J I Tay, J Moore, J J Walker
Division of Obstetrics and Gynaecology, St James’s University Hospital,
Leeds LS9 7TF
J I Tay
J J Walker
Ectopic pregnancy occurs when the conceptus implants outside the uterine
cavity. The most common implantation site is
within the fallopian tube, usually in the ampullary portion (fig 1).
Other less common sites include the ovary, the cornual segment
of the uterus, the cervix and, rarely, other peritoneal or serosal
surfaces within the abdominal cavity. Ectopic pregnancy carries
with it major maternal morbidity and risk of mortality, with loss of
The incidence of ectopic pregnancy is increasing, mainly due to the increased incidence of pelvic inflammatory disease caused by Chlamydia trachomatis
Ectopic pregnancy must be excluded in a sexually active woman with a positive pregnancy test, abdominal pain, and vaginal bleeding
Early ultrasonography should be available in subsequent pregnancies for women who have had an ectopic pregnancy Diagnosis cannot be made clinically or in the community
Treatment should be tailored to individual needs; in selected cases medical management can be as effective as laparoscopic salpingostomy
Conservative surgery results in slightly higher rates of intrauterine
pregnancy and higher recurrent ectopic pregnancies
(F1) Fig 1
Sites of ectopic pregnancies
We review the incidence, causes, diagnosis, and management of ectopic pregnancy. The evidence presented is from a combination of selected published papers identified from Medline and a reflection of clinical practice in our unit. Medline was searched with the term “ectopic pregnancy” and combined with terms such as incidence, risk factors, methotrexate, salpingectomy, salpingostomy, etc.
The incidence of ectopic pregnancy has been steadily increasing in the United Kingdom, (1) Europe, (2) (3) and the United States. (4) In 1994-6 there were an estimated 33 550 cases of ectopic pregnancy (incidence 11.5 per 1000 pregnancies) and 12 deaths due to ectopic pregnancy (a rate of 0.4 per 1000 ectopic pregnancies). (1) Compared with the previous three years this is an increase of more than 3000 cases and three more deaths. In northern Europe, population based studies have also shown an increased rate of ectopic pregnancy, from 11.2 to 18.8 per 1000 pregnancies during 1976-81 and 1988-93 respectively. (2) In the United States, the number of admissions to hospital for ectopic pregnancy increased from 17 800 in 1970 to 88 400 in 1989. (4)
Both the incidence and the increase in the incidence have been greatest in the older age group. In northern Europe, the rate in women over the age of 35 years has increased from 20.7 to 40.9 per 1000 pregnancies. (2) This association with age has also been found in England. (5) It has been suggested that this is because older women have been more exposed to the risks of developing pelvic inflammatory disease than their younger counterparts. However, other factors such as the quality of the oocyte and delayed fertilisation may affect transport of the embryo.
A significant number of ectopic pregnancies therefore occur per year in the United Kingdom, with about 30 cases per day. Healthcare provision needs to be directed towards this problem.
The reasons for development of an ectopic pregnancy are probably multifactorial,
and a proportion of women who develop
ectopic pregnancies do not seem to have any identifiable risk factors
(box 1). The main risk factors for ectopic pregnancy,
however, would seem to be previous ectopic pregnancy, (6) (7)
tubal damage from either infection (7) or previous abdominal
or pelvic surgery, (7) (8) a history of infertility, (8) treatment
for in vitro fertilisation, (9) increased age, (2) (5) and
smoking. (10) (11)
|Box 1: Risk factors for development of ectopic pregnancy|
History of pelvic inflammatory disease or acute salpingitis
Tubal factor infertility
Previous ectopic pregnancy
Previous tubal surgery
Previous acute appendicitis
History of peritonitis
History of previous pelvic or abdominal surgery
Current use of an intrauterine contraceptive device
Pelvic inflammatory disease
The association between pelvic inflammatory disease and ectopic pregnancy is well established. The increased incidence of pelvic infection has been implicated in the increased incidence of ectopic pregnancy. (12) (13) The risk of an ectopic pregnancy is increased sevenfold after acute salpingitis, (13) and women with a history of pelvic inflammatory disease are 10 times more likely to be admitted for ectopic pregnancy. (12)Chlamydia trachomatis
