Human Reproduction, Vol. 14, No. 12, 3009-3012,
December 1999
© 1999 European Society of Human Reproduction and Embryology
Screening for Chlamydia trachomatis in subfertile women
Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen AB25 2ZD, UK
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Abstract |
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Chlamydia trachomatis is the most common sexually transmitted disease in the UK and Europe. The majority of female infections are asymptomatic and recognized sequelae include pelvic inflammatory disease, infertility, and ectopic pregnancy. Women with chlamydial infection who undergo uterine instrumentation are recognized to be at risk of ascending infection. Most patients attending for infertility investigations and treatment will undergo some form of uterine instrumentation. Published data regarding the prevalence of chlamydial infection in the subfertile are few and conflicting. In this study, more than 400 consecutive women presenting for infertility investigation and treatment at a single regional fertility centre were screened for Chlamydia. Half were screened using enzyme immunoassay (EIA) and half by ligase chain reaction (LCR). Prevalence by diagnostic test was 0% with EIA and 1.9% with LCR. Overall, the low prevalence was at least partly explained by older age. Until more evidence comes from studies testing consecutive subfertile patients both with EIA and a DNA amplification method such as LCR, centres using EIA should consider using prophylactic antibiotics prior to uterine instrumentation.
Key words: Chlamydia trachomatis/infertility/prevalence/screening/uterine instrumentation
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Introduction |
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Chlamydia trachomatis is the most common sexually transmitted disease (STD) in the UK and Europe. Women bear the brunt of its effects through the recognized consequences of pelvic inflammatory disease (Cates and Wasserheit, 1991; Paavonen, 1992
), tubal infertility (Svensson et al., 1983; Henry-Suchet et al., 1987), and ectopic pregnancy (Coste et al., 1994). Not withstanding human costs, the healthcare costs of this infection are estimated at £50 million per year in the UK alone (Taylor-Robertson, 1994).
Since 1996, the Royal College of Obstetricians has recommended that all `non-pregnant women under 35 years undergoing uterine instrumentation should be screened for Chlamydia ... prior to the procedure or, failing that, should receive prophylactic antibiotics' (Templeton, 1996). This was a Grade C recommendation based on the consensus view of the Study Group. More recently, the Chief Medical Officer's Expert Advisory Group on Chlamydia (Expert Advisory Group, 1998) has called for action to reduce the prevalence and morbidity of chlamydial infection. They recommend that consideration be given to screening couples attending for fertility investigations and treatment.
Over the past 20 years, limited data regarding the prevalence of chlamydial infection in the subfertile population have emerged from prevalence studies within the UK and elsewhere. Comparing the studies, however, is difficult because of heterogeneity of sample size, criteria for case selection, diagnostic tests, and data collection. As a result, no specific data exist on which to base intervention strategies.
The purpose of this study was to provide data on the prevalence of genital chlamydial infection in women attending for infertility investigation and treatment. We also studied the effect of age and diagnostic test on prevalence.
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Materials and methods |
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All screening was undertaken in the Aberdeen Fertility Centre, comprising a Fertility Clinic (FC) and Assisted Reproduction Unit (ARU). Consecutive women were invited to participate in the study by means of an information sheet. The only exclusion criterion was antibiotic use in the past 4 weeks. Participants volunteered by giving verbal consent. Approval was received from the local Ethical Committee prior to commencement of the study.
Subjects
Screening for C.trachomatis was initiated in Aberdeen's Fertility Centre in March 1997. Those women attending the FC were tested at their first visit, while those attending the ARU were tested just prior to commencing ovulation stimulation, in-vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI). A total of 217 consecutive female patients (117 from the FC, 100 from the ARU) comprised the first cohort and underwent testing using enzyme immunoassay (EIA) (Syva Microtrack II EIA; Dade Behring Diagnostics Ltd, Milton Keynes, UK). With the introduction of the ligase chain reaction (LCR) assay (LCx probe system, Abbott Diagnostics, Maidenhead, UK), a second cohort of 210 consecutive women (106 from the FC, 104 from the ARU) underwent endocervical screening using LCR. In total, 427 women were screened over an 8 month period.
Diagnostic methods
For all tests, nursing and medical staff followed sampling protocols derived from the manufacturer's instructions. Specimens were transported directly to the microbiology department or refrigerated at source if testing was performed at the weekend. All positive EIA results were confirmed using direct immunofluorescence. A dedicated technician from the Department of Microbiology performed all LCR assays, in accordance with manufacturer instructions.
