- Email: [email protected]
Preventing infective complications relating to induced abortion
Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
Contents lists available at ScienceDirect
Best Practice & Research Clinical Obstetrics and Gynaecology journal homepage: www.elsevier.com/locate/bpobgyn
10
Preventing infective complications relating to induced abortion Nirmala Mary, MRCOG, Consultant Obstetrician and Gynaecologist a, *, Tahir A. Mahmood, MD, FRCOG, FRCPI, MBA, Consultant Obstetrician and Gynaecologist b a b
New Royal Infirmary, Edinburgh, Midlothian, U.K. Forth Park Hospital, Kirckaldy, Fife, U.K.
Keywords: infective complications chlamydia gonorrhoea bacterial vaginosis induced abortions antibiotic prophylaxis cost-effectiveness medical management surgical management
Infective complications following induced abortions are still a common cause of morbidity and mortality. This review focusses on defining the strategies to improve care of women seeking an induced abortion and to reduce infective complications .We have considered the evidence for screening and cost-effectiveness for antibiotic prophylaxis. Current evidence suggests that treating all women with prophylactic antibiotics in preference to screening and treating is the most cost-effective way of reducing infective complications following induced abortions. The final strategy to prevent infective complications should be individualized for each region/area depending on the prevalence of organisms causing pelvic infections and the resources available. Ó 2010 Elsevier Ltd. All rights reserved.
Epidemiology Induced abortions are performed all over the world. About one in five pregnancies worldwide end in an abortion. Sedgh et al1 reviewed the worldwide induced abortion figures and estimated that there were 42 million induced abortions in 2003 as compared with 46 million abortions in 1995. The induced abortion rate was 29/1000 women aged 15–44 years in 2003 compared with 35/1000 in 1995. There was a huge variation in abortion rates in different parts of the Western world, the lowest being in Western Europe at 12/1000 women. Abortion rates were 17/1000 in northern Europe, 18/1000 in southern Europe and 21/1000 women in northern America. There are approximately 20 abortions per 1000 fertile age women (Table 1).5
* Corresponding author. Tel.: þ44 131 3374613. E-mail address: [email protected] (N. Mary). 1521-6934/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpobgyn.2010.03.005
540
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
According to the Department of Health Statistics in England and Wales (2008), the total number of abortions was approximately 201 600 in 2007 with a rise of 2.5% compared with 2006. The agestandardised abortion rate was 18.6 per 1000 women aged 15–44 years.2 There is evidence to suggest that an increasing proportion of abortions are now carried out medically. Medical abortions account for 35% of abortions compared with 30% in 2006, showing a rise in the uptake of medical abortion. Scottish data published in 2008 showed 13 817 (Rate: 13.1/1000 women) induced abortions.3 United States had an estimated 1 206 200 abortions during 2006–07.4 Although induced abortion is a safe procedure in the Western and the resource-rich countries, there still remains a concern as regards unsafe abortions, which are being carried out worldwide, leading to a large number of maternal deaths. In the UK, the Abortion Act 1967 has ensured that when there is a concern about maternal well-being, two doctors can accede to the women’s request for an induced abortion. The most recently published Clinical Enquiry into Maternal and Child Health (CEMACH) report has cited one maternal death directly attributable to sepsis after unsafe abortion.6 Nearly half (48%) of all induced abortions worldwide were estimated to be unsafe in 2003. A great majority of them (97%) were carried out in the developing world. Unsafe abortions account for 13% of maternal deaths. An estimated 5 million women are hospitalised each year for abortion-related complications such as haemorrhage and sepsis. Abortions cause approximately 68 000 deaths and 5 million disability adjusted life years (disability adjusted life years) per year worldwide.7 Unsafe abortions account for 13% of maternal deaths. By achieving safe abortions and with the provision of adequate contraception, we will be able to reduce maternal mortality substantially and protect maternal health.1,5,8,9 Amongst unsafe abortions, infective complications occur most frequently, resulting in significant morbidity and mortality. Infective complications are seen in 1–45% of women following induced abortions.10–12 This rate varies globally, being prevalent at the rate of 1–4.8% in developed countries and up to 45% in developing countries. The rates of infections are particularly high in unsafe abortions where women seek medical help late.10–12 Pelvic infections not only increase short-term morbidity and mortality but also have long-term health consequences such as chronic pelvic pain, infertility (4–7-fold increase in risk, and recurring infections double the risk) and ectopic pregnancies. Causative organisms for post-abortion infections Post-abortal genital tract infection including pelvic inflammatory disease (PID) of varying degrees of severity occurs in about 10% of induced abortions.10 Post-abortal sepsis is known to be polymicrobial. Various organisms causing post-abortion sepsis are Chlamydia trachomatis (CT), Neisseria gonorrhoea Table 1 Global and regional estimates of induced abortion, 1995 and 2003. Abortion ratea
Region and sub region
No. of abortions (millions) 1995
2003
1995
2003
World Developed countries Excluding Eastern Europe Developing countriesb Excluding China
45.6 10.0 3.8 35.5 24.9
41.6 6.6 3.5 35.0 26.4
35 39 20 34 33
29 26 19 29 30
Estimates by region Africa Asia Europe Latin America Northern America Oceania
5.0 26.8 7.7 4.2 1.5 0.1
5.6 25.9 4.3 4.1 1.5 0.1
33 33 48 37 22 21
29 29 28 31 21 17
Permission to reproduce table obtained from Guttmacher Institute.5 a Abortions per 1000 women aged 15–44. b Those within Africa, the Americas, excluding Canada and the United States of America, Asia, excluding Japan, and Oceania, excluding Australia and New Zealand.
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
541
(NG) and endogenous vaginal anaerobes such as Gardenerella vaginalis (GV), Ureaplasma urealyticum (UU) and Mycoplasma genitalium (MG) causing bacterial vaginosis (BV).14 Chlamydia is an obligate Gram-negative intracellular bacterium commonly causing asymptomatic prolonged infections. N. gonorrhoea (NG) is a Gram-negative facultative intracellular aerobic diplococcic bacterium. They produce lipopolysaccharide endotoxins, which are highly toxic. BV is a polymicrobial condition where the lactobacilli – the normal commensal in the vagina – are replaced by anaerobic bacteria such as GV, UU and MG. These anaerobic organisms produce enzymes such as amino-peptidases and de-carboxylases that degrade proteins and convert amino acids to amines, which account for the characteristic ‘fishy odour’. The anaerobic organisms are thought to be permissive organisms facilitating the infection by Chlamydia, gonorrhoea and other aerobic organisms. They alter ‘the cervical mucous through enzymatic degradation of proteolytic barrier’.15 Organisms present in the lower genital tract that is, upper vagina and cervix, can therefore lead to ascending infections in the endometrium, fallopian tubes or the pelvic cavity. C. trachomatis (CT) is the most common bacterial sexually transmitted organism in Europe and Northern America. The prevalence of Chlamydia infection in the pre-abortal population is 4.9– 17.9%.16,19 In the UK, the prevalence of Chlamydia is approximately 6–8%.17,18 The prevalence of Chlamydia-positive patients was 11.4% (range: 5–15%) and NG was 2.6% (range: 1–3%) amongst women seeking first-trimester screening in Illinois.19 A study from Finland reported a nationwide increase from 23.4 per 10 000 to 29.2 per 10 000 in the incidence rates of CT, especially in the adolescents and young people.20 Bearing in mind the low prevalence of gonorrhoea (0.2%) among women in the United Kingdom undergoing abortion,18 screening for gonorrhoea is controversial.21 CT is detected more often in women with BV and may facilitate CT infection in the upper genital tract.18 Recurrent infections with Chlamydia lead to long-term problems such as tubal damage, infertility and chronic pelvic pain.17,21,22 The prevalence of Chlamydia is higher in young women (15–25 years) as they are more prone to infections because of various factors such as discussed in Hillard et al.: cervical ectopy, lower levels of protective antibodies, reduced access to medical care and high risk-taking behaviour. Strategies to diagnosis of infection Chlamydia Chlamydia infection is now widely diagnosed using nucleic acid amplification tests (NAATs). A systematic review24 has shown that self-collected vaginal swabs, urine Chlamydia tests have similar results to endo-cervical and urethral swabs, with the exception of polymerase chain reaction (PCR) (COBAS amplicor), which was less sensitive than the urine test for gonorrhoea. Sensitivities for PCR were 83.3%, transcription-mediated amplification 92.5% and strand displacement amplification assays 79.9% for Chlamydia, and specificities for all assays were more than 95% for Chlamydia urine samples. The main limitation for the use of NAAT is the higher cost compared to non- NAAT, although in the long run cost-effectiveness analysis has suggested that the use of these tests for screening of Chlamydia will be cost-effective. Gonorrhoea The pooled results of four studies of the PCR assay reported sensitivity and specificity as 55.6% (confidence interval (CI), 36.3–74.9%) and 98.7% (CI, 97.5–99.9%) for urine samples and 94.2% (CI, 90.5– 98.0%) and 99.2% (CI, 98.4–100%) for cervical samples, whereas the transcription-mediated amplification assay had the sensitivity and specificity of 91.3% (CI, 85.0–95.6%) and 99.3% (CI, 98.6–99.6%) for urine samples and 99.2% (CI, 95.7–100%) and 98.7% (CI, 98.0–99.3%) for cervical samples. For the study of strand displacement amplification, the sensitivity and specificity were 84.9% (CI, 75.6–91.7%) and 99.4% (CI, 98.9–99.8%) for urine samples and 96.5% (CI, 90.1–99.3%) and 99.5% (CI, 99.0–99.8%) for cervical samples. Is screening for Chlamydia in the general population worthwhile? Screening for Chlamydia has been shown to be cost-effective in preventing PID.25 It has been suggested that all moderate-to-high prevalence population (8%) should be screened and
542
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
treated.23,26,27 However, this observation has been challenged.28 The authors felt that the cost-effectiveness of previous studies was based on static models and did not take account of the lower uptake of screening, partner notification and lower complication rates. Screening for Chlamydia in populations with lower prevalence still showed high specificities (98– 100%) though clinicians should be aware of higher rates of false positive (as high as 1/3); therefore, a confirmatory test should be performed. These rates may be negligible if specificity of assay exceeds 99.5%.24 A meta-analysis by Watson et al. 2002 showed that non-invasive testing by NAAT for Chlamydia was more effective in detecting asymptomatic Chlamydia infection. The meta-analysis showed that DNAbased tests detected more cases of asymptomatic chlamydial infections than conventional non-culture tests. The odds ratios (ORs) showed a statistically significantly lower rate of false-negative results with urine ligase chain reaction(LCR) (0.33, 95% CI: 0.13, 0.80) and cervix PCR (0.26, 95% CI: 0.12, 0.56) than with the reference standard. The ORs showed no significant differences between the false-negative rates with urine PCR (0.84, 95% CI: 0.37, 1.89), urine gene probe (0.44, 95% CI: 0.15, 1.26), cervix gene probe (1.16, 95% CI: 0.25, 5.47), urine enzyme immunoassay (1.86, 95% CI: 0.39, 8.75), cervix direct immuno-fluorescence (1.05, 95% CI: 0.09, 12.93) and the reference standard. The OR revealed a significantly higher rate of false-negative results for cervix enzyme immunoassay than the reference standard (4.10, 95% CI: 1.15, 14.59).29 Self-taken vaginal swabs were cost-effective in preventing more cases of PID than other strategies.30 Chlamydia infections are associated with short- and long-term morbidity. Current evidence suggests that up to 20% of women with Chlamydia will suffer from PID, 4% from chronic pelvic pain and 3% from infertility.
