Clinical manifestations, diagnosis, and management of

ectopic pregnancy

Clinical manifestations, diagnosis, and management of ectopic pregnancy

Author
Togas Tulandi, MD, MHCM
Section Editor
Robert L Barbieri, MD
Deputy Editor
Sandy J Falk, MD
Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Oct 2013. | This topic last updated: Nov 2, 2012.

INTRODUCTION The diagnosis of ectopic pregnancy is based on a combination

of quantitative assay for human chorionic gonadotropin (hCG) and findings on high
resolution transvaginal ultrasonography (TVUS). These tests enable early diagnosis
of the ectopic pregnancy, before tubal rupture.

The clinical manifestations and diagnosis of ectopic pregnancy will be reviewed

here. The epidemiology, risk factors, pathology, and treatment of this disorder are
discussed separately. (See "Incidence, risk factors, and pathology of ectopic
pregnancy" and "Surgical treatment of ectopic pregnancy and prognosis for
subsequent fertility" and "Methotrexate treatment of tubal and interstitial ectopic
pregnancy" .)

CLINICAL MANIFESTATIONS Clinical manifestations typically appear six to

eight weeks after the last normal menstrual period, but can occur later, especially if
the pregnancy is not in the fallopian tube. Normal pregnancy discomforts (eg,
breast tenderness, frequent urination, nausea) are often present in addition to the
symptoms described below.

History The classic symptoms of ectopic pregnancy are [ 1 ]:

Abdominal pain

Amenorrhea

Vaginal bleeding

These symptoms can occur in both ruptured and unruptured cases. In one
representative series of 147 patients with ectopic pregnancy (78 percent were
ruptured), abdominal pain was a presenting symptom in 99 percent, amenorrhea in
74 percent, and vaginal bleeding in 56 percent [ 2 ].

Ectopic pregnancy should be suspected in any women of reproductive age with

these symptoms, especially those who have risk factors for an extrauterine
pregnancy ( table 1 ) [ 3 ]. However, these symptoms are not diagnostic of ectopic
pregnancy; they are the same as those associated with threatened abortion, which
is far more common (see 'Differential diagnosis' below).

In addition, blood leaking out of the fallopian tube may irritate the diaphragm and
cause shoulder pain, whereas blood pooling in the posterior cul-de-sac (pouch of
Douglas) may cause an urge to defecate. Lightheadedness or shock suggests tubal
rupture has occurred, resulting in severe intraabdominal hemorrhage.

Failure to diagnose ectopic pregnancy before tubal rupture limits the treatment
options and increases maternal morbidity and mortality. A population-based French
study identified four factors that increased the risk of rupture when an ectopic
pregnancy was suspected: (1) never having used contraception, (2) history of tubal
damage and infertility, (3) induction of ovulation, and (4) high level of human
chorionic gonadotropin (at least 10,000 IU/L) [ 4 ]. The overall rate of tubal rupture
in this series was 18 percent.

Physical examination Vital signs may reveal orthostatic changes and,

occasionally, low grade fever. Findings on physical examination may include
adnexal, cervical motion, and/or abdominal tenderness, an adnexal mass, and mild
uterine enlargement. However, the physical examination is often unremarkable in a
woman with a small, unruptured ectopic pregnancy.

DIAGNOSIS No constellation of historical and physical findings can confirm or

exclude the diagnosis of ectopic pregnancy with a high degree of reliability [ 5,6 ].
The diagnosis is usually made clinically, based upon results of the imaging studies
(ultrasound) and laboratory tests (hCG) described below (see 'Diagnostic
evaluation' below).

The diagnosis can also be made by observation of the ectopic gestation at surgery
or histopathologic examination, but surgery is not required in most cases. However,
in the absence of definitive surgical, histopathologic, or sonographic findings, it is
sometimes impossible to differentiate between an ectopic pregnancy and an early
failed intrauterine gestation.

Differential diagnosis The differential diagnosis of lower abdominal pain in

women includes urinary tract infection, kidney stones, diverticulitis, appendicitis,
ovarian neoplasms, endometriosis, endometritis, leiomyomas, pelvic inflammatory
disease, and pregnancy-related conditions. Vaginal bleeding also has several
pregnancy-related and nonpregnancy-related etiologies. Thus, a pregnancy test is
important in premenopausal women who present with abdominal pain or vaginal
bleeding in order to guide the direction of further evaluation. (See"Diagnostic
approach to abdominal pain in adults" and "Overview of causes of genital tract
bleeding in women" .)

