CLINICAL OBSTETRICS AND GYNECOLOGY Volume 50, Number 1, 8999 r 2007, Lippincott Williams & Wilkins

Ectopic Pregnancy
JAMES JOHNSTON WALKER, MD, FRCPS (Glas), FRCP (Edin), FRCOG Department of Obstetrics and Gynaecology, St James University Hospital, Leeds, UK LS9 7TL
Abstract: Ectopic pregnancy is a major gynecologic emergency, which results in significant morbidity for the mother and inevitable loss of the pregnancy. Its presentation can be varied from minor symptoms to sudden collapse. It produces a diagnostic dilemma and a management problem. With advances in medical care, most women survive ectopic pregnancy and many will be diagnosed early enough to allow conservative management with the resulting lower morbidity and possible anatomic conservation. This article covers what is currently known about the etiology of this condition, the best approach to the diagnoses and management and the long-term consequences for the women concerned. Key words: ectopic, pregnancy, hCG, laparoscopy, salpingotomy, salpingectomy

in the understanding of this condition, knowledge of its etiology, improvements in diagnosis, leading to earlier presentation and improvements in treatment and reduced morbidity.2,3

Incidence
The incidence of EP can be quoted as number per all pregnancies, number per live births, or number per fertile female population depending on the ease of collecting population data.4 Traditionally, the quoted rate of EP is around 1/100 pregnancies but over recent decades there has been a rise in incidence. Between 1976 and 1993, the incidence in Northern Europe increased from 11.2 to 18.8 per 1000 pregnancies,5 and reached 16 per 1000 in France. This increase was associated with an increase in pelvic infection, particularly Chlamydia and was greatest in women over 35 years of age. There is some evidence that this rise has now stopped and there may even be a decrease.4 More recent studies in France demonstrate that the incidence there is still increasing,6 but only in those classified as due to reproductive failure (up 17%) but not those associated with contraceptive failure, mostly intrauterine device failure (down by 29%). Therefore, the incidence in the Western world seems
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Ectopic pregnancy (EP) is the classic gynecologic emergency and remains a major cause of maternal morbidity and mortality.1 There is a further complication that there is the inevitable loss of the pregnancy, a factor often overlooked in the circumstances where saving the mothers life is paramount. Over the last few decades, there has been an increase
Correspondence: James Johnston Walker, MD, FRCPS (Glas), FRCP (Edin), FRCOG, Department of Obstetrics and Gynaecology, Level 9, Gledhow Wing, St James University Hospital, Beckett Street, Leeds LS9 7TL. E-mail: j.j.walker@leeds.ac.uk Conflict of interests: James Walker was one of the founders and President of the Ectopic Pregnancy Trust, Maternity Unit, Hillingdon Hospital, Pield Heath Road, Uxbridge, Middlesex UB8 3NN. www.ectopic.org.
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Walker documented tubal pathology to be strongly associated with the occurrence of EP. In utero exposure to diethylstilbestrol was similarly strongly associated. Previous pelvic inflammatory disease (PID), (usually Chlamydia or gonorrhea), infertility, or history of more than 1 sexual partner were associated with a mildly increased risk as was smoking. The association with infection is varied, with some studies suggesting a doubling of risk and some showing little association, but this is partly owing to the differences in control groups.7 If the risk factor also reduces fertility, the use of pregnant controls generally increases the relative risk. Most studies suggest that the incidence of EP increases with age and therefore the risk associated with infection may be cumulative.8 The association with PID is important as this is a potential correctable factor. Comprehensive programmes to prevent Chlamydia not only decrease the incidence of C. trachomatis infections but also the rate of EPs.9 The association of EP with contraceptive failure is more difficult to assess. Contraception is unlikely to increase the incidence of EP but its ability to stop tubal pregnancies may be less than for intrauterine pregnancies making any

to be around 16/1000 but this depends on the population assessed and the difficulty of collecting data. At least part of the increase may be due to earlier diagnosis and not an increase in the condition itself. In the developed world, the case mortality rate is low. In the United Kingdom, the last triennial report on maternal death reported 4 deaths in around 11 000 cases of EP giving a case mortality rate of 3.6/10,000.1 However, in Africa, the case fatality rates of around 100-300/10,000 because of the difficulty and lateness of diagnosis. In 95% of cases, the ectopic occurs within the fallopian tube, but others sites are seen (Fig. 1).