Should women be screened for BV? BV occurs in up to 30% of women. It is a known risk factor for infections following induced abortions. The incidence of post-abortal endometritis was 5.6% in women, who had positive swabs for bacterial vaginosis preoperatively.31 Larsson32 performed a prospective randomised trial to evaluate the effect of 2% clindamycin cream on post-surgical abortion infection. This treatment resulted in significant reduction in postoperative infections with abnormal vaginal flora (relative risk (RR): 4.2, 95% C.I.1.2– 15.9). It is well known that BV makes women more susceptible to other sexually transmitted diseases such as trichomoniasis and the bacterium, Chlamydia.33 A randomised trial31 showed that suppression of bacterial vaginosis with twice-weekly metronidazole gel offered the women protection from Chlamydia. Hamark34 studied the risk factors of post-abortal endometritis in Chlamydia-negative women and identified that women with greater than 20% clue cells had a 5.6% RR of acquiring postabortal infections. However, a randomised double blind placebo-controlled trial to evaluate the efficacy of metronidazole in preventing post-abortal infections provided weak evidence that metronidazole reduces the risk of infection after first-trimester suction termination.35 Furthermore, a recent large randomised treatment trial of BV concluded that oral metronidazole with doxycycline did not prevent post-abortal infections.36 However, a recently published comprehensive review about treatment of bacterial vaginosis37 suggests that though the available numbers in various studies are small, the slowly gathering evidence indicates that it is prudent to treat BV in women who are having surgical procedures such as induced abortions. The US Centre for Disease Control and Prevention (CDC) recommends that there are benefits of treatment of BV – reduction of infections following abortion and other operative gynaecological procedures. It has also been suggested that three or more of the following criteria could be used to confirm the diagnosis of BV ‘(i) >20% of squamous cells examined are clue cells, (ii) the bacterial population in the wet prep is dominated by cocci and coccobacilli, (iii) a vaginal pH 4.7 and (iv) a positive whiff test.’ Various regimes for treatment of BV have been suggested from the literature –metronidazole tablets 500 mg twice daily for 7 days (99% immediate cure rate and 84% cure rate at 6 weeks). Similarly, oral treatment with clindamycin or intra-vaginal metronidazole or clindamycin has also been shown to be effective. Newer therapeutic agent such as tinidazole has also been shown to be useful in the treatment of BV.37 Having reviewed the
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
543
published literature on BV, we are of the opinion that, in balance, women with BV should be medically treated and the effectiveness of the treatment should be investigated in properly designed studies. Prevention of infective morbidity There are various preventive strategies to reduce infective complications. Induced abortions are performed for unwanted or unintended pregnancies. Up to 50% of all pregnancies are unintended though not all unintended pregnancies result in abortion. Unintended pregnancies could be due to failure to use contraception, failure of the contraceptive methods mostly due to user dependence, lack of access to facilities or severe maternal disease or foetal anomalies. Various primary prevention strategies will help reduce the number of women needing induced abortions. Patient education, use of effective contraception and improving access to health care in general will reduce the number of abortions, thereby reducing complications. Legalisation of abortions, easy access to non-judgemental services, routine vaccination such as tetanus toxoid and early abortion will all help in primary prevention. Patient and partner education and support The main tool for all primary prevention is empowering patients. Educating patients regarding all the options of contraception includes the use of emergency contraception and long-acting reversible contraception, their efficacy, risks and possible side effects, and non-contraceptive benefits. They should also be informed about the option of induced abortion, advantages of early abortions and early recognition of symptoms of infections and regarding the importance of seeking medical help early. Contraception Use of effective contraception will reduce the rates of induced abortions and therefore reduce complications overall. We are all aware that some forms of contraception are more effective than the others. The use of methods such as condoms, sheaths or oral contraceptive pills are very user dependent. Long-acting reversible contraceptive methods such as the intrauterine contraceptive devices and systems, hormonal injections and contraceptive implants are more effective than other forms of contraceptives. It is estimated that approximately 73 000 unintended pregnancies can be reduced per annum, which is about a third of induced abortions in England and Wales. This would therefore significantly reduce the complications associated with abortions. They are also thought to be cost-effective. A 7% population switch from oral contraceptive pill to long-acting reversible contraception can save £100 million by reducing the rates of unintended pregnancies.38,39 Legalisation and provision of services It is a well-proven fact that legalisation of abortion services will significantly reduce the risk of complications. It will also help in the provision of services within easy access to the community where there is no stigma attached to the centre or the users. Legalisation of services will reduce the need or use of illegal premises, untrained/unqualified personnel providing services and also bring all the services under the legal guidelines for provision of high standards of care. The system should also provide training for all the staff involved so that services continue to be delivered safely. These measures will significantly reduce the risk of procedures and the complications associated with induced abortion. It has been shown that the legalisation of abortion in South Africa in 1996 led to significant reduction in morbidity and a 90% drop in mortality following abortion, especially in younger women.40 Regional measures such as routine tetanus immunisations, use of tetanus toxoid to neutralise any toxins if tetanus is suspected and antibiotic prophylaxis according to the prevalence of common organisms found should be designed regionally/nationally. Local multidisciplinary organisations should adapt available evidence to suit the needs and requirements of the local population.