Amenorrhea and abdominal pain, with or without vaginal bleeding, are common
symptoms of complications of early pregnancy other than an ectopic pregnancy,
such as threatened abortion, ruptured or torsed corpus luteum cyst, and
degenerating uterine leiomyoma. Other common etiologies of pelvic pain or
pressure in early pregnancy include constipation or ongoing uterine enlargement.
(See "Clinical manifestations and diagnosis of early pregnancy" and "Overview of
the etiology and evaluation of vaginal bleeding in pregnant women" .)
Recommended diagnostic tests TVUS is the most useful test for determining
the location of a pregnancy. If the imaging study is nondiagnostic, it may be
because the gestation is too early to be visualized on ultrasound. If so, serial
measurements of the serum human chorionic gonadotropin (hCG) concentration
should be taken until the hCG discriminatory zone is reached (see 'Discriminatory
zone' below).

This combination of TVUS and hCG will permit a definitive diagnosis in almost all
cases at a very early stage of pregnancy, thereby permitting treatment options less
invasive than surgical excision [ 7-10 ].

Other diagnostic tests (eg, serum progesterone level, curettage, laparoscopy,

culdocentesis) do not provide additional clinically useful information.

Transvaginal ultrasound Ultrasound is used to detect the presence (or

absence) of a pregnancy within or outside of the uterus. Ultrasound evaluation for
ectopic pregnancy is discussed in detail separately. (See "Ultrasonography of
pregnancy of unknown location" .)

Human chorionic gonadotropin hCG can be detected in serum and urine as

early as eight days after the LH surge, if pregnancy has occurred. The hCG
concentration in a normal intrauterine pregnancy rises in a curvilinear fashion until
about 41 days of gestation, after which it rises more slowly until approximately 10
weeks, and then declines until reaching a plateau in the second and third trimesters
[ 11,12 ]. There is a wide range in the normal hCG level across individuals at each
week of pregnancy [ 13 ]. (See "Clinical manifestations and diagnosis of early
pregnancy" .)

Studies in viable intrauterine pregnancies have reported the following changes in

serum hCG [ 12,14-16 ]:

The mean doubling time for the hormone ranges from 1.4 to 2.1 days in
early pregnancy.

In 85 percent of viable intrauterine pregnancies, the hCG concentration rises

by at least 66 percent every 48 hours during the first 40 days of
pregnancy; only 15 percent of viable pregnancies have a rate of rise less
than this threshold.

The slowest recorded rise over 48 hours associated with a viable intrauterine
pregnancy was 53 percent.

The hCG concentration rises at a much slower rate in most, but not all, ectopic and
nonviable intrauterine pregnancies [ 16,17 ]. In one series, as an example, only 21
percent of ectopic pregnancies were associated with hCG levels that followed the
minimum doubling time of a viable intrauterine pregnancy (defined in this series as
53 percent increase over two days) [ 16 ].

There is a 10 to 15 percent interassay variability in hCG measurements as well as

variability among laboratories. Thus, interpretation of serial hCG concentrations is
more reliable when the assays are performed in the same laboratory. In addition,
the possibility of falsely positive hCG test results should be considered [ 18-20 ].
(See "Gestational trophoblastic disease: Management of hydatidiform mole",
section on 'Human chorionic gonadotropin' .)

A falling hCG concentration is most consistent with a failed pregnancy (eg, arrested
pregnancy, anembryonic pregnancy, tubal abortion, spontaneously resolving ectopic
pregnancy, complete or incomplete abortion).

Discriminatory zone The discriminatory zone is based upon the correlation

between visibility of the gestational sac and the hCG concentration, and is of major
diagnostic importance (see 'Diagnostic evaluation' below). It is defined as the
serum hCG level above which a gestational sac should be visualized by ultrasound
examination if an intrauterine pregnancy is present [ 17 ]. In most institutions, this
serum hCG level is 1500 or 2000 IU/L with TVS (the level is higher [6500 IU/L] with
transabdominal ultrasound).

