This bacterial infection is the most common among curable STIs in the United States, Europe, and Eastern Mediterranean as highlighted by the WHO (2008). Therefore, this bacterium has received the most attention from earlier studies regarding infertility. Infected males can suffer from asymptomatic infection of the urethra, epididymis, and prostate. This infection can result into urethritis which can become even more symptomatic in males compared to females (Parekattil and Agarwal 2012).

Looking strictly at sperm parameters with regard to C. trachomatis infection, results are variable. One study reported no change in sperm viability, morphology, and the percentage of motile spermatozoa (Kokab et al. 2012), while another showed no change in any of the sperm parameters (Vigil et al. 2002). However, some studies have reported a reduction in the percentage of progressively motile spermatozoa (Brookings et al. 2013; Kokab et al. 2012; Gallegos et al. 2008; Gdoura et al. 2001) as well as a decline in sperm viability and increase in abnormal morphology (Brookings et al. 2013; Cengiz et al. 1997) from semen samples positive for C. trachomatis. A recent study on the effects of C. trachomatis infection on male fertility status showed a decrease in sperm concentration (Rybar et al. 2012). Another study investigating chronic prostatitis as a result of C. trachomatis infection also showed lowered sperm concentrations, reduced motility, and increased morphological abnormalities (Mazzoli et al. 2010). When investigating semen from asymptomatic male patients, it has been found that the presence of deoxyribonucleic acid (DNA) of C. trachomatis in the semen was associated with reduced sperm concentration (Bezold et al. 2007).

Limited in vivo studies have investigated the effect of C. trachomatis on the male fertility status and have reported conflicting results. When utilizing a zona-free hamster oocyte penetration assay to analyze the acrosome reaction of male partners infected with C. trachomatis, results showed that semen quality and spermatozoa function were unaffected by the presence of the bacterium (Vigil et al. 2002). In contrast to the results of the above research, another study reported conflicting results by showing a decrease in acrosome activity in men suffering from C. trachomatis (Jungwirth et al. 2003; Eley et al. 2005)

The inconsistency in the results between different studies could be attributed to several reasons and can be influenced by the duration of infection and time of semen analysis. Regarding C. trachomatis, the timing of semen analysis following bacterial contact in the reproductive tract, methods of detections in the upper genital tract, and possible relevance of differential diagnosis would have an impact on the sperm parameters (Eley et al. 2005).

Several theories regarding the mechanisms behind the resultant compromised fertility in men suffering from chlamydial infection are inconsistent. When the infection reaches the epithelial cells, the initial response is the generation of interleukin-1 (IL-1), resulting in the stimulation of polymorphonuclear WBCs which subsequently secretes IL-8. The abnormally high concentration of WBCs in the semen sample induces leukocytospermia (Flint 2012). This in turn leads to the generation of reactive oxygen species (ROS) and subsequently oxidative stress (OS) which can affect sperm parameters (Comhaire 1999). Due to scanty cytoplasm in spermatozoa and low antioxidant activity, the spermatozoa are highly susceptible to OS and sperm membrane damage due to lipid peroxidation (Smith 2013). This can impair the acrosomal reaction and subsequently has a negative impact on male fertility (Monavari et al. 2013). The link between C. trachomatis and the generation of ROS is conceivable due to the presence of lipopolysaccharides on its surface (Matthews 1951; Hosseinzadeh and Pacey 2003). This compound is able to bind to the CD14 receptor situated on the spermatozoa membrane (Harris et al. 2001). Studies suggest that lipopolysaccharides induce excessive ROS production by spermatozoa; this is confirmed by the decreases seen in sperm motility and concentration in endotoxin-treated samples (Lee and Lee 2013; Urata et al. 2001).