Data
Once screening had taken place, the patient's name, hospital unit number, date of birth, and date of screening was documented on a clinic recruitment sheet. All results were seen by S.M., who recorded the patient's demographic details and test outcome on an individual data sheet. Data were stored in a personal computer and the results analysed using the Statistical Package for Social Services (SPSS, Inc, Chicago, IL, USA).
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Results |
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Overall, 427 women aged 19–43 years were screened while attending the Fertility Centre during March 1997 to October 1997. The mean age of those attending the FC and ARU was 30.2 and 33.4 years respectively. Those from the FC were significantly younger (P < 0.0001). The mean ages of those women screened by EIA and LCR was 31.4 and 32.0 years, respectively. These were not significantly different.
The overall chlamydial infection rate was 0.9% or four out of 427, representing two patients each from the FC and ARU respectively. No positive cases were identified using EIA among the 217 consecutive women screened. All positives (95% CI) were identified using the LCR assay, 4/210 or 1.9% (0.5–4.8). Table I shows the number of women screened by EIA and by LCR, stratified by age for number screened, number positive for C.trachomatis, and resulting prevalence.
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Discussion |
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Owing to the asymptomatic nature of lower genital tract infection with C.trachomatis, most infected women can only be identified by screening. It is well known that those who undergo uterine instrumentation are at risk of upper tract dissemination of endocervical chlamydial infection (Møller et al., 1982, 1984). Those undergoing infertility investigation and treatment may be at risk through hysterosalpingography, laparoscopy and dye hydrotubation, hysteroscopy, intrauterine insemination, and/or embryo transfer. It is therefore not surprising that the Chief Medical Officer's Expert Advisory Group advised that consideration be given to screening couples with fertility problems (Expert Advisory Group, 1998
).
Prevalence rates as low as 3% have been identified as cost effective for screening (Paavonen, 1997; Rene Howell et al., 1998). Unlike those patients presenting for, e.g. therapeutic abortion or contraceptive advice, there are few studies indicating the expected prevalence in infertile women. A literature search identified eight comparative studies involving more than 100 women, with chlamydial prevalence ranging from 0–10.4% (Table II). Two studies found very high prevalence rates of ~10%. However, one report (Samra et al., 1994), gave no information on selection criteria or age distribution. Similarly, poor detail in a study from South Africa meant that there was no information to explain the high prevalence found (van Schouwenburg et al., 1992).
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Six out of the eight studies found similar low prevalence rates. A report (Eggert-Kruse et al., 1997
) on over 1000 women excluded those with signs or symptoms of infection. They found a higher prevalence rate in the cohort tested by LCR compared with that tested by culture. Another study (Ruijs et al., 1990) screened consecutive couples, reporting a similar female age range with a prevalence of <2%. Furthermore, they reported that <2% of their study population admitted to an extra-marital relationship in the past year, thereby making the group low risk for sexually transmitted infection. A similar age range and prevalence was found in another study (Ånestad et al., 1987), but included only women who had not taken antibiotics in the past year. Another group studied (Kane et al., 1984) included an older population, but selection was random rather than consecutive. The report by Møller et al. studying screening prior to salpingography was strengthened by defined exclusion criteria, but again it was not stated whether recruitment was consecutive (Møller et al., 1984). The higher prevalence found might have reflected the younger mean age of the women. Finally, the patients in the study by Gump et al. (1983) had a similar age range to ours, but may have been selected as they were recruited over 4 years. In comparison, this study was undertaken in a single fertility centre where all subfertile patients from the region are seen. We simultaneously studied consecutive patients attending the two clinics, with only antibiotic use in the past 4 weeks stipulated as an exclusion criterion. S.M. cross-checked those patients recorded on the recruitment sheets with test results received by the laboratory to ensure maximum inclusion without duplication. We are therefore confident that this study accurately reflects chlamydial prevalence in a subfertile population.
EIA is the method most widely used throughout the UK for the identification of chlamydial infection. Sensitivity of the test is normally quoted at 
70% (Black, 1997), meaning that up to 30% of infections will be missed. In comparison, LCR sensitivity is >90% (Black, 1997). Furthermore, it is recognized that women aged >30 years and those with chronic chlamydial infection more commonly have low antigen loads (Mårdh, 1997). As a test, EIA is much more dependent on bacterial load than LCR. That LCR performs better than EIA cannot be concluded from this study because each woman was not screened by both methods, but there is now evidence to support this in both high (Stary et al., 1997) and low (Grun et al., 1997) prevalence populations. It is therefore likely that the chlamydial infection rate of 1.9%, identified by LCR, reflected our true population prevalence.