The main cause of pelvic inflammatory disease in the United Kingdom is Chlamydia trachomatis. Increasing episodes of C trachomatis infection increases the risk of ectopic pregnancy. The odds ratio of a woman with a history of two chlamydial infections having an ectopic pregnancy is 2.1 (95% confidence interval 1.3 to 3.4) and after three or more infections is 4.5 (1.8 to 5.3). (14) These data suggest there is a unique opportunity for prevention by treating the primary infection. Chlamydia prevention programmes in the United States (15) and Sweden (16) have shown that screening can decrease the incidence of C trachomatis infections and the rate of ectopic pregnancy. In the United Kingdom, however, there is no national screening programme, but the Royal College of Obstetricians and Gynaecologists has provided guidelines for screening and treating women at high risk. (17) The government is funding two pilot schemes to test the general feasibility of a screening programme in this country. (18) Female sterilisation Pregnancy after female sterilisation is more likely to be ectopic, although sterilisation itself does not increase the risk of ectopic pregnancy. (19) The overall risk of ectopic pregnancy after sterilisation is 7.3 per 1000 procedures within 10 years. (19) The trend is towards a higher risk of ectopic rupture in patients who have been sterilised, suggesting a delay in diagnosis because of a lack of suspicion. (20)
Intrauterine contraceptive devices
Current use of an intrauterine contraceptive device is a risk factor for ectopic pregnancy only if cases are compared with pregnant controls (pooled odds ratio 10.63, 7.66 to 14.74). (21) Compared with non-users of contraception, women who use current copper intrauterine contraceptive devices have a 91% protection (87% to 94%) against ectopic pregnancy. (22) This suggests that the device protects against an ectopic pregnancy because pregnancy is rare, but if it does occur, it is more likely to be ectopic. Past use of an intrauterine contraceptive device mildly increases the risk of ectopic pregnancy (pooled odds ratio 1.40, 1.23 to 1.59). (21)
Assisted reproductive techniques
The incidence of ectopic pregnancy after assisted reproductive techniques is 4%, (9) which is 2-3 times greater than the background incidence. The main risk factor in patients who have had assisted reproduction is tubal infertility. Because of this increased risk and multiple embryo transfer, the incidence of heterotopic pregnancy (an ectopic pregnancy occurring together with an intrauterine pregnancy) after an assisted reproductive technique varies between 0.2% (23) and 1%, (24) compared with a rate of 1 in 30 000 in spontaneous pregnancies.
Most women with an ectopic pregnancy present early. The average gestation of presentation of an unruptured ectopic pregnancy is 6.9 (SD 1.9) weeks, and 7.2 (SD 2.2) weeks if the tube is ruptured. (7)
The history and presenting symptoms of ectopic pregnancy are non-specific
and may be confused with those of a
miscarriage, an ovarian accident, or pelvic inflammatory disease (box
2). Some patients may not have symptoms. The pain is
usually lateral and not in the midline. However, history and physical
examination do not reliably diagnose or rule out ectopic
pregnancy as up to 9% of patients report no pain and 36% lack adnexal
tenderness at presentation. (25) (26)
|Box 2: Percentage occurrence of history and presenting signs with
Abdominal pain (97%)
Vaginal bleeding (79%)
Abdominal tenderness (91%)
Adnexal tenderness (54%)
History of infertility (15%)
Use of an intrauterine contraceptive device (14%)
Previous ectopic pregnancy (11%)
Diagnosis may therefore be difficult unless the condition is suspected. The presence of known risk factors can increase suspicion, but any sexually active woman presenting with abdominal pain and vaginal bleeding after an interval of amenorrhoea has an ectopic pregnancy until proved otherwise. Within the community, there is no sure method of excluding the diagnosis of ectopic pregnancy. Pelvic examination is best avoided as this can cause rupture of the fallopian tube and further haemorrhage. In the presence of a positive pregnancy test and suggestive symptoms or signs, hospital referral for pelvic ultrasonography is mandatory.
Those who present in a collapsed state often have had prodromal symptoms of abdominal pain and spotting. The vaginal bleeding is partly from decidual loss due to failure of the pregnancy. Major abdominal bleeding is due to invasion of the tubal epithelium and muscle layer by the trophoblast, which eventually erodes the full thickness of the tube (fig 2).
(F2) Fig 2
Trophoblast invading wall of fallopian tube (x 25). A and C, tubal lumen; B, trophoblast
Referral should preferably be to a unit dedicated to managing problems early in pregnancy as this allows ease of investigations and continuity of outpatient care. The initial investigation carried out in women with bleeding early in pregnancy is ultrasonography. The presence of an intrauterine pregnancy on an ultrasonogram significantly decreases the chances of an ectopic pregnancy, although other ultrasound findings have to be considered, especially if symptoms are atypical, severe, or persistent.
The most common transvaginal ultrasound finding in an ectopic pregnancy is an extraovarian, round or elongated, solid tubal mass. (27) A tubal ring (an extrauterine sac-like structure) is the second most common finding, and it is rare to see an extrauterine yolk sac or fetal heart. Pelvic fluid may be present but it is a non-specific finding. A pseudosac may be seen in the uterus, which can be mistaken for a true gestational sac. In the presence of an ectopic pregnancy, a decidual endometrial reaction may occur and this may be difficult to differentiate from endometrial thickening in normal early pregnancy.
