In nature varying strategies are used to ensure that the best sperm arrives at the egg. Strategies to select the best sperm are far less rigorous in the setting of in vitro fertilization. In this chapter we discuss how in vitro sperm selection strategies utilize different components of the spermatozoon including their motility characteristics, size, membrane properties, and nuclear structure. Sperm selection strategies have included microfluidics, spectroscopy, label-free imaging, hyaluronan binding, and separation of sperm by charge. Although some studies have shown that sperm selection can improve embryo euploidy rates and pregnancy outcomes, in particular by reducing miscarriages, large clinical trials, focused on the male population who would benefit most from sperm selection, are still needed.

Surgical correction of Peyronie’s disease remains the gold standard of treatment. The goals of surgery should be cosmetic improvement and the preservation or restoration of sexual function. Preoperative workup should include objective assessment of both curvature and erectile function, and shared decision-making with the patient to clearly understand expectations for surgery is critical, as there is a risk of penile shortening and erectile dysfunction with any Peyronie’s surgery. Peyronie’s surgeries fall into three broad categories: plication procedures, plaque incision and grafting, and placement of a penile prosthesis. While direct comparative studies are rare, plication surgeries are the most commonly performed, as they are technically simpler and have excellent satisfaction rates. Grafting techniques are most indicated for more severe cases. Prosthetic placement is appropriate for patients with concurrent erectile dysfunction, and placement alone can correct cases of mild curvature. Additional techniques to straighten the penis can be employed if needed.

The prevalence of azoospermia in the general population is 1% and azoospermic men constitute approximately 10–15% of all infertile men. While the advent of microTESE substantially improved sperm recovery compared to standard biopsy or other techniques, the procedure remains inefficient, costly, and very time consuming, both in retrieval and separation/sorting. Three conventional sperm sorting techniques are commonly used in andrology clinics: density gradient centrifugation, sperm washing, and swim-up, all of which have provided reliable solutions to isolate normal sperm from highly concentrated semen samples. The field of microfluidics is the most rapidly developing field for sperm selection related to the field of ART. It is particularly powerful when considering applications in single-cell or low-cell number analyses. Magnetically activated cell sorting and fluorescence-activated cell sorting are alternative and promising technologies. Further research is needed to optimally identify and isolate sperm to help couples achieve the goal of biologic children.

A diagnosis of infertility in the male or female partner within a couple can cause significant stress, leading to sexual dysfunction in either or both partners. The causes of infertility and the related sexual dysfunction can be organic or psychosocial in nature but are frequently linked. Here, we discuss the interplay between infertility and sexual dysfunction, specifically in the man and the couple, and focus on psychosocial interventions for the couple as they struggle to build their family.

Male erectile dysfunction is a common condition that can significantly impact quality of life and interpersonal relationships. It is strongly associated with aging, comorbid conditions, poor lifestyle, and adverse cardiovascular health. Deficits in psychologic, neurologic, vascular, and endocrine function can all lead to erectile dysfunction. The aim of this chapter is to review the molecular biology required for erectile function as well as delve into the clinical pathophysiology that leads to erectile dysfunction.

The main functions of the male reproductive system are the synthesis and secretion of male sex steroids (androgens), production of male gametes (spermatozoa), and transport of sperm into the female genital tract. The development, maturation, and normal function of male fertility are mainly under the control of the hypothalamic-pituitary-testicular axis, which constitutes the hormonal component of an interplaying and intercommunicating neuronal and endocrine system, that will be explained in this chapter.

The worldwide prevalence of erectile dysfunction is estimated to impact 20% of men. The evaluation of the male with erectile dysfunction can serve as an opportunity to screen men for a variety of important cardiovascular risk factors. A typical visit consists of a detailed and comprehensive patient history and a focal physical exam. Patients should be put at ease and a therapeutic relationship established to move forward with a shared decision-making process regarding treatment. Considerations during the evaluation should be toward screening for underlying risks factors for erectile dysfunction, a detailed sexual history, utilization of validated questionnaires, determination of lifestyle and social history factors, basic laboratory testing, and a psychological assessment. The goal of the evaluation is to identify the underlying causes of erectile dysfunction that will allow the clinician to develop the best therapeutic strategy.

