Human Reproduction, Vol. 17, No. 3, 525-527,
March 2002
© 2002 European Society of Human Reproduction and Embryology
Chlamydia trachomatis in subfertile women undergoing uterine instrumentation
Screen or treat?*
1 Research Institute Growth and Development (GROW), Department of Obstetrics and Gynaecology and 2 Department of Medical Microbiology, Maastricht, The Netherlands
 |
Abstract |
|---|
 Top Abstract IntroductionEndocervical chlamydia...Persisting chlamydia micro...Prophylactic antibioticsConclusionsReferences |
|---|
Women who undergo uterine instrumentation are considered at risk for pelvic infections by Chlamydia trachomatis, which may derive either from ascending endocervical infections or from reactivation of micro-organisms persisting in the genital tract after previous chlamydia infections. Women presenting at fertility clinics frequently undergo uterine instrumentation (e.g. hysterosalpingography and laparoscopy with hydrotubation). Studies in subfertile women using DNA amplification techniques have shown that the prevalence of endocervical chlamydia infections is low (1.8%). In contrast, in 30–60% of subfertile women chlamydia IgG antibodies can be found in serum, indicating previous chlamydia infections. It has been demonstrated that, several years after chlamydia infections, viable micro-organisms may still be present in the upper genital tract. Therefore, subfertile women with chlamydia antibodies should be considered at risk for reactivation of persistent chlamydia infections after uterine instrumentation, even after exclusion of endocervical chlamydia infections. Moreover, in subfertile women without chlamydia antibodies, the presence of viable micro-organisms in the genital tract cannot be excluded. As a consequence, prophylactic antibiotics before uterine instrumentation should be considered in all subfertile women, instead of endocervical screening for C. trachomatis and treatment of positive cases only.
Key words: Chlamydia trachomatis/prophylactic antibiotics/screening/subfertility/uterine instrumentation
|
Introduction |
|---|
|
TopAbstractIntroductionEndocervical chlamydia...Persisting chlamydia micro...Prophylactic antibioticsConclusionsReferences |
|---|
Chlamydia trachomatis is the most common sexually transmitted disease in industrialized countries. Chlamydia infections remain often undiagnosed, as they are asymptomatic in the majority of patients. Undiagnosed and untreated chlamydia infections, however, may have considerable consequences in women, by increasing the risk for pelvic inflammatory disease, tubal factor subfertility and ectopic pregnancy. In women with asymptomatic endocervical chlamydia infections, ascending spread of micro-organisms from the cervix can cause upper genital tract infections. Women with endocervical chlamydia infections are considered particularly at risk for ascending infections during uterine instrumentation.
Hysterosalpingography (HSG) and laparoscopy with hydrotubation are common procedures of uterine instrumentation in subfertile women. Clinical pelvic infection following HSG has been reported in up to 4% of cases, and in 10% of patients with tubal disease (Forsey et al., 1990
). In a number of patients with post-HSG infections due to C. trachomatis, the organism could be isolated from the cervix prior to HSG, indicating spread of the micro-organism from the cervix into the upper genital tract. However, in some patients with post-HSG infections due to C. trachomatis, the organism could not be recovered from the cervix prior to HSG, suggesting post-HSG infection to be caused by reactivation of viable micro-organisms which had persisted in the genital tract (Forsey et al., 1990).
Although pelvic chlamydia infections may derive from ascending endocervical infections as well as from reactivation of micro-organisms persisting in the upper genital tract, different intervention strategies have been proposed for the prevention of ascending infections only. In 1996, the Royal College of Obstetricians and Gynaecologists recommended that all women undergoing uterine instrumentation should be screened for chlamydia, or should receive prophylactic antibiotics (Royal College of Obstetricians and Gynaecologists, 1996). In 2000, in its more recent guidelines, the Royal College is ambiguous in its recommendations: screening for chlamydia prior to uterine instrumentation should be considered only in patients at risk, i.e. women <25 years, but protection against upper genital tract infections should be considered in all women presenting for infertility investigation (Royal College of Obstetricians and Gynaecologists, 2000). Therefore, the controversy between the administration of prophylactic antibiotics and a screen-and-treat policy remains still unresolved.