In cases where no intrauterine pregnancy is found or there is some doubt, the use of quantitative measurements of serum concentrations of b human chorionic gonadotrophin together with transvaginal ultrasonography improves the preoperative diagnosis of ectopic pregnancy. (28) This combination was shown to have a positive predictive value of 0.95 in the diagnosis of ectopic pregnancy. Human chorionic gonadotrophin is produced by trophoblastic tissue and the amount secreted is directly proportional to the number of active trophoblastic cells. Serum concentrations increase steadily in the first trimester, reaching a peak around weeks 8-12 of pregnancy, as calculated from the last menstrual period (fig 3). (29) There is, however, no agreement about the precise threshold concentration that is diagnostic of an ectopic pregnancy in the presence of an empty uterus. (30)(31)(32) An intrauterine gestation sac can be identified with transvaginal ultrasonography as early as 30-33 days from the last menstrual period (33) and at serum concentrations of human chorionic gonadotrophin as low as 500 IU/l. (30)(33) A yolk sac may be detected at concentrations of 1000 IU/l but the concentrations vary widely and it may not be seen until concentrations reach 7000 IU/l. (33) In the absence of any signs on ultrasonography, a cut off point of 2000 IU/l should be used before an ectopic pregnancy is diagnosed. (32) Although ectopic pregnancies are also associated with serum concentrations of human chorionic gonadotrophin that are generally lower than in normal pregnancies, (34) the change of serum concentrations provides more information than absolute concentrations. (35) (36) In a normal pregnancy, serum concentrations double every 2-3.5 days in the fourth to eighth week of pregnancy. A two day sampling interval is recommended for estimation of doubling in serum concentrations if paired serum samples are being tested. (36) Up to 15% of normal pregnancies, however, have an abnormal increase in serum concentrations of human chorionic gonadotrophin. (37) Nevertheless, in the presence of an empty uterus and an abnormal increase in serum concentrations of human chorionic gonadotrophin to over 1000 IU/l, the diagnosis of ectopic pregnancy can be made with a sensitivity of 90% and a specificity of 98%. (38) (39)
(F3) Fig 3
Mean (SE) serum concentrations of human chorionic gonadotrophin in normal pregnancy (adapted fromBraunstein et al, 199629)
The value of accurately assessing the risk of ectopic pregnancy is the early diagnosis of ectopic pregnancy, which may be life saving, and the reduction of unnecessary invasive investigations, which allows expectant treatment with preservation of the tube. Although direct visualisation of an ectopic pregnancy at laparoscopy is the definitive diagnosis, it may be missed if this is performed before the tube is distended.
Medical and expectant management are possible, and should be considered in selected cases, but are not widely practised in the United Kingdom. Surgery possibly overtreats several cases but is the mainstay of treatment especially if the ectopic pregnancy is large or has ruptured and the patient is haemodynamically unstable.
Some ectopic pregnancies resolve spontaneously but there are no reliable variables for predicting this. Size of the ectopic pregnancy has little relation to the probability of spontaneous resolution. (37) Multivariate analysis has shown that both initial serum titres of human chorionic gondatrophin and trend in serum titres, but not visualisation of an ectopic gestational sac by ultrasonography, are independent predictors of a successful or failed expectant management. (40) The higher the serum concentration of human chorionic gonadotrophin the more likely expectant management is to fail. (41) The success rates of expectant management for patients with serum concentrations of human chorionic gonadotrophin less than 200 mIU/ml, less than 500 mIU/ml, and greater than 2000 mIU/ml were shown to be 98%, 73%, and 25% respectively. (41) Overall, if the initial serum concentration is less than 1000 IU/l this allows successful expectant management in most patients (88%) (40); but the failure rate is unacceptably high (40%) if concentrations are greater than 2000 IU/l. (41) Declining serum concentrations of human chorionic gonadotrophin allow expectant management provided the concentrations and the patient’s symptoms are monitored. Because of traditional teaching and the fear of potential rupture of the ectopic, surgical and medical management remain the primary treatments. Therefore, until more predictable features are identified, a proportion of woman with ectopic pregnancies that would normally resolve spontaneously will continue to be overtreated. Expectant management does not seem to adversely effect subsequent reproductive outcomes.
Treatment with methotrexate, a folic acid antagonist, can be used in selected cases of ectopic pregnancy. It is best reserved for patients who are haemodynamically stable, and diagnosis is made early in gestation so that the ectopic pregnancy is small and has not ruptured (fig 4). (42) Most stable patients with painCeven with rebound or free peritoneal fluidCcan be treated successfully without surgery, either as an inpatient, with close observation for those with severe pain, or as an outpatient for those with less severe pain. (43)
(F4) Fig 4
Unruptured tube with ectopic pregnancy. A, fimbrial end; B, cornual end
Methotrexate is given intramuscularly or injected into the ectopic pregnancy. Injection into the pregnancy delivers high concentrations of methotrexate locally, with smaller systemic distribution of the drug than with intramuscular injection, and does not seem to damage the tubal epithelium. (44) The rates of successful treatment are, however, lower than with systemic methotrexate, and injection requires a laparoscopic or ultrasound guided needle procedure. A single intramuscular injection of methotrexate is more convenient than the variable dose regimen but may carry a higher risk of persistent ectopic pregnancy. (6) Methotrexate is given at a single dose of 50 mg/m2. This is repeated if the serum concentration of human chorionic gonadotrophin does not decrease by at least 15% after 4-7 days, or if a plateau or increase is noted during weekly follow up. (43) (45) The success rate with these regimens in correctly selected patients is 91.5% (95% confidence interval 83.5% to 99.5%) although 14% require a second dose and around 10% (7% to 14%) require surgical intervention. (45)(46)(47) When treating ectopic pregnancy medically, response to treatment should be confirmed by close follow up with serial measurements of serum concentrations of human chorionic gonadotrophin. An initial increase in serum concentration occurs and transient pelvic pain is common 3-7 days after the start of treatment. This may last up to 12 hours and may cause concern and be difficult to differentiate from symptoms of a rupturing ectopic pregnancy. Close monitoring of vital signs, haemoglobin concentration, and packed cell volume is therefore important. (6) Surgical intervention is only necessary when there is hypotension or a decrease in packed cell volume. Failure of serum concentrations of human chorionic gonadotrophin to decline indicates a persistent trophoblast, and a second course of treatment may be given. Cases with increasing concentrations require surgical intervention.
