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Ultrasound Obstet Gynecol 2008; 31: 245–251
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.5277
Editorial
Ectopic pregnancies of unusual location:
management dilemmas
D. V. VALSKY and S. YAGEL
Department of Obstetrics and Gynecology, Hadassah-Hebrew
University Medical Centers, Mt. Scopus, Jerusalem, Israel
(e-mail: [email protected])
Introduction
Ectopic pregnancy is a diagnostic and management challenge. Advances in ultrasound technology and operator
expertise have provided the capability to visualize ectopic
pregnancy at its earliest stages. While tubal ectopic pregnancies are still the most commonly seen1 – 3 , the increased
use of assisted reproduction techniques has been accompanied by an increase in ectopic pregnancies of unusual
location (Figure 1), and the rise in Cesarean deliveries
has been accompanied by a rise in pregnancies implanted
in the Cesarean scar. These trends have been noted and
reviewed in the literature and the sonographic diagnostic criteria of the various types of ectopic pregnancy
have been illustrated1 – 3 . However, sparse evidence has
accrued in the literature to guide management decisions
when ectopic pregnancy is diagnosed.
There are three basic management approaches to
ectopic pregnancy: expectant management, medical treatment administered systemically or locally, and surgical
intervention, including laparotomy, laparoscopy, hysteroscopy, and dilatation and curettage (D&C). In recent
years uterine artery embolization (UAE) has become more
common, at times being applied as a first-line treatment,
but more often being used as a rescue procedure in cases
of treatment failure and hemorrhage4 – 8 .
In this light, we summarize in this Editorial what
is known regarding the outcomes of each approach,
in interstitial, cervical and Cesarean scar ectopic
pregnancies. We do not address the issues surrounding
ovarian and abdominal ectopic pregnancies due to their
extreme rarity. Our purpose is to summarize the evidence
available to support management options for these ectopic
pregnancies of unusual location, to describe the dilemmas
that may arise, and to suggest strategies to improve the
evidence base and ultimately to develop guidelines for the
management of these challenging cases.
Interstitial and cornual pregnancy
Case presentation
A 28-year-old woman who had undergone bilateral
salpingectomy was referred with a suspected heterotopic
Copyright  2008 ISUOG. Published by John Wiley & Sons, Ltd.
pregnancy 4 weeks after in-vitro fertilization (IVF).
On presentation she was asymptomatic. Sonographic
evaluation on admission revealed a heterotopic pregnancy
with intrauterine and left interstitial gestational sacs
(Figure 2). The ectopic sac was non-viable and expectant
management was planned. Laparoscopy with excision
of the interstitial pregnancy was performed (Videoclip
S1, online) on the development of pain and suspected
intra-abdominal bleeding. The intrauterine pregnancy
continued and a normal infant weighing 2565 g was
delivered at 35 + 5 gestational weeks by Cesarean section.
Analysis
Interstitial pregnancy occurs when the gestational sac is
implanted in the portion of the Fallopian tube within
the muscular wall of the uterus. This highly vascularized
area has great potential for severe hemorrhage in the case
of perforation. Two-dimensional (2D) ultrasound-based
criteria for the diagnosis of interstitial pregnancy have
been proposed9,10 , but misdiagnosis is still common10 .
An interstitial pregnancy is diagnosed when a regular
Figure 1 Three-dimensional ultrasound image using VCI-C
(volume contrast imaging in the C-plane) acquisition mode in a
woman with heterotopic intrauterine (IUP) and interstitial (IP)
pregnancies, showing the two gestational sacs with fetal pole. The
uterine fundus is indicated ( ) as well as the demarcation of the
endometrial border (arrow).
EDITORIAL
Valsky and Yagel
246
Figure 2 (a) Rendered image from static three-dimensional ultrasound acquisition of the coronal plane of the uterus in a woman with
intrauterine (G) and interstitial (IP) gestational sacs. Arrows indicate the border of the endometrium and the myometrial layer is denoted M.
Interstitial pregnancy is diagnosed when a regular endometrium without visible gestational sac or mass is visualized, and the gestational sac
is located outside the endometrium and surrounded by a continuous rim of myometrium, within the interstitial area1 . (b) Image obtained at
laparoscopy showing the protrusion of the ectopic gestational sac and active bleeding ( ). (See also supplementary material online: Videoclip
S1).
endometrium without visible gestational sac or mass is
visualized, and a gestational sac is located outside the
endometrium and surrounded by a continuous rim of
myometrium, within the interstitial area. A pregnancy
is defined as cornual when it is situated in the uterine
cavity but asymmetrically in the cornu, medial to the
round ligament1 . In the English literature, these definitions
are sometimes used interchangeably, although different
clinical courses have been described1,2 . The use of threedimensional (3D) ultrasound, with its capability to image
the coronal plane of the uterus, can have added value in the
diagnosis of cornual and interstitial ectopic pregnancies11 .
