Many benign and malignant conditions are treated with fertility-threatening medical or surgical therapies. Fertility preservation is a recourse critical to discuss prior to initiation of these therapies. This chapter describes contemporary and future fertility preservation approaches while also exploring barriers in access to their use as well as key decision-making strategies helpful for clinicians caring for patients with a range of medical conditions.

This chapter briefly introduces microfluidics as an enabling technology for medicine, focusing on microfluidic-enabled treatments for male infertility. The first section provides a brief overview of microfluidics-based applications in biomedical research and assisted reproductive technology (ART). In the following sections, we review notable demonstrations of microfluidic technology applied to sperm sample preparation and sperm identification. Finally, we conclude the chapter by providing our perspective on the application of microfluidics technology for male infertility treatment, and the challenges/opportunities for further growth of microfluidics-enabled ART for male infertility.

Paternal age is increasing with time. Increasing evidence suggests that a man’s reproductive health changes with age. A man’s fertility may decline as he ages with evidence of an association with unassisted and assisted conception. In addition, there are risks to the pregnancy and child for older fathers. While the definition of advanced paternal age remains uncertain, the consequences of paternal age are becoming more quantifiable.

Male-factor infertility contributes significantly to the burden of infertility. Fortunately, many causes of male-factor infertility are amenable to surgical intervention. These interventions can be grouped broadly into three categories: 1) those that improve sperm delivery, including vasovasostomy, vasoepididymostomy, and transurethral resection of the ejaculatory ducts, for obstruction of the vas deferens, epididymitis, and ejaculatory ducts, respectively; 2) those that improve testicular function and optimize spermatogenesis, namely varicocelectomy; and 3) those that enable direct retrieval of sperm from either the epididymis (microsurgical epididymal sperm aspiration and percutaneous epididymal sperm aspiration) or testicle (testicular sperm aspiration and testicular sperm extraction). When used in conjunction with other assisted reproductive techniques, including IVF/ICSI, these surgical procedures have vastly improved the reproductive outlook for many subgroups of infertile men who had previous been considered completely infertile.

The definition of epigenetics has been redefined in the last decades and today is generally accepted as the study of heritable factors, other than DNA base pair coding, that regulate gene expression. In this chapter, we briefly review the main epigenetic factors that exist in spermatozoa (e.g., histone and chromatin modifications, DNA methylation, and noncoding RNAs [ncRNAs]) and underline the associations and effects of aging, adiposity, and some lifestyle and environmental factors on the sperm epigenome. In conclusion, further work needs to be done to establish whether the changes of sperm epigenome triggered by aging, adiposity, diet, and smoking can have not only implications for the reproductive health but also for the future offspring.

Benign prostatic hyperplasia is the most common benign neoplasm in males in the United States. It is characterized by lower urinary tract symptoms: weak stream, urinary frequency, urgency, incomplete emptying, hesitancy, nocturia, and acute urinary retention. These symptoms are generally slowly progressive and left untreated can cause irreversible bladder damage. Diagnosis is mostly clinical and based on symptomatology; however, the use of some objective tests can be helpful. Treatment options include lifestyle modification as well as a variety of different pharmacologic agents.

The office evaluation of the infertile male involves a comprehensive history and physical structured to uncover all potential causes including congenital, medical, surgical, environmental, genetic, and psychosocial etiologies. The physical exam begins with the patient’s general appearance, body habitus, and progresses to the genital exam in which the testicles are examined for size, consistency, and location. Prior surgical scars, absence of the vas deferens, or the presence of varicoceles may be identifiable causes of infertility. The semen analysis is the cornerstone laboratory evaluation of the male undergoing an infertility workup. The semen is evaluated for several key parameters including volume as well as sperm concentration, number, motility, and form. An endocrine evaluation is indicated in men with oligospermia, azoospermia, or a history of physical examination findings suggestive of hormonal abnormalities including sexual dysfunction, decreased libido, or physical evidence of impair androgenization. Pending the initial workup genetic testing may be indicated.

Over the past 20 years, there has been growing interest in understanding the genomic integrity of human spermatozoa and the clinical relevance of sperm chromatin and DNA defects. We have learned that the etiology of human sperm DNA damage is multi-factorial and that sperm DNA defects are associated with abnormal semen parameters. While we have observed that tests of sperm DNA integrity are correlated with reproductive outcomes, use of these complementary biomarkers in the management of male infertility remains controversial. In this chapter, we review the etiologic factors associated with sperm DNA damage and the utility of these tests in clinical practice. We also review the treatment options for infertile men with sperm DNA damage.