544
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
Methods and gestation of induced abortion Induced abortions are performed medically or surgically, depending on the gestation of pregnancy. There is sufficient evidence to suggest that medical management and early gestation at abortion are helpful in reducing complications associated with induced abortions. A systematic review of 46 421 abortions has shown that the incidence of infection after medical abortion was very low (0.92%) in both first and second trimesters, irrespective of the medical regimen used.41 A total of 90% of abortions in England and Wales were performed before 13 weeks in 2007. A total of 70% were under 10 weeks old. There is evidence to suggest that earlier the gestation, lower the complication rate; the lowest ones noted were during 7–10 weeks at surgical termination of pregnancy.42 A study by Faundes43 showed that medical management using misoprostol dramatically reduced infective complications by 49%. A Cochrane review found that medical management of induced abortion with mifepristone and misoprostol was safe and effective. Their sub-analysis showed that the odds ratio for pelvic infection comparing medical to suction termination of pregnancy was 0.13 (0.01, 2.58).44 Fjerstad has analysed the trends of rates of serious infections after changes in regimens of medical abortion from vaginal misoprostol to buccal administration of misoprostol and other infectionreduction measures and they found a 73% reduction in the rate of serious infections from 0.93 per 1000 abortions to 0.25 per 1000 (95% CI 0.44–0.94; P < 0.001) with buccal route of administration of misoprostol.45 Prophylactic antibiotics Post-abortal infections occur in w10% of women undergoing induced abortions. The risk of infection is reduced by either prophylactic antibiotics or excluding infection by bacteriological screening. The Royal College of Obstetricians and Gynaecologists (RCOG) recommend that, as a minimum, all abortion services should be offering antibiotic prophylaxis. Testing for lower genital tract infections and treating positive cases would be the ideal management.13 The RCOG has recently recommended that “all women should receive a sexually transmitted infection risk assessment and should specifically be offered testing for C. trachomatis before abortion”. Everyone with a positive result should be treated and if results are unavailable at the time of abortion, they should be offered antibiotic prophylaxis.46 Universal prophylaxis The use of universal prophylaxis is proven to provide significant protection in all women including low-risk groups undergoing therapeutic abortions. The meta-analysis by Swaya et al.47 has shown a RR estimate of 0.58 (95% CI: 0.47, 0.71) for developing post-abortal upper genital tract infection in women who received antibiotics prophylactically compared with placebo. This is also a cost-effective measure compared with placebo. There is considerable debate between the use of universal prophylaxis versus screen-and-treat policy and the ‘belt-and-braces approach’ of screening and use of prophylactic antibiotics. Universal prophylaxis has shown to reduce infection rates by up to 50% and has been found to be cost-effective though there is the risk of re-infection. The advantages of screen and treat are more targeted treatment and the opportunity to perform contact tracing and appropriate treatment. This will also help reduce the reservoir of Chlamydia in the community. The approach of screening and universal prophylaxis has the benefits of both options but there are also considerable costs involved.21 Contact tracing requires considerable organisation between various departments with committed staff. Various techniques of contact tracing and treating have been described such as partner notification, patient-delivered partner therapy (PDPT) or postal testing kits (PTK). Cameron et al. has recently reported a randomised controlled trial to see if either PDPT or PTK would reduce the risk of re-infection compared with partner notification. They did not find reduction in re-infection with either techniques but felt that PDPT may offer simplicity and cost-effectiveness compared with patient referral.48 Penny et al. performed a multicentre randomised comparison between the strategies of universal prophylaxis
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
545
and the screen-and-treat policy. The policy of universal prophylaxis was at least as effective and costeffective compared with the screen-and-treat policy for reducing short-term infective sequelae. The women, who were screened negative, had slightly higher infection rates than the group who were treated with prophylactic antibiotics.17 Following the adoption of policy of antibiotic prophylaxis in the United States, a 76% decline in infection rate from 0.25 per 1000 to 0.06 per 1000 (95% CI 0.02–0.34; P ¼ 0.03) has been reported.45 Antibiotic regimen for prophylactic antibiotics Antibiotic prophylaxis inhibits the growth of contaminating bacteria, thereby reducing the risk of infections. The type of antimicrobial used is dependent on the infecting organism and its interaction with the antibiotic regimen. The timing and the method of delivery are also crucial for good prophylaxis.49 The recommendations of antibiotic regimens for pre-abortal prophylaxis are based on the common organisms involved in upper genital tract infections (Table 2).13,50 The use of doxycycline or azithromycin with metronidazole is suggested by the RCOG guideline update group bearing in mind the causative organisms C. trachomatis and Mycoplasma Genitalium, Ureapalsma Urealyticum and Gardenerella Vaginalis.13 The National Abortion Federation also advocates use of prophylactic antibiotics to all women undergoing abortion, although it does not suggest any particular regime.50 Cost-effectiveness Bignell51 favoured using azithromycin as first line for C. trachomatis as being more cost-effective. Treatment options for uncomplicated Chlamydia infections in non-pregnant women include singledose azithromycin 1 g (95–100% cure) or doxycycline 100 mg BD for 7 days (88–100%). azithromycin is 2.7- to 12-fold more expensive than the doxycycline regime. The single-dose regime of azithromycin has increased compliance and therefore increased drug efficiency. It has been suggested that azithromycin was more cost-effective compared with doxycycline for treatment of confirmed Chlamydial infection (savings of 1200 USD per major outcome avoided – 1993 values). Although, if azithromycin was used prophylactically, it was more costly than doxycycline (792 USD – 1993 value).52 Any prophylactic regimen should be designed around robust evidence on local antimicrobial sensitivity patterns, epidemiology of infections in the region, local health service accessibility, funding availability and patient preference and compliance.
Table 2 A summary of recommended Regimens – Antibiotic prophylaxis. The RCOG recommended regimes for prevention of infective complications13 are: Metronidazole 1 g rectally at the time of abortion plus Doxycycline 100 mg BD for 7 days/Azithromycin 1 g orally single dose The recommended regimes for treatment of uncomplicated Chlamydia infections are: Doxycycline 100 mg BD for 7 days or Azithromycin 1 g orally single dose or Oxytetracycline 500 mg 4 times a day for 7 days or Erythromycin 500 mg 4 times a day for 7 days or 500 mg BD for 10–14 days or Ofloxacin 400 mg orally once a day for 7 days The CDC recommends the following antibiotics for specific infections Chlamydia: Doxycycline 100 mg bid 7 days Azithromycin 1 g stat Erythromycin dosage dependant on preparation 7 days Ofloxacin 300 mg bid 7 days Levofloxacin 500 mg 7 days Bacterial vaginosis: Metronidazole 500 mg bid 7 days orally or 2 g stat. Prophylaxis for infective endocarditis is recommended for patients having genitourinary procedures only if they have a prosthetic heart valve, previous bacterial endocarditis, congenital heart defect with prosthetic material or cardiac transplantation patients who develop valvulopathy.50
546
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
Where should women be treated when presenting with pelvic infection? Women suspected to have PID should be treated promptly. Mild-to-moderate PID can be treated as outpatients and severe PID should be treated with parenteral antibiotics. The RCOG guideline ‘Management of Acute PID’ recommends the following approach: Outpatient antibiotic treatment for mild-to-moderate PID A dosage of oral oflaxacin 400 mg BD þ Oral metronidazole 40 mg BD for 14 days is recommended. Intramuscular ceftriaxone 250 mg single dose (cefoxitin has a better evidence for treatment of PID than ceftriaxone but it is not available in the United Kingdom) followed by oral doxcycline 100 mg BD þ Oral metronidazole 400 mg BD for 14 days can be followed. The best evidence for effective antibiotic treatment for PID in preventing long-term complications comes from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) study53 where women were treated with cefoxitin followed by doxycycline. Inpatient antibiotic treatment for severe PID Intravenous ceftriaxone 2 g daily with intravenous doxycycline 100 mg BD followed by oral doxycycline BD for 14 days and oral metronidazole BD for 14 days. Intravenous clindamycin 900 mg tid with intravenous gentamicin followed by either oral clindamycin 450 mg 4 times a day for total of 14 days or oral doxycycline 100 mg BD with oral metronidazole BD to complete the course of 14 days. Intravenous ofloxacin 400 mg BD with intravenous metronidazole 400 mg BD for 14 days.54 Septic shock can be a deadly complication. Prompt access to medical facilities, elimination of infection and supportive care are essential. Early systemic broad-spectrum antibiotics followed by uterine evacuation, if required, are recommended. There is no evidence to suggest that delaying curettage for antibiotics to take effect is beneficial. Unnecessary delays can lead to death. It is recommended that broad-spectrum antibiotic should be given in large doses and if the patient is haemodynamically stable, uterine evacuation should be done as soon as possible.55–57 Information sharing with women as regards probable sepsis Infections rarely occur following a safe abortion. Presence of retained products of conception is the most common associated factor. All patients must therefore be informed of all the signs and symptoms of infections such as fever, abdominal pain, heavy bleeding and foul smelling discharge. The routine use of prophylaxis should be determined by local availabilities and practicalities. Women who are considered to be at high risk for infection such as previous pelvic infections, multiple sexual partners or those who have had unsafe abortions should be considered for prophylactic antibiotics. The use of tetanus toxoid should also be considered based on local prevalences and practices. The essentials of infection control are equally important in the prevention of infection after any surgical procedures. Universal infection control protocols should be used to protect the staff, patients and the community. Essentials of infection control such as hand washing, use of protective gloves, a clean and well-ventilated facility, adequate decontamination procedures for all instruments immediately after use, meticulous attention to sterilisation and disinfection of equipment and supplies, strict asepsis during operative procedures, use of barrier precautions to protect clinical and support staff whenever they come into contact with blood and bodily fluids, precautions against accidental cuts and needle stick injuries, careful handling of all waste, linen and equipment, appropriate disposal of all blood and tissue and contaminated materials should be practiced at all centres offering surgical abortion.7
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
547
Friedman et al.58 performed a simulation of various algorithms and suggested that resource-poor settings can use risk-based algorithms for identifying pre-abortal women who will benefit from antibiotics. Future vaccines The future will depend on designing effective vaccines to provide long-term immunity against various sexually transmitted diseases including Chlamydia. He et al. (2007) tested mice by intranasal immunisation with viral recombinants generated by insertion of immunodominant T-cell epitomes of chlamydial outer membrane protein into influenza A viruses. Immunised mice showed significant protective immunity (P > 0.02).59 Developing safe and effective vaccines against Chlamydia and other sexually transmitted diseases will be the way forward for the future. Conclusions Induced abortion is one of the most common gynaecological procedures. The incidence of induced abortion is approximately 29/1000 women worldwide. Up to half the abortions are unsafe worldwide accounting for 68 000 maternal deaths. Infective complications are the most frequent complications in unsafe abortions. Simple measures such as legalisation and destigmatisation of abortions, easy and local access to health services, promotion of abortions at early gestation, use of medical abortions and use of prophylactic antibiotics according to the local guidelines based on local prevalence of infective organisms will help significantly reduce the risk of infective complications. Prevention of abortions by education regarding safe sex, contraception and easy availability of contraception, promotion of long-acting contraceptives and emergency contraception will help reduce the rate of unintended pregnancies and therefore significantly reduce abortion rates. Future developments of efficacious vaccines against sexually transmitted diseases will help reduce infectious complications of induced abortion significantly.
Practice points Non-invasive testing using urine/self-taken vaginal swabs (with NAAT) are more effective and acceptable methods for detecting Chlamydia. Screen, contact tracing and treatment is the gold standard for preventing infective complications after induced abortion, but universal antibiotic prophylaxis policy offers a better value for money. Pre- and post-abortion counselling regarding risks of infections and implementation of contraceptive provision policy, preferably long-acting methods.
Research agenda Social research into cultural and community risk factors. Research to assess factors, which prevent access to effective contraception and abortion services. Prospective risk-based algorithms to identify cost-effective treatment. Population-based interventions to reduce sexually transmitted diseases. Develop safe and efficacious vaccines for Chlamydia infection. Research effective means of popularizing medical methods of terminations in preference to surgical methods, especially in under resourced countries.
