Male Genital Infection and Infertility

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Male Genital Infection and Infertility

• Du Geon Moon, MD, Ph.D.
• Department of Urology
• Korea University College of Medicine

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Contents

• Text Controversy
• Pyospermia
• Microbiology
• Chlamydia
• Mycoplasmataceae
• Male accessory gland infection Infertility
• Urethritis, Prostatitis, Epididymitis, Orchitis

Male accessory gland infection by the WHO
1993
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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
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Whats 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
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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
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Do you think Male genital infections are related
to Infertility?
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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
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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
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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
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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
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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)

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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 2005553-57
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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 2005553-57
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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 2005553-57
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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 2005553-57
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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 2005553-57
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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)

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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

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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)

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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)

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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)

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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, Campbells Urology 9th
edition
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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
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Impact of Prostatitis IIIB (Prostatodynia) on
Ejaculate Parameters

• The first age-matched controlled study

European Urology 44 (2003) 546-548
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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

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Epididymitis

• Sexually active men lt35 yrs C. trachomatis or
  N. gonorrhoeae
• Men gt 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)

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Ejaculate analysis Impact on fertility

• Transient decrease of sperm count and forward
  motility

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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
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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

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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.

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Now, do you think Male genital infections are
related to Infertility?
Thank You for Attention !!