Risk Factors
EP is a condition seen only in primate pregnancy. This suggests that it is not something fundamentally associated with mammalian reproduction but specifically to primates. Although EP can be associated with no identifiable causal factors, 76% of cases do have demonstrable underlying causes. A metaanalysis of 27 case control studies demonstrated tubal damage from previous EP, previous tubal surgery, or

FIGURE 1. Sites 2000;7239:916919.)

of

EPs.

(Taken

from

BMJ.

Ectopic Pregnancy given pregnancy due to contraceptive failure more likely to be ectopic. In a large study in Beijing, both female sterilization and oral contraceptive use protected against EP whereas intrauterine contraceptive device (IUCD) use did not. In a meta-analysis of cases associated with IUCD use, when cases were compared with nonpregnant controls there was no difference in risk, but when compared with pregnant controls there was a ten-fold increased risk of EP which relates to its success in preventing intrauterine pregnancy. However, past IUCD use did increase the risk of EP by a small degree whether pregnant or nonpregnant controls were used suggesting an absolute risk possibly associated with infection. Therefore, current IUCD use does not increase the risk of the EP but a pregnancy with an IUCD in situ is more likely to be an ectopic one than a pregnancy with no IUCD. Previous female sterilization is similarly associated with an increased risk when compared with pregnant controls and the risk is higher where diathermy was used compared with ligation techniques. However, the risk of EP after sterilization is only 7.3 per 1000 within 10 years demonstrating its protective nature overall. A relative risk in pregnancies seen after contraceptive failure is also seen in the progestogen products whether they are oral, implant, or injected. The incidence of EP after assisted reproductive techniques is 2% to 4%, which is 2 to 3 times greater than the background incidence. This increase is seen after both in vitro fertilization and zygote intrafallopian transfer. The risk is reduced if donor eggs are used or in cases of surrogacy where there is no increased risk at all. This suggests that it is an inherent risk in the mothers themselves rather than the techniques used. The main risk factor would appear to be tubal factor infertility and endometriosis. Because of the multiple embryo transfer,

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the incidence of heterotopic pregnancy (an EP together with an intrauterine pregnancy) is significantly increased.

Presentation
EPs usually present between 6 weeks and 10 weeks of amenorrhea. Traditionally, the main presenting features are abdominal pain (69.3%) and vaginal bleeding (45.3%) in the presence of a history of amenorrhea. However, these are the classic signs and symptoms in a population where over 80% present with the ectopic already ruptured which is still common in many parts of the world. Earlier diagnosis is important to allow intervention that will reduce morbidity and maximize future fertility, but the diagnosis can be difficult and can be confused with miscarriage, an ovarian accident, or PID. This can lead to failure to diagnosis appropriately, delay in treatment, increased morbidity, and possible death. Awareness of the possibility of EP is the most important diagnostic tool as the presentation may not be obvious. With the advent of early booking ultrasound scans and early pregnancy units, the diagnosis of EP is occurring at an earlier gestation, often before symptoms, increasing the possibility to make the diagnose of EP before rupture. Of those who present with symptoms, abdominal pain is the most common usually associated with vaginal bleeding and a history of amenorrhea. However, the history and physical examination alone do not reliably diagnose or exclude EP, as up to 9% of women report no pain and 36% lack adnexal tenderness.2,3 The presence of known risk factors should increase suspicion, particularly history of previous EP, but any sexually active woman presenting with abdominal pain and vaginal bleeding after an interval of amenorrhea has an EP until proved otherwise. Women who present in a collapsed state usually