548
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
References 1. Sedgh G, Henshaw S, Singh S et al. Induced abortion: estimated rates and trends worldwide. Lancet 2007; 370: 1338–1345. 2. Abortion statistics. Department of Health. 3. ISD Scotland. Information and statistics, sexual health, abortion data 2009, http://www.isdscotland.org/isd/1918. html#tables [accessed 03.11.09]. 4. Abortion statistics and other data – Johnston’s archive, historical abortion statistics, United States. Compiled by Wm. Robert Johnston last updated 28 January 2009, http://johnstonsarchive.net/policy/abortion/ab-unitedstates.html [accessed 03.11.09]. *5. Guttmacher Institute. Facts on induced abortion worldwide, in brief. New York: Guttmacher Institute, 2008, http://www. guttmacher.org/pubs/fb_IAW.pdf [accessed 10.10.09]. 6. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer – 2003–2005, http://www.cmace.org.uk/ publications/CEMACHpublications/Maternal-and-Perinatal-Health.aspx [accessed 03.11.09]. *7. Grimes DA, Benson J, Singh S et al. Unsafe abortion: the preventable pandemic. Sexual and Reproductive Health Series. Lancet October 2006. 8. Singh S. Hospital admissions resulting from unsafe abortion: estimates from 13 developing countries. Lancet 2006; 368 (955): 1887–1892. 9. World Health Organization (WHO). Unsafe abortion: global and regional estimates of incidence of unsafe abortion and associated mortality in 2003. Geneva: WHO, 2007. 10. Ashok PW, Kidd A, Flett GMM et al. A randomized comparison of medical abortion and surgical vacuum aspiration at 10– 13 weeks gestation. Hum Reprod January 2002; 17(1): 92–98. 11. Das V, Agarwal A, Mishra A et al. Septic abortion. J Obstet Gynaecol India May/June 2006; 56(3): 236–239. 12. Henshaw SK, Adewole I, Singh S et al. Severity and cost of unsafe abortion complications treated in Nigerian hospitals. Int Fam Plan Perspect 2008; 34(1). *13. The care of women requesting induced abortion. RCOG evidence-based clinical guideline. no. 7. London: RCOG Press, 2004. *14. Penny GC. Preventing infective sequelae of abortion. Hum Reprod 1997; 12(11): 107–112. 15. Soper D, Brockwell NJ, Dalton HP et al. Observations concerning the microbial etiology of acute salpingitis. Am J Obstet Gynecol 1994; 170: 1008–1017. 16. Schiotz H & Csango PA. A prospective study of Chlamydia trachomatis in first trimester abortion. Ann Clin Res 1985; 17: 60– 63. 17. Penney GC, Thomson M, Norman J et al. Randomised comparison of strategies for reducing infective complications of induced abortion. Br J Obstet Gynaecol 1998; 105: 599–604. 18. Blackwell AL, Thomas PD, Wareham K et al. Health gains from screening for infection of the lower genital tract in women attending for termination of pregnancy. Lancet 1993; 342: 206–210. 19. Patel A, Rashid S, Godfrey EM et al. Prevalence of Chlamydia trachomatis and Neisseria gonorrhoea genital infections in a publicly funded pregnancy termination clinic: empiric vs. indicated treatment? Contraception 2008; 78: 328–331. 20. Hiltunen-Back E, Haikala O, Kautiainen H et al. Nationwide increase of Chlamydia trachomatis infection in Finland: highest rise among adolescent women and men. Sex Transm Dis 2003; 30(10): 737–741. *21. Cameron ST & Sutherland S. Universal prophylaxis compared with screen-and treat for Chlamydia trachomatis prior to termination of pregnancy. Br J Obstet Gynaecol 2002; 109: 606–609. 22. Patton DL, Wolner-Hanssen P, Cosgrove SJ et al. The effects of Chlamydia trachomatis on the female reproductive tract of the Macaca nemestrina after a single tubal challenge following repeated cervical inoculations. Obstet Gynecol 1990; 76: 643–650. 23. Hillard S, Weinstock GA, Bolan RK et al. Chlamydia trachomatis infection in women: a need for universal screening in high prevalence population. Am J Epidemiol 1992; 135: 41–47. 24. Cook RL, Hutchison SL, Ostergaard L et al. Systematic review: noninvasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med 2005; 142: 914–925. 25. Scholes D, Stergachis A, Heidrich FE et al. Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 1996; 334: 1362–1366. 26. Phillips RS, Aronson MD, Taylor WC et al. Should tests for Chlamydia trachomatis cervical infection be done during routine gynecologic visits? An analysis of the costs of alternative strategies. Ann Intern Med 1987; 107: 188–194. *27. Trachtenberg AI, Washington AE & Halldorson S. A cost-based decision analysis for chlamydia screening in California family planning clinics. Obstet Gynecol 1988; 71: 101–108. 28. Roberts TE, Robinson S, Barton PM et al. Cost effectiveness of home based population screening for Chlamydia trachomatis in the UK: economic evaluation of chlamydia screening studies (ClaSS) project. BMJ 2007; 335: 291. 29. Watson EJ, Templeton A, Russell I et al. The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review. J Med Microbiol 2002; 51(12): 1021–1031. 30. Blake DR, Maldeis N, Barnes MR et al. Cost-effectiveness of screening strategies for Chlamydia trachomatis using cervical swabs, urine, and self-obtained vaginal swabs in a sexually transmitted disease clinic setting. Sex Transm Dis 2008; 35(7): 649–655. 31. Schwebke JR & Desmond R. A randomized trial of metronidazole in asymptomatic bacterial vaginosis to prevent the acquisition of sexually transmitted diseases. Am J Obstet Gynecol 2007; 196: 517.e1–517.e6. 32. Larsson P, Platz-Christensen J, Dalaker K et al. Treatment with 2% clindamycin vaginal cream prior to first trimester surgical abortion to reduce signs of post operative infection: a prospective, double-blinded, placebo-controlled, multicentre study. Acta Obstet Gynecol Scand 2000; 79(5): 390–396. 33. Wiesenfeld HC, Hillier SL, Krohn MA et al. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 2003; 36: 663–668. 34. Hamark B & Forssman L. Postabortal endometritis in Chlamydia-neagative women – association with preoperative clinical signs of infection. Gynecol Obstet Invest 1991; 31: 102–105.
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
549
35. Crowley T, Low N, Turner A et al. Antibiotic prophylaxis to prevent post-abortal upper genital tract infection in women with bacterial vaginosis: randomised controlled trial. Br J Obstet Gynaecol 2001; 108(4): 396–402. 36. Miller L, Thomas K, Hughes JP et al. Randomised treatment trial of bacterial vaginosis to prevent post-abortion complication. Br J Obstet Gynaecol 2004; 111(9): 982–988. *37. Livengood III Charles H. Bacterial vaginosis: an overview for 2009. Rev Obstet Gynecol 2009 Winter; 2(1): 28–37. 38. Statistical bulletin, abortion statistics England and Wales 2007. National Statistics, DOH. 39. Long-acting reversible contraception: the effective and appropriate use of long-acting reversible contraception. NICE guideline CG030 Oct 2005. 40. Rachel Jewkes, Helen Rees, Kim Dickson et al. The impact of age on the epidemiology of incomplete abortions in South Africa after legislative change. Br J Obstet Gynaecol 2005; 112(3): 355–359. 41. Caitlin S, Brothers LP, Philip NM et al. Infection after medical abortion: a review of literature. Contraception 2004; 70(3): 183–190. 42. Nesheim BI. Induced abortion by the suction method. An analysis of complication rates. Acta Obstet Gynecol Scand 1984; 63 (7): 591–595. 43. Faundes A, Santos LC, Carvalho M et al. Post-abortion complications after interruption of pregnancy with misoprostol. Adv Contracept 1996; 12: 1–9. 44. Say L, Kulier R, Campana A et al. Medical versus surgical methods for termination of pregnancy. Art. No.: CD003037. Cochrane Database Syst Rev 2002; (4), 10.1002/14651858.CD003037.pub2. 45. Fjerstad M, Trussell J, Sivin I et al. Rates of serious infections after changes in regimens for medical abortion. N Engl J Med 2009; 361(2): 145–151. 46. Standards for gynaecology. Report of a working party. London: RCOG Press. *47. Sawaya GF, Grady D, Kerlikowske K et al. Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis. Obstet Gynecol 1996; 87(5 Pt 2): 884–890. 48. Cameron ST, Glasier A, Scott G et al. Novel interventions to reduce re-infection in women with Chlamydia: a randomised controlled trial. Hum Reprod 2009; 24(4): 888–895. 49. Walling AD & ACOG Practice Bulletin. Antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol January 2001; 23: 1–9. *50. National Abortion Federation, 2009 Clinical Policy guidelines, Washington. 51. Bignell CJ. Chlamydia infection in obstetrics and gynaecology. Clin Obstet Gynaecol 1997; 7: 104–109. 52. Lea AP & Lamb HM. Azithromycin. A pharmacoeconomic review of its use as a single-dose regimen in the treatment of uncomplicated urogenital Chlamydia trachomatis infections in women. Pharmacoeconomics 1997; 12(5): 596–611. 53. Ness RB, Soper DE, Holley RL et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomised Trial. Am J Obstet Gynecol 2002; 186: 929–937. *54. Management of acute pelvic inflammatory disease. Green top guideline no. 32. RCOG Press. London. 55. Goyaux N, Yace-Soumah F, Welffens-Ekra C et al. Abortion complications in Abidjan (Ivory Coast). Contraception 1999; 60: 107–109. 56. Thapa PJ, Thapa S & Shreshtha N. A hospital-based study of abortion in Nepal. Stud Fam Plann 1992; 23: 311–318. 57. Grimes DA, Coates Jr. W, Selik RM et al. Fatal septic abortion in the United States, 1975–1977. Obstet Gynecol 1981; 57: 739– 744. 58. Friedman HB, Gift TL, Susanti I et al. Risk-based versus alternative algorithms for antibiotic prophylaxis among women seeking early suction abortion: a cost-effectiveness simulation. Sex Transm Dis 2001; 28(12): 714–724. 59. He Q, Martinez-Sobrido L, Eko FO et al. Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines. Immunology 2007; 122(1): 28–37.
