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com

Review

Diagnosis and management of ectopic

pregnancy
Vanitha N Sivalingam,1 W Colin Duncan,2 Emma Kirk,3 Lucy A Shephard,4 Andrew W Horne5

1
Specialist Registrar in Obstetrics Overview
and Gynaecology, Simpson An ectopic pregnancy occurs when a fer- Key message points
Centre for Reproductive Health,
Royal Infirmary of Edinburgh, tilised ovum implants outside the normal
▶ Clinicians should be suspicious of ectopic pregnancy in any
Edinburgh, UK uterine cavity.1–3 It is a common cause of woman of reproductive age presenting with abdominal or
2
Senior Lecturer and Consultant morbidity and occasionally of mortality in pelvic symptoms.
in Reproductive Medicine, MRC ▶ The diagnosis of ectopic pregnancy can be difficult and
women of reproductive age. The aetiol-
Centre for Reproductive Health, protracted.
Queen’s Medical Research ogy of ectopic pregnancy remains uncer- ▶ A diagnosis of ‘pregnancy of unknown location’ should
Institute, University of Edinburgh, tain although a number of risk factors trigger further diagnostic pathways and follow-up until the
Edinburgh, UK have been identified.4 Its diagnosis can be final outcome of the pregnancy is known.
3
Specialist Registrar in Obstetrics ▶ Medical management with methotrexate is successful for
and Gynaecology, Department
difficult. In current practice, in developed small, stable ectopic pregnancies.
of Obstetrics and Gynaecology, countries, diagnosis relies on a combina-
North Middlesex University tion of ultrasound scanning and serial
Hospital, London, UK serum beta-human chorionic gonado- diagnosis of ectopic pregnancy ultimately
4
Reproductive Biology Honours
Student, MRC Centre for
trophin (β-hCG) measurements.5 Ectopic die from the condition.10 Ectopic preg-
Reproductive Health, Queen’s pregnancy is one of the few medical con- nancy is a considerable cause of mater-
Medical Research Institute, ditions that can be managed expectantly, nal morbidity, causing acute symptoms
University of Edinburgh, medically or surgically.1 3 6 such as pelvic pain and vaginal bleeding
Edinburgh, UK
5
MRC Clinician Scientist and and long-term problems such as infertili-
Consultant Gynaecologist, MRC Incidence ty.3 Short- and long-term consequences of
Centre for Reproductive Health, In the developed world, between 1% and ectopic pregnancy on health-related qual-
Queen’s Medical Research 2% of all reported pregnancies are ectopic ity of life and on bereavement issues are
Institute, University of Edinburgh,
Edinburgh, UK pregnancies (comparable to the incidence likely to be significant but have not been
of spontaneous twin pregnancy).7 The formally quantified.
Correspondence to incidence is thought to be higher in devel-
Dr Andrew W Horne, MRC oping countries, but specific numbers are Risk factors
Centre for Reproductive Health, unknown. Although the incidence in the Although women with ectopic pregnancy
Queen’s Medical Research
Institute, University of Edinburgh, developed world has remained relatively frequently have no identifiable risk factors,
47 Little France Crescent, static in recent years, between 1972 and a prospective case-controlled study has
Edinburgh EH16 4TJ, UK; 1992 there was an estimated six-fold rise shown that increased awareness of ectopic
andrew.horne@ed.ac.uk
in the incidence of ectopic pregnancy.8 pregnancy and a knowledge of the associ-
Received 6 February 2011 This increase was attributed to three fac- ated risk factors helps identify women at
Accepted 1 March 2011 tors: an increase in risk factors such as higher risk in order to facilitate early and
pelvic inflammatory disease and smok- more accurate diagnosis.11 Most risk fac-
ing in women of reproductive age, the tors are associated with risks of prior dam-
increased use of assisted reproductive age to the Fallopian tube (Box 1). These
technology (ART) and increased aware- factors include any previous pelvic or
ness of the condition, facilitated by the abdominal surgery, and pelvic infection.11
development of specialised early preg- Chlamydia trachomatis has been linked to
nancy units (EPUs). 30–50% of all ectopic pregnancies.12 The
exact mechanism of this association is not
Morbidity and mortality known but it has been proposed that in
In the UK, ectopic pregnancy remains addition to distortion of tubal architec-
the leading cause of pregnancy-related ture, it may to be due to an effect on the
first trimester death (0.35/1000 ectopic tubal microenvironment.13
pregnancies).3 6 9 However, in the develop- Ectopic pregnancy is more common in
ing world it has been estimated that 10% women attending infertility clinics14 even
of women admitted to hospital with a in the absence of tubal disease. In addition,

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Sivalingam et al.