Overall, 24% of patients (9% to 47%) experience side effects with methotrexate. (46) They include bone marrow suppression, stomatitis, gastritis, enteritis, impaired liver function, and photosensitivity.
Mifepristone has been used in combination with methotrexate for the medical treatment of ectopic pregnancy. (48) In a randomised, controlled trial comparing methotrexate combined with mifepristone and methotrexate alone in 50 women with unruptured tubal ectopic pregnancy, the ectopic pregnancy resolved faster in women given the combined treatment. The effect of the combined treatment was also more pronounced in women with higher serum concentrations of human chorionic gonadotrophin.
Surgical treatments may be radical (salpingectomy) or conservative (usually salpingostomy). These may be performed by laparoscopy or laparotomy. Salpingectomy is performed if there is a cornual ectopic pregnancy or if there is haemorrhage after rupture. It is also the procedure of choice if the fallopian tube is extensively diseased and damaged, has previously had an ectopic pregnancy within it, or the contralateral tube has already been removed because of an ectopic pregnancy or sterilisation. In these situations, there is a high risk of recurrence of ectopic pregnancy in the affected tube and this should be discussed with the woman before surgery.
Generally, patients treated by laparoscopy have a shorter hospital stay (1.3 days), and a shorter convalescence (2.4 weeks) than patients treated by laparotomy (3.1 days and 4.6 weeks respectively). (49) (50) Similar rates of complications are found for laparotomy and laparoscopy. (51) The overall rate of persistent trophoblast is also similar for both treatments (2.7% and 3.4% respectively), (51) although the rate is higher for laparoscopic salpingostomy (6.1%-7.2%). (50) (52)
If salpingostomy is performed, follow up with serial measurements of serum concentrations of human chorionic gonadotrophin is necessary because of the risk of persistent trophoblast either within the fallopian tube or within the abdominal cavity. No single value for postoperative concentrations of human chorionic gonadotrophin can predict persistent trophoblast, therefore follow up until complete resolution is necessary. (51) (53) However, the percentage decrease on the first postoperative day can give an indication of the likelihood of persistent trophoblast. In a retrospective cohort study, a significantly greater percentage of persistent ectopic pregnancies were noted when the serum concentrations of human chorionic gonadotrophin on the first postoperative day decreased by less than 50% from the preoperative concentration. (53) An inverse relation was found between the percentage decrease in serum concentrations of human chorionic gonadotrophin before and one day after surgery and the incidence of persistent ectopic pregnancy. It has, however, been recommended that the threshold for a second laparoscopy should be comparatively high and should be based on the presence of symptoms rather than on changes in concentrations of human chorionic gonadotrophin. (49)(50)(51)
In a randomised controlled trial comparing methotrexate and laparoscopic salpingostomy, both treatments were equally successful in treating the ectopic pregnancy. (54) The mean time from initiation of treatment to cure in women who were treated successfully was 25 (SD 15) days, which is comparable to surgical treatment. (45) Also no significant difference was found between the two treatments for tubal patency after treatment. Just as surgery is sometimes required after medical treatment, methotrexate can also be used in cases of persistent trophoblast after salpingostomy as an alternative to repeat surgery.
Surveillance of human chorionic gonadotrophin after treatment
There are no trials that specifically address surveillance of concentrations of human chorionic gonadotrophin after treatment. From the published studies, however, it is possible to outline a rough guide to the frequency of measurements of concentrations of human chorionic gonadotrophin after methotrexate treatment or conservative surgery. For expectant management, serum concentrations should be monitored every two days. (41) After methotrexate treatment the first follow up measurement should be taken 4-7 days after treatment, (43) (45) then weekly if the first concentration after treatment has decreased by 15% or more. If the decrease is less than 15%, a second dose of methotrexate is recommended and then monitored as before. After surgery, ectopic pregnancy does not persist if the concentrations of human chorionic gonadotrophin decrease by 77% or more on the first postoperative day compared with preoperative concentrations. (53) If concentrations decrease by 50% or more, clinical presentation does not occur before day 9 and a follow up measurement on day 7 is suggested. If concentrations decrease by less than 50% of the preoperative value on the first postoperative day, persistent ectopic pregnancies may present as early as day 3 and an early measurement of concentration of human chorionic gonadotrophin on day 3 is advised. Serial monitoring should be continued until concentrations decrease into the normal range.