The level of the discriminatory zone was based upon observations that an
intrauterine gestational sac could be detected by TVS in patients with serum hCG
concentrations as low as 800 IU/L and was usually identified by expert
ultrasonographers at concentrations above 1500 to 2000 IU/L [ 21 ]. In one
representative study, 185 of 188 (98 percent) intrauterine pregnancies in women
with hCG above 1500 IU/L were visualized [ 22 ]. Setting a threshold of
2000 IU/L instead of 1500 IU/L for the discriminatory zone minimizes the risk of
interfering with a viable intrauterine pregnancy, if present, but increases the risk of
delaying diagnosis of an ectopic pregnancy.

The absence of an intrauterine gestational sac at hCG concentrations above the

discriminatory zone strongly suggests an ectopic or nonviable intrauterine
pregnancy, but is nondiagnostic with hCG values below the discriminatory zone. A
negative ultrasound examination at hCG levels below the discriminatory zone is
consistent with an early viable intrauterine pregnancy or an ectopic pregnancy or
nonviable intrauterine pregnancy. Such cases are termed "pregnancy of unknown
location" and 8 to 40 percent are ultimately diagnosed as ectopic pregnancies [ 23].

The discriminatory zone is dependent upon the skill of the ultrasonographer, the
quality of the ultrasound equipment, the presence of physical factors (eg, fibroids,
multiple gestation), and the laboratory characteristics of the hCG assay used.

Diagnostic evaluation The evaluation of a pregnant woman with suspected

ectopic gestation begins with TVS and quantitative hCG level (algorithm 1 and table
2 ). TVS alone is diagnostic if a yolk sac, embryo, or embryonic cardiac activity is
demonstrable.

HCG above the discriminatory zone An hCG concentration above the

discriminatory zone is sensitive for detecting an intrauterine pregnancy.
Visualization of an intrauterine pregnancy almost always excludes the presence of
an ectopic pregnancy; exceptions include heterotopic pregnancies (see 'Heterotopic
pregnancy' below) and misdiagnoses (eg, pregnancy in a rudimentary uterine horn
or cornua).

If TVS does not reveal an intrauterine pregnancy and shows a complex adnexal
mass, an extrauterine pregnancy is almost certain. Embryonic cardiac activity or a
gestational sac with a definite yolk sac or embryo at an extrauterine location is
certain evidence of an ectopic gestation. Treatment of ectopic pregnancy should be
instituted.

The diagnosis of ectopic pregnancy is less certain if no complex adnexal mass can
be visualized, since there is variability in the level of expertise among
ultrasonographers. Furthermore, a serum hCG greater than 1500 IU/L without
visualization of intrauterine or extrauterine pathology may represent a multiple
gestation, since there is no proven discriminatory level for multiple gestations. For
these reasons, our next step in this setting is to repeat the TVS examination and
hCG concentration two days later. If an intrauterine pregnancy is still not observed
on TVS, then the pregnancy is abnormal.

An ectopic pregnancy can be diagnosed if the serum hCG concentration is

increasing or plateaued. Treatment can be instituted.

A falling hCG concentration is most consistent with a failed pregnancy (eg,

arrested pregnancy, blighted ovum, tubal abortion, spontaneously
resolving ectopic pregnancy). The rate of fall is slower with an ectopic
pregnancy than with a complete abortion. Weekly hCG concentrations
should be monitored until the result is negative for pregnancy.

HCG below the discriminatory zone TVS is not sensitive for determining the
location of the pregnancy when the hCG level is below the discriminatory zone. A
serum hCG concentration less than 1500 IU/L should be followed by repetition of
hCG in three days to follow the rate of rise. HCG concentrations usually double
every 1.4 to two days until six to seven weeks of gestation in viable intrauterine
pregnancies (and in some ectopic gestations) (see 'Human chorionic
gonadotropin' above). We find that measurement every 72 hours is more practical
than every 48 hours, and allowing 72 hours for doubling helps to avoid
misclassifying those viable pregnancies with slower than average doubling times.

A normally rising hCG concentration should be evaluated with TVS when the
hCG reaches the discriminatory zone. At that time, an intrauterine
pregnancy or an ectopic pregnancy can be diagnosed.