models that could be used to further our understand-

Box 1 Risk factors for ectopic pregnancy ing.21 However, it is thought that tubal implantation
occurs as a result of a combination of arrest of the
▶ Fallopian tube damage
Previous tubal surgery (including female sterilisation) and pelvic surgery embryo in the Fallopian tube and changes in the tubal
including Caesarean section and ovarian cystectomy microenvironment that allow early implantation to
Previous abdominal surgery including appendicectomy and bowel surgery
occur.4 Inflammation within the tube, resulting from
Confirmed genital infection and pelvic inflammatory disease, commonly caused
by chlamydial infection infection or smoking, may affect embryo-tubal trans-
▶ Infertility port by disrupting smooth muscle contractility and
Documented tubal disease
ciliary beat activity and may also provide pro-implan-
Assisted reproductive technology
Endometriosis tation signals. Molecular research generally involves
Unexplained infertility studying Fallopian tube biopsies taken from women
▶ Contraceptive failure
with ectopic pregnancies. Interpretation is limited as
Progestogen-only contraception
Intrauterine contraceptive device comparable Fallopian tube samples are not available
▶ Cigarette smoking – including past exposure. from women with an intrauterine pregnancy (IUP)
▶ Age >35 years
or in advance of an ectopic pregnancy occurring.
▶ Previous ectopic pregnancy
▶ Previous spontaneous abortion or induced abortion Thus, it is difficult to ascertain whether any molecu-
lar changes observed are a cause or a consequence of
ectopic implantation. Novel studies focusing on the
the use of ART increases the rate of ectopic pregnan- functional consequences of smoking and infection
cies. In vitro fertilisation (IVF) is associated with an on Fallopian tube physiology and pathobiology are
ectopic pregnancy risk of 2–5% and it may be higher required.
than this where there is tubal disease. Indeed the first
IVF pregnancy, before the first IVF live birth, was a Clinical presentation
tubal ectopic pregnancy.15 Patients with an ectopic pregnancy commonly present
Some types of contraception, such as progestogen- with pain and vaginal bleeding between 6 and 10 weeks’
only contraception and the intrauterine contraceptive gestation.1 However, these are common symptoms in
device, are associated with an increased incidence of early pregnancy, with one third of women experienc-
ectopic pregnancy when there is contraceptive fail- ing some pain and/or bleeding.22–24 The pain can be
ure, without necessarily increasing the absolute risk of persistent and severe and is often unilateral. However
ectopic pregnancy.16 unilateral pain is not always indicative of ectopic preg-
One third of all cases of ectopic pregnancy are nancy as, in early pregnancy, a prominent painful ovar-
thought to be associated with smoking.17 There is a ian corpus luteum cyst is common. Shoulder tip pain,
dose–effect relationship, with the highest adjusted syncope and shock occur in up to 20% of women and
odds ratio (OR) (3.9) when more than 20 cigarettes abdominal tenderness in more than 75%. Bimanual
are smoked a day.18 Several mechanisms for this asso- examination, if performed at all, should be done cau-
ciation have been suggested, including one or more tiously and gently. Cervical motion tenderness has
of the following: delayed ovulation, altered tubal and been reported in up to 67% of cases, and a palpable
uterine motility and microenvironment, or altered adnexal mass in about 50%.23–25 More recently, it has
immunity.19 20 been reported that one third of women with ectopic
The risk of ectopic pregnancy increases with advanc- pregnancy have no clinical signs and 9% have no
ing maternal age, with age over 35 years being a sig- symptoms.26 27
nificant risk factor.6 Hypotheses for this association A ruptured ectopic pregnancy should be strongly
include the higher probability of exposure to most suspected if a woman has a positive pregnancy test
other risk factors with advancing age, increase in chro- and presents with syncope and signs of shock includ-
mosomal abnormalities in trophoblastic tissue and ing tachycardia, pallor and collapse. There may be
age-related changes in tubal function delaying ovum abdominal distension and marked tenderness. While
transport, resulting in tubal implantation.18 a bimanual examination may reveal tenderness, cer-
Women with a previous history of ectopic pregnancy vical excitation and an adnexal mass, great caution is
also have an increased risk, which increases further in required as this may exacerbate bleeding. As ectopic
proportion to the number of previous ectopic preg- pregnancy affects young, fit women they are often
nancies. In one study the OR for having an ectopic able to mount remarkable haemodynamic compensa-
pregnancy was 12.5 after one previous ectopic preg- tion. Tachycardia is a particularly important sign, but
nancy and 76.6 after two.18 decompensation with shock is a sign of significant
intraperitoneal bleeding. In an emergency, where the
Aetiology patient has collapsed and there is high clinical suspi-
The exact aetiology of ectopic pregnancy is unknown. cion of tubal rupture, extensive clinical examination
It is notable that it is unique to humans, and perhaps is inappropriate and immediate surgical intervention
the higher apes, so that there are no good animal is indicated.

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Ectopic pregnancy

Unfortunately, atypical presentation is also relatively of the women with an eventual diagnosis of ectopic
common. Ectopic pregnancy may mimic other gynae- pregnancy are not diagnosed at their first presenta-
cological disorders and gastrointestinal or urinary tract tion.31 32 Early diagnosis reduces the risk of tubal rup-
disease, including appendicitis, salpingitis, ruptured ture and allows more conservative medical treatments
corpus luteum or follicular cysts, threatened or inevi- to be employed.1 33
table spontaneous abortion, ovarian torsion and uri- Currently, diagnosis in unruptured ectopic pregnancy
nary tract infection. The 1997–1999 and 2003–2005 is achieved using a combination of transvaginal ultra-
Confidential Enquiries into Maternal Deaths reports sonography and measurement of serum β-hCG con-
highlighted that most of the women who died from centrations. One of the key elements in the diagnosis
ectopic pregnancy were misdiagnosed in the primary is the exclusion of a viable or non-viable IUP. Diagnosis
care or accident and emergency settings.28 29 It was can be straightforward when a transvaginal ultrasound
therefore recommended that all clinicians should be scan (TVS) positively identifies an IUP or ectopic preg-
made aware of the atypical clinical presentations of nancy34 (Figure 1). However, TVS fails to identify the
ectopic pregnancy. While there has been a welcome location of a pregnancy in a significant number of
decline in the case death rate in women with ectopic women and such women are currently diagnosed as
pregnancies, a key lesson emphasised in these reports having a ‘pregnancy of unknown location’ (PUL).35 36
does not appear to have been learnt. In the 2006–2008 The 2006–2008 CMACE report drew attention to
Centre for Maternal and Child Enquiries (CMACE) a maternal death secondary to ruptured ectopic preg-
report, four of the six women who died from early nancy where a diagnosis of PUL had been made.30
ectopic pregnancy complained of diarrhoea, dizziness Although most patients with a PUL will subsequently
or vomiting as early symptoms, without triggering any be diagnosed with either a failed IUP (a spontane-
consideration of extrauterine pregnancy by their medi- ous abortion) or viable IUP, the report highlights
cal attendants.30 that 7–20% will be diagnosed with an ectopic preg-
However, it remains difficult to diagnose an ectopic nancy. It is therefore very important that a diagnosis
pregnancy from risk factors, history and examination of PUL should trigger further diagnostic pathways and
alone. Clinicians should be suspicious of pregnancy follow-up until the final outcome of the pregnancy is
in any such woman who presents with abdominal known.
or pelvic symptoms and should always bear in mind The concept of a ‘discriminatory β-hCG level’ was
the possibility of ectopic pregnancy in any woman of introduced in 1985 to highlight the serum concentra-
reproductive age who presents with any of the symp- tion of β-hCG when a pregnancy should be visible on
toms mentioned above. an ultrasound scan. Using transabdominal ultrasound
examination, it was reported then that the absence of an
Diagnosis intrauterine gestational sac at a β-hCG concentration
Diagnosis of ectopic pregnancy has improved signifi- over 6500 IU/l had a sensitivity of 100%, specificity
cantly due to advances in ultrasound technology, rapid of 96%, positive predictive value of 87% and negative
and sensitive serum hormone assays, the development predictive value of 100% for the prediction of ectopic
of EPUs and an increased awareness and understanding pregnancy. In the context of a 19.4% prevalence of
of the associated risk factors. Despite this, around half ectopic pregnancies in the study group, this diagnostic