In this study, screening by LCR gave a prevalence with upper limit confidence intervals in excess of the quoted 3% cut-off for cost effective screening using a DNA-amplification method (Paavonen, 1997; Rene Howell et al., 1998). Coupled with a high chance of undergoing uterine instrumentation of some form, protection against disseminated chlamydial infection should be considered in this group. The frequency of serious infection following hysterosalpingography, for example, is reported to be between 0.3–4% (Marshak et al., 1950; Stumpf and March, 1980; Forsey et al., 1990). Our results and those of Eggert-Kruse et al. suggest that a DNA amplification method may be the test of choice (Eggert-Kruse et al., 1997). We recognize, however, that this test is not yet widely available. Prior to changing current practice, more evidence is required from studies testing patients by both diagnostic methods. Until then, centres using EIA might consider using prophylactic antibiotics, as suggested in higher risk groups (Penney et al., 1998), rather than rely on a relatively insensitive test. Another study (Pittaway, 1983) found that the risk of pelvic inflammatory disease post-hysterosalpingography could be eliminated with doxycycline prophylaxis. This recommendation has obvious cost implications, but these are minor compared with the cost of `routine' infertility investigation and treatment or that of inpatient management of infective complications.
There is now increasing availability of information about chlamydial prevalence in different clinical settings. Recognized risk factors include younger age, number/change of sex partner(s), and single status (Expert Advisory Group, 1998). A recent study of over 13 000 female military recruits found a prevalence of 9.2% using LCR (Gaydos et al., 1998). Their age range was similar to our study population, but their average age was much younger at 21 years. Positivity was age-related with a prevalence of 10% among women aged 25 years. As only 11% of our patients were aged 25 years and all were married or in a stable partnership, it is not surprising that this older and probably monogamous population had a low carriage rate of chlamydial infection. However, using 35 years as an age cut-off for Chlamydia screening, as currently recommended by the RCOG, would have missed half of the positives in this study.
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Conclusions |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConclusionsReferences |
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There is now strong evidence that chlamydial infection is one of the major preventable causes of infertility and many infertile women have serological evidence of past infection (Mol et al., 1997
). Preventative efforts should therefore continue to focus on the detection and eradication of lower genital tract chlamydial infection in high-risk groups. The infertile are older than most at-risk groups and carriage rates are likely to be lower for this reason. However, they still are at risk of dissemination or reinfection at the time of uterine instrumentation. Further evidence is needed before recommending the `best test', but, until then, prophylactic antibiotics should be considered in centres using relatively insensitive testing such as EIA.
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Acknowledgments |
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We wish to thank those women attending Aberdeen's Fertility Centre who agreed to be tested for Chlamydia. We acknowledge the assistance of the Fertility Centre's nursing and medical staff in performing the swabs.
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Notes |
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1 To whom correspondence should be addressed
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References |
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Anestad, G., Lunde, O., Moen, M. and Dalaker, K. (1987) Infertility and chlamydial infection. Fertil. Steril., 48, 787–790.[Web of Science][Medline]
Black, C.M. (1997) Current methods of laboratory diagnosis of Chlamydia trachomatis infections. Clin. Microbiol. Rev., 10, 160–184.[Abstract]
Cates Jr, W. and Wasserheit, J.N. (1991) Genital chlamydial infections: epidemiology and reproductive sequelae. Am. J. Obst. Gynecol., 164, 1771–1781.[Web of Science][Medline]
Coste, J., Laumon, B., Bremond, A. et al. (1994) Sexually transmitted diseases as major causes of ectopic pregnancy: results from a large case control study in France. Ferti. Steril., 62, 289–295.[Web of Science][Medline]
Eggert-Kruse, W., Rohr, G., Demirakca, T. et al. (1997) Chlamydial serology in 1303 asymptomatic subfertile couples. Hum. Reprod., 12, 1464–1475.
Expert Advisory Group (1998) Chlamydia trachomatis – Summary and Conclusions of CMO's Expert Advisory Group. Department of Health, London, UK, pp. 1–22.
Forsey, J.P., Caul, E.O. 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.
Gaydos, C.A., Rene Howell, M.S., Pare, B. et al. (1998) Chlamydia trachomatis infections in female military recruits. N. Engl. J. Med., 339, 739–744.
Grun, L., Tassano-Smith, J., Carder, C. et al. (1997) Comparison of two methods of screening for genital chlamydial infection in women attending in general practice: cross sectional survey. Br. Med. J., 315, 226–230.
