Male Genital Infection
and Infertility
Du Geon Moon, MD, Ph.D.
Department of Urology
Korea University College of Medicine
Contents
Text & Controversy
Pyospermia
Microbiology

Chlamydia

Mycoplasmataceae
Male accessory gland infection & Infertility

Urethritis, Prostatitis, Epididymitis, Orchitis*
* Male accessory gland infection by the WHO [1993]
EAU Guidelines on Male Infertility
One of the potentially correctable causes of male
infertility is symptomatic and asymptomatic infection of
the male urogenital tract.
European Urology 48 (2005) 703-711
What’s on Text?
Components of the History in
the Evaluation of Infertile Male

Past Medical History
 Urinary infections
 STD
 Viral orchitis
 Epididymitis
 Tuberculosis
Classification of Male Infertility
by Criteria of Semen Analysis
 Azoospermia
 Spermatogenic
abnormalities
:
Viral orchitis
 Asthenospermia
 Genital tract infection
Campbell-Walsh Urology 9th edition
Controversy
Evident infertility


Male accessory organ destruction
Seminal tract obstruction
Lack of evidence for negative influence on sperm quality

Basic ejaculate analysis does not reveal a link between
accessory gland infection and impaired sperm characteristics
Antibiotic treatment





symptomatic relief, eradicates micro-organisms
no positive effect on inflammatory alterations
cannot reverse functional deficits and anatomical dysfunctions
may provide improvement in sperm quality
not always enhance the probability of conception
Campbell-Walsh Urology 9th edition
Do you think Male genital infections
are related to Infertility?
Pyospermia, Infection and Fertility
POSITIVE

Infertile couples tend to have greater concentrations of WBCs
than fertile populations (Wolff & Anderson, 1988)

Infection and infertility have been associated with pyospermia
(Caldamone, 1980; Maruyama, 1985)
NEGATIVE

Presence of bacteria in semen has not always correlated with
the presence of pyospermia (Rodin, 2003)

Many patients of pyospermia do not have genital tract infections

Not all studies of patients with increased leukocytes in the
semen report decreased fertility rates (Tomlinson, 1993)
Campbell-Walsh Urology 9th edition
Pyospermia
S/A reports that list numbers or conc. of WBCs

should be viewed with skepticism
Immature germ cells (spermatocytes) and leukocytes



appear similar under wet mount microscopy
known as round cells
cannot usually be differentiated without special stain
Increased numbers of round cells


should list as round cells unless special stains
true pyospermia: 1/3, spermatocytes: 2/3(Sigman & Lopes, 1993)
WBC staining of semen


not generally used during semen analysis
more than 10 to 15 round cells/HPF or 1 million round cells/mL
Campbell-Walsh Urology 9th edition
Management of Pyospermia
If the majority are WBCs and  1 million cells/mL



considered abnormal
possible genital tract infection or inflammation
should be evaluated for a genital tract infection
Absence of infection




anti-inflammatory medication
empirical antibiotic therapy
frequent ejaculations
prostatic massage
Lack of proven efficacy (Yanushpolsky, 1995)
Semen processing to remove the WBCs

combined with IUI or IVF
Campbell-Walsh Urology 9th edition
Microbiology (semen culture)
Human semen culture


Many aerobic and anaerobics (Upadhyaya, 1984)
Mycoplasma (Naessens, 1986)
Effects of seminal bacteria on fertility


may be spermicidal (Paulson, 1977)
no consistent effect on fertility (Berger, 1982)
Routine genital tract cultures are not indicated

clinical symptoms (-) or documented pyospermia(-)
Culture(+) genital infection with clinical symptoms

appropriate treatment
Campbell-Walsh Urology 9th edition
I. Chlamydia trachomatis
Obligate intracellular bacterium




One of the most common STD
Up to 50% of infected may be asymptomatic
Cause of nongonococcal urethritis & epididymitis
Those with symptom, urethritis is most common
Can C. trachomatis directly damage sperm?