Figure 1 Transvaginal ultrasound images of an intrauterine pregnancy (IUP) and ectopic pregnancy. (A) An IUP at 6 weeks. The
central dark area is the intrauterine gestational sac and within the sac is a circular ringed structure that is the yolk sac. The small oval
structure below the yolk sac is the fetus. (B) An ectopic pregnancy. To the right of the image is the normal uterus and to the left of
the uterus is the doughnut-shaped ectopic pregnancy.

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paradigm was 98% efficient.37 With the introduction

Box 2 Useful ultrasonographic findings in the
of high-resolution TVS, the discriminatory β-hCG
diagnosis of ectopic pregnancy
level of 6500 IU/l is now less helpful.35 38 An ectopic
pregnancy can be detected at β-hCG concentrations
▶ Absence of intrauterine pregnancy (IUP)
well below this level and an ultrasound scan should ▶ Positive identification of an ectopic pregnancy mass: inhomogenous mass, empty
not be delayed because of low β-hCG concentrations. adnexal gestation sac or adnexal sac containing yolk sac or fetal pole
▶ Free fluid (i.e. blood): suggestive of ectopic pregnancy in the absence of IUP, but
not diagnostic (small amount may be physiological)
Transvaginal ultrasonography
High-definition ultrasonography, particularly using the
transvaginal route, has revolutionised the assessment identification of which can help in the search for an
of patients with early pregnancy problems, allowing adnexal mass. The mass may appear as an inhomog-
for clearer visualisation of both normal and abnormal enous echogenic area adjacent to the ovary that moves
gestations.39 In a healthy IUP, a TVS should identify separately from it on gentle pressure; a gestation sac
the intrauterine gestation sac with almost 100% accu- enclosed by a hyperechoic ring (the so-called ‘bagel’
racy at a gestational age of 5.5 weeks.40 41 Even so, it appearance); or a gestation sac with a fetal pole, with
is recognised radiographic practice that an IUP is only or without cardiac activity.
definitively diagnosed by ultrasound visualisation of a Suspicion of an ectopic pregnancy increases if free
yolk sac or embryo in addition to a gestation sac.42–44 fluid (representing blood) is visualised, either surround-
This is because an ectopic pregnancy can be accom- ing the uterus or in the Pouch of Douglas,48 although
panied by a ‘pseudosac’, a collection of fluid within a small amount of free fluid in the Pouch of Douglas,
the endometrial cavity that may be the result of local- a transudate due to increased vascular permeability, is
ised breakdown of the decidualised endometrium. common in early pregnancy.
However, its central location within the endometrial Box 2 summarises ultrasonographic findings that are
cavity distinguishes it from the very early gestation useful in diagnosing an ectopic pregnancy.
sac that is typically eccentrically placed.45 In addi-
tion, pseudosacs are transient rather than consistent Serum β-hCG concentrations
and they do not have a hyperechoic decidual reaction The changes in serum β-hCG concentrations over time
around them. Additional embryonic features including have been used to predict the outcome of PULs.49 Kadar
the yolk sac and cardiac activity should be clearly vis- and Romero50 were the first to describe these serial
ible after 6 weeks’ gestation. A sonographer with expe- changes on the basis of a small sample of 20 women
rience in early pregnancy scanning should generally be using an 85% confidence interval (CI). They showed
able to tell the difference between a pseudosac and an that in a normal ongoing pregnancy, the minimal rate
empty early intrauterine sac. of increase in β-hCG is 66% in 2 days. In a recent study
The identification of an IUP can rule out ectopic of 287 patients with pain or bleeding, the minimum
pregnancy in most settings unless a heterotopic preg- rise in β-hCG for a viable IUP was 24% at 24 hours
nancy is suspected, where an ectopic pregnancy coex- and 53% at 48 hours.51 In addition, Seeber et al.52 pro-
ists with an IUP.46 They are rare (1 in 40 000), although duced data with a 99% CI that suggested a more con-
more common after assisted conception, and difficult servative minimum rise of 35% over 2 days. In current
to diagnose. practice most units use a minimum value of between
In the absence of an intrauterine gestation sac, an 50% and 66% for the acceptable 48-hour increase in
ectopic pregnancy can be diagnosed by the presence of β-hCG in a normal pregnancy.53 Some non-viable IUPs
an adnexal mass, often visible within the Fallopian tube. will also demonstrate an exponential increase in serum
The positive identification of a non-cystic adnexal mass β-hCG, so normal β-hCG changes do not necessarily
with an empty uterus has a sensitivity of 84–90% and a confirm viability. However, absence of this expected
specificity of 94–99% for the diagnosis of an ectopic ges- rise suggests early pregnancy failure.
tation.47 In one large prospective study of 6621 patients, A rapid decline in β-hCG concentrations over 2 days,
ectopic pregnancy was correctly diagnosed by TVS with commonly by 21–35% or more, is indicative of a spon-
a sensitivity of 90.9% and specificity of 99.9%.24 False taneous abortion52 or a resolving ectopic pregnancy. In
positives can, however, occur if other structures such as an ectopic pregnancy, β-hCG concentrations are just
the corpus luteum, bowel, a paratubal cyst, a hydros- as likely to fall as to rise, with no single pattern able
alpinx or an endometrioma are mistaken for an ectopic to characterise the condition.54 However, 71% have
pregnancy. False negatives can occur if the ectopic is serial serum β-hCG values that increase more slowly
small or if it is concealed by bowel or uterine anomalies than would be expected with a viable IUP and decrease
such as fibroids. It is therefore possible for an ectopic more slowly than would be expected with a spontane-
pregnancy to go unnoticed on an ultrasound scan, espe- ous abortion.9
cially if the patient is asymptomatic. If the history is not compatible with a spontane-
Around 80% of ectopic pregnancies will be on ous abortion, or the β-hCG concentrations continue
the same side as the ovarian corpus luteum, the to rise and the scan location of the pregnancy is still