Contents lists available at ScienceDirect
Best Practice & Research Clinical Obstetrics and Gynaecology journal homepage: www.elsevier.com/locate/bpobgyn
10
Preventing infective complications relating to induced abortion Nirmala Mary, MRCOG, Consultant Obstetrician and Gynaecologist a, *, Tahir A. Mahmood, MD, FRCOG, FRCPI, MBA, Consultant Obstetrician and Gynaecologist b a b
New Royal Infirmary, Edinburgh, Midlothian, U.K. Forth Park Hospital, Kirckaldy, Fife, U.K.
Keywords: infective complications chlamydia gonorrhoea bacterial vaginosis induced abortions antibiotic prophylaxis cost-effectiveness medical management surgical management
Infective complications following induced abortions are still a common cause of morbidity and mortality. This review focusses on defining the strategies to improve care of women seeking an induced abortion and to reduce infective complications .We have considered the evidence for screening and cost-effectiveness for antibiotic prophylaxis. Current evidence suggests that treating all women with prophylactic antibiotics in preference to screening and treating is the most cost-effective way of reducing infective complications following induced abortions. The final strategy to prevent infective complications should be individualized for each region/area depending on the prevalence of organisms causing pelvic infections and the resources available. Ó 2010 Elsevier Ltd. All rights reserved.
Epidemiology Induced abortions are performed all over the world. About one in five pregnancies worldwide end in an abortion. Sedgh et al1 reviewed the worldwide induced abortion figures and estimated that there were 42 million induced abortions in 2003 as compared with 46 million abortions in 1995. The induced abortion rate was 29/1000 women aged 15–44 years in 2003 compared with 35/1000 in 1995. There was a huge variation in abortion rates in different parts of the Western world, the lowest being in Western Europe at 12/1000 women. Abortion rates were 17/1000 in northern Europe, 18/1000 in southern Europe and 21/1000 women in northern America. There are approximately 20 abortions per 1000 fertile age women (Table 1).5
* Corresponding author. Tel.: þ44 131 3374613. E-mail address: [email protected] (N. Mary). 1521-6934/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpobgyn.2010.03.005
540
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
According to the Department of Health Statistics in England and Wales (2008), the total number of abortions was approximately 201 600 in 2007 with a rise of 2.5% compared with 2006. The agestandardised abortion rate was 18.6 per 1000 women aged 15–44 years.2 There is evidence to suggest that an increasing proportion of abortions are now carried out medically. Medical abortions account for 35% of abortions compared with 30% in 2006, showing a rise in the uptake of medical abortion. Scottish data published in 2008 showed 13 817 (Rate: 13.1/1000 women) induced abortions.3 United States had an estimated 1 206 200 abortions during 2006–07.4 Although induced abortion is a safe procedure in the Western and the resource-rich countries, there still remains a concern as regards unsafe abortions, which are being carried out worldwide, leading to a large number of maternal deaths. In the UK, the Abortion Act 1967 has ensured that when there is a concern about maternal well-being, two doctors can accede to the women’s request for an induced abortion. The most recently published Clinical Enquiry into Maternal and Child Health (CEMACH) report has cited one maternal death directly attributable to sepsis after unsafe abortion.6 Nearly half (48%) of all induced abortions worldwide were estimated to be unsafe in 2003. A great majority of them (97%) were carried out in the developing world. Unsafe abortions account for 13% of maternal deaths. An estimated 5 million women are hospitalised each year for abortion-related complications such as haemorrhage and sepsis. Abortions cause approximately 68 000 deaths and 5 million disability adjusted life years (disability adjusted life years) per year worldwide.7 Unsafe abortions account for 13% of maternal deaths. By achieving safe abortions and with the provision of adequate contraception, we will be able to reduce maternal mortality substantially and protect maternal health.1,5,8,9 Amongst unsafe abortions, infective complications occur most frequently, resulting in significant morbidity and mortality. Infective complications are seen in 1–45% of women following induced abortions.10–12 This rate varies globally, being prevalent at the rate of 1–4.8% in developed countries and up to 45% in developing countries. The rates of infections are particularly high in unsafe abortions where women seek medical help late.10–12 Pelvic infections not only increase short-term morbidity and mortality but also have long-term health consequences such as chronic pelvic pain, infertility (4–7-fold increase in risk, and recurring infections double the risk) and ectopic pregnancies. Causative organisms for post-abortion infections Post-abortal genital tract infection including pelvic inflammatory disease (PID) of varying degrees of severity occurs in about 10% of induced abortions.10 Post-abortal sepsis is known to be polymicrobial. Various organisms causing post-abortion sepsis are Chlamydia trachomatis (CT), Neisseria gonorrhoea Table 1 Global and regional estimates of induced abortion, 1995 and 2003. Abortion ratea
Region and sub region
No. of abortions (millions) 1995
2003
1995
2003
World Developed countries Excluding Eastern Europe Developing countriesb Excluding China
45.6 10.0 3.8 35.5 24.9
41.6 6.6 3.5 35.0 26.4
35 39 20 34 33
29 26 19 29 30
Estimates by region Africa Asia Europe Latin America Northern America Oceania
5.0 26.8 7.7 4.2 1.5 0.1
5.6 25.9 4.3 4.1 1.5 0.1
33 33 48 37 22 21
29 29 28 31 21 17
Permission to reproduce table obtained from Guttmacher Institute.5 a Abortions per 1000 women aged 15–44. b Those within Africa, the Americas, excluding Canada and the United States of America, Asia, excluding Japan, and Oceania, excluding Australia and New Zealand.
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
541
(NG) and endogenous vaginal anaerobes such as Gardenerella vaginalis (GV), Ureaplasma urealyticum (UU) and Mycoplasma genitalium (MG) causing bacterial vaginosis (BV).14 Chlamydia is an obligate Gram-negative intracellular bacterium commonly causing asymptomatic prolonged infections. N. gonorrhoea (NG) is a Gram-negative facultative intracellular aerobic diplococcic bacterium. They produce lipopolysaccharide endotoxins, which are highly toxic. BV is a polymicrobial condition where the lactobacilli – the normal commensal in the vagina – are replaced by anaerobic bacteria such as GV, UU and MG. These anaerobic organisms produce enzymes such as amino-peptidases and de-carboxylases that degrade proteins and convert amino acids to amines, which account for the characteristic ‘fishy odour’. The anaerobic organisms are thought to be permissive organisms facilitating the infection by Chlamydia, gonorrhoea and other aerobic organisms. They alter ‘the cervical mucous through enzymatic degradation of proteolytic barrier’.15 Organisms present in the lower genital tract that is, upper vagina and cervix, can therefore lead to ascending infections in the endometrium, fallopian tubes or the pelvic cavity. C. trachomatis (CT) is the most common bacterial sexually transmitted organism in Europe and Northern America. The prevalence of Chlamydia infection in the pre-abortal population is 4.9– 17.9%.16,19 In the UK, the prevalence of Chlamydia is approximately 6–8%.17,18 The prevalence of Chlamydia-positive patients was 11.4% (range: 5–15%) and NG was 2.6% (range: 1–3%) amongst women seeking first-trimester screening in Illinois.19 A study from Finland reported a nationwide increase from 23.4 per 10 000 to 29.2 per 10 000 in the incidence rates of CT, especially in the adolescents and young people.20 Bearing in mind the low prevalence of gonorrhoea (0.2%) among women in the United Kingdom undergoing abortion,18 screening for gonorrhoea is controversial.21 CT is detected more often in women with BV and may facilitate CT infection in the upper genital tract.18 Recurrent infections with Chlamydia lead to long-term problems such as tubal damage, infertility and chronic pelvic pain.17,21,22 The prevalence of Chlamydia is higher in young women (15–25 years) as they are more prone to infections because of various factors such as discussed in Hillard et al.: cervical ectopy, lower levels of protective antibodies, reduced access to medical care and high risk-taking behaviour. Strategies to diagnosis of infection Chlamydia Chlamydia infection is now widely diagnosed using nucleic acid amplification tests (NAATs). A systematic review24 has shown that self-collected vaginal swabs, urine Chlamydia tests have similar results to endo-cervical and urethral swabs, with the exception of polymerase chain reaction (PCR) (COBAS amplicor), which was less sensitive than the urine test for gonorrhoea. Sensitivities for PCR were 83.3%, transcription-mediated amplification 92.5% and strand displacement amplification assays 79.9% for Chlamydia, and specificities for all assays were more than 95% for Chlamydia urine samples. The main limitation for the use of NAAT is the higher cost compared to non- NAAT, although in the long run cost-effectiveness analysis has suggested that the use of these tests for screening of Chlamydia will be cost-effective. Gonorrhoea The pooled results of four studies of the PCR assay reported sensitivity and specificity as 55.6% (confidence interval (CI), 36.3–74.9%) and 98.7% (CI, 97.5–99.9%) for urine samples and 94.2% (CI, 90.5– 98.0%) and 99.2% (CI, 98.4–100%) for cervical samples, whereas the transcription-mediated amplification assay had the sensitivity and specificity of 91.3% (CI, 85.0–95.6%) and 99.3% (CI, 98.6–99.6%) for urine samples and 99.2% (CI, 95.7–100%) and 98.7% (CI, 98.0–99.3%) for cervical samples. For the study of strand displacement amplification, the sensitivity and specificity were 84.9% (CI, 75.6–91.7%) and 99.4% (CI, 98.9–99.8%) for urine samples and 96.5% (CI, 90.1–99.3%) and 99.5% (CI, 99.0–99.8%) for cervical samples. Is screening for Chlamydia in the general population worthwhile? Screening for Chlamydia has been shown to be cost-effective in preventing PID.25 It has been suggested that all moderate-to-high prevalence population (8%) should be screened and
542
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
treated.23,26,27 However, this observation has been challenged.28 The authors felt that the cost-effectiveness of previous studies was based on static models and did not take account of the lower uptake of screening, partner notification and lower complication rates. Screening for Chlamydia in populations with lower prevalence still showed high specificities (98– 100%) though clinicians should be aware of higher rates of false positive (as high as 1/3); therefore, a confirmatory test should be performed. These rates may be negligible if specificity of assay exceeds 99.5%.24 A meta-analysis by Watson et al. 2002 showed that non-invasive testing by NAAT for Chlamydia was more effective in detecting asymptomatic Chlamydia infection. The meta-analysis showed that DNAbased tests detected more cases of asymptomatic chlamydial infections than conventional non-culture tests. The odds ratios (ORs) showed a statistically significantly lower rate of false-negative results with urine ligase chain reaction(LCR) (0.33, 95% CI: 0.13, 0.80) and cervix PCR (0.26, 95% CI: 0.12, 0.56) than with the reference standard. The ORs showed no significant differences between the false-negative rates with urine PCR (0.84, 95% CI: 0.37, 1.89), urine gene probe (0.44, 95% CI: 0.15, 1.26), cervix gene probe (1.16, 95% CI: 0.25, 5.47), urine enzyme immunoassay (1.86, 95% CI: 0.39, 8.75), cervix direct immuno-fluorescence (1.05, 95% CI: 0.09, 12.93) and the reference standard. The OR revealed a significantly higher rate of false-negative results for cervix enzyme immunoassay than the reference standard (4.10, 95% CI: 1.15, 14.59).29 Self-taken vaginal swabs were cost-effective in preventing more cases of PID than other strategies.30 Chlamydia infections are associated with short- and long-term morbidity. Current evidence suggests that up to 20% of women with Chlamydia will suffer from PID, 4% from chronic pelvic pain and 3% from infertility.