If the hCG concentration does not double over 72 hours (as discussed
above, the minimum rise [99th percentile] over 48 hours for a potentially
viable intrauterine pregnancy is 53 percent), then the pregnancy is
abnormal (an ectopic gestation or intrauterine pregnancy that is destined
to abort). The clinician can be reasonably certain that a normal
intrauterine pregnancy is not present.

If an adnexal mass is visualized on TVS, then medical or surgical treatment is

administered for a presumed ectopic pregnancy. If an adnexal mass is not
visualized, some clinicians administer methotrexate and others perform curettage
to determine the type of nonviable pregnancy and thereby avoid medical therapy of
nonviable intrauterine pregnancies [ 24 ]. (See 'Curettage' below.)

Treatment of ectopic pregnancy is discussed separately. (See "Methotrexate

treatment of tubal and interstitial ectopic pregnancy" and"Surgical treatment of
ectopic pregnancy and prognosis for subsequent fertility" .)
 A falling hCG concentration is most consistent with a failed pregnancy (eg,
arrested pregnancy, blighted ovum, tubal abortion, spontaneously
resolving ectopic pregnancy). The rate of fall is slower with an ectopic
pregnancy than with a completed abortion. Weekly hCG concentrations
should be monitored until the result is negative for pregnancy.

Ancillary diagnostic tests

Progesterone Serum progesterone concentrations are higher in viable

intrauterine pregnancies than in ectopic pregnancies and intrauterine pregnancies
that are destined to abort [ 25 ]. A meta-analysis of 26 cohort studies including
9436 women in the first trimester of pregnancy evaluated use of a single
measurement of serum progesterone for the diagnosis of a nonviable pregnancy
[ 26 ]. For women with bleeding or pain and an inconclusive pelvic ultrasound, a
progesterone <3.2 to 6 ng/mL (10.2 to 19.1 nmol/L) had a sensitivity of 75 percent
and a specificity of 98 percent. For women with bleeding or pain alone, a
progesterone <10 ng/mL (31.8 nmol/L) had a sensitivity of 67 percent and a
specificity of 96 percent.

The predictive value of a low serum progesterone for identifying nonviable

pregnancies varies with the patient population. The sensitivity and specificity of a
low serum progesterone concentration for predicting a nonviable pregnancy in
spontaneously pregnant patients are different from those in infertile patients who
have undergone controlled ovarian hyperstimulation for in vitro fertilization or
intrauterine insemination [27 ].

In our experience, progesterone measurements merely confirm diagnostic

impressions already obtained by hCG measurements and transvaginal sonography.
We do not routinely measure serum progesterone. However, serum progesterone
may be useful in a patient with abdominal pain and bleeding and who has a serum
hCG level below that expected for her gestational age. It should be noted, however,
that the definition of a low progesterone is unclear.

Curettage The intrauterine location of a pregnancy is diagnosed with certainty

if trophoblastic tissue is obtained by uterine curettage. Obviously, the use of
curettage as a diagnostic tool is limited by the potential for disruption of a viable
pregnancy [ 7 ]. Moreover, false negatives can occur: chorionic villi are not detected
by histopathology in 20 percent of curettage specimens from elective termination of
pregnancy [ 28 ]. Pipelle endometrial biopsy is even less sensitive than curettage
for detection of villi; sensitivities reported in two small series were 30 and 60
percent [ 29,30 ]. If curettage is performed, serum hCG levels can be followed post
curettage if histopathology does not confirm the clinical impression. When an
intrauterine pregnancy has been evacuated, hCG levels should drop by at least 15
percent the day after evacuation [ 24 ].