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Walker Three-dimensional ultrasound has little to offer except maybe in the location of unusually sited EPs such as in a cesarean section scar, which appears to be on the increase. Magnetic resonance imaging seems to have some advantages but seems to require active bleeding to make the diagnosis. Therefore at the present time, transvaginal ultrasound is the visualization technique of choice; it is easy to perform, readily available, and relatively cheap. Ultrasound on its own can be suggestive but the addition of the quantitative measurement of serum concentrations of hCG has improved the diagnostic accuracy. There is, however, controversy about both the absolute level and rise in concentration of serum hCG that is diagnostic.2 In the presence of an ectopic mass or fluid in the pouch of Douglas in the presence of an empty uterus, a diagnostic cut-off point for a serum concentration of hCG of 1500 IU/L is recommended, but in the absence of any ultrasound signs the higher concentration of 2000 IU/L should be the cut-off point before an EP is diagnosed. This is because that at this concentration, an intrauterine pregnancy should be seen. However, in practice, at hCG concentrations of less than 1500 IU/L, using single values and ultrasound was of poor diagnostic value. The change in concentration over time improves the diagnostic accuracy and is helpful in deciding treatment. In a normal pregnancy, serum concentrations of hCG double every 2 to 3.5 days in the fourth to eighth week of gestation reaching a peak around the eighth to 12th week, as calculated from the last menstrual period. A failure of this increase is suggestive of an EP although it is also associated with early pregnancy failure. A 2-day sampling interval has been recommended if paired serum samples are being tested. However, with improving assay techniques, these findings have been found to be less

have had prodromal symptoms that have been overlooked. Tubal rupture is rarely sudden because it is due to invasion by the trophoblast, a relatively slow process. A vaginal examination is not informative and, because it is potentially dangerous, should be avoided. Therefore, if there is any suspicion of an EP, hospital referral for investigation is mandatory. In the United Kingdom, this would be to an Early Pregnancy Assessment Unit but it should preferably be to a unit dedicated to managing problems early in pregnancy as this allows ease of investigations and continuity of outpatient care.

Hospital Diagnosis
The investigation of suspected EP has been revolutionized by the use of high definition ultrasound and rapid human chorionic gonadotrophin (hCG) assays. The presence of an intrauterine pregnancy generally excludes EP, although other ultrasound findings have to be considered, especially if symptoms are atypical, severe, or persistent. The risk of heterotopic pregnancy should be suspected in cases of women undergoing infertility treatment. Whereas, an intrauterine pregnancy can be seen as an accurate diagnostic sign, an empty uterus only raises the suspicion as this can be found in cases of miscarriage. The use of transvaginal ultrasound has greatly improved the diagnostic value but endometrial thickness has no diagnostic value. Findings of a systematic review demonstrated that transvaginal ultrasound should not be expected to find the EP but can accurately identify any noncystic adnexal mass. Therefore, an empty uterus with an adnexal mass is highly suggestive of EP. If the pregnancy is seen, this is useful for deciding treatment options but not necessary for the diagnosis. Other forms of visualization have been tried in an effort to improve the diagnostic value.

Ectopic Pregnancy certain. Although the average rise is 124% over 2 days, a rise of only 53% is compatible with a normal pregnancy and a decline of at least 21% over 2 days and 60% at 7 days is associated with spontaneous miscarriage. Using an even stricter cut-off rise of 35% over 2 days for viable pregnancy and a fall of 21% for miscarriage, 88% of EPs can be diagnosed accurately and, on average, 2.5 days sooner than by traditional methods.10 Although the majority of women with EP will present with hCG levels either rising or falling too slowly to be either a viable pregnancy or a miscarriage, around 20% of women will have a rise similar to the minimal rise for women with a viable gestation, and 8% of women will have a fall in values similar to women with miscarriage. The accurate diagnosis of EP can be life saving, reduce invasive investigations, and allow conservative treatment. With the use of ultrasound and hCG assays, the diagnosis of EP can be made with reasonable certainty without the need of laparoscopy. Confusing an EP with a miscarriage is of less clinical importance but the use of the new diagnostic curves will minimize the potential interruption of a wanted pregnancy if medical therapy is contemplated.10

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Treatment
Surgery remains the mainstay of treatment, but this is probably at the cost of over treating a significant number of cases. Expectant and medical management are possible in the appropriate clinical situation.
EXPECTANT

