongly depends on how exhaustive evaluation of the patient is done.22 Table 1 depicts the etiologic classification of male infertility. Figure 2 Schematic representation of the testis and its The most commonly observed abnormality in related structures infertile men seeking evaluation is varicocele followed by obstruction and cryptorchidism. Table 2 shows the about 12 days. The epididymides are in continuity with distribution of the causes of male infertility in tertiary the vasa deferentia, which in turn join the emerging care infertility center. It should be noted, however, that ducts from the seminal vesicles to form the ejaculatory the frequency distribution of primary infertility causes ducts. They enter the prostate, a gland responsible for is different from secondary infertility causes in which production of a fluid enriched with zinc, citric acid, acid varicocele accounts for 70–80% of the cases, followed by phosphatase and proteases that contributes to liquefac- infection of genital tract.25-27 tion and accounts for approximately 0.5 ml of the ejacu- late. The seminal vesicles produce an alkaline fluid with prostaglandins and fructose that composes 1.5–2.0 ml of PROBABILITIES OF CONCEPTION FOR the seminal fluid. Both seminal vesicles and vas defer- FERTILE AND INFERTILE COUPLES ens have a common embryologic origin. As such, when congenital bilateral absence of vas deferens (CBAVD) is Epidemiology studies indicate that the chance of a cou- diagnosed, it is often associated with seminal vesicles ple to achieve conception is 80–90% after 1 year of regu- hypoplasia/agenesis. This is an important aspect in the lar well-timed intercourse while the monthly chance for differential diagnosis of azoospermia. In CBAVD, dimin- conception is 20–25%.27 The optimum fertility age for ished or no fructose can be found in the seminal fluid and, conception in both sexes is 24 years. Henceforth, the fer- hence, volume is low (< 1 ml). Under normal conditions, tility potential declines, particularly for female partner spermatozoa are stored in the epididymides rather than after the age of 31 years.28-30 the seminal vesicles. At the time of ejaculation, ductal and On the other hand, the spontaneous pregnancy rate epididymal muscle contractions under sympathetic stim- for infertile couples, due to idiopathic reasons, notice- ulation conduct the spermatozoa towards the prostatic ably depends on the result of semen analysis. For non- urethra where they join fluids excreted by the prostate, azoospermic men, the pregnancy rate is 1–3% per month, and form the semen. Periurethral muscle contraction
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