Cost of treatment
No randomised controlled trials have compared the costs of salpingectomy and conservative surgery. A retrospective economic analysis of conservative surgery compared with salpingectomy for tubal pregnancy has shown that the cost of conservative surgery is slightly more than salpingectomy in the short term. (55) Both treatments are equally effective at treating the ectopic pregnancy, but additional treatment for persistent ectopic pregnancies is occasionally required in conservative treatment. In the long term, however, salpingectomy with in vitro fertilisation is more costly than conservative treatment. In a five year retrospective review of the various management modalities of ectopic pregnancy, the total cost for laparotomy and laparoscopy was found to be similar (£4200 ($6720) and £4280 ($6849) respectively). Although it may be comparatively simple to calculate the costs of treating the acute episode, calculating the long term economic costs of subsequent infertility treatment and treatment for recurrent ectopic pregnancy is more difficult. Methotrexate treatment in outpatients was significantly cheaper, with an average cost of £511 ($818) per case.
The psychological cost of ectopic pregnancy is often overlooked, as it is not generally viewed in the same way as a miscarriage of an intrauterine pregnancy. Support networks such as the Miscarriage Association are often recommended to women who have had a miscarriage, but until recently women who have had an ectopic pregnancy have had no specific support group. The recently formed Ectopic Pregnancy Trust evolved out of such a need and it works closely with the Miscarriage Association to help such women. In our experience women who have had an ectopic pregnancy grieve in a similar way to those who have had a miscarriage but that they have the additional trauma of a lost fallopian tube and the prospect of infertility or reduced fertility.
Fertility after treatment
Rates of intrauterine pregnancy after expectant management are comparable to those after medical or surgical management (between 80% and 88%), (56) (57) and rates of recurrent ectopic pregnancy vary between 4.2% and 5%. A review of studies using methotrexate for the treatment of ectopic pregnancy showed that between 62% and 70% of women had a subsequent intrauterine pregnancy and around 8% had recurrent ectopic pregnancy. (37) (42) These studies show that methotrexate does not have unfavourable effects on subsequent fertility.
In a population based cohort study of 155 women treated for ectopic pregnancy, 66% conceived during the follow up period (mean 16 months) regardless of whether they were treated surgically or medically. (58) The mean time to pregnancy was 4.8 months. Of those who conceived, 90% achieved an intrauterine pregnancy and 10% had a further ectopic pregnancy. The risk factors for infertility and recurrent ectopic pregnancy were previous spontaneous miscarriage, tubal damage, and age greater than 30. (42)
No randomised controlled studies comparing the effect of conservative and radical surgery on subsequent fertility have yet been published, and the results from retrospective studies are conflicting. A review of retrospective and prospective relevant studies on ectopic pregnancy showed no significant difference in rates of intrauterine or recurrent ectopic when radical and conservative surgical treatment were compared. (58) Retrospective cohort studies, however, showed lower rates of intrauterine pregnancy and recurrent ectopic pregnancy after salpingectomy. (37) (59) (60) After salpingostomy, the rates of intrauterine pregnancy and recurrent ectopic pregnancy were 61% and 15% respectively whether performed by laparotomy or laparoscopy. After partial or total salpingectomy the rate of intrauterine pregnancy was 38.1% and that of recurrent ectopic pregnancy was 9.8%. (37) The three year cumulative pregnancy rate was significantly higher with conservative surgery as was the rate of ectopic pregnancy. (59) Laparoscopy was superior to laparotomy irrespective of type of tubal surgery (59) resulting in a higher rate of intrauterine pregnancy (77% versus 66%) and a lower rate of recurrent ectopic pregnancy (7% versus 17%). (50) A history of infertility, however, may be more important than mode of surgery, (61) with an overall conception rate of 77% for all methods of treatment and a recurrence rate of around 10%. (52) (56) Women with a healthy contralateral tube had significantly higher rates of intrauterine pregnancy than those with tubal damage (75% versus 36%), with a 9.6% and 18.3% risk of recurrent ectopic pregnancy respectively. (62) (63) If the contralateral tube was blocked or absent, the rate for intrauterine pregnancy was poor (31.2%) and that for recurrent ectopic pregnancy was high (16.0%), suggesting that most subsequent pregnancies are achieved through the contralateral tube. (64) In a retrospective follow up of 1025 patients with at least one patent remaining tube the pregnancy rate was similar after wedge resection (45.9%) and salpingostomy or “milk out” (42.0%), and the recurrence rates did not differ between the groups (7.5% versus 8.2%). (64) Although tubal rupture seriously affects immediate health, it seems to have no independent effect on subsequent fertility. (65)
Despite tubal preservation in around 90% of patients, and patencies between 55% and 59%, neither systemic treatment with methotrexate nor laparoscopic salpingostomy improved subsequent pregnancy performance. (54) Treatment should therefore be directed at the therapeutic need and the wishes of the patient wherever possible.