|
Endocervical chlamydia infections in subfertile women |
|---|
|
TopAbstractIntroductionEndocervical chlamydia...Persisting chlamydia micro...Prophylactic antibioticsConclusionsReferences |
|---|
Studies published on endocervical chlamydia colonization in subfertility patients have reported the prevalence to range from 0–10.4% (Macmillan and Templeton, 1999
; for summary). Most studies used cell culture, which has a sensitivity of <70%. In DNA amplification tests, polymerase chain reaction (PCR) and ligase chain reaction (LCR), sensitivity is >90% (Puolakkainen et al., 1998) and therefore these must be considered the tests of choice for diagnosing C. trachomatis infections. Studies in subfertility patients using LCR on endocervical specimens have reported prevalences of 1.3% (95% CI 0.2–4.7%) (Eggert-Kruse et al., 1997) and 1.9% (95% CI 0.5–4.8%) (Macmillan and Templeton, 1999). We performed a study in 255 female subfertility patients by PCR, and found endocervical chlamydia infections in 2.0% (95% CI 0.6–4.5%) (unpublished data). From the combined data of the three studies using DNA amplification tests, it can be concluded that endocervical chlamydia infections are infrequent in subfertility patients (prevalence 1.8%, 95% CI 0.9–3.2%). Screening women for asymptomatic endocervical chlamydia infections, in order to reduce the rate of pelvic inflammatory disease, has been debated. It has been demonstrated that screening by DNA amplification tests, and subsequent treatment of women with positive test results, is only cost-effective in populations with a prevalence of C. trachomatis of 
4% (Paavonen et al., 1998).
In order to identify high prevalence populations for chlamydia infections, criteria have been developed for high-risk patients. Age <25 years, two or more sexual partners in the past year, and single status have independently been associated with an increased risk for endocervical chlamydia infection (Stergachis et al., 1993). The majority of female subfertility patients are >25 years of age (in our study 4.0% of women were <25 years old), and couples attending fertility clinics usually have had monogamous relationships for several years. Therefore, factors identifying high-risk patients for chlamydia infections in a general population are not applicable in subfertility patients.
Chlamydia IgG antibodies have been found in 30–60% of subfertile women (Mol et al., 1997; for review), and are considered markers for past pelvic infections. Cervical infection only rarely causes a rise in chlamydia antibody titre (Tayler-Robinson, 1997). Therefore, chlamydia IgG antibody testing is not helpful in identifying patients with active endocervical infections. This is in agreement with findings by others (Eggert-Kruse et al., 1997) who found no relation between LCR results and chlamydia IgG antibody titres in 150 patients, of whom two were LCR positive. In fact, more data on LCR/PCR positive subfertile women are needed to confirm these findings, but the low prevalence of endocervical infections in subfertility patients makes studies with adequate numbers difficult to perform.
|
Persisting chlamydia micro-organisms in the upper genital tract: the role of screening |
|---|
|
TopAbstractIntroductionEndocervical chlamydia...Persisting chlamydia micro...Prophylactic antibioticsConclusionsReferences |
|---|
PCR testing of endocervical swabs is based on DNA amplification of chlamydia antigen obtained from the lower genital tract. Evidence exists however that C. trachomatis may persist in the upper genital tract despite negative PCR test results from the cervix. In patients with bilateral tubal occlusion due to chlamydia infection, tubal biopsies have been evaluated by a fluorescent antibody test for the presence of the major outer membrane protein (MOMP) of C. trachomatis (Dieterle et al., 1998
). MOMP was found in tubal specimens from 11/56 women, in whose endocervical specimens the presence of C. trachomatis could not be demonstrated. PCR testing of Fallopian tube tissue from 10 women with ectopic pregnancies (Gérard et al., 1998) showed that 7/10 tubes were positive for chlamydia DNA. In each PCR-positive sample, transcripts from chlamydia genes were present, indicating that the chlamydia cells identified were viable and metabolically active at the time of biopsy. Evaluation by in-situ hybridization or immunoperoxidase staining technique of tubal specimens of patients with tubal pathology showed DNA or antigens in 19/24 women (Patton et al., 1994). There was no difference in detection rate of C. trachomatis between patients who had been treated by antibiotics (tetracycline, ofloxacin or roxythromycin) and untreated patients. These studies indicate that C. trachomatis may persist in a viable state in Fallopian tubes for a long period, even after antibiotic treatment. Reactivation of chlamydia infection may occur, but it is still speculative which stimuli may induce reactivation of upper genital tract infection. Uterine instrumentation might be such a stimulus. Therefore, reactivation of chlamydia upper genital infections may occur in subfertility patients with chlamydia antibodies (indicating a previous infection), despite the fact that no chlamydia DNA can be detected in the cervix. This questions the use of screening by cervical swabs in subfertile women before uterine instrumentation, and also raises questions considering PCR-negative patients not at risk for subsequent upper genital tract chlamydia infections. |
