male genital infection and infertility du geon moon, md, ph.d. department of urology korea...
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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 th
e 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
ControversyEvident 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 FertilityPOSITIVE Infertile couples tend to have greater concentrations of WBCs t
han 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 t
he 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 sem
en report decreased fertility rates (Tomlinson, 1993)
Campbell-Walsh Urology 9th edition
PyospermiaS/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 PyospermiaIf 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 epidid
ymal 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
Bacterial adherence to spermatozoa Bacterial hitch hikers (Eley A, 2001) Explanation of disease spread
C. trachomatis elementary bodies decline in sperm mortility (Hosseinz
adeh S, 2001) Premature sperm death
Attachment of green fluorescent C. trachomatis elementary bodies to humen sperm
Lancet Infect Dis 2005;5:53-57
Most in-vitro studies concentrated on the effect of the bacterium on sperm function directly
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 c
ells via CD14 in seminal plasma & on spermatozoa
Reactive oxygen species (ROS) decrease sperm mortility disrupt sperm function by peroxida
tion
Apoptosis ROS, act as molecular mediators o
f apoptosis
Lancet Infect Dis 2005;5:53-57
II. Mycoplasmataceae
Include Mycoplasma and Ureaplasma : Gram's stain (-)
Mycoplasma hominis and Ureaplasma urealyticumAss.with nongonococcal urethritis in humans
U. urealyticum attacks spermatozoa directlyAttachment on head, midpiece of sperm by EM (Gnarpe, 1972)Attachment on sperm decrease sperm quality (Grossgebauer, 19
84)
U. urealyticum elevated levels of leukocyte-derived ROS
damage sperm by lipid peroxidation (Potts, 2000)
Recent Evidence of MycoplasmataceaeM. 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, 200
4) 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 di
stal 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 infertilitySexually acquired urethritis Neisseria gonorrhoeae Chlamydia trachomatis Ureaplasma urealyticum
Negative influence is under debatePast infection with N. gonorrhoeae associated with leukocytospermia (Trum, 1998)
Impair fertility Urethral stricture & ejaculatory disturbance (WHO 1993) Urethral obstruction & ejaculatory disturbance (Purv
is 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”
Krieger et al, 1999, Campbell’s Urology 9th edition
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
Chronic pelvic pain syndrome affect the acrosomal reaction in human spermatozoa
Sperm membrane for normal sperm functionGenital 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 spermiogra
m 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 thr
ough prostasome function
Acrosomal function in chronic prostatitis Balance between ROS and antioxidant capacity in semen plays c
ritical role in the pathophysiology of genital tract inflammations and their impact on sperm functions and fertilization
EpididymitisSexually 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 tub
ules by large smooth muscle cells (SMCs) Increased mechanical forces from the obstruction activate the differ
entiation 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 transportatio
n (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 analysisLeukocytic exudate inside and outside the seminiferous tubules resulting in tubular sclerosis
Acute epididymo-orchitis, transient decrease of sperm count and forward motility (Dieme
r & 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 MessagesUnlike 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 !!