Oxidative Stress and MAGI

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MAGI are a consequence of microorganism canalicular spreading via urethra, prostate gland, seminal vesicles, deferent duct, epididymis, and testis. Hematogenous infections are rare.

In the diagnostic workup of MAGI, sperm analysis is viewed as a fundamental step. Indeed, MAGI is diagnosed in the presence of one or more sperm parameter abnormalities (OAT) associated with a combination of two or more of the following factors (Fig. 25.1):

• Factor A: history positive for urinary tract infections and/or sexually transmitted diseases and/or physical urogenital examination

• Factor B: expressed prostate signs of infection and/or inflammation

• Factor C: ejaculate signs of infection

The initiators of the infections responsible for MAGI are microorganisms originated from the urinary tract or sexually transmitted diseases [ 39]. A retrograde ascent of the pathogens is the usual route of infection. The main infectious agents are Neisseria gonorrhoeae and C. trachomatis, as well as Enterobacteria, although with a lower frequency [40] [ Signs characteristic of MAGI are leukocytospermia and increased cytokines and ROS production. The following complications may also occur: epididymal and extraepididymal duct obstruction, spermatogenesis impairment in orchitis, sperm function impairment, and dysfunctions of the male accessory glands [40] .

The initiating pathogens trigger an intermediate chronic inflammation, including a series of multiple persistent components, such as presence of specific leukocyte subpopulations, cytokine kinetic, morphostructural abnormalities of the infected accessory glands [ 19, 41-44], and a final sperm damage which impairs conventional and nonconventional sperm parameters. Thus, the negative impact on sperm quality during MAGI recognizes one or more of the following mechanisms: (1) secretory dysfunction of one or more accessory gland, (2) spermatogenesis deterioration, and (3) unilateral or bilateral obstruction or dysfunctional sperm distal urinary tracts (ampullar-vesiculo-ductal uro-sperm dyssynergia).

Chronic, mainly symptomless MAGI may contribute to infertility to a various extent depending on the site of inflammation [9,18-20] and/or on the inflammatory response in terms of leukocytospermia and its products: ROS [16, 19, 22, 23] and/ or cytokine production [17, 25, 45] . The glandular secretory dysfunction plays a relevant role, and it is expressed through a nonspecific chronic inflammatory reaction (leukocytospermia, increased seminal plasma proinflammatory cytokines, and ROS overproduction) and/or specific autoimmune response (production of anti-sperm antibodies) [19, 25, 41, 44] . These bioactive substances may persist even after an apparent postantibiotic microbial eradication, because of a constant OS, as antioxidant and scavengers are depleted gradually during the chronic inflammatory response [41, 44].

Gland structural abnormalities may, in addition, play a negative role. In fact, infertile patients with MAGI and elevated bacteriospermia (>105 CFU/mL) or with C. trachomatis or U. urealyticum infection (at the urethral swabs after prostate massage) have the highest number of ultrasound abnormalities involving more glands (PVE) [19, 45]. These patients show an increased inflammatory response and an impaired semen quality directly related to the extension of MAGI (prostatitis < PV < PVE) [19 [ or a strong association with sperm abnormality [46] .

Table 25.1 Ultrasound findings suggestive of prostatitis, vesiculitis, and/or epididymitis [19] Prostatitis alone

Prostatitis alone is suspected in presence of two or more of the following ultrasound signs:

• Glandular asymmetry

• Hypoechogenicity associated with edema

• Hyperechogenicity associated with areas of calcification

• Dilation of the periprostatic venous plexus Prostatovesiculitis

Prostatovesiculitis is suspected when in addition to the above-mentioned ultrasound features present in the prostate gland, two or more of the following ultrasound signs are present in the seminal vesicles:

• Enlargement and asymmetry

• Thickening and calcification of the glandular epithelium

• Polycyclic areas separated by hyperechogenic septa Prostatovesiculoepididymitis

Prostatovesiculoepididymitis is suspected when in addition to the above-mentioned ultrasound features present in the prostate gland and in the seminal vesicles, two or more of the following ultrasound signs are present in the epididymis:

• Increased size of the head (craniocaudal diameter >12 mm) and/or tail (craniocaudal diameter >6 mm)

• Presence of multiple microcystic lesions confined to the epididymal head and/or tail

• Edematous hyperechoic epididymis

• Large hydrocele

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