Should women be screened for BV? BV occurs in up to 30% of women. It is a known risk factor for infections following induced abortions. The incidence of post-abortal endometritis was 5.6% in women, who had positive swabs for bacterial vaginosis preoperatively.31 Larsson32 performed a prospective randomised trial to evaluate the effect of 2% clindamycin cream on post-surgical abortion infection. This treatment resulted in significant reduction in postoperative infections with abnormal vaginal flora (relative risk (RR): 4.2, 95% C.I.1.2– 15.9). It is well known that BV makes women more susceptible to other sexually transmitted diseases such as trichomoniasis and the bacterium, Chlamydia.33 A randomised trial31 showed that suppression of bacterial vaginosis with twice-weekly metronidazole gel offered the women protection from Chlamydia. Hamark34 studied the risk factors of post-abortal endometritis in Chlamydia-negative women and identified that women with greater than 20% clue cells had a 5.6% RR of acquiring postabortal infections. However, a randomised double blind placebo-controlled trial to evaluate the efficacy of metronidazole in preventing post-abortal infections provided weak evidence that metronidazole reduces the risk of infection after first-trimester suction termination.35 Furthermore, a recent large randomised treatment trial of BV concluded that oral metronidazole with doxycycline did not prevent post-abortal infections.36 However, a recently published comprehensive review about treatment of bacterial vaginosis37 suggests that though the available numbers in various studies are small, the slowly gathering evidence indicates that it is prudent to treat BV in women who are having surgical procedures such as induced abortions. The US Centre for Disease Control and Prevention (CDC) recommends that there are benefits of treatment of BV – reduction of infections following abortion and other operative gynaecological procedures. It has also been suggested that three or more of the following criteria could be used to confirm the diagnosis of BV ‘(i) >20% of squamous cells examined are clue cells, (ii) the bacterial population in the wet prep is dominated by cocci and coccobacilli, (iii) a vaginal pH 4.7 and (iv) a positive whiff test.’ Various regimes for treatment of BV have been suggested from the literature –metronidazole tablets 500 mg twice daily for 7 days (99% immediate cure rate and 84% cure rate at 6 weeks). Similarly, oral treatment with clindamycin or intra-vaginal metronidazole or clindamycin has also been shown to be effective. Newer therapeutic agent such as tinidazole has also been shown to be useful in the treatment of BV.37 Having reviewed the
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
543
published literature on BV, we are of the opinion that, in balance, women with BV should be medically treated and the effectiveness of the treatment should be investigated in properly designed studies. Prevention of infective morbidity There are various preventive strategies to reduce infective complications. Induced abortions are performed for unwanted or unintended pregnancies. Up to 50% of all pregnancies are unintended though not all unintended pregnancies result in abortion. Unintended pregnancies could be due to failure to use contraception, failure of the contraceptive methods mostly due to user dependence, lack of access to facilities or severe maternal disease or foetal anomalies. Various primary prevention strategies will help reduce the number of women needing induced abortions. Patient education, use of effective contraception and improving access to health care in general will reduce the number of abortions, thereby reducing complications. Legalisation of abortions, easy access to non-judgemental services, routine vaccination such as tetanus toxoid and early abortion will all help in primary prevention. Patient and partner education and support The main tool for all primary prevention is empowering patients. Educating patients regarding all the options of contraception includes the use of emergency contraception and long-acting reversible contraception, their efficacy, risks and possible side effects, and non-contraceptive benefits. They should also be informed about the option of induced abortion, advantages of early abortions and early recognition of symptoms of infections and regarding the importance of seeking medical help early. Contraception Use of effective contraception will reduce the rates of induced abortions and therefore reduce complications overall. We are all aware that some forms of contraception are more effective than the others. The use of methods such as condoms, sheaths or oral contraceptive pills are very user dependent. Long-acting reversible contraceptive methods such as the intrauterine contraceptive devices and systems, hormonal injections and contraceptive implants are more effective than other forms of contraceptives. It is estimated that approximately 73 000 unintended pregnancies can be reduced per annum, which is about a third of induced abortions in England and Wales. This would therefore significantly reduce the complications associated with abortions. They are also thought to be cost-effective. A 7% population switch from oral contraceptive pill to long-acting reversible contraception can save £100 million by reducing the rates of unintended pregnancies.38,39 Legalisation and provision of services It is a well-proven fact that legalisation of abortion services will significantly reduce the risk of complications. It will also help in the provision of services within easy access to the community where there is no stigma attached to the centre or the users. Legalisation of services will reduce the need or use of illegal premises, untrained/unqualified personnel providing services and also bring all the services under the legal guidelines for provision of high standards of care. The system should also provide training for all the staff involved so that services continue to be delivered safely. These measures will significantly reduce the risk of procedures and the complications associated with induced abortion. It has been shown that the legalisation of abortion in South Africa in 1996 led to significant reduction in morbidity and a 90% drop in mortality following abortion, especially in younger women.40 Regional measures such as routine tetanus immunisations, use of tetanus toxoid to neutralise any toxins if tetanus is suspected and antibiotic prophylaxis according to the prevalence of common organisms found should be designed regionally/nationally. Local multidisciplinary organisations should adapt available evidence to suit the needs and requirements of the local population.
544
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
Methods and gestation of induced abortion Induced abortions are performed medically or surgically, depending on the gestation of pregnancy. There is sufficient evidence to suggest that medical management and early gestation at abortion are helpful in reducing complications associated with induced abortions. A systematic review of 46 421 abortions has shown that the incidence of infection after medical abortion was very low (0.92%) in both first and second trimesters, irrespective of the medical regimen used.41 A total of 90% of abortions in England and Wales were performed before 13 weeks in 2007. A total of 70% were under 10 weeks old. There is evidence to suggest that earlier the gestation, lower the complication rate; the lowest ones noted were during 7–10 weeks at surgical termination of pregnancy.42 A study by Faundes43 showed that medical management using misoprostol dramatically reduced infective complications by 49%. A Cochrane review found that medical management of induced abortion with mifepristone and misoprostol was safe and effective. Their sub-analysis showed that the odds ratio for pelvic infection comparing medical to suction termination of pregnancy was 0.13 (0.01, 2.58).44 Fjerstad has analysed the trends of rates of serious infections after changes in regimens of medical abortion from vaginal misoprostol to buccal administration of misoprostol and other infectionreduction measures and they found a 73% reduction in the rate of serious infections from 0.93 per 1000 abortions to 0.25 per 1000 (95% CI 0.44–0.94; P < 0.001) with buccal route of administration of misoprostol.45 Prophylactic antibiotics Post-abortal infections occur in w10% of women undergoing induced abortions. The risk of infection is reduced by either prophylactic antibiotics or excluding infection by bacteriological screening. The Royal College of Obstetricians and Gynaecologists (RCOG) recommend that, as a minimum, all abortion services should be offering antibiotic prophylaxis. Testing for lower genital tract infections and treating positive cases would be the ideal management.13 The RCOG has recently recommended that “all women should receive a sexually transmitted infection risk assessment and should specifically be offered testing for C. trachomatis before abortion”. Everyone with a positive result should be treated and if results are unavailable at the time of abortion, they should be offered antibiotic prophylaxis.46 Universal prophylaxis The use of universal prophylaxis is proven to provide significant protection in all women including low-risk groups undergoing therapeutic abortions. The meta-analysis by Swaya et al.47 has shown a RR estimate of 0.58 (95% CI: 0.47, 0.71) for developing post-abortal upper genital tract infection in women who received antibiotics prophylactically compared with placebo. This is also a cost-effective measure compared with placebo. There is considerable debate between the use of universal prophylaxis versus screen-and-treat policy and the ‘belt-and-braces approach’ of screening and use of prophylactic antibiotics. Universal prophylaxis has shown to reduce infection rates by up to 50% and has been found to be cost-effective though there is the risk of re-infection. The advantages of screen and treat are more targeted treatment and the opportunity to perform contact tracing and appropriate treatment. This will also help reduce the reservoir of Chlamydia in the community. The approach of screening and universal prophylaxis has the benefits of both options but there are also considerable costs involved.21 Contact tracing requires considerable organisation between various departments with committed staff. Various techniques of contact tracing and treating have been described such as partner notification, patient-delivered partner therapy (PDPT) or postal testing kits (PTK). Cameron et al. has recently reported a randomised controlled trial to see if either PDPT or PTK would reduce the risk of re-infection compared with partner notification. They did not find reduction in re-infection with either techniques but felt that PDPT may offer simplicity and cost-effectiveness compared with patient referral.48 Penny et al. performed a multicentre randomised comparison between the strategies of universal prophylaxis
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
545
and the screen-and-treat policy. The policy of universal prophylaxis was at least as effective and costeffective compared with the screen-and-treat policy for reducing short-term infective sequelae. The women, who were screened negative, had slightly higher infection rates than the group who were treated with prophylactic antibiotics.17 Following the adoption of policy of antibiotic prophylaxis in the United States, a 76% decline in infection rate from 0.25 per 1000 to 0.06 per 1000 (95% CI 0.02–0.34; P ¼ 0.03) has been reported.45 Antibiotic regimen for prophylactic antibiotics Antibiotic prophylaxis inhibits the growth of contaminating bacteria, thereby reducing the risk of infections. The type of antimicrobial used is dependent on the infecting organism and its interaction with the antibiotic regimen. The timing and the method of delivery are also crucial for good prophylaxis.49 The recommendations of antibiotic regimens for pre-abortal prophylaxis are based on the common organisms involved in upper genital tract infections (Table 2).13,50 The use of doxycycline or azithromycin with metronidazole is suggested by the RCOG guideline update group bearing in mind the causative organisms C. trachomatis and Mycoplasma Genitalium, Ureapalsma Urealyticum and Gardenerella Vaginalis.13 The National Abortion Federation also advocates use of prophylactic antibiotics to all women undergoing abortion, although it does not suggest any particular regime.50 Cost-effectiveness Bignell51 favoured using azithromycin as first line for C. trachomatis as being more cost-effective. Treatment options for uncomplicated Chlamydia infections in non-pregnant women include singledose azithromycin 1 g (95–100% cure) or doxycycline 100 mg BD for 7 days (88–100%). azithromycin is 2.7- to 12-fold more expensive than the doxycycline regime. The single-dose regime of azithromycin has increased compliance and therefore increased drug efficiency. It has been suggested that azithromycin was more cost-effective compared with doxycycline for treatment of confirmed Chlamydial infection (savings of 1200 USD per major outcome avoided – 1993 values). Although, if azithromycin was used prophylactically, it was more costly than doxycycline (792 USD – 1993 value).52 Any prophylactic regimen should be designed around robust evidence on local antimicrobial sensitivity patterns, epidemiology of infections in the region, local health service accessibility, funding availability and patient preference and compliance.