Some authors have recommended performing curettage only on women with both a
hCG concentration below the discriminatory zone and a low doubling rate (see 'HCG
below the discriminatory zone' above) [ 31,32 ]. Approximately 30 percent of these
patients have a nonviable intrauterine gestation and the remainder have an ectopic
pregnancy [ 32,33 ]. Knowing the results of curettage avoids
unnecessarymethotrexate treatment of the 30 percent of patients without ectopic
pregnancy.
A decision analysis comparing the cost/complication rates in patients who undergo
diagnostic curettage before administration of methotrexateto those who do not
have a curettage concluded there was no significant benefit of one approach over
the other [ 33 ]. However, the authors' preference was to perform curettage in
these patients to be more certain of the diagnosis, and felt this information was
useful prognostically (eg, risk of recurrence) and for future decision making. In
contrast, we and others believe it is more practical and less invasive to continue
observation or administer one dose of methotrexate than to perform curettage
[ 34,35 ]. The side effects of one dose of methotrexate are negligible. In addition,
curettage carries a risk of intrauterine adhesion formation. (See "Methotrexate
treatment of tubal and interstitial ectopic pregnancy" and "Intrauterine
adhesions" .)

Doppler Blood flow in the arteries of the fallopian tube containing an ectopic
pregnancy is 20 to 45 percent higher than in the opposite tube and the Doppler
waveform shows low impedance [ 11,36 ]. Color Doppler may demonstrate a ring of
blood flow. These findings on Doppler support the diagnosis of ectopic pregnancy,
especially if a complex adnexal mass is also visualized. Doppler examination can be
performed when an adnexal mass is seen. In one study, the resistive index of
ectopic pregnancies was higher than that of corpus luteum cyst [37 ]. A resistive
index of less than 0.39 had a specificity of 100 percent and a positive predictive
value of 100 percent for diagnosing ectopic pregnancy, but was present in only 15
percent of ectopic pregnancies. A resistive index of greater than 0.7 had a
specificity of 100 percent and a positive predictive value of 100 percent for
diagnosing ectopic pregnancy and was present in 31 percent of ectopic pregnancies.
However, the use of TVS and hCG measurements is usually sufficient in establishing
the diagnosis in routine clinical practice.

Laparoscopy Laparoscopy is rarely required for diagnostic purposes only;

transvaginal ultrasound examination and hCG measurements are usually sufficient
for diagnosis. However, an ectopic pregnancy detected at laparoscopy should be
treated immediately by surgery. In this situation, a medical approach confers
additional risk and has no proven benefit.

Culdocentesis Culdocentesis is employed to detect blood in the posterior cul-

de-sac; however, this finding can be easily demonstrated by transvaginal ultrasound
(see 'Transvaginal ultrasound' above). Blood in the posterior cul-de-sac may be
from bleeding from an unruptured or ruptured tubal pregnancy, but it may also be
the result of a ruptured ovarian cyst. Therefore, a culdocentesis positive for blood is
nondiagnostic. (See "Culdocentesis" .)

Magnetic resonance imaging Magnetic resonance imaging can be used to

diagnose ectopic pregnancy, but is not a cost effective approach [ 38 ].

SCREENING ASYMPTOMATIC WOMEN As discussed above, over 50 percent

of women are asymptomatic before tubal rupture and do not have an identifiable
risk factor for ectopic pregnancy [ 39 ]. Identifying these women at a very early
stage of pregnancy could reduce their risk of adverse outcome and permit
treatment options less invasive than surgical excision.

A decision analysis model showed that screening asymptomatic pregnant women

for ectopic pregnancy reduced the frequency of rupture, but approximately three
false positive diagnoses would occur per tubal rupture prevented if the prevalence
of ectopic pregnancy was 2 percent [40 ]. Screening only appeared to be cost-
effective in populations with a high prevalence (at least 8 percent) of ectopic
pregnancy.

We monitor women at high risk of ectopic pregnancy, such as those with a previous
ectopic pregnancy, with laboratory and imaging studies as soon as their first missed
menses. The diagnosis can then be established early, possibly before the
occurrence of any symptoms. (See"Incidence, risk factors, and pathology of ectopic
pregnancy", section on 'In vitro fertilization' .)

UNCOMMON TYPES OF ECTOPIC PREGNANCY The possibility that an ectopic

pregnancy may occur in a nontubal location, in conjunction with an intrauterine
pregnancy, or even bilaterally [ 41 ], should be considered. These types of
pregnancies are uncommon, and include heterotopic, hysterotomy scar, cervical,
ovarian, rudimentary uterine horn, and abdominal pregnancy. Regardless of the
location, the endometrium often responds to ovarian and placental production of
pregnancy related hormones, so vaginal bleeding is a common symptom.

