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Male accessory gland infection and subfertility: a diagnostic challenge - Chapter 4: Accurate detection of male subclinical genital tract infection via cervical culture and DNA hybridization assay of the female partn

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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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Chapter

J W Trum, Y Pannekoek, L Spanjaard, OP Bleker, F van der Veen

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Abstract

The accuracy of the PACE2 DNA hybridization assay of the cervix and the cervical culture in female partners in the diagnosis of male subclinical genital tract infection were assessed in a male infertility population. One hundred and eighty-four men were screened for the presence of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis. Seventy-one men were identified with a positive test for one or more of the above mentio-ned microorganisms. The overall prevalence of bacterial infection was 39%.

Female partners of all men were tested with the PACE2 DNA hybridization assay to detect a C. trachomatis infection. Sensitivity was 100% and specificity was 100%. In 67 female partners (94%) of men who tested positive for U. urealyticum and/or M. hominis a cervical swab culture was performed. The sensitivity of the cervical swab culture was 100%. In view of the high prevalence of U. urealyticum and M. hominis in the male genital tract and the role these sexually transmitted pathogens may play in infertility, one might question whether all couples should be screened for the presence of these pathogens. Transurethral swab culture after digital prostatic massage is disincentive to men. The cervi-cal culture in their female partner, performed as part of the routine fertility work-up, is a suitable alternative to detect the presence of these microorganisms in the male genital tract.

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I N T R O D U C T I O N

Non gonococcal subclinical genital tract infection in the male can be caused by

Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis (Taylor-Robinson

and Furr, 1998; Bar-Chama and Fisch, 1993; Purvis and Christiansen, 1993;Bruce et al., 1989). In a previous study we found that the overall prevalence of these microorganisms was 38.5% in a large male infertility population (Trum et al.,1998). U. urealyticum and M.

hominis were the most prevalent microorganisms. All men underwent digital prostatic

mas-sage after which trans- urethral swab cultures were performed. This procedure is the most reliable way to detect these pathogens in the male genital tract (Barratt et al., 1989; American Fertility Society, 1988). This procedure, however, is experienced negatively by most men. Since these pathogens are sexually transmitted the question arises whether a cervical swab culture in their female partners is a suitable alternative to diagnose a subclini-cal genital tract infection in men.

The purpose of this study was to assess the accuracy of the cervical culture and PACE2 DNA hybridization assay (PDHA) to diagnose male subclinical genital tract infection, with culture and PDHA of the male urethra after digital prostatic massage as reference strategies.

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Materials and methods

Between April 1994 and September 1996 we asked men and their female partners older than 18 years who presented at the Center for Reproductive Medicine of our hospital to participate in the study. Reasons for referral were primary or secondary infertility of the couple. This study was carried out as part of a study in the detection of sexually transmit-ted disease (STD) as a cause of male infertility. Approval by the Institutional Review Board of our hospital was obtained. All patients gave written informed consent.

Screening of subfertile men:

All men underwent digital prostatic massage after which two cotton urethral swabs were taken to investigate the presence of bacteria according to standard methods. An urethral smear was gram stained and examined for the presence of Neisseria gonorrhoeae. One cot-ton 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. urealyticum

and M. hominis was done using a Shepard broth and a Shepard plate. The presence of

C. trachomatis was investigated with the PDHA (Gen-Probe Inc., San Diego, CA).

A positive bacterial culture or chemiluminescence signal was considered to indicate bacterial infection.

Screening of female partners:

All women were screened for the presence of N. gonorrhoeae and C. trachomatis using the above mentioned modified Thayer-Martin plate and the PDHA during the routine inferti-lity work-up. Culture of U. urealyticum and M. hominis was not performed on routine cer-vical swabs. In partners of men with a positive culture for U. urealyticum and/or M.

homi-nis a second cervical swab culture was performed to determine the presence of U. urealyti-cum and M. hominis before antibiotic treatment was started.

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Analysis:

Sensitivity and specificity of the cervical PDHA for detection of C. trachomatis and sensiti-vity of the cervical swab culture for U. urealyticum and M. hominis were calculated toge-ther with their 9 5 % confidence intervals. PDHA and culture of the male urethra were the reference strategies.