Many EPs will resolve spontaneously allowing expectant management in selected cases. These cases may well have previously been diagnosed as miscar-

riages but with earlier referral and sensitive assays, they are now redefined as potential EPs or pregnancies of unknown location. The range of success in observational studies of expectant management is 44% to 69%. The problem with expectant management is the need to have signs and symptoms sufficient enough to make the diagnosis but not to be so established as to make success less likely. Although EP was subsequently proven in 14% to 28% of these pregnancies, most resolve without a definite diagnosis being made and it is often impossible to differentiate between resolving EPs and failed intrauterine pregnancies. The success of expectant management depends on the ultrasound appearances and the level of hCG at the time of presentation. Most studies show that an adnexal mass no bigger than 40 mm should be present, with the absence of a gestational sac and less than 100 mL of fluid in the pouch of Douglas. But the most predictive factor for success is the initial hCG level. If the initial serum concentration of hCG is less than 1000 IU/L and falls by at least 15% in the first 24 hours, expectant management is successful in up to 88% of patients and as good as medical treatment in a randomized trial.11 Women undergoing expectant management need serial hCG measurements twice a week and weekly transvaginal ultrasound examinations to ensure resolution. This is marked by a rapidly decreasing hCG level to less than 50% of its initial level and a reduction in the size of adnexal mass by 7 days. Thereafter, weekly hCG and transvaginal ultrasound examinations should be carried out until serum hCG levels are less than 20 IU/L as there are case reports of tubal rupture at low levels of bhCG. In addition, women selected for expectant management should be counseled about the importance of compliance with

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Walker wide range of serum hCG concentrations. The failure of treatment, measured by the need for repeat doses or surgical intervention, increases with higher serum hCG concentration at presentation. Therefore, although medical therapy can be successful at high serum hCG concentrations, it would appear that methotrexate is most appropriate for women with an hCG below 3000 IU/L at presentation. Data concerning the effect of various ultrasound findings on success are less clear but women with a large adnexal mass are more likely to have already ruptured and medical therapy is not appropriate. Those where cardiac activity or a yolk sac are seen on ultrasound have a reduced chance of success and should be considered a contraindication to medical therapy. If the patient fits the criteria, a single dose of methotrexate should be given at a dose of 50 mg/m2. Then serum hCG levels are checked on the fourth and seventh day. There may be a rise at day 4, but there should be a fall of at least 15% between day 4 and day 7. If this fall is not seen then a further dose is of methotrexate should be given. Around 14% of women will require a second dose of methotrexate and using this regimen less than 10% of women will require surgical intervention with 7% experiencing tubal rupture. Abdominal pain is common, occurring in around 75% of treated women and some women need admitted for observation and ultrasound examination if tubal rupture is suspected. Other side effects include conjunctivitis, stomatitis, and gastrointestinal upset. Women should also be advised to avoid sexual intercourse and maintain ample fluid intake during the treatment. As with expectant management, the women need to understand the treatment and its potential problems and be compliant to the management follow-up.

follow-up and should have easy access to the hospital. If expectant management fails, further intervention is required, either by medical or surgical means.
MEDICAL

Methotrexate, a folic acid antagonist, has been used for medical management of EP for over 20 years. This treatment is aimed at patients before the ectopic ruptures and who are hemodynamically stable. There is now a great amount of experience with this therapy.12 It is usually given intramuscularly as a single dose of 50 mg/m2 but has been given orally at a slightly higher dose with no obvious advantage. Studies have also evaluated methotrexate injected directly into the EP either by laparoscope or under ultrasound control. This route delivers high concentrations locally with smaller systemic distribution but seems to have no great advantages and needs more skill and intervention. The addition of mefipristone does not seem to give success rates significantly greater than methotrexate alone. Although metaanalysis has shown that a multiple dose regimen has a higher success rate,12 the single dose regimen produces less side effects and with proper selection can be as successful as the multiple doses. Most of the early studies used folic acid rescue to reduce side effects, but these were often multiple high dose regimens and there is no need for this therapy in the single dose regimen. As with expectant management, the success of this therapy depends on patient selection. Again, findings have to be enough to make the diagnosis but be early enough to allow successful treatment. In this situation, it is important to exclude an intrauterine pregnancy because methotrexate is teratogenic and inappropriate treatment can be harmful. Clinical studies using methotrexate have treated women presenting with