Table 2 A summary of recommended Regimens – Antibiotic prophylaxis. The RCOG recommended regimes for prevention of infective complications13 are: Metronidazole 1 g rectally at the time of abortion plus Doxycycline 100 mg BD for 7 days/Azithromycin 1 g orally single dose The recommended regimes for treatment of uncomplicated Chlamydia infections are: Doxycycline 100 mg BD for 7 days or Azithromycin 1 g orally single dose or Oxytetracycline 500 mg 4 times a day for 7 days or Erythromycin 500 mg 4 times a day for 7 days or 500 mg BD for 10–14 days or Ofloxacin 400 mg orally once a day for 7 days The CDC recommends the following antibiotics for specific infections Chlamydia: Doxycycline 100 mg bid 7 days Azithromycin 1 g stat Erythromycin dosage dependant on preparation 7 days Ofloxacin 300 mg bid 7 days Levofloxacin 500 mg 7 days Bacterial vaginosis: Metronidazole 500 mg bid 7 days orally or 2 g stat. Prophylaxis for infective endocarditis is recommended for patients having genitourinary procedures only if they have a prosthetic heart valve, previous bacterial endocarditis, congenital heart defect with prosthetic material or cardiac transplantation patients who develop valvulopathy.50
546
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
Where should women be treated when presenting with pelvic infection? Women suspected to have PID should be treated promptly. Mild-to-moderate PID can be treated as outpatients and severe PID should be treated with parenteral antibiotics. The RCOG guideline ‘Management of Acute PID’ recommends the following approach: Outpatient antibiotic treatment for mild-to-moderate PID A dosage of oral oflaxacin 400 mg BD þ Oral metronidazole 40 mg BD for 14 days is recommended. Intramuscular ceftriaxone 250 mg single dose (cefoxitin has a better evidence for treatment of PID than ceftriaxone but it is not available in the United Kingdom) followed by oral doxcycline 100 mg BD þ Oral metronidazole 400 mg BD for 14 days can be followed. The best evidence for effective antibiotic treatment for PID in preventing long-term complications comes from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) study53 where women were treated with cefoxitin followed by doxycycline. Inpatient antibiotic treatment for severe PID Intravenous ceftriaxone 2 g daily with intravenous doxycycline 100 mg BD followed by oral doxycycline BD for 14 days and oral metronidazole BD for 14 days. Intravenous clindamycin 900 mg tid with intravenous gentamicin followed by either oral clindamycin 450 mg 4 times a day for total of 14 days or oral doxycycline 100 mg BD with oral metronidazole BD to complete the course of 14 days. Intravenous ofloxacin 400 mg BD with intravenous metronidazole 400 mg BD for 14 days.54 Septic shock can be a deadly complication. Prompt access to medical facilities, elimination of infection and supportive care are essential. Early systemic broad-spectrum antibiotics followed by uterine evacuation, if required, are recommended. There is no evidence to suggest that delaying curettage for antibiotics to take effect is beneficial. Unnecessary delays can lead to death. It is recommended that broad-spectrum antibiotic should be given in large doses and if the patient is haemodynamically stable, uterine evacuation should be done as soon as possible.55–57 Information sharing with women as regards probable sepsis Infections rarely occur following a safe abortion. Presence of retained products of conception is the most common associated factor. All patients must therefore be informed of all the signs and symptoms of infections such as fever, abdominal pain, heavy bleeding and foul smelling discharge. The routine use of prophylaxis should be determined by local availabilities and practicalities. Women who are considered to be at high risk for infection such as previous pelvic infections, multiple sexual partners or those who have had unsafe abortions should be considered for prophylactic antibiotics. The use of tetanus toxoid should also be considered based on local prevalences and practices. The essentials of infection control are equally important in the prevention of infection after any surgical procedures. Universal infection control protocols should be used to protect the staff, patients and the community. Essentials of infection control such as hand washing, use of protective gloves, a clean and well-ventilated facility, adequate decontamination procedures for all instruments immediately after use, meticulous attention to sterilisation and disinfection of equipment and supplies, strict asepsis during operative procedures, use of barrier precautions to protect clinical and support staff whenever they come into contact with blood and bodily fluids, precautions against accidental cuts and needle stick injuries, careful handling of all waste, linen and equipment, appropriate disposal of all blood and tissue and contaminated materials should be practiced at all centres offering surgical abortion.7
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
547
Friedman et al.58 performed a simulation of various algorithms and suggested that resource-poor settings can use risk-based algorithms for identifying pre-abortal women who will benefit from antibiotics. Future vaccines The future will depend on designing effective vaccines to provide long-term immunity against various sexually transmitted diseases including Chlamydia. He et al. (2007) tested mice by intranasal immunisation with viral recombinants generated by insertion of immunodominant T-cell epitomes of chlamydial outer membrane protein into influenza A viruses. Immunised mice showed significant protective immunity (P > 0.02).59 Developing safe and effective vaccines against Chlamydia and other sexually transmitted diseases will be the way forward for the future. Conclusions Induced abortion is one of the most common gynaecological procedures. The incidence of induced abortion is approximately 29/1000 women worldwide. Up to half the abortions are unsafe worldwide accounting for 68 000 maternal deaths. Infective complications are the most frequent complications in unsafe abortions. Simple measures such as legalisation and destigmatisation of abortions, easy and local access to health services, promotion of abortions at early gestation, use of medical abortions and use of prophylactic antibiotics according to the local guidelines based on local prevalence of infective organisms will help significantly reduce the risk of infective complications. Prevention of abortions by education regarding safe sex, contraception and easy availability of contraception, promotion of long-acting contraceptives and emergency contraception will help reduce the rate of unintended pregnancies and therefore significantly reduce abortion rates. Future developments of efficacious vaccines against sexually transmitted diseases will help reduce infectious complications of induced abortion significantly.
Practice points Non-invasive testing using urine/self-taken vaginal swabs (with NAAT) are more effective and acceptable methods for detecting Chlamydia. Screen, contact tracing and treatment is the gold standard for preventing infective complications after induced abortion, but universal antibiotic prophylaxis policy offers a better value for money. Pre- and post-abortion counselling regarding risks of infections and implementation of contraceptive provision policy, preferably long-acting methods.
Research agenda Social research into cultural and community risk factors. Research to assess factors, which prevent access to effective contraception and abortion services. Prospective risk-based algorithms to identify cost-effective treatment. Population-based interventions to reduce sexually transmitted diseases. Develop safe and efficacious vaccines for Chlamydia infection. Research effective means of popularizing medical methods of terminations in preference to surgical methods, especially in under resourced countries.
