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Male accessory gland infection and subfertility: a diagnostic challenge
Trum, J.W.
Publication date
1999
Link to publication
Citation for published version (APA):
Trum, J. W. (1999). Male accessory gland infection and subfertility: a diagnostic challenge.
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JWTrum, RA Schipper, FM Gubler, L Spanjaard, OP Bleker, KH Kurth, F van der Veen.
Abstract
Objective: To assess the accuracy of transrectal and scrotal ultrasonography in the
diagno-sis of subclinical genital tract infection in a male subfertility population.
Methods: One hundred and eighty four men of infertile couples attending our infertility
clinic, were studied. Urethral swab culture after digital prostatic massage and a DNA hybridization assay were used as reference strategies in relation to ultrasonographic features to diagnose male subclinical genital tract infection.
Results: A subclinical bacterial infection was present in 39% of men. Reproducible
ultra-sonographic features associated with male genital tract infection were seen in 94.9% of men. None of these ultrasonographic features were associated with the presence of micro-organisms in the genital tract.
Conclusion: Ultrasonography of the male genital tract is of no diagnostic value with
Introduction
Non gonococcal subclinical tract infection in the male can be caused by Chlamydia
tracho-matis, Ureaplasma urealyticum and Mycoplasma hominis [1-4]. The impact of these
patho-gens on sperm quality and sperm fertility potential is controversial [5-13].
Detection, however, is important because these pathogens are sexually transmitted and may cause ascending infections that lead to severe damage in the female genital tract [1,14-18]. The impact of the presence of these micro-organisms in the female genital tract in the absence of clinical symptoms on the outcome of assisted reproduction, is still a sub-ject of debate [19-22]. The most reliable way to detect the above mentioned bacteria in men is the polymerase chain reaction (PCR) on semen or urine [23-26]. PCR for the de-tection of C. trachomatis is widely used but its application for the other microorganisms needs further development. Culture of an urethral swab after digital prostatic massage to detect these organisms is advocated [27,28].
Both transrectal ultrasonography (TRUS) and scrotal ultrasonography (SUS) have proven their usefulness in the diagnosis of conditions associated with male subfertility like conge-nital absence of seminal vesicles, Müllerian cysts and varicocele [29,30]. The role of ultra-sonography in the diagnosis of subclinical genital tract infection is not clear. Ultrasono-graphic features indicating a chronic genital tract infection are dilatation of the periprosta-tic plexus, thickening of the prostate capsule, beehive configuration of the seminal vesicles, prostatic or testicular cysts, calcifications, hypervascularity of the testes and dilatation of the epididymes [31-34]. However, some of these characteristics are found in healthy con-trols as well [35]. To date no study has been performed to see whether reproducible ultra-sonographic findings like calcifications, cysts and dilatation of the plexus are associated with the presence of C. trachomatis, U. urealyticum and M. hominis.
The objective of this study was to assess the accuracy of TRUS and SUS in the diagnosis of subclinical genital tract infection in a male subfertility population.
Materials and Methods
Between April 1994 and January 1997 two hundred randomly chosen men older than 18 years who presented at the Center for Reproductive Medicine at the Academic Medical Center in Amsterdam, were asked to participate in the study. Reasons for referral were pri-mary or secondary infertility of the couple. Approval was obtained by the Institutional Review Board of our hospital. All patients gave written informed consent.
All men underwent digital prostatic massage after which two cotton urethral swabs were taken to investigate the presence of bacteria in accordance with standard methods. An urethral smear was gram stained and examined for the presence of Neisseria gonorrhoeae. One cotton swab was placed in a Stuart medium and used for bacterial culture. Culture for N. gonorrhoeae was done using a modified Thayer-Martin plate and culture of U.
urea-lyticum and M. hominis was done using a Shepard broth and a Shepard plate. The presence
of C. trachomatis was investigated with a DNA hybridization assay (Genprobe Inc, San Diego, CA). A positive bacterial culture or chemiluminescence signal was considered to indicate bacterial infection.
All men had a TRUS that was performed by one observer, a skilled urologist trainee, who was unaware of the infectious status of the patient. The ultrasound signs calcifications, dilatation of the venous plexus >150 mm2 and cysts that may be related to infection were previously defined after an intra- and inter observer analysis (chapter 7). All examinations were performed with a 7.5 Mhz probe (Briiel and Kjaer, Naerun, Denmark). The prostate and seminal vesicles were scanned in transverse planes and sagittal planes.
who was also unaware of the infectious status of the patient. The scrotal contents were examined with a 7.5 MHz high resolution linear array transducer (Acuson, Mountain view, Calif.) with pulsed and color Doppler capabilities. Ultrasound signs that may be rela-ted to an epididymo-orchitis like testicular cysts, calcifications, hypervascularity of the testes and dilatation of the epididymes (corpus, cauda >3mm, caput > 7mm) were noted. Size and volume of the testes were measured. The sensitivity, specificity, positive predictive value and negative predictive value of the different ultrasonographic features together with their 95% Confidence Interval (CI) to identify men with a positive culture for C.
tracho-matis, U. urealyticum and M. hominis were calculated.
Results
Of the two hundred men that were asked to participate in the study, 12 men refused parti-cipation and four men were excluded because of hypergonadotropic hypogonadism. Data of 184 men were available for analysis. Seventeen men did not complete the study, six men because their wives conceived, one man refused TRUS, and another 10 men were lost to follow up before a TRUS was performed. Therefore, ultrasonographic data of 167 men could be analyzed. The mean age was 34.7 years (standard deviation 6.7). Primary infertili-ty was present in 135 (74%). None of the patients indicated genito-urinary complaints.
