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Sperm DNA fragmentation testing has been recognized as an important additive evaluation tool for examining male fertility potential. This is because SDF can significantly influence fertilization, embryogenesis, and live birth rate. Several indications for SDF testing have been recently recognized. Once detected, the SDF level can aid the clinician in making sound decisions in attempting to normalize the SDF value and improve a man’s fertility status. Treatments such as frequent ejaculations, treatment of infection, avoidance of risk factors, antioxidant therapy, varicocelectomy, sperm selection, and use of testicular sperm for intracytoplasmic sperm injection have been utilized with promising results.

Infertility has become a major social concern, with high demand for treatment. Due to the high prevalence of genetic abnormalities among men suffering from infertility with severe oligozoospermia and azoospermia, cytogenetic testing is highly warranted. These tests can diagnose some, but not all, of the causes of poor reproductive potential in men. Unfortunately, these genetic tests are considered a monetary burden to some patients. As a result, these patients are deprived of the proper diagnosis and treatment for their infertility problems. In addition, these genetic tests are not readily available in centres, especially in developing countries, and are not covered by insurance. Genetic diagnoses are valuable for the determination of the prognosis, decisions regarding treatment options and management for both the male partner and the couple as a whole. Inadequate evaluation of the genetic causes of male infertility may affect management due to a lack of proper counselling and the suboptimal prevention of vertical transmission of genetic defects during assisted reproductive technologies. Despite recent advances in technology and diagnostic examinations, many men do not have identifiable causes of their infertility. The epidemiology of male infertility is difficult to study for several reasons. There are considerable variations in the frequency of male infertility and its aetiologies worldwide, and its nature has been poorly studied in heterogeneous data. Knowing the global epidemiology of different causes of infertility is fundamental for the effective delivery of care to these affected individuals. Only a handful of large-scale studies have addressed the epidemiology of genetic aetiologies of male infertility, and the published data are littered with significant shortcomings. Further high-quality methodological studies are needed to establish the true epidemiology of each genetic cause of male infertility. A deep understanding of all the aspects of the genetic conditions causing male infertility is needed in order to offer infertile couples the most appropriate treatment for their disorders.

Chromosomal abnormalities are major contributors of idiopathic male infertility. Anomalies or mutations of the chromosomal DNA lead to different forms of chromosomal abnormalities. An array of functional gene expressions determines normal testicular development and robust spermatogenesis. In case of any anomalies in these genes, testicular dysgenesis as well as spermatogenic arrest may occur leading to a comprised state of male fertility. The present chapter will review two of the most sophisticated structural chromosomal abnormalities, translocation and inversion. Chromosomal translocation refers to the transfer of chromosomal part to another chromosome, while genetic inversion takes place when a chromosomal part breaks off, rotates 180 degrees, and reattaches to the same chromosome. Moreover, the chapter aims to present the underlying mechanisms by which chromosomal translocations and inversions pave the way to male infertility, clinical presentations of related conditions, and management approach in cases of chromosomal abnormalities-induced male infertility.

The field of male infertility has witnessed many advancements in the past few decades that have refined our understanding of the sperm contribution to conception. The extent of sperm DNA fragmentation is currently believed to play a key role on fertilization and embryogenesis making it an important test of sperm function. This belief has triggered many scientists to explore SDF testing in clinical practice. Many tests can assess DNA damage directly through dyes and probes or indirectly though measuring the denaturation of DNA. Regardless of the method used, SDF testing is gaining popularity and is extensively investigated to evaluate its value in the management of male infertility. Recent publication of clinical practice guidelines on the utility of SDF testing has provided a strong evidence-based approach to the utilization of this test by fertility specialists. This chapter aims at exploring the evidence highlighting the significance of SDF testing in clinical practice.