Cervical pregnancy is estimated to occur in 1/2500 to 1/18,000 pregnancies

and accounts for 1 percent of ectopic pregnancies [ 42-44 ].

Ovarian pregnancy occurs in 1/2100 to 1/60,000 pregnancies and accounts

for 1 to 3 percent of ectopic pregnancies [ 45 ].

Interstitial pregnancy accounts for up to 1 to 3 percent of ectopic

pregnancies [ 46,47 ].

Abdominal pregnancy accounts for up to 1.4 percent of ectopic pregnancies

[ 48-50 ]. These pregnancies can go undetected until an advanced age
and often result in severe hemorrhage [ 51 ]. Rates of maternal mortality
have been reported as high as 20 percent [52,53 ].

Intramural pregnancy refers to pregnancy implanted within the myometrium

of the uterus. This type of pregnancy is extremely rare with less than 50
reported cases in the literature [ 54 ].

Heterotopic pregnancy The investigation for ectopic pregnancy can be

terminated, under most circumstances, if a transvaginal sonogram reveals an
intrauterine pregnancy. Combined intrauterine and extrauterine pregnancy
(heterotopic pregnancy) is rare, except among women conceiving through IVF. The
extrauterine pregnancy is usually in the fallopian tube, but can be at another
location, such as the cervix. (See"Abdominal pregnancy, cesarean scar pregnancy,
and heterotopic pregnancy" .)

Early diagnosis of heterotopic pregnancy is difficult because of lack of symptoms.

Thus, a high index of suspicion for this diagnosis is important, especially in patients
who have undergone IVF and who experience pelvic pain.

Serial hCG concentrations are not interpretable in the presence of both a viable
intrauterine and ectopic pregnancy. On ultrasound examination, the diagnosis is
suggested by visualization of both an ectopic and intrauterine pregnancy or the
presence of echogenic fluid in the posterior cul de sac in the presence of an
intrauterine pregnancy. Heterotopic tubal pregnancies have been reported as late as
16 weeks of gestation, while abdominal or rudimentary horn pregnancies can
continue to develop late in gestation [ 52,55 ].

The ultrasonographer should carefully examine not only the uterus, but also the
adnexae of women who conceive following IVF. We suggest that women with a
confirmed intrauterine pregnancy who are experiencing abdominal or pelvic pain
undergo serial TVS examinations every week until the possibility of a concomitant
tubal ectopic pregnancy can be eliminated.

Surgery (salpingectomy) is the standard treatment of heterotopic pregnancy with a

tubal component, since the intrauterine pregnancy is a contraindication to medical
therapy. If the ectopic pregnancy has not ruptured, then local injection of 5
mEq potassium chloride into the sac is another option [ 56-60 ]. Injection of
potassium chloride can be guided sonographically, thus avoiding a surgical
procedure. Methotrexate is absolutely contraindicated.

Cervical pregnancy The most common symptom of cervical pregnancy is

vaginal bleeding, which is often profuse and painless. Lower abdominal pain or
cramps occur in fewer than one-third of patients; pain without bleeding is rare.
Diagnosis and management of cervical pregnancy are discussed in detail separately.
(See "Cervical pregnancy" .)

Hysterotomy scar pregnancy Symptoms are similar to tubal ectopic

pregnancy, and include vaginal bleeding and abdominal pain. The diagnosis is made
by sonographically visualizing an enlarged hysterotomy scar with an embedded
mass [ 61 ]. Features which should be present include presence of trophoblast
between the bladder and the anterior uterine wall, no fetal parts in the uterine
cavity, absence of myometrium between the gestational sac and the bladder, and
Doppler evidence of perfusion of the peritrophoblastic vasculature [ 61-63 ].
(See "Abdominal pregnancy, cesarean scar pregnancy, and heterotopic
pregnancy" .)

If the pregnancy has not ruptured, then local injection of potassium chloride into
the sac under sonographic guidance is an effective treatment. Rupture can result in
significant bleeding [ 64 ].

Ovarian pregnancy Sonographic diagnosis of an ovarian pregnancy is difficult.

Ultrasound evaluation for ovarian pregnancy is discussed in detail separately.
(See "Ultrasonography of pregnancy of unknown location" .)