Prophylactic antibiotics |
|---|
|
TopAbstractIntroductionEndocervical chlamydia...Persisting chlamydia micro...Prophylactic antibioticsConclusionsReferences |
|---|
Since the presence of viable chlamydia micro-organisms in the upper genital tract can be excluded by invasive methods only, there is no feasible screening method available in daily practice. Therefore, prophylactic antibiotics may be considered in subfertility patients before uterine instrumentation. Guidelines for the treatment of patients with genital chlamydia infections (Centers for Disease Control and Prevention, 1998
) have recommended azithromycin as a single oral 1 g dose as equivalent to the 7 day regimen of doxycycline (100 mg twice daily) for treating uncomplicated genital chlamydia infections. Pharmacokinetic studies in man have shown the time to adequate tissue concentrations after a single oral dose to be 12–14 h, tissue concentrations being 10–100 times higher than in serum and remaining high for several days (Foulds et al., 1990). These pharmacokinetic characteristics of azithromycin encourage its use as prophylaxis in subfertility patients before procedures which might reactivate chlamydia infections. |
Conclusions |
|---|
|
TopAbstractIntroductionEndocervical chlamydia...Persisting chlamydia micro...Prophylactic antibioticsConclusionsReferences |
|---|
Upper genital tract chlamydia infections may derive from ascending endocervical infections, but reactivation of dormant micro-organisms in the upper genital tract is another possibility. Endocervical infections can be excluded by LCR or PCR, but the prevalence of active endocervical chlamydia infections in subfertile women is low (1.8%). Concerning reactivation, it has been shown that several years after chlamydia infections viable C. trachomatis micro-organisms may still be present in the upper genital tract. Therefore, subfertile women with chlamydia antibodies (indicating a previous chlamydia infection) should be considered at risk for reactivation of persistent chlamydia micro-organisms after uterine instrumentation, even after exclusion of chlamydia in the cervix. From this point of view, prophylactic antibiotics should be considered in subfertile women who have chlamydia antibodies in serum and have to undergo uterine instrumentation, as opposed to endocervical screening for C. trachomatis and treatment of positive patients only. In subfertile women who have no chlamydia antibodies in serum, the presence of chlamydia in the genital tract cannot be excluded however. Since iatrogenic spread of chlamydia in subfertile women has severe consequences for the preservation of fertility, prophylactic antibiotics before uterine instrumentation should also be considered in subfertile women without chlamydia antibodies. Clinical studies which allow the assessment of the effectiveness of antibiotic therapy in preventing pelvic infections after uterine instrumentation are impracticable, since the majority of chlamydia infections will remain subclinical and therefore will go undiagnosed. Thus, clinical guidelines concerning precautions in subfertile women undergoing uterine instrumentation can be based on theoretical arguments only. Prophylactic antibiotics (e.g. azithromycin in a single oral 1 g dose, 12 h before the planned procedure) should replace endocervical screening for C. trachomatis and treatment of positive cases only.
|
Notes |
|---|
3 Department of Obstetrics and Gynaecology, Academisch Ziekenhuis Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail: jlan{at}sgyn.azm.nl.
* Part of this work has been presented at the IVth European Chlamydia Congress (August 20-23, 2000) in Helsinki, Finland.
|
References |
|---|
|
TopAbstractIntroductionEndocervical chlamydia...Persisting chlamydia micro...Prophylactic antibioticsConclusionsReferences |
|---|
Centers for Disease Control and Prevention (1998) 1998 guidelines for treatment of sexually transmitted diseases. MMWR, 47, RR-1.
Dieterle, S., Rummel, C., Bader, L.W., Petersen, H. and Fenner, T. (1998) Presence of the major outer membrane protein of Chlamydia trachomatis in patients with chronic salpingitis and salpingitis isthmica nodosa with tubal occlusion. Fertil. Steril., 70, 774–776.[Web of Science][Medline]
Eggert-Kruse, W., Rohr, G., Demirakca, T., Rusu, R., Näher, H., Petzoldt, D. and Runnebaum, B. (1997) Chlamydial serology in 1303 asymptomatic subfertile couples. Hum. Reprod., 12, 1464–1475.
