Neisseria gonorrhea is a gram-negative intracellular diplococcus, which is a common cause of urethritis [2]. Most infected men will be symptomatic, with only 10% of those infected being asymptomatic [2]. Ascending infection of the genital urinary tract is rare with the exception of the urethra. However, infection of the epididymis or testis may result in testis damage, epididymal obstruction, and significantly raised seminal leukocytes [2].

Chlamydia trachomatis (Ct) is the most common STI in industrialized countries with an estimated incidence of 92 million worldwide in 1999 [2, 10]. A systematic review in the UK reported a prevalence of 11% in men [11]. It is estimated that up to 50% of men infected may be asymptomatic, with only 5% of those diagnosed treated compared to 25% in women [2, 12, 13]. The result of these figures is that the infection is allowed to persist in the general population, enabling further spread and disease [3, 4]. In addition a recent study has suggested that early diagnosis and treatment may be associated with higher reinfection rates; the authors further add that the only viable option for long-term eradication is the development of a vaccine [14].

C. trachomatis (Ct) is associated with significant genital pathology and may be a cause of urethritis, epididymitis, orchitis, and prostatitis [2, 4]. There remains controversy as to whether Ct causes prostatitis [2, 4]. Semen may be contaminated by passage through the urethra infected with Ct [4]. However, several studies have now detected Ct in up to 30% of prostate biopsies where there was no urethral infection [15–18].

The role of Ct in infertility is also controversial. C. trachomatis attaches to sperm in vitro resulting in an increase in ROS and caspase-mediated apoptosis [4]. This interaction may result in a reduction in sperm motility and sperm density [2, 4]. This has been supported by a large number of studies, which have revealed that Ct is associated with a reduction in:

C. trachomatis has also been shown to be associated with an increase in DNA fragmentation, the production of anti-sperm antibodies (ASA), reduction in α(alpha)-glucosidase, and an increase in leukocytes [2, 3, 26, 27]. α(alpha)-glucosidase is a marker of epididymal function. In addition, coinfection with Mycoplasma resulted in a 3.2-fold greater incidence of DNA fragmentation in a study by Gallegos et al. [28]. A different study of men with at least 6 months of chronic prostatitis-related symptoms and coinfection with human papillomavirus (HPV) resulted in a significant reduction in motility, normal morphology, and an increase in proportion with subfertility [27]. Other studies have found none of the alterations described [4, 29–35]. However, this may have been due to diagnostic difficulties with Ct [2].

Genital ureaplasma (U. urealyticulum and U. parvum) and genital mycoplasma (M. genitalalium and M. hominis) are natural inhabitants of the male urethra [36]. They may contaminate semen during ejaculation. However, only U. urealyticulum (UU) and M. hominis are pathogenic in humans [2, 36].

U. urealyticulum is a significant cause of urethritis. Its presence in semen was first described by Gnarpe and Friberg when they demonstrated a higher prevalence in the semen of infertile men (76%) compared with fertile men (19%) [37, 38]. U. urealyticulum attaches to the head and mid-piece of spermatozoa, reducing motility and increasing ROS and DNA damage [2, 39]. Overall, studies have also demonstrated that UU is associated with semen with increased viscosity and lower pH [39]. Treatment of UU has, in some studies, resulted in improved motility and pregnancy rates; however, this finding has not been uniform [40–42].

The herpes group of viruses consist of:

In a study by Bezold et al. [26], which reviewed the prevalence of STIs in asymptomatic infertile males, herpes simplex viruses were the most frequent with CMV most common. All the STIs studied were associated with a significant reduction in motility and total sperm count; there was a nonsignificant trend toward a reduction in sperm density [2, 26, 43]. HSV was the only STI associated with a significant reduction in density, citrate, and α(alpha)-glucosidase [2, 26, 43]. Citrate is a marker of prostate function. This suggests that HSV may also have an adverse effect on prostate and epididymal function [26]. HSV is also implicated in raised levels of ROS and leukocytospermia [2, 43].