The prevalence of the different bacteria in the genital tract is shown in table I. The overall prevalence of actual bacterial infection was 39%.
Table I: Prevalence of bacteria in the genital tract of 184 subfertile men
men with positive test result Prevalence (%)
Ureaplasma urealyticum 56 30
Mycoplasma hominis 4 3
Chlamydia trachomatis 0 0
U.urealyticum +M.hominis 10 5
U.urealyticum+M.hominis+ C.trachomatis 1 0.5
Both TRUS and SUS were well tolerated by all men. The prevalence and distribution of the different ultrasonographic features in this male subfertility population is shown in table II. The overall prevalence of these ultrasonographic features as seen with TRUS was 7 0 . 1 % and with SUS: 76.7%. When calcifications were present, there were no differences in the number or intraprostatic distribution of calcifications.
Table II: Prevalence of ultrasonographic features in a male subfertility population
N= men with ultrasonographic feature (%) N= men without ultrasonographic feature (%) SUS calcifications Testis left 12(6.8) 164 (93.2) Testis right 13 (7.4) 162 (92.6) Epididymis left 3 (1.7) 173 (98.3) Epididymis right 3 (1.7) 172 (98.3) SUS cysts Testis left 2(1.1) 174 (98.9) Testis right 1 (0.5) 174 (99.5) Epididymis left 18 (50.1) 87 (49.5) Epididymis right 20(11.4) 155 (88.6) SUS dilatation Epididymis left 89 (50.1) 87 (49.5) Epididymis right 82 (46.9) 93 (53.2) SUS CDF hyperemia testis/epidydimis 0 0 OVERALL SUS features 135 (76.7) 41 (23.3) TRUS calcifications Prostate 74 (44.3) 93 (55.7) Seminal vesicle left 2 (1.2) 165 (98.8) Seminal vesicle right 3 (1.8) 163 (98.2) TRUS cysts
Prostate 16 (9.6) 151 (90.4) Seminal vesicle left 44 (26.4) 123 (73.6) Seminal vesicle right 37 (22.3) 129 (77.7) TRUS dilatation peri-prostate plexus 61 (40.4) 89 (59.6) OVERALL TRUS features 117(70.1) 50 (29.9) OVERALL SUS/TRUS features 166 (94.9) 9(5.1)
CDF: color Doppler flow SUS: scrotal ultrasonography TRUS: transrectal ultrasonography
The accuracy of the ultrasonographic features as calcifications, cysts, dilatation of the peri-prostatic plexus and dilatation of the epididymes to identify men with a subclinical bacte-rial genital tract infection is shown in table III. None of these features were associated with the presence of U. urealyticum or M. hominis in the genital tract (p>0.05).
Table III: The accuracy of the different ultrasonographic features in relation to subclinical genital tract
infection in a male subfertility population.
TRUS
Sensitivity Specificity Pos.pred.value Neg.pred.value % ( 9 5 % C I ) % ( 9 5 % C I ) % (95%CI) % (95%CI) Calcifications 39 (0.27-0.52) 52(0.42-0.62) 36(0.25-0.48) 55(0.45-0.66) cys t s 50 (0.25-0.75) 60(0.53-0.68) 12(0.05-0.22) 92(0.85-0.96) Dilatation peri-prostatic plexus 38 (0.26-0.52) 56(0.45-0.67) 37(0.25-0.5) 58(0.46-0.68)
sus '
Calcifications 3.5 (0.02-0.06) 95 (0.92-0.97) 32 (0.17-0.51) 60 (0.56-0.63) Crs t s 7 (0.04-0.1) 95 (0.92-0.97) 48 (0.32-0.64) 60 (0.56-0.64) Dilatation epididymides 55 (0.47-0.64) 48 (0.41-0.55) 42 (0.35-0.5) 61 (0.53-0.69) TRUS: transrectalultrasonography SUS: scrotalultrasonography DiscussionThis study shows a high prevalence of anatomical changes in the genital tract of a male subfertility population. Men with a positive culture for U. urealyticum and M.
homi-nis did not have more anatomical changes in the genital tract when compared with men
without these pathogens. Therefore, the transrectal and scrotal ultrasonography are of no value in selecting men with a positive culture for U. urealyticum and M. hominis.
Subclinical genital tract infection may be difficult to diagnose due to the paucity of symptoms, the antibacterial effects of semen, contamination from urethral organisms,
The reference strategy to diagnose a genital tract infection is the transurethral swab culture after digital prostatic massage [27,28]. This test, however, is experienced negatively by most men and a less disincentive test is preferable.
Transrectal and scrotal ultrasonography have been proposed for the detection of genital tract infection [29,31,32,34]. Urethritis may lead to an ascending infection of the prostate, seminal vesicles, epididymides and testes giving rise to anatomical changes that can be visualized with ultrasonography.
Of all the different ultrasonographic features, dilatation of the epididymis, was the finding with the highest sensitivity to identify men with a positive urethral culture. Still the sensitivity was only 55%. The positive predictive value was as low as 42%. This would result in overtreatment, if men were to receive antibiotic treatment when selected by ultra-sonography. None of the ultrasonographic features can be used to select men with a positi-ve urethral culture.
In conclusion, ultrasonographic features with TRUS or SUS were not associated with the different pathogens. Whether the presence of these pathogens is associated with ascending infection, functional loss of the male sex glands, and impairment of fertility, is subject for further research.
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