The effect on male infertility is unclear and controversial.
Cultured from semen, prostatic secretions, urine (Thompson &
Washington, 1983)
Past infection in men, in-vivo
Correlation of serological markers with infertility
status or semen quality
Semen quality is not different from uninfected
controls (Ness RB, 1997)

not seem to affect semen parameters in the absence of
epididymal obstruction
Independent association between infertility and
chlamydial IgG antibodies (Idahl A, 2004)
Lancet Infect Dis 2005;5:53-57
Ongoing infection in men, in-vivo
Obvious ethical and technical difficulties
Unaffected by the bacterium


Semen quality (Hosseinzadeh S, 2004)
Key aspects of sperm function (Vigil P, 2002)
Chlamydia (+) men

significant reduction in sperm acrosomal reaction
(Jungwirth A, 2003)
Lancet Infect Dis 2005;5:53-57
C. trachomatis infection, in-vitro
Most in-vitro studies concentrated on
the effect of the bacterium on sperm function directly
Bacterial adherence to spermatozoa


Bacterial hitch hikers (Eley A, 2001)
Explanation of disease spread
C. trachomatis elementary bodies


decline in sperm mortility
(Hosseinzadeh S, 2001)
Premature sperm death
Attachment of green fluorescent
C. trachomatis elementary
bodies to humen sperm
Lancet Infect Dis 2005;5:53-57
C trachomatis lipopolysaccharide
Primary cause of spermatozoa death


premature sperm death (Hosseinzadeh S, 2003)
same as female genital tract
Most spermicidal in human beings


65% mortality in spermatozoa (0.1ug/mL, 1hr)
500 times more active than E. coli
Lancet Infect Dis 2005;5:53-57
Proposed hypothesis on Future research
CD14
lipopolysaccharide interacts with
cells via CD14 in seminal plasma
& on spermatozoa
Reactive oxygen species (ROS)


decrease sperm mortility
disrupt sperm function by
peroxidation
Apoptosis

ROS, act as molecular mediators
of apoptosis
Lancet Infect Dis 2005;5:53-57
II. Mycoplasmataceae
Include Mycoplasma and Ureaplasma : Gram's stain (-)
Mycoplasma hominis and Ureaplasma urealyticum
 Ass.with nongonococcal urethritis in humans
U. urealyticum attacks spermatozoa directly
 Attachment
on head, midpiece of sperm by EM (Gnarpe, 1972)
 Attachment on sperm decrease sperm quality (Grossgebauer,
1984)
U. urealyticum
 elevated
levels of leukocyte-derived ROS
 damage sperm by lipid peroxidation (Potts, 2000)
Recent Evidence of Mycoplasmataceae
M. hominis and U. urealyticum in semen culture (+)

represents colonization and not infection

no evidence of inflammatory reactions (Pannekoek, 2000)
U. urealyticum

decrease motility and membrane changes (Nunez, 1998)

no differences in semen parameters between culture (+) and (-)
(Busolo, 1984; Soffer, 1990; Andrade-Rocha, 2003)
M. genitalium

clearly pathogenic, a common cause of urethritis (Jensen,
2004)

Lack of studies regarding the role on male infertility
Test for M. genitalium & C. trachomatis
Clinical evidence of inflammatory or infectious process
Urine culture

should be in patients with evidence of cystitis or urethritis
Semen culture


frequently yield low concentrations of multiple organisms for
distal urethral contamination.
Antibacterial skin preparation and voiding before ejaculation

decreases the incidence of false (+) (Kim & Goldstein, 1999)
First-void urine PCR


higher sensitivity than culture
less uncomfortable than urethral swabs (Maeda, 2004)
Urethritis - Impact on infertility
Sexually acquired urethritis