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Ectopic pregnancy

unknown, an ectopic pregnancy is likely and a clear Management

management strategy should be put in place. Ectopic pregnancy may be managed surgically, medically
or expectantly. In these days of increasing outpatient
Serum progesterone diagnosis and management it is important to remember
Although there are no definitive values that demarcate the risks of ruptured ectopic pregnancy. Clear documen-
an ectopic pregnancy from an IUP, the measurement tation of diagnostic and management strategies – with
of serum progesterone levels is a potentially useful clinical, sonographic and biochemical assessment of the
adjunct in the assessment of PULs.55 Serum proges- patient – is therefore important. Which management is
terone concentrations in a viable IUP are >50 ng/ml. most appropriate depends on ongoing assessment and
Although progesterone assessment cannot easily dis- on numerous clinical factors. Management is tailored to
criminate between an ectopic pregnancy and a failing individual patients, based on their presentation and on
IUP56 some EPUs use a low progesterone (<5 ng/ml) to the severity of their condition, suitability of treatment
differentiate between ‘low-risk’ patients, when a PUL options and patient preference. Figure 2 demonstrates a
may be suitable for conservative management, and ‘at- suggested diagnosis and management pathway.
risk’ patients who require definitive treatment.57
Surgery
Other serum biomarkers Surgical management is imperative in the clinical sce-
Although other potential serum biomarkers have been nario of a ruptured ectopic pregnancy. A laparoscopic
proposed,58 none of these are used in common clinical approach is preferable to an open approach in a patient
practice. New biomarkers with clinical utility would who is haemodynamically stable. Laparoscopic proce-
be helpful in improving the diagnosis of ectopic preg- dures are associated with shorter operative times, less
nancy, with the potential benefits of greater safety and intraoperative blood loss, shorter hospital stays and
reduced diagnostic costs.5 32 lower analgesia requirements.59–61 Laparotomy should
be reserved for patients who present with rupture and
Diagnostic laparoscopy are in a state of hypovolaemic shock and compro-
In cases where an ectopic pregnancy is suspected and mise. If the contralateral tube is healthy, the preferred
ultrasound is inconclusive, a diagnostic laparoscopy may option is salpingectomy, where the entire Fallopian
be required. This is believed by many to be the ‘gold tube, or the affected segment containing the ectopic
standard’ investigation in ectopic pregnancy. Indeed gestation, is removed (Figure 3). A salpingostomy is
reluctance or delay in performing a diagnostic laparos- the removal of the ectopic pregnancy, by dissecting it
copy has been highlighted as a factor in fatal cases.30 out of the tube, leaving the Fallopian tube in situ in
However, some small ectopic pregnancies may be missed an attempt to preserve fertility on that side.
at the time of laparoscopy or laparotomy. In one study, A number of systematic reviews have examined
2 of 44 (4.5%) women reported to have no evidence of reproductive outcomes following the two procedures
an ectopic pregnancy at the time of laparoscopy were in patients with a healthy contralateral tube. Studies in
subsequently diagnosed with one.55 An alternative to this area can be criticised with regard to patient selec-
diagnostic laparoscopy may involve a repeat ultrasound tion, surgical techniques and follow-up times62–64 and
examination, particularly when β-hCG concentrations some studies report conflicting results.65 66 However, it
are close to 1500 IU/l. Other strategies include alter- is generally accepted that the chance of subsequent IUP
native diagnostic tests, such as serum progesterone or is not increased after salpingostomy compared with
an endometrial biopsy, or empirical medical treatment salpingectomy. In addition, the use of conservative sur-
as the patient may well have an ectopic pregnancy. If gical techniques exposes women to a small risk of tubal
β-hCG concentrations are falling but an ectopic has not bleeding in the immediate postoperative period and
been excluded, consideration should be given to per- the potential need for further treatment of persistent
forming serial β-hCG measurements until levels become trophoblast.9 This supports current guidelines stating
undetectable, as rupture can still occur.40 that the operation of choice, where there is a healthy
contralateral tube, is laparoscopic salpingectomy.67
Endometrial biopsy In the presence of contralateral tubal disease, a lapar-
In selected cases of PUL, an endometrial biopsy may oscopic salpingostomy should be considered if future
be taken and analysed for the presence or absence of fertility is desired. Persistent trophoblast is the main
chorionic villi. Their absence in the presence of a static concern after a salpingostomy. This is usually detected
β-hCG is suggestive of an ectopic pregnancy. A dilata- by a failure of serum β-hCG levels to fall and is more
tion and curettage may be useful when performed in common following active tubal bleeding, where the
association with a ‘negative’ diagnostic laparoscopy for ectopic pregnancy size was >2 cm or if serum β-hCG
a suspected ectopic pregnancy. The clinician should be concentrations are >3000 IU/l or rising prior to sur-
certain that the pregnancy, if intrauterine, is non-viable gery.68 Women should be followed up with serial β-hCG
and appropriate consent obtained, as this procedure measurements and systemic methotrexate treatment
could potentially interrupt a continuing pregnancy. may be required if the levels fail to fall as expected.

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Figure 2 Recommended diagnostic and management approach for suspected ectopic pregnancy. It is important to highlight
that the figure of 66% is used as a practical guide only and that all cases of pregnancy of unknown location should be considered
as a potential ectopic pregnancy until assessment proves otherwise or management is complete. β-hCG, beta-human chorionic
gonadotrophin.

