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Review
. 2017 May 12;114(19):339-346.
doi: 10.3238/arztebl.2017.0339.

Urogenital Infection as a Risk Factor for Male Infertility

Hans-Christian Schuppe  1 , Adrian Pilatz, Hamid Hossain, Thorsten Diemer, Florian Wagenlehner, Wolfgang Weidner
Affiliations
Review

Urogenital Infection as a Risk Factor for Male Infertility

Hans-Christian Schuppe et al. Dtsch Arztebl Int. .

Abstract

Background: Infections of the genital tract are considered common causes of male fertility disorders, with a prevalence of 6-10%. Most of the affected men are asymptomatic. The diagnostic evaluation is based mainly on laboratory testing. Inconsistent diagnostic criteria have been applied to date, and this may explain the controversial debate about the role of infection and inflammation in the genital tract as a cause of infertility. The risk of an irreversible fertility disorder should not be underestimated.

Methods: This review is based on pertinent publications retrieved by a selective literature search in PubMed, including guidelines from Germany and abroad and systematic review articles.

Results: The main causes of inflammatory disease of the male genital tract are ascending sexually transmitted infections (STIs) and uropathogens. Chronic prostatitis has no more than a limited influence on ejaculate variables. By contrast, approximately 10% of men who have had acute epididymitis develop persistent azoospermia thereafter, and 30% have oligozoospermia. Obstruction of the excurrent ducts can ensue, as can post-infectious disturbances of spermatogenesis. The differential diagnostic evaluation includes the determination of testicular volumes, hormone concentrations, and ejaculate variables. Epidemiological data are lacking with regard to infertility after primary orchitis of infectious origin; however, up to 25% of testicular biopsies obtained from infertile men reveal focal inflammatory reactions. Multiple studies have suggested a deleterious effect of leukocytes and inflammatory mediators on sperm para - meters. On the other hand, the clinical significance of bacteriospermia remains unclear.

Conclusion: Any suspicion of an infectious or inflammatory disease in the male genital tract should prompt a systematic diagnostic evaluation and appropriate treatment. For patients with obstructive azoospermia, the etiology and site of the obstruction determine the surgical approach to be taken. In the near future, the elucidation of underlying pathophysiological mechanisms and the identification of suitable biomarkers may enable new strategies for conservative treatment.

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Figures

Figure 1
Figure 1
Fractionated sampling and analysis of urogenital secretions: Combination of 2-glass test and subsequent semen analysis (modified according to [e8]) *1 approx. 5 mL; *2 10 x higher bacterial count (CFU/mL) in post-massage (exprimate) urine versus first void urine; bacteriospermia *3facultative; *4 = 15 granulocytes/ high-power microscopic field in sediment (magnification x 400) → urethritis; post-massage (exprimate) urine =10/µL → prostatitis; ejaculate: >106/mL (peroxidase-positive leukocytes; no reference ranges available for macrophages, lymphocytes) CFU, colony-forming units; PCR, polymerase chain reaction; STI, sexually transmitted infection
Figure 2
Figure 2
Algorithm for the management of urogenital infections/inflammation in men with infertility *1 In case of isolated findings: Confirmation by follow-up examinations; in case of increased levels of inflammatory markers in the ejaculate: advanced diagnostic assessment (2-glass test) *2 Bacterial count in the ejaculate >103 CFU/mL, for urine samples see Figure 1 *3 Always antimicrobial therapy with co-treatment of partner according to guideline recommendations; cycle-adapted administration/contraception to prevent negative effects on early pregnancy (37, 38, e46) *4 In case of symptom-free patients with positive inflammatory markers in the ejaculate (see Table 2): Treatment only in case of significant bacterial count and positive confirmatory test (see above; [e1, e2]); treatment duration 2 to 4 weeks, subject to pathogen/indication and medication (with the exemption of azithromycin; WARNING: current warnings for fluoroquinolones [e57]; tentative antibiotic treatment, e.g. in patients with non-significant bacterial count/isolated signs of inflammation, is not indicated). Because of the risk of negative effects on spermatogenesis/sperm function: Follow-up ejaculate testing or use of ART only after a treatment-free interval (several weeks) (cf. [22]). *5 In case of sign of inflammation in the ejaculate (see Table 2), primarily without pathogen detection/after antibiotic treatment: Administration of nonsteroidal anti-inflammatory drugs (NSAIDs; e.g. diclofenac [100–150 mg/d] or equivalent medications, including cyclooxygenase-2 inhibitors; treatment duration 3–6 weeks); mast cell blocker, if needed; subsequent adjuvant treatment with antioxidants (e.g. vitamin E) optional. ART, assisted reproductive technology (with TESE: in-vitro fertilization with intracytoplasmic sperm injection; IVF/ICSI); CESI, chronic epididymitis symptom index (e58); CPSI, chronic prostatitis symptom index (e40); CFU, colony-forming units; LUTS, lower urinary tract symptoms; NIH, National Institute of Health; STI, sexually transmitted infections; TESE, testicular sperm extraction; ↑, increased
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