1 Department of Obstetrics and Gynaecology, Aberdeen Maternity Hospital, Foresterhill, Aberdeen, UK. E-mail: ogy167{at}abdn.ac.uk
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Abstract |
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Key words: Chlamydia trachomatis/prophylactic antibiotics/screening/subfertility/uterine instrumentation
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Introduction |
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The vast majority of subfertile women will have their cervical mucus breached either diagnostically (hysterosalpingogram/laparoscopy and dye hydrotubation) or therapeutically (intrauterine insemination/embryo transfer). Thus, the above question pertains to virtually all of a clinic's female population.
Regarding C. trachomatis infection in subfertile women, what are we, as clinicians, trying to achieve? Firstly, we want to prevent LGT infection spreading to the upper genital tract (UGT). This is achieved by secondary prevention, i.e. screening. Secondly, we wish to prevent further morbidity in those with established UGT colonization. This is tertiary prevention and where serology comes in. However, in the case of C. trachomatis infection tertiary prevention is less effective than secondary because substantial tubal damage will have occurred by the time a woman presents with an ectopic pregnancy (EP) or tubal factor infertility (TFI). Finally, the use of prophylactic antibiotics may supersede secondary prevention, though their role in tertiary prevention is uncertain.
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Screening |
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In addition to women <25 years of age, it has been recommended that women >25 years with risk factors should be screened (Chief Medical Officer, 1998). While it is assumed that a couple embarking on a pregnancy are monogamous, subfertility places great stress on relationships (Appleton, 1990
; Tarlatzis et al., 1993
). Up to 16% of the general population admit to concurrent partnerships (Johnson et al., 2001
), with one Greek paper reporting higher levels of infidelity by infertile couples (Tarlatzis et al., 1993
). This may or may not be generalized to infertile couples on the whole, as this area is under-researched. However, this sensitive issue could be addressed at the couple's first visit, by separate examination. Unit counsellors should encourage disclosure to clinical staff. Oocyte donors, regardless of age, should be screened routinely (Scottish Intercollegiate Guidelines Network, 2000
).
The evidence to support screening men is less clear. Eggert-Kruse et al. found a prevalence of <1% testing 150 subfertile men (Eggert-Kruse et al., 1997). However, a recent large general population study found men and women to have a similar overall prevalence (Fenton et al., 2001
). The highest age-specific prevalence for men was older at 2535 years. Further research is required before a screening age limit can be recommended. This precludes sperm donors who should always be screened (Scottish Intercollegiate Guidelines Network, 2000
).
So, if women <25 years, those older with risk factors [i. e. concurrent sexual partners, partners working in STI endemic regions, or those with a past history of STI, pelvic inflammatory disease (PID), EP or TFI], men with risk factors, and gamete donors should be screened, what about the rest of the clinic population?
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Chlamydial antibodies |
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In our own unit, 219 consecutive women underwent medical history, transvaginal ultrasound, C. trachomatis Ab testing by ELISA, and laparoscopy and dye hydrotubation. The prevalence of tubal pathology was 31%. The sensitivity of positive C. trachomatis IgG Abs was 31% (95% confidence interval 2143). Poorer than flipping a coin.
While the sensitivity and positive predictive value will increase by choosing higher cut-off titre levels, in their present form, non-MIF Ab tests are not sensitive enough to label positive women as `C. trachomatis exposed'. Furthermore, the action of then validating the Ab result by giving antibiotics cannot be justified. New recombinant protein ELISAs may overcome the problem, but the impact of antibiotics on Ab titre has still not been established.
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Uterine instrumentation |
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The risk of post-procedure PID is higher if tubal pathology is present (Pittaway et al., 1983; Forsey et al., 1990
). The studies quoted by Land et al. reporting evidence of persistent C. trachomatis micro-organisms in the upper genital tract (Land et al., 2002
) all took their specimens from macroscopically damaged tubes (Patton et al., 1994
; Dieterle et al., 1998
; Gérard et al., 1998
). In addition to screening, it would therefore seem sensible to administer prophylactic antibiotics to those women with a past history of PID (Chief Medical Officer, 1998
), EP (Coste et al., 1994
) and known or diagnosed tubal pathology, regardless of evidence of LGT infection. The partner should also be screened for STIs. This is really tertiary prevention, aiming to prevent progression of mild disease in the UGT. Theoretically, this leaves surgery as a therapeutic option (RCOG, 1998b
) and might improve live birth rates (Csemiczky et al., 1996
). However, there is no conclusive evidence that antibiotic treatment leads to the re-establishment of adequate tubal function in chlamydial infected UGTs.
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Prophylactic antibiotics |
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Regarding cost, prescribing azithromycin [Phizer, UK National Health Service (NHS) cost £8.95] to all women undergoing diagnostic and therapeutic uterine instrumentation in our unit would cost ~£7000 per annum. This may seem small in the overall expense of assisted reproduction, but must be highlighted as moves are being made to make fertility services NHS funded and available to all. Furthermore, this figure would only cover one diagnostic or therapeutic episode per couple, as their infection status would be unknown.
Finally, the issue of antibiotic resistance has recently been highlighted (Huovinen and Cars, 1998; Wise et al., 2001) with national strategies in Europe and North America promoting judicious antibiotic use. Data suggest that up to 75% of antibiotic use is questionable (Wise et al., 2001). To prescribe prophylactic antibiotics when the overall prevalence of chlamydial infection in the LGT is low, post-procedure PID rates in cases of no relevant past history or actual tubal pathology are low, and with unproven benefit to the UGT, does not make for prudent prescribing.
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Conclusions |
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More specific serology tests are eagerly awaited. In their present form they cannot be recommended as a screening tool.
Those women with a past history of chlamydial morbidity or a diagnosis of tubal pathology should, in addition to screening, be covered with prophylactic antibiotics when undergoing uterine instrumentation. The partner should be screened for STIs.
Units should audit the above recommendations using prevalence, PID and GUM attendance rates as outcome measures.
Non-selective use of prophylactic antibiotics serves to increase the problem of resistance and maintain the bacterial load of C. trachomatis in the community.
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Acknowledgements |
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References |
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