While the short-term costs of postoperative follow-up haemodynamically stable and have minimal symp-
and treatment of persistent trophoblast are greater fol- toms and a low volume of free intraperitoneal fluid
lowing a salpingostomy,69 the potential avoidance of on ultrasound scan.70 Intramuscular methotrexate is
the subsequent need for assisted conception will make the most widely used and successful medical therapy
it more cost effective compared with salpingectomy.66 for ectopic pregnancy and is generally administered
in a single-dose protocol.34 69 Methotrexate is a folic
Medical treatment with methotrexate acid antagonist that targets rapidly dividing cells and
Medical treatment is useful for patients with an arrests mitosis.9 71 In ectopic pregnancy, the drug
unruptured tubal ectopic pregnancy who are prevents the proliferation of cytotrophoblast cells,

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Figure 3 (A) Left tubal ectopic pregnancy at laparoscopy. (B) Tubal ectopic pregnancy has been removed by salpingectomy.

reducing cell viability and β-hCG secretion and thus Box 3 Inclusion criteria for medical management
progesterone support for the pregnancy. This facili- of ectopic pregnancy with methotrexate
tates the resolution of the ectopic pregnancy and tis-
sue remodelling. ▶ Patient characteristics
After assessing patient suitability for medical man- Would prefer medical option
Willing to attend follow-up for up to 6 weeks
agement (Box 3), body surface area is calculated using Willing to abstain from alcohol for 7 days following the treatment
height and weight measurements. In addition, a base- Not breastfeeding or willing to stop
line full blood count and renal and liver function tests ▶ Clinical features
Haemodynamically stable
are obtained. In general, apart from some abdominal Minimal abdominal pain
discomfort 1–3 days after treatment and abdominal ▶ Ultrasound scan findings
bloating, side effects are not common and return to No fetal heart activity or clear yolk sac in adnexal mass
Small amount of free fluid
normal activities is quicker than after surgery. Potential Unlikely to be early intrauterine pregnancy failure
serious side effects such as significant hepatotoxicity, ▶ Serum beta-human chorionic gonadotrophin (β-hCG) concentrations
bone marrow toxicity or alopecia are extremely rare Usually <3000 IU/l (Although limits of <5000 IU/l are used in some units and
earlier studies, treatment success rates are higher when this more commonly
with ectopic pregnancy treatment regimens. Patients used lower limit applies.)
require careful monitoring to ensure complete resolu- ▶ Medical history
tion of the ectopic gestation using serial assessment of No active peptic ulcer disease
No severe medical conditions including renal disease, hepatic disease, severe
β-hCG levels every 4–7 days (protocols vary between anaemia, leucopenia or thrombocytopenia
units) until the β-hCG level is <5 IU/l.72 ▶ Should not be on concurrent medication
The commonly used single-dose methotrexate treat- Non-steroidal anti-inflammatory agents (NSAIDs), aspirin, penicillins,
sulphonamides, trimethoprim, tetracyclines, diuretics, phenytoin, antimalarials,
ment regimen involves a deep intramuscular injection ciclosporin, retinoids, probenecid, folic acid, hypoglycaemics, live vaccines,
at a dose of 50 mg/m2 of the calculated body surface nephrotoxic or hepatotoxic drugs
area. Approximately 14–20% of patients receiving
single-dose treatment will require a repeat dose,73 74
usually decided on following a fall of the β-hCG con- for patients who present with a larger adnexal masses
centration of less than 15% from Day 4 to 7 after treat- and greater initial β-hCG levels (>5000 IU/l). Direct
ment. This timescale is used as methotrexate can cause injection of methotrexate into the ectopic sac, either
a transient rise in serum β-hCG after initial treatment. laparoscopically or with ultrasound guidance, limits
Approximately 10% of women will require surgical systemic toxicity and maintains a higher therapeu-
intervention,75 although most of these are for slowly tic level. However, local injection has no significant
falling β-hCG levels rather than for acute tubal rup- advantage in most patients and is accompanied by a
ture. However, rupture still remains a possibility dur- risk of provoking tubal rupture.
ing treatment. Close treatment surveillance, and staff Methotrexate treatment is very successful for small
and patient awareness of potential treatment failure, stable ectopic pregnancies. A meta-analysis of non-
are vital. randomised studies showed success rates of 93% (95%
Two much less common uses of methotrexate for CI 89–96%) for multi-dose protocols and 88% (95%
the treatment of ectopic gestation are the multi-dose CI 86–90%) for single dose therapy.76 Failure of sin-
protocol and direct injection of methotrexate into the gle-dose medical management is associated with initial
ectopic pregnancy. The multi-dose regimen consists serum β-hCG concentrations >5000 IU/l, a moderate
of methotrexate treatment on Days 1, 3, 5 and 7 to or large amount of free fluid on ultrasound, the pres-
a maximum of four doses and leucovorine ‘rescue- ence of fetal cardiac activity and a pretreatment increase
therapy’ at a dose of 0.1 mg/kg on alternate Days 2, in serum β-hCG of >50% over a 48-hour period. It is
4, 6 and 8. This treatment may be more appropriate not known whether methotrexate treatment has better

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Sivalingam et al.