The incidence of ectopic pregnancy is increasing and its diagnosis may not be straightforward. Symptoms may be similar to a spontaneous miscarriage or even pelvic inflammatory disease. Obvious risk factors need not be present, therefore any sexually active woman who presents with an interval of amenorrhoea followed by vaginal bleeding and abdominal pain needs to have an ectopic pregnancy ruled out. This is best done by a combination of ultrasonography and measurement of serum concentrations of human chorionic gonadotrophin, carried out serially if diagnosis is not immediately obvious. These investigations are best carried out in hospital within a unit dedicated to managing problems early in pregnancy. A diagnostic laparoscopy is necessary if the clinical situation cannot be clarified or if the patient’s condition deteriorates. Women with a history of ectopic pregnancy should have early access to ultrasonography to verify a viable intrauterine pregnancy in their subsequent pregnancy because of their increased risk of recurrent ectopic pregnancy.
Expectant and medical management of ectopic pregnancy are effective options and should be considered in selected cases as long as adequate facilities for monitoring are available. If surgery is necessary, salpingostomy seems to give better rates of future fertility although there is a higher incidence of persistent ectopic, which may require further intervention. After salpingostomy, monitoring of serum concentrations of human chorionic gonadotrophin is necessary to ensure that there is no persistent trophoblast. The decision to perform salpingectomy or salpingostomy should be made on an individual basis, taking into account the patient’s wishes for future fertility and her risk factors for recurrence of ectopic pregnancy.
Adequate treatment of pelvic inflammatory disease and C trachomatis infections can reduce the incidence of ectopic pregnancy. However, the most effective methods of screening and prevention are not yet known. The cost benefits of screening for C trachomatis in young women are also unproved. Two screening programmes have, however, been funded by the government and are being piloted this year. (18) The results are unlikely to be available for some time, so opportunistic screening of women attending for termination of pregnancy and family planning clinics are the options available.
Partners of women found to have a positive result on screening should be treated to reduce reinfection, and contact tracing is recommended.
We thank Dr N Wilkinson for preparation and use of the histology slides. The address for the Ectopic Pregnancy Trust is Maternity Unit, Hillingdon Hospital, Pield Heath Road, Uxbridge, Middlesex UB8 3NN.
Department of Health. Why women die. Report on confidential enquiries into maternal deaths in the United Kingdom 1994-1996. Norwich: Stationery Office, 1998.
- Storeide O, Veholmen M, Eide M, Bergsjo P, Sanderi R. The incidence of ectopic pregnancy in orlaland County, Norway 1976-1993. Acta Obstet Gynecol Scand 1997;76:345-9
- Skjeldstad FE, Kendrick JS, Atrash HK, Dalveit A K. Increasing incidence of ectopic pregnancy in one Norwegian county–a population based study, 1970-1993. Acta Obstet Gynecol Scand 1997;76:159-65.
- Ectopic pregnancy–United States, 1990-1992. MMWR 1995;44:46-8.
- Simms I, Rogers P A, Nicoll A. The influence of demographic change and cumulative risk of pelvic inflammatory disease on the change of ectopic pregnancy. Epidemiol Infect 1997;119:49-52.
- Pisarska M D, Carson S A, Buster J E. Ectopic pregnancy. Lancet 1998;351:1115-20.
- Ankum W M , Mol B W J, van der Veen F, Bossuyt PMM. Risk factors for ectopic pregnancy–a meta analysis. Fertil Steril 1996;65:1093-9.
- Marchbanks PA, Annegers J F, Coulam C B, Strathy J H, Kurland L T. Risk factors for ectopic pregnancy. A population based study. JAMA 1988;259:1823-7.
- Strandell A, Thorburn J, Hamberger L. Risk factors for ectopic pregnancy in assisted reproduction. Fertil Steril 1999;71:282-6.
- DeMouzon J, Spira A, Schwartz D. A. prospective study of the relation between smoking and fertility. Int J Epidemiol 1988;17:378-84.
- Castles A, Adams E K, Melvin C L, Kelsch C, Boulton M L. Effects of smoking during pregnancy. Five meta-analyses. Am J Prev Med 1999;16:208-15.
- Buchan H, Vessey M, Goldacre M, Fairweather J. Morbidity following pelvic inflammatory disease. Br J ObstetGynaecol 1993;100:558-62.
- Westrom L, Bengtsson L P H, Mardh P-A. Incidence, trends and risks of ectopic pregnancy in a population of women. BMJ 1981;282:15-8.
- Hillis S D, Owens L M, Marchbanks P A, Amsterdam L F, MacKenzie WR. Recurrent chlamydial infections increase the risks of hospitalisation for ectopic pregnancy and pelvic inflammatory disease. Am J Obstet Gynecol 1997;176:103-7.
- Hillis S D, Nakashima A, Amsterdam L, Pfister J, Vaughn M, Addiss D, et al. The impact of a comprehensive chlamydia prevention programme in Wisconsin. Fam Plann Perspect 1995;27:108-11.