The internet constantly evolves and facilitates the development of new avenues for users to interact and communicate internationally. Social media and search engines represent the forefront of internet technologies that enable users to produce content, develop digital participatory networks, and share information across various topics. These internet tools are reshaping the continuum of care by enabling patients to acquire medical information, consult peers and healthcare practitioners, and even make treatment decisions without leaving their connected device. The consequences of circumventing traditional pathways to care are amplified in men’s health due to the fact that men frequently do not engage with the healthcare system and that erectile dysfunction and male infertility are stigmatized. The focus of this chapter is to evaluate the emerging online landscape for common men’s health conditions including male infertility, erectile dysfunction, hypogonadism, and Peyronie’s disease.

For many years sperm epigenetics has been a focus of studies hoping to identify novel mechanisms that drive infertility and offspring health abnormalities. This effort has yielded many exciting prospects but to date no direct and firm mechanistic pathways have been fully elucidated. This is largely a result of the unique nature of the mature sperm that is reflected in the distinct epigenetic signatures that are found therein. This unique landscape makes traditional approaches for understanding mechanisms difficult. However, the utility of sperm epigenetic marks in the prediction of specific reproductive outcomes is becoming clearer. While the mechanisms that explain the biological underpinnings of some of the associations between sperm epigenetics and reproductive health have yet to be elucidated, the value that these marks offer in prediction of various reproductive outcomes is becoming clearer.

Sperm banking, or male fertility preservation, is widely used prior to medical, surgical, and nonmedical procedures that might affect a male’s fertility. Both federal and state regulations have been instituted to regulate the sperm banking industry, requiring rigorous screening and testing of sperm donors and detailed records of the donors and clients that choose to store their own sperm. Cryopreservation consents are detailed and cover long-term storage, use of the specimens, and disposition of the specimens in case of incapacitation or death of the sperm banker or lack of need for the frozen specimens. Sperm cryopreservation is relatively simple in the laboratory, but does require trained staff working with cryopreservatives and liquid nitrogen. With the increased use of ART, cryopreservation of even the poorest specimens with only a few sperm has become routine. Sperm can be retrieved with testicular biopsy or epididymal aspiration even in the case of purported azoospermia. Use of fresh or frozen specimens have been shown to yield comparable results. The future of sperm cryopreservation is promising as we look to storage of testicular tissue for future autotransplantation as well as prepubertal spermatogonial stem cell storage for future in vitro maturation, or transplantation and growth of testicular tissue and sperm production.

Exogenous testosterone functions as a male contraceptive. As a result, men treated with testosterone who desire fertility will need help when trying to restore or preserve fertility. In this chapter, we provide a framework for counseling and managing hypogonadal men who desire fertility. We explore strategies ranging from cessation of exogenous testosterone to using human chorionic gonadotropin, selective estrogen receptor modulators, aromatase inhibitors, or recombinant follicle-stimulating hormone with or without testosterone to preserve Sertoli and Leydig cell function. Furthermore, we provide strategies to maintain fertility while starting testosterone and clinical pathways for a hypogonadal man to recover fertility based on his desired timeline for a pregnancy.

Although semen analysis is the main routine test used in the diagnosis of male infertility, it is considered to be poorly predictive of male fertility status. Only recently, research in sperm biology focused on the development of assays to evaluate sperm functions necessary to reach and fertilize the oocyte and to allow a correct embryo development. However, the clinical utility of the currently proposed tests/assays remains a matter of debate, especially after introduction of ICSI. Ideally, since fertilization proceeds in a cascade-like manner, the goal would be to develop a single test able to evaluate all the aspects involved in this process and introduce it in ART laboratories. Such test should be simple, cheap, and not requiring expensive technology. Unfortunately, this aim is still far from being achieved. In this chapter, we discuss the most promising tests assessing sperm functions, describing their validity, limits, and potential use in clinical practice.

Spermatogenesis is a complex process that ensures daily production of mature male gametes. The differentiation of spermatogonia stem cells into spermatozoa requires the unfolding of several events that are highly regulated in time and space. During spermatogenesis, which takes place inside the seminiferous tubules, germ cells undergo profound morphological rearrangement as can be observed by classical histological analysis of human testis specimens. Spermatogenesis also brings about the dramatic rearrangement of genetic makeover of developing germ cells including homologous recombination and changes in the epigenetic landscape. In this chapter the different phases of human spermatogenesis and cell types involved are described with an emphasis on their morphological arrangements. In parallel, an update on novel findings concerning the cycle of the seminiferous epithelium, the kinetic of spermatogonial compartment, and the implications of single-cell transcriptome analysis of testicular cells will be provided.

