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UROGENITAL INFECTIONS AND DISTURBED MALE FERTILITY

URETHRITIS AND PROSTATITIS

Introduction

It is generally accepted that infections of the male urogenital tract are potentially correctable causes of male infertility [1 -3]. In this context, urethritis and prostatitis have been mentioned as male accessory gland infection by the WHO [2]. However, concrete data are lacking to confirm a negative influence of these diseases on sperm quality.

Urethritis

Infectious, sexually acquired urethritis may be caused by a variety of pathogens, most commonly by Chlamydia trachomatis, Ureaplasma urealyticum and Neisseria gonorrhoeae [4]. Non-infectious causes of urethritis include irritations due to allergic reactions, trauma and manipulations. Urethral discharge and bladder voiding difficulties are the predominant symptoms of acute urethritis.

Diagnosis and treatment

Diagnosis is based on the analysis of urethral smear and first-catch urine. Evidence of > 4 granulocytes per microscopic field (1000X) in urethral smear, or of 15 granulocytes per microscopic field (400X) in the smear of the sediment of 3 ml VB 1, has been considered pathognomonic [4]. In urethritis, defined by inflammatory discharge, an examination to detect fertility disturbances is not credible as the anterior urethra is full of infectious and inflammatory material, which hampers any useful semen analysis [5].

Due to contamination of the ejaculate with inflammatory material from the urethra, the impact of urethritis on semen quality and fertility is not really proven.

A negative influence of sexually transmitted microorganisms on sperm function is a matter of debate [1,6,7]. Urethral strictures and ejaculatory disturbances have been claimed to impair male fertility [2], as has the development of obstruction [8], either as normal urethral stricture or lesion in the posterior urethra in the area of the veromontanum, both of which can lead to ejaculatory disturbances [2].

Sexually transmitted disease treatment is standardized by the guidelines of the Centers of Disease Control and Prevention Atlanta, USA [9]. As the aetiology of acute urethritis is unknown in most cases at the time of diagnosis, empiric therapy is suggested, with one single dose of a fluoroquinolone, followed by a 2-week regimen of doxycycline. Treatment is effective both for gonococcal and (co-existing) chlamydial/ureaplasmal infections.

8.1.3 Prostatitis

Prostatitis represents the most common urological diagnosis in men under 50 years of age [10]. Traditionally, the diseasae has been classified into four clinical entities:

? acute bacterial prostatitis (ABP) and prostatic abscess as sequela of ABP,

? chronic bacterial prostatitis (???),

? non- or abacterial prostatitis (NBP) and

? prostatodynia (Pd).

To improve the definition and understanding of the prostatitis syndrome, a new classification system has been proposed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Washington DC, USA [10] (Table 13).

Table 13. New NIDDK classification of the prostatitis syndrome. Adapted from [10]

Microbiology

ABR ??? and more significantly, prostatic abscesses are important, but uncommon diseases. The most common aetiological causes of bacterial prostatitis are gram-negative pathogens, predominantly strains of Escherichia coli [11]. The role of gram-positive bacteria in bacterial prostatitis is controversial. Whereas enterococci may cause bacterial prostatitis and associated recurrent urinary tract infection (UTI), the significance of other gram-positive bacteria is doubtful [11], as is that of ? trachomatis and mycoplasma, particularly U. urealyticum, in chronic prostatitis [11-15]. Hidden bacteria may be aetiologically involved in patients with chronic idiopathic prostatitis after exclusion of typical bacterial infection [16].

Diagnosis

Evaluation of symptoms has to be done by means of standardized scores, especially the new National Institutes of Health symptom score [17]. Further procedures include laboratory diagnosis of ??? using the four-specimen test for bacterial localization [10,11]. Its principle is to perform sequential quantitative bacteriological cultures of the urethra, bladder urine and prostatic secretions both in EPS and urine after prostatic massage [12]. Simplified techniques compare bacterial and leukocyte counts in the urine before and after prostatic massage [18]. Screening of bladder voiding and imaging analysis of the prostate gland are clinical procedures that need to be integrated.

The key point for diagnosis is the demonstration of leukocytes in expressed prostatic secretions, urine after prostatic massage and/or ejaculate to differentiate between inflammatory and noninflammatory CPPS.

Ejaculate analysis

An ejaculate analysis (see above Andrological investigations and spermatology) helps clarify whether the prostate is part of a generalized infection of the accessory sex glands (male accessory gland infection) and provides information about the sperm quality. Furthermore, leukocyte analysis allows differentiation between inflammatory and noninflammatory CPPS.

Microbiological findings

After exclusion of urethritis and bladder infection, > 10⁶ peroxidase-positive white blood cells per ml_ ejaculate are indicative of an inflammatory process. In these cases, a culture should be performed for common urinary tract pathogens, particularly gram-negative bacteria.

A concentration of > 10³ cfu/mL of urinary tract pathogens in the ejaculate is regarded as significant bacteriospermia. Usually, various microorganisms are cultured from the genital tract of men seen in infertility clinics, with more than one strain of bacteria in most cases [1]. Furthermore, the time of sample taking influences the positive rate of microorganisms in semen and the frequency of isolation of different strains [19]. In patients with prostatitis symptoms without proven bacterial findings, cryptic infections, especially evidence of silent ? trachomatis or mycoplasma infections, remain a diagnostic challenge.