548
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
References 1. Sedgh G, Henshaw S, Singh S et al. Induced abortion: estimated rates and trends worldwide. Lancet 2007; 370: 1338–1345. 2. Abortion statistics. Department of Health. 3. ISD Scotland. Information and statistics, sexual health, abortion data 2009, http://www.isdscotland.org/isd/1918. html#tables [accessed 03.11.09]. 4. Abortion statistics and other data – Johnston’s archive, historical abortion statistics, United States. Compiled by Wm. Robert Johnston last updated 28 January 2009, http://johnstonsarchive.net/policy/abortion/ab-unitedstates.html [accessed 03.11.09]. *5. Guttmacher Institute. Facts on induced abortion worldwide, in brief. New York: Guttmacher Institute, 2008, http://www. guttmacher.org/pubs/fb_IAW.pdf [accessed 10.10.09]. 6. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer – 2003–2005, http://www.cmace.org.uk/ publications/CEMACHpublications/Maternal-and-Perinatal-Health.aspx [accessed 03.11.09]. *7. Grimes DA, Benson J, Singh S et al. Unsafe abortion: the preventable pandemic. Sexual and Reproductive Health Series. Lancet October 2006. 8. Singh S. Hospital admissions resulting from unsafe abortion: estimates from 13 developing countries. Lancet 2006; 368 (955): 1887–1892. 9. World Health Organization (WHO). Unsafe abortion: global and regional estimates of incidence of unsafe abortion and associated mortality in 2003. Geneva: WHO, 2007. 10. Ashok PW, Kidd A, Flett GMM et al. A randomized comparison of medical abortion and surgical vacuum aspiration at 10– 13 weeks gestation. Hum Reprod January 2002; 17(1): 92–98. 11. Das V, Agarwal A, Mishra A et al. Septic abortion. J Obstet Gynaecol India May/June 2006; 56(3): 236–239. 12. Henshaw SK, Adewole I, Singh S et al. Severity and cost of unsafe abortion complications treated in Nigerian hospitals. Int Fam Plan Perspect 2008; 34(1). *13. The care of women requesting induced abortion. RCOG evidence-based clinical guideline. no. 7. London: RCOG Press, 2004. *14. Penny GC. Preventing infective sequelae of abortion. Hum Reprod 1997; 12(11): 107–112. 15. Soper D, Brockwell NJ, Dalton HP et al. Observations concerning the microbial etiology of acute salpingitis. Am J Obstet Gynecol 1994; 170: 1008–1017. 16. Schiotz H & Csango PA. A prospective study of Chlamydia trachomatis in first trimester abortion. Ann Clin Res 1985; 17: 60– 63. 17. Penney GC, Thomson M, Norman J et al. Randomised comparison of strategies for reducing infective complications of induced abortion. Br J Obstet Gynaecol 1998; 105: 599–604. 18. Blackwell AL, Thomas PD, Wareham K et al. Health gains from screening for infection of the lower genital tract in women attending for termination of pregnancy. Lancet 1993; 342: 206–210. 19. Patel A, Rashid S, Godfrey EM et al. Prevalence of Chlamydia trachomatis and Neisseria gonorrhoea genital infections in a publicly funded pregnancy termination clinic: empiric vs. indicated treatment? Contraception 2008; 78: 328–331. 20. Hiltunen-Back E, Haikala O, Kautiainen H et al. Nationwide increase of Chlamydia trachomatis infection in Finland: highest rise among adolescent women and men. Sex Transm Dis 2003; 30(10): 737–741. *21. Cameron ST & Sutherland S. Universal prophylaxis compared with screen-and treat for Chlamydia trachomatis prior to termination of pregnancy. Br J Obstet Gynaecol 2002; 109: 606–609. 22. Patton DL, Wolner-Hanssen P, Cosgrove SJ et al. The effects of Chlamydia trachomatis on the female reproductive tract of the Macaca nemestrina after a single tubal challenge following repeated cervical inoculations. Obstet Gynecol 1990; 76: 643–650. 23. Hillard S, Weinstock GA, Bolan RK et al. Chlamydia trachomatis infection in women: a need for universal screening in high prevalence population. Am J Epidemiol 1992; 135: 41–47. 24. Cook RL, Hutchison SL, Ostergaard L et al. Systematic review: noninvasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med 2005; 142: 914–925. 25. Scholes D, Stergachis A, Heidrich FE et al. Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 1996; 334: 1362–1366. 26. Phillips RS, Aronson MD, Taylor WC et al. Should tests for Chlamydia trachomatis cervical infection be done during routine gynecologic visits? An analysis of the costs of alternative strategies. Ann Intern Med 1987; 107: 188–194. *27. Trachtenberg AI, Washington AE & Halldorson S. A cost-based decision analysis for chlamydia screening in California family planning clinics. Obstet Gynecol 1988; 71: 101–108. 28. Roberts TE, Robinson S, Barton PM et al. Cost effectiveness of home based population screening for Chlamydia trachomatis in the UK: economic evaluation of chlamydia screening studies (ClaSS) project. BMJ 2007; 335: 291. 29. Watson EJ, Templeton A, Russell I et al. The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review. J Med Microbiol 2002; 51(12): 1021–1031. 30. Blake DR, Maldeis N, Barnes MR et al. Cost-effectiveness of screening strategies for Chlamydia trachomatis using cervical swabs, urine, and self-obtained vaginal swabs in a sexually transmitted disease clinic setting. Sex Transm Dis 2008; 35(7): 649–655. 31. Schwebke JR & Desmond R. A randomized trial of metronidazole in asymptomatic bacterial vaginosis to prevent the acquisition of sexually transmitted diseases. Am J Obstet Gynecol 2007; 196: 517.e1–517.e6. 32. Larsson P, Platz-Christensen J, Dalaker K et al. Treatment with 2% clindamycin vaginal cream prior to first trimester surgical abortion to reduce signs of post operative infection: a prospective, double-blinded, placebo-controlled, multicentre study. Acta Obstet Gynecol Scand 2000; 79(5): 390–396. 33. Wiesenfeld HC, Hillier SL, Krohn MA et al. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 2003; 36: 663–668. 34. Hamark B & Forssman L. Postabortal endometritis in Chlamydia-neagative women – association with preoperative clinical signs of infection. Gynecol Obstet Invest 1991; 31: 102–105.
N. Mary, T.A. Mahmood / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 539–549
549
35. Crowley T, Low N, Turner A et al. Antibiotic prophylaxis to prevent post-abortal upper genital tract infection in women with bacterial vaginosis: randomised controlled trial. Br J Obstet Gynaecol 2001; 108(4): 396–402. 36. Miller L, Thomas K, Hughes JP et al. Randomised treatment trial of bacterial vaginosis to prevent post-abortion complication. Br J Obstet Gynaecol 2004; 111(9): 982–988. *37. Livengood III Charles H. Bacterial vaginosis: an overview for 2009. Rev Obstet Gynecol 2009 Winter; 2(1): 28–37. 38. Statistical bulletin, abortion statistics England and Wales 2007. National Statistics, DOH. 39. Long-acting reversible contraception: the effective and appropriate use of long-acting reversible contraception. NICE guideline CG030 Oct 2005. 40. Rachel Jewkes, Helen Rees, Kim Dickson et al. The impact of age on the epidemiology of incomplete abortions in South Africa after legislative change. Br J Obstet Gynaecol 2005; 112(3): 355–359. 41. Caitlin S, Brothers LP, Philip NM et al. Infection after medical abortion: a review of literature. Contraception 2004; 70(3): 183–190. 42. Nesheim BI. Induced abortion by the suction method. An analysis of complication rates. Acta Obstet Gynecol Scand 1984; 63 (7): 591–595. 43. Faundes A, Santos LC, Carvalho M et al. Post-abortion complications after interruption of pregnancy with misoprostol. Adv Contracept 1996; 12: 1–9. 44. Say L, Kulier R, Campana A et al. Medical versus surgical methods for termination of pregnancy. Art. No.: CD003037. Cochrane Database Syst Rev 2002; (4), 10.1002/14651858.CD003037.pub2. 45. Fjerstad M, Trussell J, Sivin I et al. Rates of serious infections after changes in regimens for medical abortion. N Engl J Med 2009; 361(2): 145–151. 46. Standards for gynaecology. Report of a working party. London: RCOG Press. *47. Sawaya GF, Grady D, Kerlikowske K et al. Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis. Obstet Gynecol 1996; 87(5 Pt 2): 884–890. 48. Cameron ST, Glasier A, Scott G et al. Novel interventions to reduce re-infection in women with Chlamydia: a randomised controlled trial. Hum Reprod 2009; 24(4): 888–895. 49. Walling AD & ACOG Practice Bulletin. Antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol January 2001; 23: 1–9. *50. National Abortion Federation, 2009 Clinical Policy guidelines, Washington. 51. Bignell CJ. Chlamydia infection in obstetrics and gynaecology. Clin Obstet Gynaecol 1997; 7: 104–109. 52. Lea AP & Lamb HM. Azithromycin. A pharmacoeconomic review of its use as a single-dose regimen in the treatment of uncomplicated urogenital Chlamydia trachomatis infections in women. Pharmacoeconomics 1997; 12(5): 596–611. 53. Ness RB, Soper DE, Holley RL et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomised Trial. Am J Obstet Gynecol 2002; 186: 929–937. *54. Management of acute pelvic inflammatory disease. Green top guideline no. 32. RCOG Press. London. 55. Goyaux N, Yace-Soumah F, Welffens-Ekra C et al. Abortion complications in Abidjan (Ivory Coast). Contraception 1999; 60: 107–109. 56. Thapa PJ, Thapa S & Shreshtha N. A hospital-based study of abortion in Nepal. Stud Fam Plann 1992; 23: 311–318. 57. Grimes DA, Coates Jr. W, Selik RM et al. Fatal septic abortion in the United States, 1975–1977. Obstet Gynecol 1981; 57: 739– 744. 58. Friedman HB, Gift TL, Susanti I et al. Risk-based versus alternative algorithms for antibiotic prophylaxis among women seeking early suction abortion: a cost-effectiveness simulation. Sex Transm Dis 2001; 28(12): 714–724. 59. He Q, Martinez-Sobrido L, Eko FO et al. Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines. Immunology 2007; 122(1): 28–37.