fertility outcomes than surgery but this is likely to be one previous ectopic pregnancy and a risk of 32%
the case when the ectopic gestation occurs in the only or more following more than one previous ectopic.79
functioning tube. However, the risk is reduced after each subsequent
IUP.80 Even when there has been a bilateral salpingec-
Expectant management tomy there is still a risk of ectopic pregnancy in the
Some ectopic pregnancies resolve spontaneously interstitial tube or in tubal remnants following IVF.
through either regression or tubal abortion, without Women should receive an early scan in their next preg-
causing harm to the patient. Expectant management nancy to exclude a recurrent ectopic pregnancy.
is a conservative strategy consisting of observation and
assessment of whether the ectopic pregnancy is contin- The future
uing to resolve spontaneously and successfully without There have been major advances in the diagnosis
intervention.34 A suitable candidate for expectant man- and management of ectopic pregnancies during the
agement must have an ectopic pregnancy with no evi- last 20 years. However, even now a significant pro-
dence of rupture, be clinically stable and asymptomatic, portion of ectopic pregnancies are not diagnosed at
and have consistently declining β-hCG concentrations. presentation and there are wide variations in man-
A low serum progesterone is also a possible marker agement strategies between different units. Current
of suitability for the expectant approach. Follow-up screening methods have a high false-positive rate,
should be between one and three times weekly with and are not cost effective. Consequently, there are
β-hCG measurement and ultrasonography as required. a number of ongoing studies developing biomark-
Expectant management is reported to be most use- ers that allow definitive diagnosis.53 58 81 In addition,
ful when the initial β-hCG is <1000 IU/l.58 A rapidly there is a lack of randomised trials investigating the
declining β-hCG level also appears to predict a favoura- optimal management of ectopic pregnancy, particu-
ble outcome.77 Success rates between 47% and 82% are larly focusing on recurrence rates and impact on
reported, depending on the patient’s initial status.78 future fertility. Results are awaited from a large ran-
The importance of compliance with follow-up and domised trial comparing laparoscopic salpingectomy
ease of access to the hospital should be emphasised. with salpingostomy.82
If β-hCG levels remain static or decline suboptimally,
consideration should be given to reverting to surgical Acknowledgements The authors thank Ronnie Grant for
or medical management. graphics support and Dr Graeme Walker for images.
Funding Andrew Horne receives grant support
Unusual sites of implantation from the UK Medical Research Council (2009–
Over 98% of ectopic pregnancies implant in the 2013), IKTF (2009–2011) and an Albert McKern
Fallopian tube, in its ampullary region (70%), isthmus Bequest (2010–2011). Colin Duncan holds a
(12%) or fimbria (11.1%). Interstitial or cornual ectop- Scottish Senior Clinical Fellowship and has
ics, where the pregnancy implants in the intramyome- grant support from The Cunningham Trust.
trial portion of the Fallopian tube, are less common Competing interests Andrew Horne holds a
(2.4%) but have a mortality twice that of any other UK patent for a diagnostic biomarker for
type of Fallopian tube ectopic pregnancy.77 Rarely, ectopic pregnancy (# 0712801.0).
an ectopic pregnancy implants at an extratubal loca-
Provenance and peer review Commissioned;
tion, such as the cervix, ovary, abdomen, liver, spleen
externally peer reviewed.
or Caesarean section scar.1 This produces a diagnos-
tic challenge and colour Doppler visualisation aids in References
the identification of the ectopic pregnancy by creat- 1 Walker JJ. Ectopic pregnancy. Clin Obstet Gynecol 2007;
ing awareness of vasculature supplying the implanted 50:89–99.
gestation.77 Surgical treatment is difficult and systemic 2 Della-Giustina D, Denny M. Ectopic pregnancy. Emerg Med
methotrexate is considered first-line treatment, with an Clin North Am 2003;21:565–584.
early recourse to more than one dose, for the majority 3 Varma R, Gupta J. Tubal ectopic pregnancy. Clin Evid (Online)
of extratubal ectopic pregnancies.78 A more detailed 2009;2009:pii:1406.
description of the management of these unusual cases 4 Shaw JL, Dey SK, Critchley HO, et al. Current knowledge of
the aetiology of human tubal ectopic pregnancy. Hum Reprod
is beyond the scope of this review.
Update 2010;16:432–444.
5 Horne AW, Duncan WC, Critchley HO. The need for
Subsequent pregnancies
serum biomarker development for diagnosing and excluding
Studies suggest that around 60% of women affected by tubal ectopic pregnancy. Acta Obstet Gynecol Scand
an ectopic pregnancy go on to have a viable IUP.79 This 2010;89:299–301.
figure includes those who do not plan to have another 6 Farquhar CM. Ectopic pregnancy. Lancet 2005;366:583–591.
pregnancy and so the proportion will be higher if fur- 7 Goldner TE, Lawson HW, Xia Z, et al. Surveillance for ectopic
ther pregnancy is planned. There is thought to be a pregnancy – United States, 1970–1989. MMWR CDC Surveill
5–20% risk of a recurrence of ectopic pregnancy with Summ 1993;42:73–85.

8 of 10 Sivalingam VN, Duncan WC, Kirk E, et al. J Fam Plann Reprod Health Care (2011). doi:10.1136/jfprhc-2011-0073
 Downloaded from jfprhc.bmj.com on June 19, 2014 - Published by group.bmj.com