Gump, D.W., Gibson, M. and Ashikaga, T. (1983) Evidence of prior pelvic inflammatory disease and its relationship to Chlamydia trachomatis. Am. J. Obstet. Gynecol., 146, 153–159.[Web of Science][Medline]
Henry-Suchet, J., Utzmann, C., DeBrux, J. et al. (1987) Microbiologic study of chronic inflammation associated with tubal factor infertility. Fertil. Steril., 47, 274–277.[Web of Science][Medline]
Kane, J.L., Woodland, R.M., Forsey, T. et al. (1984) Evidence of chlamydial infection in infertile women with and without fallopian tube obstruction. Fertil. Steril., 42, 843–848.[Web of Science][Medline]
Mardh, P.A. (1997) Is Europe ready for STD screening? Genitour. Med., 73, 96–98.
Marshak, R.H., Poole, C.S. and Goldberger, M.A. (1950) Hysterography and hysterosalpingography. Surg. Gynecol. Obstet., 91, 182–185.[Web of Science][Medline]
Mol, B.W.J., Dijkman, B., Wertheim, P. et al. (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]
Moller, B.R., Ahrons, S., Laurin, J. and Mardh, P.A. (1982) Pelvic infection after elective abortion associated with Chlamydia trachomatis. Obstet. Gynecol., 59, 210–213.[Web of Science][Medline]
Moller, B.R., Allen, J., Toft, B. et al. (1984) Pelvic inflammatory disease after hysterosalpingography associated with Chlamydia trachomatis and Mycoplasma hominis. Br. J. Obstet. Gynaecol., 91, 1181–1187.[Web of Science][Medline]
Paavonen, J. (1992) Genital Chlamydia trachomatis infections in the female. J. Infect., 25, 39–45.[Web of Science][Medline]
Paavonen, J. (1997) Is screening for Chlamydia trachomatis infection cost-effective? Genitour. Med., 73, 103–104.
Penney, G.C., Thompson, M., Norman, J. et al. (1998) A randomised comparison of strategies for reducing infective complications of induced abortion. Br. J. Obstet. Gynaecol., 105, 599–604.[Web of Science][Medline]
Pittaway, D.E., Winfield, A.C., Maxson, W. et al. (1983) Prevention of acute pelvic inflammatory disease after hysterosalpingography: Efficacy of doxycycline prophylaxis. Am. J. Obstet. Gynecol., 147, 623–626.[Web of Science][Medline]
Rene Howell, M.S., Quinn, T.C., Braithwaite, W. and Gaydos, C.A. (1998) Screening women for Chlamydia trachomatis in family planning clinics. The cost-effectiveness of DNA amplification assays. Sex. Trans. Dis., 25, 108–117.[Web of Science][Medline]
Ruijs, G.J., Kauer, F.M., Jager, S. et al. (1990) Epidemiological aspects of chlamydial infections and tubal abnormalities in infertile couples. Eur. J. Obstet., Gynaecol. Reprod. Biol., 36, 107–116.[Web of Science][Medline]
Samra, Z., Soffer, Y. and Pansky, M. (1994) Prevalence of genital chlamydia and mycoplasma infection in couples attending a male infertility clinic. Eur. J. Epidemiol., 10, 69–73.[Web of Science][Medline]
Stary, A., Najim, B. and Lee, H.H. (1997) Vulval swabs as alternative specimens for ligase chain reaction detection of genital chlamydial infection in women. J. Clin. Microbiol., 35, 836–838.[Abstract]
Stumpf, P.G. and March, C.M. (1980) Febrile morbidity following hysterosalpingography: identification of risk factors and recommendations for prophylaxis. Fertil. Steril., 33, 487–492.[Web of Science][Medline]
Svensson, L., Mardh, P.A. and Westrom, L. (1983) Infertility after acute salpingitis with special reference to Chlamydia trachomatis. Fertil. Steril., 40, 322–329.[Web of Science][Medline]
Taylor-Robinson, D. (1994) Chlamydia trachomatis and sexually transmitted disease. Br. Med. J., 308, 150–151.
Templeton, A. (1996) The Prevention of Pelvic Infection. RCOG Press, London, UK, pp. 3–278.
van Schouwenburg, J., de Bruyn, O., Fourie, E. et al. (1992) A randomised, comparative study of the efficacy and tolerance of roxithromycin and doxycycline in the treatment of women with positive endocervical cultures for Chlamydia trachomatis and Mycoplasma spp. in an in vitro fertilization program. Diagn. Microbiol. Infect. Dis., 15, 129S–131S.[Medline]
Submitted on May 13, 1999; accepted on September 9, 1999.
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