Ectopic Pregnancy Because of the teratogenic risk, women should use reliable contraception for 3 months after methotrexate has been given. One oft quoted benefit of single dose methotrexate treatment is the associated cost saving due to outpatient management. In comparison with laparoscopic surgery, the direct costs for medical therapy is less than half of those associated with laparoscopy. Indirect costs are also reduced. However, in the randomized trials, the cost savings were only seen when the serum hCG level was below 1500 IU/L due to the increased need for further treatment and prolonged follow-up.
SURGICAL

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Surgical treatment for EP is still the norm and the gold standard. Studies would suggest that less than half those presenting with the diagnosis of EP are suitable for expectant or medical therapy. Even in some of those eligible for nonsurgical approach, surgery may still be preferable or desired. In cases where there is rupture of the fallopian tube and/or the woman is hemodynamically unstable, laparotomy is the preferred approach although laparoscopic management has been described. The decision on approach and management should be made by assessing the womens clinical state and the skill of the operator. It is clear, however, that in the majority of cases where the women is hemodynamically stable, surgery can and should be carried out laparoscopically.13 The main benefits of laparoscopy are shorter operation times, less intraoperative blood loss, shorter hospital stays, lower analgesic requirements, and shorter convalescence than with laparotomy. Laparotomy is also associated with a lower subsequent pregnancy rate but this may be due to the relative severity of the cases. In the small number of randomized trials car-

ried out, there is no difference in overall tubal patency and subsequent intrauterine pregnancy rates but a trend towards lower repeat EPs if a laparoscopic approach was used.14 Surgical treatments may be radical (salpingectomy) or conservative (usually linear salpingotomy). Salpingectomy is the treatment of choice if the fallopian tube is extensively diseased or damaged as there is a high risk of recurrent EP in that tube, although the case for salpingectomy in all cases where the contralateral tube is healthy has been questioned.15 The argument for this is based on the belief that in the presence of a healthy contralateral tube, the future pregnancy rates are similar, but salpingotomy is associated with an increased risk of repeat EP. In cases where the tube has not ruptured (Fig. 2), linear salpingotomy is a therapeutic option in an attempt to maintain fertility. However, there are no randomized controlled trials that specifically compare laparoscopic salpingectomy and salpingotomy and the effects on subsequent fertility are uncertain and need further investigation.16 Reviews of observational studies show no evidence that there is an increase in the rate of subsequent intrauterine pregnancy after salpingotomy compared with salpingectomy.16,17 However, recent cohort studies question this, suggesting that the future success has more to do with the underlying pathology than the surgery undertaken.15,18,19 Although some show that the intrauterine pregnancy rates were similar, others demonstrate a trend towards improved subsequent intrauterine pregnancy rates with conservative surgery18,19; this is particularly true if there is contralateral tubal disease. The most recent study shows significant benefit of salpingotomy in all cases.15 However, all the studies suggest a trend towards an increased repeat ectopic rate with salpingotomy compared with salpingectomy.

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FIGURE 2. Unruptured tube with EP. A, fimbrial end; B, cornual end. (Taken from BMJ. 2000;7239:916919.)

Because salpingotomy is associated with higher risks of intraoperative and postoperative bleeding and persistent trophoblast, these risks and the possibility of further EPs in the conserved tube should be considered before deciding on salpingotomy rather than salpingectomy in women with a healthy contralateral tube. However, it is clear that salpingotomy is the treatment of choice in the presence of contralateral tubal disease where there is a desire for future fertility as there is a greater subsequent intrauterine pregnancy rate.15,18,19 Because of the risk of persistent trophoblast after salpingotomy, close follow-up is required with regular hCG assessment. This results in the short-term costs of salpingotomy being greater than salpingectomy. However, if the subsequent need for assisted conception is taken into account, an increase in intrauterine pregnancy rate of only 3% would make salpingotomy more cost effective than salpingectomy.19