An additional theory regarding the relationship between chlamydial infection and male infertility is the development of antisperm antibodies. The bacterium induces invasion of lymphocytes, macrophages, plasma cells, and eosinophils in response to the infection. The release of cytokines then stimulates the inflammatory cascade, invoking a humoral cell response of secretory IgA and circulatory IgM and IgG antibodies (Lee and Lee 2013). In infertile men, C. trachomatis antibodies, IgG and IgA, were shown to be associated with a negative impact on semen characteristics and pregnancy outcome (Idahl et al. 2010). Problems arise, when chlamydia IgG or IgA antibodies in semen do not reflect the bacterial presence in the genital tract because some routine antibody analysis are done by specific antibody detection tests instead of cultures, and can provide conflicting results (Parekattil and Agarwal 2012). Sometimes, a negative relation between chlamydial antibodies (IgA and IgG) and semen characteristics is difficult to establish (Eggert-Kruse et al. 1996).

Direct detection tests would be more effective in isolation of the bacteria and to understand its impact on sperm parameters for successful fertilization. During the event of capacitation, tyrosine phosphorylation of sperm proteins was observed to be associated with spermatozoa capacitation in vitro. Thus, C. trachomatis attachment to target cells could involve contact with host signal transduction pathways (Hosseinzadeh et al. 2000). Further, genitourinary infection of C. trachomatis has been found to be associated with an increase in sperm DNA fragmentation (Gallegos et al. 2008). Semen analysis positive for C. trachomatis revealed a significant loss of sperm mitochondrial potential and nonsignificant increase in sperm DNA fragmentation compared to C. trachomatis-negative semen samples (Sellami et al. 2014).

N. gonorrhoeae is a Gram-negative bacterium which infects both men and women. Based on the WHO estimates (2005), each year more than 82 million individuals are infected by this pathogen across the world. Despite its common prevalence, N. gonorrhoeae is least studied compared to other STI-causing microorganisms in relation to male infertility. It affects the male urethra, causing urethritis, and has also been found to interact with spermatozoa through its lipooligosaccharides. Gonococcal lipooligosaccharides are immunochemically similar to human glycosphingolipid antigens, which favor the gonococci to evade the host immune response during infection. The importance of the similarity was observed when there was an increased frequency of this structure in gonorrhea-positive males (Schneider et al. 1991). Gonococci attach to the spermatozoa by asialoglycoprotein receptor (ASGP-R) present on sperm and are subsequently transmitted to the female partner (Harvey et al. 2000). Prevalence of N. gonorrhoeae, as detected by the presence of its DNA in semen, has been found to be higher in infertile men (6.5 %) compared to fertile men (0 %) (Abusarah et al. 2013).

N. gonorrhoeae contributes to urethritis (Lee and Lee 2013) and chronic infections and, if left untreated, can cause complications in the epididymis. Additionally, epididymitis can largely affect the sperm concentration leading to oligospermia and azoospermia in cases of bilateral epididymitis or vas deferens occlusion (Ndowa and Lusti-Narasimhan 2012). The link between N. gonorrhoeae infection and male fertility is further supported by a cohort modeling Swedish study reporting a decline in secondary subfertility with the eradication of gonorrhea (Akre et al. 1999).

Two genital mycoplasmas, Mycoplasma hominis and Mycoplasma genitalium, are found in both male and female reproductive tracts (Gimenes et al. 2014). Although in men mycoplasmas were isolated about a decade ago, their exact role in the development of male infertility is still under debate (Maeda et al. 2004; Al-Sweih et al. 2012). Different studies have reported varying prevalence rates of mycoplasma infection based on the laboratory detection method of bacteria. When urine samples of patients with persistent or recurrent urethritis were examined, 41 % of the population was positive for M. genitalia (Wikstrom and Jensen 2006). In Tunisian infertile men, M. genitalium DNA was detected in 4.8 % of semen samples, while the detection for M. hominis DNA was 9.6 %. The prevalence of M. genitalium DNA was significantly higher in azoospermic semen samples compared to non-azoospermic. However, no association of M. genitalium and M. hominis was found attributing to the abnormal semen characteristics (concentration, motility, morphology, viability, volume, and leukocyte count) (Gdoura et al. 2008). Although the relation of mycoplasmas with male infertility is not clearly documented, attachment of M. genitalium to spermatozoa was observed. This attachment is of significant importance not only in transmitting the infection to the female partner but also in causing sperm agglutination, thereby rendering them immotile and ultimately resulting in male infertility (Svenstrup et al. 2003; Pellati et al. 2008). In another study, negative effects of M. hominis infection on semen viscosity, volume, sperm morphology, motility, and concentration have been documented (Zinzendorf et al. 2008). In vitro incubation of mycoplasmas with semen has shown significant reduction in sperm motility and morphology and increase in the higher rates of the acrosome reaction and capacitation. This means mycoplasma species can negatively impair the fertilizing capacity of spermatozoa (Rose and Scott 1994).

Ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) reside in the male urethra where they contaminate the semen at the time of ejaculation (Zeighami et al. 2009). The incidence of U. urealyticum infection in infertile men is variable, ranging from 5 to 42 % (Abusarah et al. 2013). A total of 18.3 % infertile Tunisian men were found positive for ureaplasmas, of which, the percentage of men infected with U. urealyticum was higher (15.4 %) compared to U. parvum (2.9 %) (Gdoura et al. 2001). In another study 27.6 % infertile men were found positive for U. urealyticum (Zinzendorf et al. 2008). The data on effects of ureaplasmas on semen parameters are conflicting. Some studies found no relation between the U. urealyticum infection and the quality of sperm parameters (Andrade-Rocha 2003), while others documented low sperm motility, reduced concentration, and morphology (Zeighami et al. 2009; Zinzendorf et al. 2008). Furthermore, in an animal study where rats were experimentally infected with U. urealyticum, remarkable change in spermatogenesis was observed. When these rats were allowed to mate, in 33 % of the cases, post-mating plug was not observed, while in the rest of the cases who mated successfully, offspring were significantly smaller compared to uninfected or control rats (Xu et al. 1997). In a later study, in vitro experiments on co-incubation of human and ram sperm with U. urealyticum revealed a dose-dependent decrease in viability and motility in human spermatozoa and only motility in ram spermatozoa compared to controls. The same study found time- and dose-dependent DNA damage both in human and ram spermatozoa, which suggests that ureaplasmas can affect quantitative (motility, concentration) as well as qualitative (DNA, morphology) sperm parameters (Reichart et al. 2000). Damage to quality of spermatozoa can have serious effects on the fertility of the couple as reduced pregnancy rates have been reported after embryo transfer in U. urealyticum-infected groups compared to normal (Montagut et al. 1991). Care must be taken while using ureaplasma-infected semen samples for assisted reproductive technology (ART) as semen washing procedures may not always remove the pathogens completely from the spermatozoa (Knox et al. 2003).

T. pallidum is most commonly acquired through close sexual contact and results in syphilis. Despite the curable nature of the disease, it remains a big challenge, infecting around 12 million people worldwide every year (Rodriguez-Cerdeira and Silami-Lopes 2012). This pathogen gets significant attention due to its link with HIV (human immunodeficiency virus) transmission (Spielmann et al. 2010). Although nothing much is documented on the role of T. pallidum and male infertility, complications of the disease can have a negative impact on fertility. One proposed indication regards the inflammation of the epididymis which can cause epididymal obstruction. In tertiary syphilis, gummatous lesions cause destruction of local tissue. If lesions occur in the testicles, the infection may have an impact on testicular function and therefore infertility. Effects of this pathogen are even more severe and drastic on pregnancy and the infant with evidence of 50 % abortions and stillbirths and more than 10 % infant mortality (Brookings et al. 2013). Therefore, during ART procedures it is imperative that both partners are screened for the pathogen and should be treated accordingly.

HIV is a lentivirus belonging to the subgroup of retrovirus that causes acquired immune deficiency syndrome (AIDS). The two types of this virus are known as HIV-1 and HIV-2. Despite similarities between both types of HIV, they differ in pathogenicity, infectivity, and prevalence. HIV-1 transmission is easy and rapid resulting in vast majority of infections worldwide (Weiss 1993; Gimenes et al. 2014). Common routes of HIV-1 transmission include blood, breast milk, and vaginal as well as seminal fluid. There have been some studies validating the viral impact on male infertility. The concept of how viral infections could weaken the male genital function is by direct invasion of the male genital tract cells or indirect inflammatory or immunological responses. Semen parameters of men with asymptomatic disease can be in normal range (van Leeuwen et al. 2008); nevertheless, with disease progression it can negatively affect sperm motility, morphology (Bujan et al. 2007; Pavili et al. 2010), and concentration (Crittenden et al. 1992; Nicopoullos et al. 2004).