More than one-third of American adults fail to achieve the 7–9 hours of sleep recommended by the American Academy of Sleep Medicine and the Sleep Research Society needed for optimal health and well-being. In addition to primary sleep disorders, such as sleep apnea, insomnia, and restless legs syndrome, many modern societal factors are also thought to contribute to chronic sleep deficiency, such as technology and work-related factors. Interruptions in the natural sleep–wake cycle can be associated with shift work and numerous chronic health conditions. A few studies have investigated the impact of nonstandard shift work on male reproductive health, and a compelling association between sleep and male urogenital health has been demonstrated. This chapter will review the literature on the effect of sleep and shift work on ED, LUTS, hypogonadism, male infertility, and how improved sleep quality can possibly improve common men’s health conditions.

Erectile dysfunction (ED) is a complex, multifactorial disease caused by multiple factors including difficulty with erection initiation, arterial filling, and occlusion to maintain turgor. It may be a manifestation of poor overall health or specific medical conditions. Treatment of underlying causative conditions may resolve ED. Medical treatment options for ED include oral medications, such as phosphodiesterase type-5 inhibitors, as well as locally acting agents and nonsurgical devices. Locally acting agents include alprostadil, which may be administered by intracavernosal injection, intraurethral suppository, or topical cream, as well as other intracavernosal injection agents. Vacuum erection devices are available. Surgical management options for ED include penile prosthesis placement or vascular surgery. Penile prostheses may be malleable or inflatable. Arterial vascular surgery has shown some efficacy in ideal candidates, but venous surgery is not recommended. Treatment options that are currently being studied and show promise include low-intensity extracorporeal shockwave therapy and regenerative treatments such as stem cells and platelet-rich plasma.

In this review we reflect on the many attempts highlighting key achievements in the field of in vitro spermatogenesis made so far. The research in this field is at a crucial juncture. The evolving technologies (like biofabricated 3D organoids, 3D bioprinting, microfluidics, or organ-on-a-chip) may offer excellent tools and in vitro testicular model systems to advance our understanding and bridge the existing knowledge gaps. Each of these culture systems offers unique advantages and may complement each other to address the common goal of achieving primate spermatogenesis in vitro. There are various possibilities and future scenarios for applying in vitro spermatogenesis as a tool for research and clinical applications in the future.

The quality of selected spermatozoa is crucial for the success of assisted reproduction. However, selecting the “best sperm” from an ejaculate or surgically retrieved sample remains challenging. In this chapter, we have reviewed conventional, advanced, and emerging sperm selection techniques, including the most up-to-date reliable evidence-based resources, with emphasis on sperm selection methods and clinical outcomes. Current selection techniques are manual and prone to subjective judgment or experience and effort of laboratory personnel. Despite the large number of publications, the available evidences are not sufficient to support any specific sperm selection technique. The only unanimous agreement thus far is that well-designed, large-scale, sufficiently powered randomized controlled studies are required to evaluate sperm selection techniques; these may include personalized sperm selection, machine learning, and robotics strategies aimed at improving outcomes of assisted reproduction.

Approximately one out of every 15 men will exhibit subfertility or infertility, and some data suggest the incidence of male infertility is increasing. While a number of factors can cause male infertility, there is strong and growing evidence that genetic factors contribute to a significant proportion of cases. Several significant genetic factors have long been recognized as clinically relevant causes of male infertility including Klinefelter syndrome, microdeletions of the Y chromosome, and cystic fibrosis transmembrane conductance regulator mutations. Since the discovery of these factors in the 1950s, 1970s, and 1980s respectively, there has been a relative dearth in the discovery of additional clinically relevant genetic factors underlying male infertility until recently. However, with the application of emerging genome-wide genetic approaches, along with the collaborative efforts from a growing number of groups, male infertility genetics has experienced a renaissance of sorts in the past decade with significant new discoveries being reported frequently over recent years. This chapter will briefly review the history of male infertility genetics as well as some of the more recent discoveries and efforts beyond gene screening approaches that have and will continue to advance the field.

Male factors significantly contribute to the issues faced by couples who are experiencing difficulties with conception. Management of the infertile male is complicated and based on a multitude of factors. Each couple is unique and has diverse issues, necessitating unique interventional approaches. Management can range from the optimization of lifestyle factors to treatment with surgery and medications. Several options exist in the medical optimization of the infertile, or subfertile male including treatment with gonadotropins (HCg, FSH), selective estrogen receptor modulators (i.e., clomiphene citrate), aromatase inhibitors (i.e., arimidex, letrozole), and prolactin altering agents (i.e., dostinex, bromocriptine). The use of the agents, both alone and in combination, is detailed in the current chapter.

In developed countries, infertility is generally estimated to occur in 15 percent of married couples, and male factors contribute to about 50 percent of the causes [1]. However, due to a lack of registration, shortage of resources, or other cultural, psychosocial, or religious constraints, the exact prevalence of infertility in developing countries is unknown or underestimated, especially with regard to male factors [2]. The rates are believed to be higher than in developed countries [3].