PERSISTENT TROPHOBLAST

This is mostly a problem after salpingotomy with an incidence of around 8%.16,20 Persistent trophoblast is more likely if the preoperative serum hCG levels are above 3000 IU/L, there is a rising preoperative hCG or there is active tubal bleeding.21 The presence of persistent trophoblast can be assessed by the clearance curve.20 The proportion of women treated for persistent trophoblast will depend on the cut-off point used. Currently, there are insufficient data to recommend the correct definition and every unit needs to develop their own criteria. Suggested criteria for starting the treatment are if hCG levels fail to fall below 65% of their initial level at 48 hours postsurgery or serum hCG is greater than 10% of the preoperative level 10 days postsurgery. If persistent trophoblast is diagnosed, methotrexate at a dose of 50 mg/m2 is preferable to a repeat surgical procedure.

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Follow-up
The need for nonsensitized women who are rhesus negative to receive anti-D immunoglobulin is often overlooked in this situation. Anti-D immunoglobulin at a dose of 250 IU (50 mg) should be given to all nonsensitized women who are rhesus negative and who have an EP. Although the woman has lost a usually wanted pregnancy, most of the follow-up relates to the postsurgical aspects of the condition. The psychologic cost is often over-looked as it is not generally viewed in the same way as other pregnancy loss. It would seem that the women have similar grief reactions to those with miscarriages but have the additional trauma of the potential reduction in fertility. Support networks such as the Miscarriage Association are recommended to women after miscarriage but, until recently, there has been no specific support group for woman after EP. In the United Kingdom, the EP Trust evolved out of this need and provides both information and support. Because previous EP is the biggest risk factor for subsequent EP, early followup in the next pregnancy to assess viability and position should be offered. Because the average gestation of presentation of EP is around 6 to 7 weeks, ultrasound scanning needs to be before this. The presence of an intrauterine pregnancy sac is reassuring and can relieve much anxiety.

88%, and rates for recurrent EP vary between 4.2% and 5%. Therefore, in those women suitable for expectant management, there is no benefit from the use of methotrexate unless hCG fails to fall satisfactorily. In the case of medical management, a population-based cohort study reported a pregnancy rate of 66% regardless of whether treatment was surgical or medical13,18 with a 10% risk of recurrent EP. However, it is only in those women with starting hCG levels of below 3000 IU/L that the results are comparable with laparoscopic surgery.13,16,22 Surgery should always be by laparoscope as long as the women is hemodynamically stable and/or the appropriately trained staff are available.13 However, the evidence supporting conservative or radical treatment is conflicting. Generally, around 65% of women will be pregnant within a year of the ectopic and over 80% in the long term and the recurrence risk of another EP of around 10% to 15%.15 This has not changed over 30 years. Overall, the outcome in the next pregnancy is as much to do with the underlying pathology as the therapeutic option chosen. Treatment should therefore be directed at therapeutic need and the wishes of the patient.

Unusual Sites
Although 95% of EPs occur in the fallopian tube, other sites occur, including ovarian, corneal, cervical, and in cesarean section scars. The importance of these rarer sites is that they generally carry with them an increased maternal risk requiring specific management options. There is no large series of any of them but various case reports of successful or disastrous treatment outcomes. In these situations, usual approaches including direct injection of methotrexate into the sac, systemic methotrexate,

Comparison Between Treatment Methods

In women with criteria suitable for expectant management, the outcome was as good as medical treatment in a randomized trial.11 The rates of intrauterine pregnancy after expectant management are comparable with those achieved after medical or surgical management, varying between 80% and