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Results

One hundred and eighty-four men were screened for the presence of N. gonorrhoeae, C.

trachomatis , U. urealyticum and M. hominis. The mean age was 34.7 years (standard

devia-tion 6.7 years). None of the patients showed any symptoms of genito-urinary tract infecti-on. In none of the men N. gonorrhoeae was detected. C. trachomatis was present in two cases (1%), U. urealyticum in 67 cases (36%) and M. hominis in 14 cases (8%). The overall prevalence of bacterial infection was 39%.

In the female partners of all men C. trachomatis was only detected in the two part-ners of the men who tested positive for C. trachomatis. Sixty-seven female partpart-ners (94%) of men with a positive culture for U. urealyticum or M. hominis were available for analysis. Data was lacking in two cases due to technical errors, in one case because antibiotic treat-ment was started before the cervical swabs could be taken, and in yet another case because the woman was lost for follow-up. In all women the same pathogens as cultured in their partners were found. In only one case a cervical culture was positive for both U.

urealyti-cum and M. hominis, whereas the urethral culture of the male genital tract was positive for U. urealyticum only.

The sensitivity and specificity of the PDHA in women to detect a C. trachomatis infection in their male partners was 100% (95% CI; 0.16 to 1) and 100% (95% CI: 0.98 to 1) respectively. The sensitivity for the cervical culture for the detection of M. hominis and U. urealyticum in the male partners was 100% (95% CI: 0.95 to 1).

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Discussion

This study shows that the cervical culture and PDHA in women are excellent tests for the diagnosis of subclinical genital tract infection in male sexual partners. The preva-lence of C. trachomatis in this infertility population was low (1%). When choosing a test for screening asymptomatic persons in a population with a low prevalence of infection, the specificity of the test must be high. The specificity of the cervical PDHA for C. trachomatis was 100% (CI: 0.98 to 1) and therefore it proved to be a good screening test.

The overall prevalence of U. urealyticum and M. hominis in this large male inferti-lity population was 39%. When choosing a test for screening asymptomatic persons in a population with a high prevalence, the sensitivity of the test must be good. The sensitivity of the cervical culture to detect U. urealyticum and M. hominis WAS, 100% (CI: 0.95 to 1) and therefore it proved to be a good screening test.

The presence of these bacteria in the male genital tract indicates colonization of the distal urethra rather than infection (Trum et al 1998). Still, detection might be important, since these pathogens are sexually transmitted. It is well established that sexually transmitted C.

trachomatis may lead to severe damage in the female genital tract (Mol et al., 1997; Sellors et al., 1988). Salpingitis and pelvic inflammatory disease due to ascending Mycoplasma

infections have been reported (Stray-Pederson et al. 1991, Moller et al. 1984, Mârdh and Weström 1970). In contrast to C. trachomatis, the clinical significance of U. urealyticum and M. hominis in male and female infertility is still a subject of debate. Male genital tract infection with U. urealyticum and M. hominis is more frequent when the female part-ner has tubal infertility (Soffer et al, 1990). The impact of these microorganisms on sperm parameters: concentration, motility and morphology is controversial (Kjaergaard et

al.,1997,

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Purvis and Christiansen, 1995). Some authors report an adverse effect on outcome of IVF when mycoplasmas are cultured (Shalika et al. 1996, Montagut et al. 1991), while others cannot confirm this finding (Witkin et al, 1995, Stovall et al, 1993). Since the role U.

urealyticum and M. hominis may play in infertility is not fully understood, cervical culture

for these microorganisms should be performed as part of the routine work-up in infertility evaluation in women (Guzick et al, 1994).

.J

Most men in whom these microorganisms are cultured from the distal urethra do not experience symptoms of a genito- urinary tract infection (Trum et ^/.,1998). This results in a large reservoir of unrecognized, colonized men who are capable of transmitting the microorganism to sexual partners.

In view of the high prevalence of microorganisms in the male genital tract, and the role sexually transmitted microorganisms may play in infertility, one might consider whether all infertile couples should be screened for the presence of C. trachomatis, U. urealyticum and

M. hominis. This study shows that the PDHA and the cervical culture are excellent tests to

diagnose the presence of C. trachomatis, U. urealyticum and M. hominis in the male genital tract thereby removing the need for collection of specimens from the male partner. Therefore, we feel that these tests are suitable to diagnose male subclinical tract infection. Furthermore, when large volumes have to be tested, costs become an important issue. Costs of screening will be reduced by twofold, when a single cervical swab specimen can be used to detect the presence of pathogens in both partners.