Forsey, J.P., Caul, E.O., Paul, I.D. and Hull, M.G.R. (1990) Chlamydia trachomatis, tubal disease and the incidence of symptomatic and asymptomatic infection following hysterosalpingography. Hum. Reprod., 5, 444–447.
Foulds, G., Shepard, R.M. and Johnson, R.B. (1990) The pharmacokinetics of azithromycin in human serum and tissues. J. Antimicrob. Chemother., 25, (Suppl. A), 73–82.
Gérard, H.C., Branigan, P.J., Balsara, G.R., Heath, C., Minassian, S.S. and Hudson, A.P. (1998) Viability of Chlamydia trachomatis in fallopian tubes of patients with ectopic pregnancy. Fertil. Steril., 70, 945–948.[Web of Science][Medline]
Macmillan, S. and Templeton, A. (1999) Screening for Chlamydia trachomatis in subfertile women. Hum. Reprod., 14, 3009–3012.
Mol, B.W.J., Dijkman, B., Wertheim, P., Lijmer, J., van der Veen, F. and Bossuyt, P.M.M. (1997) The accuracy of serum chlamydial antibodies in the diagnosis of tubal pathology: a meta analysis. Fertil. Steril., 67, 1031–1037.[Web of Science][Medline]
Paavonen, J., Puolakkainen, M., Paukku, M. and Sintonen, H. (1998) Screening for Chlamydia trachomatis would be cost-effective, even in low-prevalence situations. Obstet. Gynecol., 92, 292–298.[Web of Science][Medline]
Patton, D.L., Askienazy-Elbhar, M., Henry-Suchet, J., Campbell, L.A., Cappuccio, A., Tannous, W., Wang, S. and Kuo, C. (1994) Detection of Chlamydia trachomatis in fallopian tube tissue in women with postinfectious infertility. Am. J. Obstet. Gynecol., 171, 95–101.[Web of Science][Medline]
Puolakkainen, M., Hiltunen-Back, E., Reunala, T., Suhonen, S., Lähteenmäki, P., Lehtinen, M. and Paavonen, J. (1998) Comparison of performances of two commercially available tests, a PCR assay and a ligase chain reaction test, in detection of urogenital Chlamydia trachomatis infection. J. Clin. Microbiol., 36, 1489–1493.
Royal College of Obstetricians and Gynaecologists (1996) The initial investigation and management of the infertile couple. RCOG Press, London, UK, p. 12.
Royal College of Obstetricians and Gynaecologists (2000) The management of infertility in tertiary care. www.rcog.org.uk/guidelines/tertiarycare.html.
Stergachis, A., Scholes, D., Heidrich, F.E., Sherer, D.M., Holmes, K.K. and Stamm, W.E. (1993) Selective screening for Chlamydia trachomatis infection in a primary care population of women. Am. J. Epidemiol., 138, 143–153.
Tayler-Robinson, D. (1997) Evaluation and comparison of tests to diagnose Chlamydia trachomatis genital infections. Hum. Reprod., 12 (Suppl. 2), 113–120.[Abstract]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J.A. Land, J.E.A.M. Van Bergen, S.A. Morre, and M.J. Postma Epidemiology of Chlamydia trachomatis infection in women and the cost-effectiveness of screening Hum. Reprod. Update, October 14, 2009; (2009) dmp035v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Idahl, J. Boman, U. Kumlin, and J.I. Olofsson Demonstration of Chlamydia trachomatis IgG antibodies in the male partner of the infertile couple is correlated with a reduced likelihood of achieving pregnancy Hum. Reprod., May 1, 2004; 19(5): 1121 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hung, Y. Ng, C. S. W. Ngai, and P. C. Ho Chlamydia trachomatis in infertile women undergoing uterine instrumentation: Screen or treat Hum. Reprod., August 1, 2002; 17(8): 2215 - 2216. [Full Text] [PDF]
|
|
|
|
|
|
S. Macmillan Chlamydia trachomatis in subfertile women undergoing uterine instrumentation: The clinician's role Hum. Reprod., June 1, 2002; 17(6): 1433 - 1436. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||