- Egger M, Low N, Smith G D, Lindblom B, Herrmann B. Screening for chlamydial infections and the risk of ectopic pregnancy in a county in Sweden: ecological analysis. BMJ 1998;316:1776-80.
- Royal College of Obstetricians and Gynaecologists. In: Templeton A, ed. Recommendations arising from the 31ststudy group: the prevention of pelvic infection. London: RCOG, 1996.
- Chief Medical Officer’s Expert Advisory Group. Chlamydia trachomatis. Report of the Chief Medical Officer’sExpert Advisory Group. London: Department of Health, 1998.
- Peterson H B, Xia Z, Hughes J M, Wilcox L S, Tylor L R, Trussell J. The risk of ectopic pregnancy after tubal sterilisation. US Collaborative Review of Sterilisation Working Group. New Engl J Med 1997;336:762-7.
- Hendrix N W, Chauhan S P, Maier R C. Ectopic pregnancy in sterilized and nonsterilized women. A comparison. J Reprod Med 1998;43:515-20.
- Xiong X, Beukens P, Wollast E. IUD use and the risk of ectopic pregnancy: a meta-analysis of case-control studies. Contraception 1995;52:23-34.
- Skjeldestad FE. How effectively do copper intrauterine devices prevent ectopic pregnancy? Acta Obstet Gynecol Scand 1997;76:684-90.
- Serour GI, Aboulghar M, Mansour R, Sattar MA, Amin Y, Aboulghar H. Complications of medically assisted conception in 3,500 cycles. Fertil Steril 1998;70:638-42.
- Tal J, Haddad S, Gordon N, Timor-Tritsch I. Heterotopic pregnancy after ovulation induction and assisted reproductive technologies: a literature review from 1971-1993. Fertil Steril 1996;66:1-12.
- Aboud E. A five year-review of ectopic pregnancy. Clin Exp Obstet Gynecol 1997;24:127-9.
- Kaplan BC, Dart RG, Moskos M, Kuligowska E, Chun B, Adel Hamid M, et al. Ectopic pregnancy–prospective-study with improved diagnostic accuracy. Ann Emerg Med 1996;28:10-7.
- Atri M, Leduc C, Gillett P, Bret PM, Reinhold C, Kintzen G, et al. Role of endovaginal sonography in the diagnosis and management of ectopic pregnancy. Radiographics 1996;16:755-74.
- Ankum W M, Hajenius PJ, Schrevel L S, van der Veen F. Management of suspected ectopic pregnancy. Impact of new diagnostic tool in 686 consecutive cases. J Reprod Med 1996;41:724-8.
- Braunstein G D, Rasor J, Adler D, Danzer H, Wade M E. Serum human chorionic gonadotrophin levels throughout normal pregnancy. Am J Obstet Gynecol 1976;126:678-81.
- Nyberg D A, Laurence A M, Laing F C, Jeffery R B. Early pregnancy complications: endovaginal sonographic findings correlated with human chorionic gonadotrophin levels. Radiology 1988;167:620-2.
- Mehta T S, Levine D, Beckwith B. Treatment of ectopic pregnancy: is a human chorionic gonadotrophin level of 2,000 mIU/ml a reasonable threshold? Radiology 1997;205:569-73.
- Mol B W J, Hajenius PJ, Engelsbel S, Ankum WM, Van der Veen F, Hemrika DJ, et al. Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive. Fertil Steril 1998;70:972-81.
- Cacciatore B, Tiitinen A, Stenman U-H, Ylostalo P. Normal early pregnancy: serum hCG levels and vaginal ultrasonography findings. Br J Obstet Gynaecol 1990;97:899-903.
- Cartwright P S, DiPietro D L. Ectopic pregnancy: changes in serum human chorionic gonadotrophin concentrations. Obstet Gynecol 1984;63:76-80.
- Kadar N, Bohrer M, Kemman E, Shelden R. A prospective, randomised study of the chorionic gonadotropin-time relationship in early gestation: clinical implications. Fertil Steril 1993;60:409-12.
- Pittaway D E, Reish R L, Wentz A C. Doubling times of human chorionic gonadotropin increase in early viable intra-uterine pregnancies. Am J Obstet Gynecol 1985;152:299-302.
- Yao M, Tulandi T. Current status of surgical and nonsurgical management of ectopic pregnancy. Fertil Steril 1997;67:421-33.
- Hajenius P J, Mol B W J, Ankum W M Van der Veen, Bossuyt P M M, Lammes F B. Suspected ectopic pregnancy: expectant management in patients with negative sonographic findings and low serum hCG concentrations. Early Pregnancy 1995;1:1258-62.
- Ankum W M, VanderVeen F, Hamerlynck J V T H, Lammes F B. Suspected ectopic pregnancy: what to do when hCG levels are below the discriminatory hCG zones? J Reprod Med 1995;40:525-8.
- Trio D, Strobelt N, Picciolo C, Lapinski RH, Ghidini A. Prognostic factors for successful expectant management of ectopic pregnancy. Fertil Steril 1995;63:469-72.
