Page 149 - Remedial Andrology

colonisation of the urethra hampers the significance of mycoplasma-associated urogenital infections, using
samples such as the ejaculate [1747].

A meta-analysis indicated that Ureaplasma parvum and Mycoplasma genitalium were not associated with
male infertility, but a significant relationship existed between U. urealyticum (OR: 3.03 95% CI: 1.02–8.99) and
Mycoplasma hominis (OR: 2.8; 95% CI: 0.93– 3.64) [1748].

The prevalence of human papilloma virus (HPV) in the semen ranges from 2 to 31% in the general population
and is higher in men with unexplained infertility (10-35,7%) [1749, 1750]. Recent systematic reviews have
reported an association between male infertility, poorer pregnancy outcomes and semen HPV positivity
[1751-1753]. However, data still needs to be prospectively validated to clearly define the clinical impact of
HPV infection in semen. Additionally, seminal presence of Herpes Simplex virus (HSV)-2 in infertile men may
be associated with lower sperm quality compared to that in HSV-negative infertile men [1738]. However, it is
unclear if anti-viral therapy improves fertility rates in these men.

10.4.4.2.3 White blood cells
The clinical significance of an increased concentration of leukocytes in the ejaculate is controversial [1754].
Although leukocytospermia is a sign of inflammation, it is not necessarily associated with bacterial or viral
infections, and therefore cannot be considered a reliable indicator [1755]. According to the WHO classification,
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leukocytospermia is defined as > 10 WBCs/mL. Only two studies have analysed alterations of WBCs in the
ejaculate of patients with proven prostatitis [1756, 1757]. Both studies found more leukocytes in men with
prostatitis compared to those without inflammation (CPPS, type NIH 3b). Furthermore, leukocytospermia
should be further confirmed by performing a peroxidase test on the semen. There is currently no evidence that
treatment of leukocytospermia alone without evidence of infective organisms improves conception rates [1758].

10.4.4.2.4 Sperm quality
The deleterious effects of chronic prostatitis (CP/CPPS) on sperm density, motility and morphology has been
demonstrated in a recent systematic review based on case-controlled studies [1759]. Both C. trachomatis
and Ureoplasma spp. can cause decreased sperm density, motility, altered morphology and increased
DNA damage. Data from a recent retrospective cross-sectional study showed that U. urealyticum was the
most frequent single pathogen in semen of asymptomatic infertile men; a positive semen culture was both
univariably (P < .001) and multi-variably (P = .04) associated with lower sperm concentration [1760]. Human
papilloma virus can also induce changes in sperm density, motility and DNA damage [1749, 1750]. Mycoplasma
spp. can cause decreased motility and development of antisperm antibodies [1738].

10.4.4.2.5 Seminal plasma alterations
Seminal plasma elastase is a biochemical indicator of polymorphonuclear lymphocyte activity in the ejaculate
[1737, 1761, 1762]. Various cytokines are involved in inflammation and can influence sperm function. Several
studies have investigated the association between interleukin (IL) concentration, leukocytes, and sperm
function through different pathways, but no correlations have been found [1763-1765].

The prostate is the main site of origin of IL-6 and IL-8 in the seminal plasma. Cytokines, especially IL-6, play an
important role in the male accessory gland inflammatory process [1766]. However, elevated cytokine levels do
not depend on the number of leukocytes in expressed prostatic secretion [1767].

10.4.4.2.6 Glandular secretory dysfunction
The secretory function of the prostate gland can be evaluated by measuring seminal plasma pH, citric acid,
or γ-glutamine transpeptidase levels; the seminal plasma concentrations of these factors are usually altered
during infection and inflammation. However, they are not recommended as diagnostic markers for MAGIs
[1768].

10.4.4.2.7 Reactive oxygen species
Reactive oxygen species may be increased in infertile patients with asymptomatic C. trachomatis and
M. hominis infection, with subsequent decrease in ROS upon antibiotic treatment. However, the levels of ROS
in infertile patients with asymptomatic C. trachomatis and M. hominis in the semen are low, making it difficult
to draw any firm conclusions [1769]. Chronic urogenital infections are also associated with increased leukocyte
numbers [1770]. However, their biological significance in prostatitis remains unclear [1737].

148 SEXUAL AND REPRODUCTIVE HEALTH - MARCH 2021