This virus is also known to cause secondary hypogonadism resulting in low testosterone levels. Reduced concentration of the androgen would have an impact on spermatogenesis reducing the sperm count (Crum-Cianflone et al. 2007). The viral infection resides in the germ cells of the testes, and an extended duration of infection is associated with germ cell loss (Shevchuk et al. 1999). In one study, a positive correlation between CD4+ count and sperm concentration as well as motility together with a negative correlation with normal sperm morphology has been documented as reviewed by Brookings et al. (2013).

With the introduction of highly active antiretroviral therapy (HAART) for HIV-positive patients, survival rate and life expectancy have tremendously improved (Sabin 2013). HAART has given a new direction of investigation because changes in semen of HIV-positive men currently found are largely attributed to this therapy (Kehl et al. 2011). In addition to the changes in semen as discussed earlier, sperm mitochondrial toxicity and high aneuploidy have also been reported in HIV-positive men (Pavili et al. 2010). When spermatozoa from healthy men were incubated in vitro with different concentrations of HAART agents, decreases in sperm motility and mitochondrial potential and an increase in acrosome reaction were observed at higher doses of saquinavir (a protease inhibitor used in HAART) (Ahmad et al. 2011).

ART are the best options for HIV-positive men who wish to father a child. The use of HAART decreases the viral load in semen; further sperm washing procedures have improved the utility of semen from HIV-positive men in intrauterine insemination or in vitro fertilization (IVF). Washed spermatozoa from HIV-positive men have been used in assisted reproduction and have resulted in successful live births without HIV transmission to mother or the child (Nicopoullos et al. 2004).

HPV is considered the most common sexually transmitted viral disease among young men and women. Out of 100 identified genotypes, 40–50 are found to infect the genital tract. High-risk genotypes 16, 18, 31, and 45 are associated with malignancy of the squamous cells localized in the genital tract and anus (Medicine 2013). Identification of HPV through polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) in semen cultures revealed reduced sperm motility (Foresta et al. 2010) and sperm concentration (Bezold et al. 2007). In contrast, a study of 308 HPV-positive males showed that the infection does not correlate with an impact on the sperm parameters (Schillaci et al. 2013). In addition, the gene-targeting region of HPV in sperm reports no change in hyperactivation of spermatozoa, which proposes preservation of the fertilizing capacity of spermatozoa (Lee et al. 2002). In view of published data, a clear link between HPV and male infertility remains inconclusive (Fr 2008). Nevertheless, a significant increase in the abortion rate was observed in couples where the semen sample of the male was positive for viral DNA. Similarly, a recent study reported a significant increase in pregnancy loss after IVF in couples where semen samples were positive for viral DNA (Perino et al. 2011). Therefore, HPV infection should be dealt with seriously in all couples seeking fertility treatment.

Herpes simplex virus contains two genital virus strains: HSV-1 and HSV-2. HSV-1 is commonly involved in oral and occasionally in genital infections, but HSV-2 is the most common etiology of genital herpes (Wald et al. 2000). Prevalence of both HSV strains is quite variable ranging from 2 to 50 % as detected in semen of asymptomatic men, but no association to change in sperm parameters or male infertility was established (Neofytou et al. 2009). In contrast, reduced sperm motility and concentration was attributed to the presence of HSV DNA detected through nested PCR in 49.5 % of semen samples from infertile men compared to controls (Kapranos et al. 2003). Further, decline in sperm concentration, higher rates of apoptosis, and disrupted spermatogenesis were observed in patients infected with HSV.

An animal study utilized transgenic mice as subjects to investigate the molecular impact of HSV on spermatogenesis. The expression of the pathogen’s thymidine kinase in the testis correlated with sperm structural abnormalities and defects in spermatogenesis (Braun et al. 1990). This was substantiated in 2009, when results confirmed the correlation of the thymidine kinase activity to the loss of germ cells in the testes (Cai et al. 2009). Apparently, the published data accord the negative effects of HSV on sperm parameters and male fertility.