Despite modern DNA detection techniques the ideal diagnostic test for C. trachomatis in semen has not yet been established [14]. In contrast to the serological findings in women, antibody tests for ? trachomatis in seminal plasma are not indicative if no type-specific methods are used [14].

By analogy with mycoplasma, U. urealyticum seems only to be pathogenic in high concentrations (> 10³ cfu/ml ejaculate). No more than about 10% of samples analysed for ureaplasmas exceed this number [20]. Normal colonization of the urethra hampers the necessary clarification of 'mycoplasma-associated' urogenital infections using samples such as the ejaculate [15].

White blood cells

The clinical significance of an increased concentration of white blood cells (WBC) in the ejaculate is highly

controversial [21]. It seems to be generally accepted that only an increased number of leukocytes, particularly

neutrophilic granulocytes, and their products secreted into the seminal fluid, e.g. leukocyte elastase, is an

indicator of infection. The great majority of leukocytes are neutrophilic granulocytes, as suggested by the

specific staining of the peroxidase reaction (WHO; see above Andrological investigations and spermatology).

Although most authors consider leukocytospermia a sign of inflammation, it is not necessarily associated with

bacterial or viral infections [7].

This is in accordance with earlier findings that elevated leukocyte numbers are not a natural cause of male

infertility [22].

According to WHO classification, > 1 x 10⁶ WBC per ml_ are defined as leukocytospermia. Only two studies have analysed alterations of WBC in the ejaculate of patients with proven prostatitis [23,24]; both demonstrated a higher number of leukocytes than in men without inflammation (CPPS, type NIB).

Sperm quality

Deteriorative effects of chronic prostatitis on sperm density, motility and morphology are under debate [1]. All investigations to date have contradictory results and do not really confirm a decisive role of chronic prostatitis in alterations of these parameters (Table 14).

Table 14. Influence of chronic prostatitis on sperm density, motility and morphology. Adapted from [1]

EPS = expressed prostatic secretions

Seminal plasma alterations

Seminal plasma elastase is accepted as a biochemical indicator of granulocyte activity in the ejaculate

[1,28,29], with a suggested cutpoint of about 600 ng/mL [1]. Various cytokines are involved in inflammation and

may influence sperm function. In this respect, several studies investigated the association between interleukin

concentration, leukocytes and sperm function [30-32]. No differences were found among the subgroups

defined on the basis of progressive motility, percentage of abnormal forms and diagnosis of prostatitis. The

prostate seems to be the main site of origin of interleukin-6 (IL-6) in the seminal plasma. Although it is accepted

that cytokines, especially IL-6, must play an important role in the male accessory gland inflammatory process

[33], elevated cytokine levels do not depend on the number of leukocytes in EPS [34].

Glandular secretory dysfunction

Infections of the sex glands can impair their excretory function. Decreased quantities of citric acid,

phosphatase, fructose, zinc and alpha-glutamyltransferase activity have been evaluated as disturbed prostatic

secretory parameters [1] and reduced fructose concentration as an indicator of impaired vesicular function

[20,35].

Sperm antibodies

Serum antibodies to sperm antigens are not useful in the diagnosis of immune infertility. Early reports stated an association between increased levels of sperm antibodies in serum and NBP [36,37]. However, except in cases of suspected chlamydial infections [38], only a history of vasectomy seems to be predictive of sperm antibody formation [39].

Reactive oxygen species

It is generally accepted that ROS may be increased in chronic urogenital infections associated with increased

leukocyte numbers [40]. However, the biological significance in prostatitis remains unclear [1].

Therapy

Treatment of chronic prostatitis is normally targeted at relieving symptoms [10]. Andrologically, therapy for altered semen composition in male adnexitis is aimed at:

? reduction or eradication of microorganisms in prostatic secretions and semen

? normalization of inflammatory parameters, such as leukocytes and secretory parameters

? possible improvement of sperm parameters to counteract fertility impairment [41]

Treatment includes antibiotics, anti-inflammatory drugs, surgical procedures, normalization of urine flow, physical therapy and changes in general and sexual behaviour.

Only antibiotic therapy of ??? has proved to be efficacious in providing symptomatic relief, eradication of microorganisms and a decrease in cellular and humoral inflammatory parameters in urogenital secretions.

None of the other treatment schedules mentioned above have been evaluated in the same manner.

Although antibiotic procedures may provide improvement in sperm quality [41], therapy does not always enhance the probability of conception [1,42].

8.1.5 Conclusions

Urethritis and prostatitis are not always associated with male sub- or infertility. In many cases, basic ejaculate analysis does not reveal a link between accessory sex gland infection and impaired sperm characteristics. Furthermore, antibiotic treatment often only eradicates microorganisms; it has no positive effect on inflammatory alterations and/or cannot reverse functional deficits and anatomical dysfunctions.

References

Date: 2016-06-12; view: 307