Ectopic pregnancy

8 Chang J, Elam-Evans LD, Berg CJ, et al. Pregnancy-related 30 O’Herlihy C. Deaths in early pregnancy. In: Cantwell R,
mortality surveillance – United States, 1991–1999. MMWR Clutton-Brock T, Cooper G et al. (eds), Centre for Maternal and
Surveill Summ 2003;52:1–8. Child Enquiries (CMACE). Saving Mothers’ Lives: Reviewing
9 Nama V, Manyonda I. Tubal ectopic pregnancy: diagnosis and Maternal Deaths to Make Motherhood Safe 2006–2008.
management. Arch Gynecol Obstet 2009;279:443–453. London, UK: RCOG Press, 2011;81–84
10 Leke RJ, Goyaux N, Matsuda T, et al. Ectopic pregnancy 31 Robson SJ, O’Shea RT. Undiagnosed ectopic pregnancy:
in Africa: a population-based study. Obstet Gynecol a retrospective analysis of 31 ‘missed’ ectopic pregnancies at
2004;103:692–697. a teaching hospital. Aust N Z J Obstet Gynaecol 1996;
11 Karaer A, Avsar FA, Batioglu S. Risk factors for ectopic 36:182–185.
pregnancy: a case-control study. Aust N Z J Obstet Gynaecol 32 Wedderburn CJ, Warner P, Graham B, et al. Economic
2006;46:521–527. evaluation of diagnosing and excluding ectopic pregnancy. Hum
12 Akande V, Turner C, Horner P, et al.; British Fertility Society. Reprod 2010;25:328–333.
Impact of Chlamydia trachomatis in the reproductive setting: 33 Murray H, Baakdah H, Bardell T, et al. Diagnosis and treatment
British Fertility Society Guidelines for practice. Hum Fertil of ectopic pregnancy. CMAJ 2005;173:905–912.
(Camb) 2010;13:115–125. 34 Barnhart KT. Clinical practice. Ectopic pregnancy. N Engl J Med
13 Shaw JL, Wills GS, Lee KF, et al. Chlamydia trachomatis 2009;361:379–387.
infection increases fallopian tube PROKR2 via TLR2 and NF?B 35 Condous G, Timmerman D, Goldstein S, et al. Pregnancies of
activation resulting in a microenvironment predisposed to unknown location: consensus statement. Ultrasound Obstet
ectopic pregnancy. Am J Pathol 2011;178:253–260. Gynecol 2006;28:121–122.
14 Clayton HB, Schieve LA, Peterson HB, et al. Ectopic pregnancy 36 Barnhart K, van Mello NM, Bourne T, et al. Pregnancy of
risk with assisted reproductive technology procedures. Obstet unknown location: a consensus statement of nomenclature,
Gynecol 2006;107:595–604. definitions, and outcome. Fertil Steril 2011;95:857–866.
15 Steptoe PC, Edwards RG. Reimplantation of a human embryo 37 Romero R, Kadar N, Jeanty P, et al. Diagnosis of ectopic
with subsequent tubal pregnancy. Lancet 1976;1:880–882. pregnancy: value of the discriminatory human chorionic
16 Furlong LA. Ectopic pregnancy risk when contraception fails. gonadotropin zone. Obstet Gynecol 1985;66:357–360.
A review. J Reprod Med 2002;47:881–885. 38 Barnhart KT, Simhan H, Kamelle SA. Diagnostic accuracy of
17 Ankum WM, Mol BW, Van der Veen F, et al. Risk factors for ultrasound above and below the beta-hCG discriminatory zone.
ectopic pregnancy: a meta-analysis. Fertil Steril 1996;65: Obstet Gynecol 1999;94:583–587.
1093–1099. 39 Kirk E, Bourne T. Diagnosis of ectopic pregnancy with ultra-
18 Bouyer J, Coste J, Shojaei T, et al. Risk factors for ectopic sound. Best Pract Res Clin Obstet Gynaecol 2009;23:501–508.
pregnancy: a comprehensive analysis based on a large case- 40 Barnhart K, Mennuti MT, Benjamin I, et al. Prompt diagnosis of
control, population-based study in France. Am J Epidemiol ectopic pregnancy in an emergency department setting.
2003;157:185–194. Obstet Gynecol 1994;84:1010–1015.
19 Shaw JL, Oliver E, Lee KF, et al. Cotinine exposure 41 Shalev E, Yarom I, Bustan M, et al. Transvaginal sonography
increases Fallopian tube PROKR1 expression via nicotinic as the ultimate diagnostic tool for the management of
AChRalpha-7: a potential mechanism explaining the link ectopic pregnancy: experience with 840 cases. Fertil Steril
between smoking and tubal ectopic pregnancy. Am J Pathol 1998;69:62–65.
2010;177:2509–2515. 42 American Institute of Ultrasound in Medicine. AIUM
20 Talbot P, Riveles K. Smoking and reproduction: the oviduct as a practice guideline for the performance of obstetric ultrasound
target of cigarette smoke. Reprod Biol Endocrinol 2005;3:52. examinations. J Ultrasound Med 2010;29:157–166.
21 Corpa JM. Ectopic pregnancy in animals and humans. 43 Morin L, Van den Hof MC; Diagnostic Imaging Committee,
Reproduction 2006;131:631–640. Society of Obstetricians and Gynaecologists of Canada.
22 Hasan R, Baird DD, Herring AH, et al. Patterns and predictors Ultrasound evaluation of first trimester pregnancy
of vaginal bleeding in the first trimester of pregnancy. complications. J Obstet Gynaecol Can 2005;27:581–591.
Ann Epidemiol 2010;20:524–531. 44 Royal College of Obstetricians and Gynaecologists and Royal
23 Weckstein LN, Boucher AR, Tucker H, et al. Accurate diagnosis College of Radiologists Faculty of Clinical Radiology. Guidance
of early ectopic pregnancy. Obstet Gynecol 1985;65:393–397. on Ultrasound Procedures in Early Pregnancy. London, UK:
24 Jehle D, Krause R, Braen GR. Ectopic pregnancy. Emerg Med RCOG Press, 2005.
Clin North Am 1994;12:55–71. 45 Ahmed AA, Tom BD, Calabrese P. Ectopic pregnancy diagnosis
25 Chez RA, Moore JG. Diagnostic errors in the management of and the pseudo-sac. Fertil Steril 2004;81:1225–1228.
ectopic pregnancy. Surg Gynecol Obstet 1963;117:589–596. 46 Reyftmann L, Dechaud H, Hedon B. Alert for heterotopic
26 Tay JI, Moore J, Walker JJ. Ectopic pregnancy. BMJ pregnancy. Fertil Steril 2007;88:759–60.
2000;320:916–919. 47 Condous G, Okaro E, Khalid A, et al. The accuracy of
27 Kaplan BC, Dart RG, Moskos M, et al. Ectopic pregnancy: transvaginal ultrasonography for the diagnosis of ectopic
prospective study with improved diagnostic accuracy. pregnancy prior to surgery. Hum Reprod 2005;20:1404–1409.
Ann Emerg Med 1996;28:10–17. 48 Perriera L, Reeves MF. Ultrasound criteria for diagnosis of early
28 Lewis G, Drife J. Why Mothers Die 1997–1999: The pregnancy failure and ectopic pregnancy. Semin Reprod Med
Confidential Enquiries into Maternal Deaths in the United 2008;26:373–382.
Kingdom. London, UK: RCOG Press, 2001. 49 Condous G, Lu C, Van Huffel SV, et al. Human chorionic
29 Lewis G. The Confidential Enquiry into Maternal and Child gonadotrophin and progesterone levels in pregnancies of
Health (CEMACH). Saving Mothers’ Lives: Reviewing Maternal unknown location. Int J Gynaecol Obstet 2004;86:351–357.
Deaths to Make Motherhood Safe 2003–2005. London, UK: 50 Kadar N, Romero R. HCG assays and ectopic pregnancy.
RCOG Press, 2007. Lancet 1981;1:1205–1206.

Sivalingam VN, Duncan WC, Kirk E, et al. J Fam Plann Reprod Health Care (2011). doi:10.1136/jfprhc-2011-0073 9 of 10
 Downloaded from jfprhc.bmj.com on June 19, 2014 - Published by group.bmj.com

Sivalingam et al.