Neisseria gonorrhoeae
Chlamydia trachomatis
Ureaplasma urealyticum
Negative influence is under debate
Past infection with N. gonorrhoeae

associated with leukocytospermia (Trum, 1998)
Impair fertility


Urethral stricture & ejaculatory disturbance (WHO 1993)
Urethral obstruction & ejaculatory disturbance
(Purvis and Christiansen, 1995)
“Prostatitis is associated with Infertility”
5-12% of infertile man

history of past infection (Dohle, 2003)
12% of abnormal semen quality

male genital infection (Everaert, 2003)
Bacteria itself can produce IL-8

deleterious effect on fertility (Depuydt, 1996)
Chlamydia, E. coli

decrease acrosomal reaction (Kohn, 1998)
“Prostatitis is not associated with Infertility”
Nonbacterial prostatitis/prostatodynia vs normal control
 No difference in density, motility, morphology (Weidner, 1999)
Nonbacterial prostatitis (Ludwig, 2003)
 leukocytospermia(+)
 no effect on density, motility, morphology
Krieger et al, 1999, Campbell’s Urology 9th edition
Chronic pelvic pain syndrome affect the
acrosomal reaction in human spermatozoa
Sperm membrane for normal sperm function
Genital tract infection, reactive oxygen species:


responsible for damage of sperm via sperm membrane function
resulting in loss of sperm motility, compromised fertility
World J Urol (2006) 24: 39-44
Impact of Prostatitis IIIB (Prostatodynia)
on Ejaculate Parameters
The first age-matched controlled study
European Urology 44 (2003) 546-548
Summary of Prostatitis
Fertility and prostatitis relations remain obscure
Limitations of current studies on semen quality

exact classification criteria, control groups, complete
spermiogram data
Reduced fructose conc. in prostatitis NIH IIIB


impaired secretion of the seminal vesicles, somatic factor
reduction of motility, indirectly linked to forward sperm motility
through prostasome function
Acrosomal function in chronic prostatitis

Balance between ROS and antioxidant capacity in semen plays
critical role in the pathophysiology of genital tract inflammations
and their impact on sperm functions and fertilization
Epididymitis
Sexually active men <35 yrs : C. trachomatis or N. gonorrhoeae
Men > 35 yrs : Gram-negative enteric organism
Pathophysiology of epididymal duct stenosis, obstruction



Wall thickening and altered contractility (Pelliccione, 2004)
replacement of spindle-shaped myoid cells in normal contractile
tubules by large smooth muscle cells (SMCs)
Increased mechanical forces from the obstruction activate the
differentiation of myoid cells into SMCs
Reduction of sperm count, eventual azoospermia


Rare azoospermia after initial 14-day epididymitis (Weidner, 1990)
Initial antibiotic therapy prevent worse effect on sperm
transportation (Purvis & Christiansen, 1995)
Ejaculate analysis & Impact on fertility
Transient decrease of sperm count and forward motility
Tb epididymitis
Vasal infection in 20-41%
Asymtomatic inflammation of epididymis and vas
deference

eventual epididymal & vasal obstruction
Semen analysis


decrease semen volume : 33%
oligospermia : 11%
Ko et al. Korea J Urol 1994
Orchitis - Ejaculate analysis
Leukocytic exudate inside and outside the
seminiferous tubules resulting in tubular sclerosis
Acute epididymo-orchitis,


transient decrease of sperm count and forward motility
(Diemer & Desjardins, 1999)
Acute obstructive azoospermia is rare complication
Chronic inflammation of seminiferous tubules



disrupt normal spermatogenesis, alterations in sperm number
and quality (Purvis & Christiansen, 1995)
spermatogenic arrest (Weidner & Krause, 1999)
testicular atrophy and azoospermia in mumps-orchitis
Take Home Messages
Unlike female sterility, the significance of genital infections for male
infertility is still debating.
Male accessory glands are reservoirs for organisms(C. trachomatis
and M. genitalium) hence increase transmission to the partners.
Cautious use of leukospermia or bacteriospermia as parameters for
glandular infection. Instead of classical parameters, e.g. the
determination of microorganisms and/or counting leukocytes,
functional parameters such as cytokines, ROS or other indicators of
inflammation should be estimated if available.
Proper antibiotic treatment and empirical treatment are important
for eradicating microorganism, symptom improvement, prevention
of transmission to others and decrease of potential complications,
e.g. stricture, obstruction or atrophy.
Now, do you think Male genital
infections are related to Infertility?
Thank You for Attention !!