72 I.3 Male Factor Fertility Problems I.3.13 Infection/Inflammation of the Accessory Sex Glands F. Comhaire, A. Mahmoud Key Messages Infection causes inflammation characterized by the ■ Infection of the accessory sex glands is diag- classical symptoms such as pain, swelling, and im- nosed in a variable proportion of cases with paired function. The latter is responsible for deficient abnormal semen quality depending on secretion of minerals, enzymes and fluids that are regional differences. needed for optimal function and transport of the sper- ■ The influence of infection/inflammation of the matozoa. The abnormal biochemical make-up of the epididymis on semen quality and fertility is seminal plasma results in decreased seminal volume, I.3 more important than that of infection/inflam- abnormal viscosity and liquefaction, abnormal pH, mation of the prostate or seminal vesicles. and impaired functional capacity of the spermatozoa. ■ Whereas bacteria themselves have little influ- These are commonly poorly motile and may have anti- ence on the fertilizing capacity of sperma- sperm antibodies attached of the IgG and/or IgA class, tozoa, changes in the function of the affected causing immunological infertility. glands and reactive oxygen species generated In addition, infection or inflammation increase the by white blood cells damage spermatozoa. number of peroxidase-positive white blood cells (pus ■ The diagnosis of male accessory sex gland cells) generating reactive oxygen species that change infection is based on a combination of the lipid composition of the sperm membrane, reduc- elements in the patient’s history, clinical signs, ing its fluidity and fusogenic capacity with impaired and biological analysis of urine and semen. acrosome reactivity and ability to fuse with the oolem- ■ Treatment uses antibiotics and antioxidants, ma (Comhaire et al. 1999). Reactive oxygen species in- complemented with intrauterine insemination duceoxidativedamagetospermDNA,withexcessive and/or assisted reproduction, depending on production of a.o. 8-hydroxy-2-deoxyguanosin and the severity and reversibility or irreversibility mutagenesis (Chen et al. 1997). Also, inflammation in- of damage to sperm cells. creases the production of a number of cytokines such as interleukin 1 (alpha and beta), interleukin 6 and 8, and tumour necrosis factor, which further impair I.3.13.1 sperm function and fertilizing capacity (Depuydt et al. 1996; Gruschwitz et al. 1996). Definition Chronic inflammation of the epididymis may result The diagnosis of male accessory gland infection is in(partial)obstructionofthespermpassagewitholi- givenwhensemenclassificationisazoospermiaor go- or azoospermia (Dohle et al. 2003). Rupture of the abnormal spermatozoa and this is considered to result blood-testis barrier from obstruction causes anti- from present or past infection of the accessory sex sperm antibodies (Hendry 1986). glands, or inflammatory disease of the urogenital tract (Rowe et al. 2000). I.3.13.3 Clinical and Laboratory Findings I.3.13.2 History taking commonly reveals one or several epi- Aetiology and Physiopathology sodes of dysuria and/or pollakisuria, which may have Infection of the accessory sex glands includes epididy- disappeared spontaneously or after a short treatment mitis, vesiculitis and/or prostatitis, which are caused by with an antibiotic or urinary antiseptic. However, the either pathogens transmitted by sexual contact or by patient may be unaware of any acute urinary symptoms so-called trivial urological pathogens. Among the in the past. Sometimes, the patient mentions recurrent former, Chlamydia trachomatis is the most common episodes of intrascrotal pain that usually feels rather pathogen (Keck et al. 1998), but gonococcus may also dull and is exacerbated by pressure. Ejaculatory symp- occur. The urological pathogens commonly identified toms may occur such as reduced ejaculation force or are Escherichia coli, Streptococcus faecalis, Proteus volume, painful sensation during or immediately after mirabilis and pseudomonas. The role of coagulase- ejaculation, or blood staining of the ejaculate. Finally, negative staphylococcus is uncertain, while Staphylo- sexual complaints may be mentioned, including de- coccus aureus is usually a laboratory contaminant creased libido and orgasmic feeling, or even erectile (Rodin et al. 2003). dysfunction. I.3.13 Infection/Inflammation of the Accessory Sex Glands 73 Clinical examination should focus on the careful B. Abnormal urine after prostatic massage and/or de- palpation of the scrotal content, particularly the epi- tection of Chlamydia trachomatis in urine didymis and vas deferens. Any swelling or nodularity C. Ejaculate abnormalities: should be noted, as well as pain during soft pressure. – Elevated