- Shalev E, Peleg D, Tsabari A, Romano S, Bustan M. Spontaneous resolution of ectopic tubal pregnancy: natural history. Fertil Steril 1995;63:15-9.
- Jimenez-Caraballo A, Rodriguez-Donoso G. A 6-year clinical trial of methotrexate therapy in the treatment of ectopic pregnancy. Eur J Obstet Gynecol 1998;79:167-71.
- Lipscomb G H, Puckett K J, Bran D, Ling F W. Management of separation pain after single-dose methotrexate therapy for ectopic pregnancy. Obstet Gynecol 1999;3:590-3.
- Lecuru F, Robin F, Taurelle R, Bernard J P, Vilde F. Effect of methotrexate on tubal epithelium. A report of three cases. J Reprod Med 1999;44:46-8.
- Thoen L D, Creinin M D. Medical treatment of ectopic pregnancy with methotrexate. Fertil Steril 1997;68:727-30.
- Parker J, Bisits A, Proietto A M. A systematic review of single-dose intramuscular methotrexate for the treatment of ectopic pregnancy. Aust N Z J Obstet Gynaecol 1998;38:145-50.
- Lipscomb G H, Bran D, Mccord M L, Portera J C, Ling F W. Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 1998;178:1354-8.
- Gazvani M R, Baruah D N, Alfirevic Z, Emery S J. Mifepristone in combination with methotrexate for the medical treatment of tubal pregnancy: a randomised, controlled trial. Hum Reprod 1998;13:1987-90.
- Lundorff P. Laparoscopic surgery in ectopic pregnancy. Acta Obstet Gynecol Scand 1997;76:81-4.
- Hidlebaugh D, Omara P. Clinical and financial analyses of ectopic pregnancy management at a large health plan. J Am Asso Gynecol Laparo 1997;4:207-13.
- Dwarakanath L S, Mascarenhas L, Penketh R J A, Newton J R. Persistent ectopic pregnancy following conservative surgery for tubal pregnancy. Br J Obstet Gynaecol 1996;103:1021-4.
- Clasen K, Camus M, Tournaye H, Devroey P. Ectopic pregnancy: let’s cut! Strict laparoscopic approach to 194 consecutive cases and review of literature on alternatives. Hum Reprod 1997;12:596-601.
- Spandorfer S D, Sawin S W, Benjamin I, Barnhart K T. Postoperative day 1 serum human chorionic gonadotrophin level as a predictor of persistent ectopic pregnancy after conservative surgical management. Fertil Steril 1997;68:430-4.
- Harjenius P J, Engelsbel S, Mol B W, Van der Veen F, Ankum W M, Bossuyt PM, et al. Randomised trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy. Lancet 1997;350:774-9.
- Mol B W J, Hajenius P J, Engelsbel S, Ankum W M, Hemrika D J, van der Neen F. Is conservative surgery for tubal pregnancy preferable to salpingectomy? An economic analysis. Br J Obstet Gynaecol 1997;104:834-9.
- Zohav E, Gemer O, Segal S. Reproductive outcome after expectant management of ectopic pregnancy. Eur J ObstetGynecol Reprod Biol 1996;66:1-2.
- Rantala M, Mäkinen J. Tubal patency and fertility outcome after expectant management of ectopic pregnancy. Fert Steril 1997;68:1043-6.
- Job-Spira N, Bouyer J, Pouly JL, Germain E, Coste J, Aublet-Cuvelier B. Fertility after ectopic pregnancy: first results of a population-based cohort study in France. Hum Reprod 1996;11:99-104.
- Fernandez H, Marchal L, Vincent Y. Fertility after radical surgery for tubal pregnancy. Fertil Steril 1998;70:680-6.
- Mol B W, Matthijsse H C, Tinga D J, Huynh T, Hajenius P J, Ankum W M, et al. Fertility after conservative and radical surgery for tubal pregnancy. Hum Reprod 1998;13:1804-9.
- delaCruz A, Cumming DC. Factors determining fertility after conservative or radical surgical treatment for ectopic pregnancy. Fert Steril 1997;68:871-4.
- Dubuisson J B, Morice P, Chapron C, Degayffier A, Mouelhi T. Salpingectomy–the laparoscopic surgical choice for ectopic pregnancy. Hum Reprod 1996;11:1199-203.
- Bouyer J, Job-Spira N, Pouly J L, Germain E, Coste J, Aublet-Cuvelier B, et al. Fertility after ectopic pregnancy–results of the 3 first years of the auvergne-registre. Contraception Fertilite Sexualite 1996;24:475-81.
- Korell M, Albrich W, Hepp H. Fertility after organ-preserving surgery of ectopic pregnancy: results of a multicenter study. Fertil Steril 1997;68:220-3.
- Job-Spira N, Fernandez H, Bouyer J, Pouly JL, Germain E, Coste J. Ruptured tubal ectopic pregnancy: risk factors and reproductive outcome: results of a population-based study in France. Am J Obstet Gynecol 1999;180:938-44.