Klinefelter syndrome (KS) is the most frequent sex chromosomal anomaly that occurs in about 85–223 males per 100,000 live-born males and occurs mostly due to meiotic nondisjunction. The clinical presentation of KS patients varies according to the age of the patient and his phenotypic expression that manifests as a variety of symptoms due to androgen deficiency that characterize the syndrome. In addition to compromised testicular function and hypogonadism, KS patients are also at an increased risk of metabolic disturbances, such as type 2 diabetes mellitus and cardiovascular disease. They also present with cognitive and psychiatric disturbances. However, it is estimated that only 25–40% of the subset of patients with KS are ever diagnosed and only around 10% of these patients are identified during their childhood and adolescent years. The reason behind the underdiagnosis of KS can be explained by the wide variability in its presentation requiring a great deal of conjecture from the clinician caring for such patients. A multidisciplinary approach toward the management of KS patients is essential to encounter the multiple features of the disease. The hypogonadism in KS patients needs to be treated by testosterone replacement (TRT) at some point during the course of the therapy. Cryopreservation of sperm is offered to the adolescent KS patients who are able to provide a semen sample. Pharmacological therapy with aromatase inhibitors prior to microsurgical testicular sperm extraction has the highest sperm retrieval rates in azoospermic men.

Infertility is a common clinical condition known to induce significant psychological stress to the couple. Conventional semen analysis is commonly used for the initial evaluation of infertile men. However, this test cannot accurately detect sperm function, therefore, it cannot differentiate infertile from fertile men. Reactive oxygen species (ROS) are known to cause lipid peroxidation of the sperm plasma membrane, which in turn could lead to sperm DNA fragmentation (SDF). This shows the positive relationship between these two distinct entities. Therefore, it is necessary to detect their presence as this will determine one of the possible explanations of male infertility. Elevated SDF has been shown to negatively correlate with semen parameters and reproductive outcomes. Indications for its testing has been well studied by a panel composed of experts in this field. Although not recommended for routine use, it is still a valid test for male infertility assessment. Many surgical and nonsurgical treatment options have been offered to reduce the level of SDF. One of these is the use of antioxidants which are readily available compounds used in the treatment of male infertility. Several studies have demonstrated improved sperm kinetics with antioxidant therapy and subsequently improved reproductive outcomes. However, additional research is needed. Despite this limitation, antioxidant use is still a reasonable option for men suffering from infertility due to elevated SDF.

The role of sperm DNA fragmentation (SDF) in the pathophysiology of varicocele-associated male infertility has been increasingly recognized. The expanding utilization of SDF testing among andrology laboratories worldwide is made possible by the development of various SDF assays which allows the important genetic content of male gametes to be assessed. The application of SDF testing in patients with varicocele has been explored in an attempt to better select patients who will benefit from varicocele treatment. Current evidence supports the potential value of the test based on the association between clinical varicocele and high SDF and the reduction of SDF in the majority of patients after varicocelectomy. Recent guidelines have provided indications of SDF testing in patients with varicocele to whom the results may guide management decision.

Oxidative stress (OS) has been recognized as a common mediator through which various etiologies can alter a man’s fertility potential. Varicocele is not an exception in this regard. The different pathophysiologic mechanisms linking varicocele to male infertility are thought, at least partially, to incite a state of seminal OS. In support of this notion is the current evidence which has confirmed the presence of significantly high OS measures in varicocele patients and reported their sound reductions after varicocele treatment.

Numerous studies have explored the pathophysiology of varicocele as it is recognized as an important factor contributing to male infertility. The focus of these studies is to understand the impact of varicocele on testicular function. Among the most common investigated pathophysiologies in literature were testicular hyperthermia, hormonal disturbances, testicular hypoperfusion, and backflow of toxic metabolites. The focus of this chapter is to thoroughly assess the mechanisms linking varicocele to male infertility.

Varicocele is a common presentation in men seeking fertility. While its impact on semen quality has long been recognized, not all men with varicocele require treatment. Clinical guidelines on varicocele management should therefore be reviewed before counselling and treatment decisions are made. This chapter reviews the clinical presentation and the evaluation of adult varicoceles and explores the present clinical guidelines for its diagnosis and treatment. The various treatment options are also portrayed along with their outcomes and complication rates.

Varicocele is a clinical diagnosis commonly encountered during the evaluation of men presenting with infertility. Much controversy still surrounds the diagnosis and treatment of men with varicocele. Although its detrimental effect on conventional semen parameters and male fertility potential has been recognized in literature, its prevalence in fertile men is perhaps the main reason for the never-ending varicocele debate. Current evidence does recognize an improvement in pregnancy rate following varicocelectomy; however, this effect is mainly observed in correctly selected patients. Several tests of sperm function have been utilized in conjunction with conventional semen analysis in varicocele patients to help understand the implications of this disease on human reproduction and to better select surgical candidates. Among all tests of sperm function, tests of oxidative stress and sperm DNA fragmentation proved to be independent measures of infertility in varicocele patients. This chapter explores the influence of varicocele on male fertility measured through conventional semen analysis and advanced tests of sperm function. It also explores emerging technologies that serve to increase our understanding of male infertility and varicocele.