HPV has a well-established role in the development of genital disease in both sexes [2]. In a study of 104 men attending an infertility clinic, 41% had seminal HPV [44]. In another study of 185 men with azoospermia undergoing testis biopsy, 6.5% had HPV isolated compared with 0% of normal controls [45]. However, each of the patients had other possible causes for their infertility [45]. This would suggest a possible role for HPV in the etiology of infertility. A systematic review, including 9 studies evaluating the effects of HPV on semen analysis, demonstrated a reduction in motility (8 studies) and sperm count (9 studies) [2, 46, 47]. The effects on morphology are a more mixed picture [2, 46, 47].

Human immunodeficiency virus (HIV) is a cause of significant morbidity worldwide. Early infection is not usually associated with semen abnormalities; however, progression to acquired immunodeficiency syndrome (AIDS) is associated with impaired sperm density, morphology, motility, and semen viscosity [2]. There is also an increased level of leukocytospermia [2, 43]. HIV is also associated with symptomatic androgen deficiency [2]. The prevalence increases with progression to AIDS and with the clinical status of the disease [3]. The advent of highly active antiretrovirals (HAART) has reduced the prevalence dramatically [3]. However, it is unclear if these effects on fertility are due to the virus or to the use of antiretrovirals [2, 3].

Mumps is a contagious RNA virus belonging to the Paramyxoviridae family [7]. Prior to the introduction of a vaccine in the 1960s, it commonly affected children between the ages of 5–7 years with a global prevalence of 290 cases per year per 100,000 population between 1977 and 1985 [7]. Following the introduction of the vaccine, the incidence fell by a reported 99% in the USA [7]. Unfortunately, there has been a recent resurgence in the virus, which started in 2004 due to sustained negative media coverage about the vaccine [7]. This resulted in a reduction in vaccine uptake from 91 to 55% in some urban areas of the UK. This resurgence in the virus has mainly affected adolescents and young adults aged 15–25 years [7].

The effect on male fertility is not completely clear. There is direct infection of the seminiferous tubules with resultant infiltration of inflammatory markers and necrosis of the tubules [3, 7]. This may lead to fibrosis and testicular atrophy [3, 7]. Direct testicular damage may also result in a reduction in serum testosterone and an increase in gonadotrophins [3, 7]. However, there is conflicting evidence about the effect on testosterone and gonadotrophins [7]. Abnormal spermatogenesis has been reported in up to 50% for up to 3 months post-recovery [7]. Abnormal sperm count, motility, and morphology have also been reported [7].

Subfertility is reported in 13% and may occur without testis atrophy [7]. Infertility is rare [7].

See Table 6.3 for other organisms that cause infections [2, 3].

The testes are immunologically sequestered organs [2]. This is achieved through Sertoli cells’ tight linkage, which creates a blood–testis barrier [2]. Several authors have described the constituents of the normal genitourinary tract. The epithelial lining of the prostate, seminal vesicles, and epididymis contain mainly lymphocytes; however, the testes do not contain any lymphocytes [2]. An abnormal concentration of leukocytes (>1 × 10⁶ WBCs/mL of semen) in the semen (leukocytospermia) may indicate a pathological process contributing to infertility (Table 6.4) [2]. The most common leukocytes found in semen are granulocyes [2].

Several studies have found that infertile men have a raised incidence of leukocytopspermia compared with their fertile counterparts [48–58]. In addition, leukocytospermia is associated with a significant reduction in sperm total numbers, motility, normal forms, and seminal fructose [26, 48–58]. Fructose is a marker of seminal vesicle function. These findings have not been replicated in all studies [59]. Leukocytospermia has also been implicated in a reduction in sperm penetration assays and pregnancy outcomes [60, 61].

Oxidative stress is a pathophysiological process mediated by oxygen and oxygen derivatives called reactive oxygen species (ROS) [2]. ROS are part of normal cellular responses to destroy toxins such as infectious agents [43]. The human body has several strategies for protecting itself from damage that may be induced by ROS [43]. ROS injury occurs when these strategies are overwhelmed [43]. ROS-mediated sperm injury may be implicated in 30–80% of cases of idiopathic infertility [2, 3, 6, 43, 62]. Elevated ROS levels have been demonstrated in the semen of 25–40% of infertile men [63, 64]; this rises to 90% in men with spinal cord injury (SCI) [65, 66].