The diagnosis of ovarian pregnancy is typically made at the time of surgery, but
differentiation from a hemorrhagic ovarian cyst or pregnancy in the distal fallopian
tube can be difficult. Ultrasound may suggest the diagnosis preoperatively [ 45 ].
Strict histopathological criteria are used to distinguish ovarian pregnancies from
those originating in the fallopian tube. The exact diagnosis is not clinically important
as these pregnancies are usually treated by surgical excision of the involved
organs. Methotrexate treatment has been successful in case reports [ 65-67 ].
(See "Incidence, risk factors, and pathology of ectopic pregnancy", section on
'Ovarian pregnancy' .)

Abdominal pregnancy Because of the variable location in the abdomen,

abdominal pregnancy is associated with a wide range of signs and symptoms. These
include abdominal pain, vaginal bleeding, vomiting, painful fetal movement,
oligohydramnios, persistent unusual fetal lie, failure to deliver an intrauterine fetal
demise, and labor abnormalities. In one report, hemothorax developed from
implantation on the diaphragm [ 68 ]. Abdominal pregnancies rarely result in the
birth of a viable infant. (See "Abdominal pregnancy, cesarean scar pregnancy, and
heterotopic pregnancy" .)

Interstitial pregnancy The interstitial portion of the fallopian tube is the

proximal segment that is embedded within the muscular wall of the uterus. A
pregnancy implanted at this site is called an interstitial pregnancy ( figure 1 ); the
term cornual pregnancy is also widely used to describe a pregnancy at this location.
Originally, the term cornual pregnancy referred only to pregnancies implanted in
either the horn of a bicornuate uterus, a rudimentary horn of a unicornuate uterus,
or in the lateral half of a septated or partially septated uterus [ 47,69 ].

An interstitial pregnancy can be difficult to distinguish on ultrasound from an

intrauterine pregnancy that is eccentrically positioned. Ultrasound evaluation for
interstitial pregnancy is discussed in detail separately. (See "Ultrasonography of
pregnancy of unknown location" .)

Grossly, an interstitial pregnancy appears as a gestational swelling lateral to the

insertion of the round ligament ( figure 1 ) [ 47 ]. The unique anatomic location of
an interstitial pregnancy often leads to a delay in diagnosis, although an average
delay of only four days in comparison with tubal pregnancies was reported in a
large series [ 70 ].

Interstitial pregnancy presents with rupture in approximately 20 to 50 percent of

cases [ 71-73 ]. A series of cases of interstitial pregnancy reported to a surgical
registry included 14 patients with tubal rupture, all of which were before 12 weeks
[ 71 ]. This is in contrast to previous reports that rupture of interstitial pregnancy
occurred late in pregnancy. Other clinical manifestations are the same as for all
ectopic gestations (pelvic or abdominal pain, vaginal bleeding) [ 70 ].

Although the maternal mortality rate associated with tubal pregnancy is decreasing,
the rate for interstitial pregnancies remains at 2 to 2.5 percent because of
misdiagnosis of these gestations as intrauterine pregnancies.

NATURAL HISTORY If left untreated, an ectopic pregnancy in the fallopian

tube can progress to a tubal abortion or tubal rupture, or it may regress
spontaneously.

Rupture Tubal rupture is usually associated with profound hemorrhage,

which can be fatal if surgery is not performed expeditiously to remove the
ectopic gestation. Salpingectomy is the most common surgical approach
when the tube has ruptured. Ruptured ectopic pregnancy is the major
cause of pregnancy-related maternal mortality in the first trimester [ 74 ].
Most of these deaths occur prior to hospitalization or proximate to the
woman's arrival in the emergency department.

Abortion Tubal abortion refers to expulsion of the products of conception

through the fimbria. This can be followed by resorption of the tissue or by
reimplantation of the trophoblasts in the abdominal cavity (ie, abdominal
pregnancy) or on the ovary (ie, ovarian pregnancy). Tubal abortion may
 be accompanied by severe intraabdominal bleeding, necessitating surgical
intervention, or by minimal bleeding, not requiring further treatment.