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References

American Fertility Society. (1990) Revised new guidelines for the use of semen for donor insemination. Fertility and

Sterility,53,{Sanp\.I).

Bar-Chama.N., Fisch,H. (1993) Infection and pyospermia in male infertility. World Journal of Urology, 11, 76-81. Barratt.CL.R., Monteiro.E.E, Chauhan,M.C, et al.(1989) Screening potential semen donors for sexually

transmitted disease in donor insemination centers in the UK: a survey. British Journal of Obstetrics and

Gynecology,96,46\-466.

Bruce,A-W., Reid.G. (1989) Prostatitis associated with Chlamydia trachomatis infection in 6 patients Journal of c/ra%,l42,1006-1007.

Guzick,D.S., GrefenstetteJ., Baffone.K .et al. (1994) Infertility evaluation in fertile womema model for assessing the efficacy of infertility testing. Human Reproduction^,2306-2310.

Kjaergaard.N., Kristensen,B., Hansen,E.S. et al. (1997) Microbiology of semen specimens from males attending a fertility clinic^4/>Mß',105,566-570.

MârdhjP.A., Weström,L. (1970) Tubal and cervical cultures in acute salpingitis with special reference to M. hominis and T-strain mycoplasmata. British Journal of Venereal Diseases,46,179-186.

Mol.B.W.J, Dijkman,B„ Wertheim,P.<tf al. (1997) The accuracy of serum chlamydial antibodies in the diagnosis of tubal pathology: A meta-analysis. Fertility and Sterility,67,1031-1037.

Moller,B.R-, AllenJ., Toft,B- et al. (1984) Pelvic inflammatory disease after hysterosalpingography associated with Chlamydia trachomatis and Mycoplasma hominis. British Journal of Obstetrics and

Gynaecology,9\,\\8\-\\87.

MontagutJ.M., Lepretre,S., DegoyJ. et al. (1991) Ureaplasma in semen and IVE Human Reproduction,6,727-729. Purvis,K., Christiansen.E. (1995) The impact of infection on sperm quality. Journal of 'the British Fertility

Society,l,3l-4l.

Purvis,K., Christiansen.E. (1993) Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. International Journal ofAndrology,l6,l-l3.

SellorsJ.W., MahonyJ.B., CherneskyM.A. et al. (1988) Tubal factor infertility: an association with prior Chlamydial infection and asymptomatic salpingitis. Fertility and Sterility,49, 451-457.

Shalika,S., Dugan,K., Smith.R.D. et al. (1996) The effect of positive semen and bacterial Ureaplasma cultures on in-vitro fertilization success. Human Reproduction,\\,2789-2792.

Soffer,Y., Ron-El,R., Golan.A. et al. (1990) Male genital mycoplasmas and C. trachomatis culture: its relationship with accessory gland function, sperm quality, and autoimmunity. Fertility and Sterility,53, 331-336. Stovall.D.W., BaileyL-E., Talbert,L-M. (1993) The role of aerobic and anaerobic semen cultures in asymptomatic

couples undergoing in vitro fertilization: effects on fertilization and pregnancy rates. Fertility

and Sterility,,59,197'-201.

Stray-Pedersen,B., BiornstadJ., Dahl.M. et al. (1991) Induced abortion: microbiological screening and medical complications. Infection,5,305-308.

Taylor-Robinson,D., Furr,P.M. (1998) Update on sexually transmitted mycoplasmas. Z««c<*.,351,(suppl III),12-15. TiumJ.W., MoLB.W., Pannekoek,Y. et al. (1998) Value of detecting leukocytospermia in the diagnosis of

genital tract infection in subfertile men. Fertility and Sterility,7,3\5-3\9 •

Witkin,S.S., Kligman,!., GrifoJA. et al. (1995) Ureaplasma urealyticum and Mycoplasma hominis detected by the polymerase chain reaction in the cervices of women undergoing in vitro fertilization: prevalences and consequences. Journal of Assisted Reproduction and Genetics, 12,610-614.

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