51 Barnhart KT, Sammel MD, Rinaudo PF, et al. Symptomatic 67 Royal College of Obstetricians and Gynaecologists. The
patients with an early viable intrauterine pregnancy: HCG Management of Tubal Pregnancy (Guideline No. 21). London,
curves redefined. Obstet Gynecol 2004;104:50–55. UK: RCOG Press, 2004.
52 Seeber BE, Sammel MD, Guo W, et al. Application of 68 Gracia CR, Barnhart KT. Diagnosing ectopic pregnancy:
redefined human chorionic gonadotropin curves for the decision analysis comparing six strategies. Obstet Gynecol
diagnosis of women at risk for ectopic pregnancy. Fertil Steril 2001;97:464–470.
2006;86:454–459. 69 Rulin MC. Is salpingostomy the surgical treatment of choice
53 Horne AW, McBride R, Denison FC. Normally rising hCG for unruptured tubal pregnancy? Obstet Gynecol
does not predict live birth in women presenting with pain and 1995;86:1010–1013.
bleeding in early pregnancy. Eur J Obstet Gynecol Reprod Biol 70 Mukul LV, Teal SB. Current management of ectopic pregnancy.
2011;156:120–121. Obstet Gynecol Clin North Am 2007;34:403–19, x.
54 Silva C, Sammel MD, Zhou L, et al. Human chorionic 71 Calabresi P, Chabner BA. Antineoplastic agents. In: Gilman A,
gonadotropin profile for women with ectopic pregnancy. Obstet Goodman LS, Goodman A (eds), The Pharmacologic Basis of
Gynecol 2006;107:605–610. Therapeutics (8th edn). New York, NY: Macmillan Publishing,
55 Li TC, Tristram A, Hill AS, et al. A review of 254 ectopic 1990;1275–1276.
pregnancies in a teaching hospital in the Trent Region, 72 Stovall TG, Ling FW, Gray LA. Single-dose methotrexate
1977–1990. Hum Reprod 1991;6:1002–1007. for treatment of ectopic pregnancy. Obstet Gynecol
56 Stovall TG, Kellerman AL, Ling FW, et al. Emergency 1991;77:754–757.
department diagnosis of ectopic pregnancy. Ann Emerg Med 73 Lipscomb GH, McCord ML, Stovall TG, et al. Predictors of
1990;19:1098–1103. success of methotrexate treatment in women with tubal ectopic
57 McCord ML, Muram D, Buster JE, et al. Single serum pregnancies. N Engl J Med 1999;341:1974–1978.
progesterone as a screen for ectopic pregnancy: exchanging 74 Lipscomb GH, Bran D, McCord ML, et al. Analysis of three
specificity and sensitivity to obtain optimal test performance. hundred fifteen ectopic pregnancies treated with single-dose
Fertil Steril 1996;66:513–516. methotrexate. Am J Obstet Gynecol 1998;178:1354–1358.
58 Horne AW, Shaw JL, Murdoch A, et al. Placental growth factor: 75 Sowter MC, Farquhar CM, Petrie KJ, et al. A randomised trial
a promising diagnostic biomarker for tubal ectopic pregnancy. comparing single dose systemic methotrexate and laparoscopic
J Clin Endocrinol Metab 2011;96:E104–E108. surgery for the treatment of unruptured tubal pregnancy. BJOG
59 Lundorff P, Thorburn J, Hahlin M, et al. Laparoscopic surgery 2001;108:192–203.
in ectopic pregnancy. A randomized trial versus laparotomy. 76 Barnhart KT, Gosman G, Ashby R, et al. The medical
Acta Obstet Gynecol Scand 1991;70:343–348. management of ectopic pregnancy: a meta-analysis comparing
60 Vermesh M, Silva PD, Rosen GF, et al. Management of “single dose” and “multidose” regimens. Obstet Gynecol
unruptured ectopic gestation by linear salpingostomy: a 2003;101:778–784.
prospective, randomized clinical trial of laparoscopy versus 77 Korhonen J, Stenman UH, Ylöstalo P. Serum human chorionic
laparotomy. Obstet Gynecol 1989;73:400–404. gonadotropin dynamics during spontaneous resolution of
61 Murphy AA, Nager CW, Wujek JJ, et al. Operative laparoscopy ectopic pregnancy. Fertil Steril 1994;61:632–636.
versus laparotomy for the management of ectopic pregnancy: a 78 Shalev E, Peleg D, Tsabari A, et al. Spontaneous resolution
prospective trial. Fertil Steril 1992;57:1180–1185. of ectopic tubal pregnancy: natural history. Fertil Steril
62 Parker J, Bisits A. Laparoscopic surgical treatment of ectopic 1995;63:15–19.
pregnancy: salpingectomy or salpingostomy? Aust N Z J Obstet 79 Lozeau AM, Potter B. Diagnosis and management of ectopic
Gynaecol 1997;37:115–117. pregnancy. Am Fam Physician 2005;72:1707–1714.
63 Clausen I. Conservative versus radical surgery for 80 Butts S, Sammel M, Hummel A, et al. Risk factors and clinical
tubal pregnancy. A review. Acta Obstet Gynecol Scand features of recurrent ectopic pregnancy: a case control study.
1996;75:8–12. Fertil Steril 2003;80:1340–1344.
64 Thornton KL, Diamond MP, DeCherney AH. Linear 81 Horne AW, van den Driesche S, King AE, et al. Endometrial
salpingostomy for ectopic pregnancy. Obstet Gynecol Clin inhibin/activin beta-B subunit expression is related to
North Am 1991;18:95–109. decidualization and is reduced in tubal ectopic pregnancy.
65 Bangsgaard N, Lund CO, Ottesen B, et al. Improved fertility J Clin Endocrinol Metab 2008;93:2375–2382.
following conservative surgical treatment of ectopic pregnancy. 82 Mol F, Strandell A, Jurkovic D, et al.; European Surgery in
BJOG 2003;110:765–770. Ectopic Pregnancy study group. The ESEP study: salpingostomy
66 Mol BW, Matthijsse HC, Tinga DJ, et al. Fertility after versus salpingectomy for tubal ectopic pregnancy; the impact
conservative and radical surgery for tubal pregnancy. on future fertility: a randomised controlled trial. BMC Womens
Hum Reprod 1998;13:1804–1809. Health 2008;8:11.

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Diagnosis and management of ectopic

pregnancy
Vanitha N Sivalingam, W Colin Duncan, Emma Kirk, et al.

J Fam Plann Reprod Health Care published online July 4, 2011

doi: 10.1136/jfprhc-2011-0073

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