Spontaneous resolution The incidence of spontaneous resolution of an

ectopic pregnancy is unknown. In one older (1955) series of 119
hospitalized patients with typical ectopic pregnancy symptoms, 57 were
safely managed expectantly, without surgical or medical intervention
(except opiates) [ 75 ]. It is difficult to predict which patients will
experience uncomplicated spontaneous resolution. Potential candidates
are hemodynamically stable women with an initial hCG concentration less
than 2000 IU/L that is declining [ 76-78 ].

Gestational products left in the fallopian tube may resorb completely or, less
commonly, may cause tubal obstruction [ 79 ]. Alternatively, a tubal abortion may
occur.

MANAGEMENT Virtually all women diagnosed with an ectopic gestation

undergo medical or surgical treatment because the frequency and
potential morbidity/mortality of rupture are high.

Specific indications for surgical therapy include:

Hemodynamic instability

Impending or ongoing ectopic mass rupture

Not able or willing to comply with medical therapy posttreatment follow-up

Lack of timely access to a medical institution for management of tubal

rupture

Failed medical therapy

In the absence of these criteria, medical therapy is an option. (See "Surgical

treatment of ectopic pregnancy and prognosis for subsequent
fertility" and "Methotrexate treatment of tubal and interstitial ectopic pregnancy",
section on 'Medical versus surgical treatment' .)

Expectant management is considered rarely in women with low and declining hCG
levels. (See "Expectant management of ectopic pregnancy".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient

education materials, The Basics and Beyond the Basics. The Basics patient
education pieces are written in plain language, at the 5 th to 6 th grade reading level,
and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who
prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the
10 th to 12 th grade reading level and are best for patients who want in-depth
information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on patient info and the
keyword(s) of interest.)

Basics topics (see "Patient information: Ectopic pregnancy (The Basics)" )

Beyond the Basics topics (see "Patient information: Ectopic (tubal)

pregnancy (Beyond the Basics)" )

SUMMARY AND RECOMMENDATIONS

Abdominal pain, amenorrhea, and vaginal bleeding are the classic symptoms
of ectopic pregnancy. Ectopic pregnancy should be suspected in any
women of reproductive age with these symptoms, especially those who
have risk factors for an extrauterine pregnancy ( table 1 ).

However, over 50 percent of women are asymptomatic before tubal rupture and do
not have an identifiable risk factor for ectopic pregnancy. (See 'Clinical
manifestations' above.)

The diagnosis is usually made clinically based upon results from ultrasound
examination and human chorionic gonadotropin hormone (hCG) testing.
Confirmation of the diagnosis by visualization at surgery or
histopathological examination of tissue is not necessary. However, in the
absence of definitive surgical, sonographic, or histopathological findings, it
may not be possible to differentiate between a failed intrauterine
pregnancy and an ectopic pregnancy. (See 'Diagnosis' above.)

The evaluation of a woman with suspected ectopic gestation begins with a

transvaginal ultrasound examination and quantitative human chorionic
gonadotropin (hCG) level. Transvaginal ultrasound is diagnostic if a true
gestational sac, yolk sac, embryo, or embryonic cardiac activity is
demonstrable inside or outside of the uterus. (See 'Diagnostic
evaluation' above.)

An extrauterine pregnancy is almost certain when the hCG concentration is

greater than 1500 IU/L (discriminatory zone threshold) and transvaginal
ultrasound examination reveals a complex adnexal mass and no
intrauterine pregnancy. (See 'HCG above the discriminatory zone' above.)

A serum hCG concentration less than 1500 IU/L with a negative transvaginal
ultrasound examination should be followed by repetition of both of these
tests in three days to follow the rate of rise of the hCG.

A normally rising hCG concentration should be evaluated with ultrasound

examination when the hCG reaches the discriminatory zone. At that time,
an intrauterine pregnancy or an ectopic pregnancy can be diagnosed.

If the hCG concentration rises but does not double over 72 hours, then the
pregnancy is abnormal (an ectopic gestation or intrauterine pregnancy
that is destined to abort).

A falling hCG concentration is most consistent with a failed pregnancy.

(See 'HCG below the discriminatory zone' above.)
 Uncommon types of ectopic pregnancy include heterotopic, cervical,
hysterotomy scar, ovarian, interstitial, and abdominal pregnancy.
(See 'Uncommon types of ectopic pregnancy' above.)

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