Ejaculatory dysfunction or the inefficient ejaculation of semen at the moment of sexual climax is the most prevalent form of male sexual dysfunction. It is a well-recognized consequence to a variety of clinical conditions and medical and surgical therapies. Four different types of ejaculatory dysfunctions occur; they include premature ejaculation, delayed ejaculation, retrograde ejaculation, and anejaculation. A thorough understanding of physiology and pathophysiology of ejaculation is necessary for effective management. A stepwise approach to therapy is generally favored which includes behavioral therapy, pharmacotherapy, penile vibratory stimulation, electroejaculation, and surgical sperm retrieval.

Erectile dysfunction (ED) is defined as the persistent inability to attain or maintain penile erection sufficient for satisfactory sexual performance. Despite its benign nature, ED may affect the physical and psychosocial well-being of sufferers, causing a significant impact on their quality of life (QoL). Recent evidence has pondered ED as an early manifestation of cardiovascular disease suggesting that its occurrence should not be dealt with as only a QoL issue, but also as a potential warning sign of a more serious medical condition. With an increasing knowledge about possible disturbances of penile erection, new organically oriented therapeutic options have been developed, which have revolutionized the treatment of ED. Through the use of clinical scenarios, this chapter reviews the available approaches for the evaluation and management of patients presenting with ED.

The field of male infertility has witnessed major advancements over the past few decades both in the diagnostic and treatment modalities being utilized. Such advancements resulted in a better understanding of the pathophysiology of male infertility and allowed for a cause directed approach to management. In this chapter, we aim to review these diagnostic tools exploring the evidence associated with them.

Azoospermia is defined as absence of spermatozoa in the ejaculate. It is found in around 15% of men presenting with infertility. The introduction of intracytoplasmic sperm injection in the early 1990s was coupled with major advances in surgical sperm retrieval. This dramatically changed the concept in management of azoospermia patients, giving them the hope of having their biological child. The current chapter will discuss the management of these cases according to the best medical practice.

Right after its discovery in the 1950s a plethora of testosterone abuse (or its synthetic metabolites) has been practiced by many to either improve athletic performances or physical appearance. In supraphysiologic doses, androgenic anabolic steroids (AAS) can affect multiple organ systems causing an increased morbidity and mortality in abusers. Exogenous testosterone shuts down the hypothalamic–pituitary–gonadal axis subsequently inhibiting testicular function and causing infertility in male patients. Recognizing the potential harm from using such substances, the international Olympic committee as well as other health agencies are constantly updating their diagnostic technology to cope with the growing spread and progression of AAS. The management of patients presenting with infertility following AAS abuse entails substance discontinuation followed by medical therapy to regenerate the endocrine axis and stimulate testicular function.

Reactive oxygen species (ROS) are highly reactive oxidizing agents that, at physiologic levels, play an essential role in the health and well-being of aerobic organisms. When supraphysiological levels of ROS are produced or when the cells’ antioxidant defense mechanisms fail, a state of oxidative stress (OS) ensues. Immature sperm cells and leukocytes are the principal sources of ROS in seminal fluid. OS has been recognized as an important factor in the pathophysiology of male infertility as it can enhance sperm apoptosis, lipid peroxidation (LPO), and DNA fragmentation. Several assays that can directly or indirectly measure the amount of ROS in seminal fluid have been developed and should be considered during male fertility assessment. Once detected, OS should be properly managed through lifestyle modification, elimination of potential sources of ROS production, and oral antioxidant supplementation.

Semen analysis remains the most important initial diagnostic tool in the evaluation of male fertility. It not only provides valuable information for creating a management strategy, it also offers insight into the patient’s overall prognosis. However, semen analysis leaves the clinician on many occasions with unanswered questions. For this reason, efforts were made to help establish new diagnostic modalities capable of addressing specific queries. Sperm viability, genetic function, and fertilizing ability can be assessed with viability studies, sperm DNA fragmentation, and acrosome reaction, respectively. In this chapter, we aim to present a practical guide on different diagnostic modalities used in the evaluation of male infertility.