Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen AB25 2ZD, UK
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Abstract |
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Key words: Chlamydia trachomatis/infertility/prevalence/screening/uterine instrumentation
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Introduction |
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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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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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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% (0.54.8). 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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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 010.4% (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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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 0.34% (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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Acknowledgments |
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Notes |
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References |
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Submitted on May 13, 1999; accepted on September 9, 1999.