Ejaculation is a complex physiologic phenomenon and may have been historically necessary to achieve pregnancy. The advent of successful assisted reproductive technologies (ART), such as intracytoplasmic sperm injection and surgical sperm removal, have become an area of interest in reproductive medicine research. As such, interest has shifted away from ejaculatory disorders in part due to the tremendous success of assisted reproduction. Ejaculatory disorders are poorly understood and frequently misdiagnosed. While sperm retrieval procedures are highly effective in achieving the goal of reproduction, accurate diagnoses and management of these disorders to minimize complexity of ART are required. Additionally, many of these symptoms induce distress in patients, despite having any concerns involving fertility, resulting in significant quality of life implications for them. The evaluation of this entity requires a careful and appropriate treatment strategy. A carefully planned workup is needed to determine an accurate diagnosis and treatment that can result in high levels of patient satisfaction.

Men with spinal cord injury often suffer from erectile dysfunction, ejaculatory dysfunction, infertility, and hypogonadism. Restoration of sexual and reproductive functions is a top priority and efficient treatment modalities exist. Erectile dysfunction can be treated with phosphodiesterase-5 inhibitors and if unsuccessful intracavernosal injections can be tried. When injections fail a penile implant can ultimately be an option. Anejaculation and the resulting infertility are treated in a stepwise approach with penile vibratory stimulation, electroejaculation and surgical sperm retrieval followed by assisted reproduction. Assisted ejaculation is an effective and safe procedure but carries a risk of autonomic dysreflexia, especially in men with injuries at the level of T6 or above. Autonomic dysreflexia is an unregulated and uncontrolled response of the sympathetic nervous system but it can be safely managed. Hypogonadism is more prevalent in men with spinal cord injury compared to the general population and testosterone replacement therapy can be beneficial for alleviating symptoms of low testosterone, but testosterone-related spermatogenic suppression needs to be considered in men who wish to initiate a pregnancy.

Over the last decade it has become increasingly clear that semen analysis is insufficient to diagnose male infertility. With 30% of infertile men diagnosed as idiopathic, the ethics of continuing to rely on outdated diagnostic parameters must be questioned. Sperm DNA damage is a strong biomarker of male infertility. It also correlates significantly with increased risk of miscarriage after both natural and ART conception. Thirdly, sperm DNA damage is a useful predictive tool for both IVF and ICSI live birth success. DNA fragmentation can occur as double or single strand breaks. Oxidative stress is a common cause of single strand breaks and can be prevented by endogenous and dietary supplemented antioxidants. In contrast, double strand breaks are caused by dysfunction during spermatogenesis, and are harder for oocytes to repair post fertilization. Greater awareness of the relevance of DNA damage and its origins could aid fertility choices and outcomes.

Chronic pain genital pain in men generally falls into chronic testicular pain or chronic prostatitis/chronic pelvic pain (CP/CPPS), which has considerable overlap. This is a common complaint, but the etiology, treatment, and response to treatment vary widely. There is still a paucity of high-quality data regarding chronic orchialgia and CP/CPPS, but a widening variety of treatment options is coming to light. We review the etiology and treatment options.

The examination of the human ejaculate constitutes a complicated branch of medical laboratory science. To understand the complexity of the human ejaculate knowledge about the physiology and pathology is facilitating. It is also essential to understand that the main value of ejaculate examination is the information that can be obtained on the functional capacity of the male reproductive organs. Still, the main focus has for a long time only been on the prognostic value for the outcome of the fertility of the couple. In this chapter the focus is on how the functional capacity of the male reproductive trace can reflect in the ejaculate examined in the laboratory. Important principles for reliable laboratory techniques for ejaculate volume, sperm concentration and sperm count, sperm motility, sperm vitality, and sperm morphology are described with requirements for reliability, assessment of uncertainties, need for staff training, internal quality control, and interlaboratory comparisons (external quality control).