number of peroxidase-positive white Rectal examination can be performed, but transrectal blood cells or transabdominal echography may reveal more rele- – Culture with significant growth of pathogenic vant information. bacteria General blood analysis may reveal signs of infection, – Abnormal viscosity and/or abnormal biochemi- such as increased number of white blood cells, in- cal composition, and/or high levels of inflamma- creased sedimentation rate or abnormal globulin pro- tory markers or highly elevated reactive oxygen portions upon electrophoresis. Specific tests for circu- species lating antibodies against Chlamydia should be includ- ed in the routine investigation for male infertility. The The diagnosis requires either two signs from different laboratory may detect antisperm antibodies of the IgG headings, or at least two ejaculate signs in each of two class in serum. subsequent semen samples. If bacteria are detected, I.3 Urine analysis may reveal bacterial infection or an they should be identical in urine and in semen, or in the increased number of white blood cells, but the analysis two semen samples. of urine obtained after prostate massage should be Male accessory sex gland infection may be com- more relevant. However, the absence of urinary abnor- bined with other diseases such as varicocele, in which mality does not exclude male accessory gland infec- case a lower number of white blood cells may cause tion, particularly epididymitis. complementary damage (Everaert et al. 2003), or an Semenanalysisisofpivotalimportancetothediag- immunological factor, or sexual or ejaculatory dys- nosis. Semen must be collected as described in the sec- function. These diseases will require adequate manage- tion on semen analysis, in order to avoid contamina- mentandmayinterferewiththefertilityoutcomeafter tion with cells and bacteria from the skin or urethra. treatment of the infection. When semen culture is performed for the counting and identification of bacteria, preparatory dilution of the I.3.13.5 sample is required, reducing the bacteriostatic capacity of seminal plasma, prostate fluid in particular. The Treatment number of round cells must be counted, and these must Thetreatmentoftheinfectionshouldbethesameasfor be differentiated into peroxidase-negative cells, mostly urinary tract infections. However, abnormal secretion spermatogenetic cells, and peroxidase-positive white of the prostate results in an alkaline environment in blood cells (WHO 1999). Also, it is mandatory to per- this gland, by which antibiotics such as doxycycline are form biochemical analysis of the seminal plasma in or- not concentrated and are therefore inefficient. The der to measure the markers of secretion of the sex third-generation quinolones (e.g. ofloxacin and peflo- glands, including, for example, alpha-glucosidase for xacin) are concentrated in both an alkaline and acidic the epididymides, citric acid or gamma glutamyl trans- milieu, and therefore do penetrate well into the dis- ferase (or calcium or zinc) for the prostate, and, possi- eased prostate and the seminal vesicles (Comhaire bly, fructose for the seminal vesicles. 1987). In case of streptococcus infection, the quinolo- Finally, the presence of antisperm antibodies on nesarepoorlyactive,andtreatmentwithamoxicillinor spermatozoa must be traced by means of, for example, cephalosporins may be indicated. the direct MAR test for both IgG and IgA (WHO 1999). Commonly, bacterial infestation is eradicated, but it may return, sometimes with a different pathogen. It I.3.13.4 may be necessary to add a second, longer-term treat- ment with another antibiotic. Diagnosis and Differential Diagnosis The diagnosis is accepted in patients with abnormal se- I.3.13.6 men quality – oligo- and/or asteno- and/or teratozoo- spermia, or azoospermia – who combine abnormalities Results of Treatment under the following headings (Comhaire et al. 1980; Whereas bacteria can usually be eliminated from the Rowe et al. 2000): genitourinary region, white blood cells may persist for severalmonths,andfunctionalimpairmentoftheac- A. A history of urinary infection, epididymitis, sexual- cessory glands is commonly irreversible. This implies ly transmitted disease, and/or physical signs: thick- that the processes impairing the fertilizing capacity of ened or tender epididymis, thickened vas deferens, spermatozoa remain active, and that fertility is not re- abnormal rectal examination stored. Complementary treatment with food supple- 74 I.3 Male Factor Fertility Problems ments containing antioxidants may be required, and let alone cure. Therefore, any episode of urinary com- treatment similar to that of idiopathic oligozoospermia plaints suggestive for infection in the male must be treat- can be indicated. ed adequately,