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4. Irvine LM, Setchell ME. Declining incidence of ectopic pregnancy in a UK city health district between 1990 and 1999. Hum Reprod. 2001;16:22302234. 5. Storewide O, Vehement M, Eide M, et al. The incidence of ectopic pregnancy in Hordaland County, Norway 19761993. Acta Obstet Gynecol Scand. 1997;76:345349. 6. Coste J, Bouyer J, Ughetto S, et al. Ectopic pregnancy is again on the increase. Recent trends in the incidence of ectopic pregnancies in France (19922002). Hum Reprod. 2004;19:20142018. 7. Ankum WM, Mol BW, Van der Veen F, et al. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril. 1996;65: 10931099. 8. Simms I, Rogers PA, Nicoll A. The influence of demographic change and cumulative risk of pelvic inflammatory disease on the incidence of ectopic pregnancy. Epidemiol Infect. 1997;119: 4952. 9. Egger M, Low N, Smith GD, et al. Screening for chlamydial infections and the risk of ectopic pregnancy in a county in Sweden: ecological analysis. BMJ. 1998;316:17761780. 10. Seeber BE, Sammel MD, Guo W, et al. Application of redefined human chorionic gonadotropin curves for the diagnosis of women at risk for ectopic pregnancy. Fertil Steril. 2006. 11. Korhonen J, Stenman UH, Ylostalo P. Low-dose oral methotrexate with expectant management of ectopic pregnancy. Obstet Gynecol. 1996;88:775778. 12. Barnhart KT, Gosman G, Ashby R, et al. The medical management of ectopic pregnancy: a meta-analysis comparing single dose and multidose regimens. Obstet Gynecol. 2003;101:778784. 13. Seeber BE, Barnhart KT. Suspected ectopic pregnancy. Obstet Gynecol. 2006;107(2 Pt 1):399413. 14. Hidlebaugh D, OMara P. Clinical and financial analyses of ectopic pregnancy management at a large health plan. J Am Assoc Gynecol Laparosc. 1997;4: 207213. 15. Bangsgaard N, Lund CO, Ottesen B, et al. Improved fertility following

uterine artery embolization, and specific surgical approaches. These cases have to be treated on an individual basis.

Conclusions
Because the diagnosis of EP is not easy and rarely performed in the community, all sexually active women with a history of lower abdominal pain and vaginal bleeding should be referred to hospital early for ultrasonography and, if necessary, measurement of serum concentrations of hCG. Clinical examination is not necessary except to assess the hemodynamic state. In women where the diagnosis is unsure but the condition is stable, expectant management as an outpatient is suitable. Where the diagnosis is reasonably certain and if an intrauterine pregnancy has been excluded, medical management under close supervision is safe. Diagnostic laparoscopy is necessary if the clinical situation cannot be clarified or if the patients condition deteriorates. If surgery is necessary, the laparoscopic route results in shorter hospital stay, but there is no clear advantage of salpingotomy over salpingectomy. The decision should therefore be made on an individual basis. The emotional aspects of pregnancy loss should not be underestimated. Women with a history of EP should have early access to ultrasonography to verify a viable intrauterine pregnancy in their subsequent pregnancies.

References
1. Lewis G, Drife JO. Why Mothers Die. Report on Confidential Inquiries Into Maternal Deaths in the United Kingdom 2000-2002. London: RCOG Press; 2004. 2. Farquhar CM. Ectopic pregnancy. Lancet. 2005;366:583591. 3. Tay JI, Moore J, Walker JJ. Ectopic pregnancy. BMJ. 2000;320:916919.

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conservative surgical treatment of ectopic pregnancy. Bjog. 2003;110:765770. Sowter MC, Farquhar CM. Ectopic pregnancy: an update. Curr Opin Obstet Gynecol. 2004;16:289293. Mol BW, Hajenius PJ, Engelsbel S, et al. Is conservative surgery for tubal pregnancy preferable to salpingectomy? An economic analysis. Br J Obstet Gynaecol. 1997;104:834839. Job-Spira N, Bouyer J, Pouly JL, et al. Fertility after ectopic pregnancy: first results of a population-based cohort study in france. Hum Reprod. 1996;11:99104. Mol BW, Matthijsse HC, Tinga DJ, et al. Fertility after conservative and

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18.

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radical surgery for tubal pregnancy. Hum Reprod. 1998;13:18041809. 20. Hajenius PJ, Mol BW, Ankum WM, et al. Clearance curves of serum human chorionic gonadotrophin for the diagnosis of persistent trophoblast. Hum Reprod. 1995;10:683687. 21. Kemmann E, Trout S, Garcia A. Can We predict patients at risk for persistent ectopic pregnancy after laparoscopic salpingotomy? J Am Assoc Gynecol Laparosc. 1994;1:122126. 22. Hajenius PJ, Mol BW, Bossuyt PM, et al. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev. 2000:CD000324.