Expectant management of interstitial pregnancy may
be possible with close monitoring for falling beta-human
chorionic gonadotropin (β-hCG) levels and shrinking
gestational mass. The follow-up period for expectantly
managed cases can be very long; a sonographically visible
mass can persist for many weeks. These findings can be
densely vascular (Figure 3) and raise the dilemma as to
whether to continue waiting with close monitoring or to
intervene. If the patient is asymptomatic and β-hCG levels
are falling, patience and a long follow-up are appropriate.
Systemic medical management has been reported in
these cases. A single dose of methotrexate (MTX) is
usually sufficient, with a second dose required only in a
minority of cases if β-hCG levels do not fall10 . In their
review of 65 cases of conservatively managed interstitial
pregnancy, Jermy et al. found the overall success rate of
systemic MTX treatment (of varying one- or multi-dose
regimens) to be 40/45 (88%)10 . One case required a local
injection of MTX as well.
Local medical management involves ultrasound-guided
injection of MTX into the gestational sac. If cardiac
Copyright  2008 ISUOG. Published by John Wiley & Sons, Ltd.
activity is present, potassium chloride (KCl) may be
administered intra-amniotically. In cases of heterotopic
interstitial pregnancy, KCl administered exclusively to the
ectopic gestational sac can be particularly effective3,10 .
Technical issues of local injection, however, may preclude
this therapy in some cases. The review of 65 cases by Jermy
et al. found the success rate of local MTX injection to be
19/20 (95%), although one patient required laparoscopy
for hemostasis10 .
As for expectant management, a long period of close
monitoring is required following medical therapy in these
cases, until full sonographic resolution is observed.
Surgical management usually involves cornual resection or hysterectomy at laparotomy. Minimally invasive
procedures such as laparoscopy are becoming more common. This approach requires technical skill and carries a
risk of hemorrhage. As this management option becomes
available in more centers and more evidence is accrued, it
may be found to be suitable in symptomatic women, while
laparotomy will be reserved for acute, actively bleeding
cases.
Cervical pregnancy
Case presentation
A 27-year-old woman, whose history included two
pregnancy terminations, presented for a routine dating
scan at 8 weeks’ amenorrhea. Ultrasound examination
revealed a gestational sac with a viable fetus in the uterine
cervix. She was treated with intra-amniotic KCl and local
MTX injection. Two days following the procedure she
returned with severe vaginal bleeding. Curettage was
Ultrasound Obstet Gynecol 2008; 31: 245–251.
Editorial
247
Figure 3 Series of three-dimensional (3D) ultrasound images in a woman with interstitial pregnancy managed conservatively. (a) Multiplanar 3D static imaging (coronal plane) of the uterus at presentation, showing the non-viable left interstitial gestational sac. The patient
was asymptomatic with a beta-human chorionic gonadotropin (β-hCG) level of 750 mIU/mL. (b) Rendered image on day 52 from static 3D
acquisition, showing the highly vascularized area (arrow) indicative of the changes in the endometrium at the area of implantation of the
gestational sac. The patient’s β-hCG at this visit was 75 mIU/mL. (c) VCI-C (volume contrast imaging in the C-plane) acquisition on day 69:
the vascularized area was still visible. (d) Nearly 4 months following presentation, this rendered 3D ultrasound image showed complete
resolution; the normal uterine cornu is demonstrated ( ).
attempted but the bleeding intensified. Bilateral UAE was
performed and the bleeding abated.
Analysis
Cervical pregnancy is diagnosed when the entire
gestational sac, having a well-formed shape, is
Copyright  2008 ISUOG. Published by John Wiley & Sons, Ltd.
demonstrated in the dilated cervix. The sac may contain
a yolk sac and embryo, with or without cardiac activity,
located below the level of the internal os. Except in the
case of heterotopic pregnancy, the endometrial stripe is
visualized and an hourglass shape of the uterus is evident. Color Doppler scanning is useful in differentiating
between inevitable miscarriage of a gestational sac in the
Ultrasound Obstet Gynecol 2008; 31: 245–251.
248
cervix and true cervical pregnancy. In true cervical pregnancy, Doppler studies show characteristic patterns of
trophoblast with high flow velocity and low impedance,
while in miscarriage the sac will be mobile, with no
Doppler evidence of blood flow1,2 .
Expectant management of cervical pregnancy is
usually not an option, though it has been described12 .
Conservative management is possible if it is diagnosed
early, as described for interstitial pregnancy. In a review
of 90 cases of conservative management of cervical
pregnancy, which included both systemic and local
injection of MTX and/or KCl, 61 (78%) cases were
Valsky and Yagel
successful and reached full resolution, while 19 required
intervention, including insertion of a Shirodkar suture,
UAE or Foley catheter balloon tamponade. Thirty-two
patients were also treated with curettage. Three patients
required hysterectomy12 .
The surgical management of interstitial and Cesarean
scar pregnancies essentially involves excision of the
gestational sac, but this is not possible in the case of
cervical pregnancy. The anatomy of the cervix makes
it prone to hemorrhage as trophoblast is sloughed. So,
while these pregnancies are candidates for conservative
management to preserve fertility, they may often require
Figure 4 (a) Three-dimensional ultrasound image using VCI-C (volume contrast imaging in the C-plane) showing the coronal plane of the
uterus in a woman with Cesarean scar defect ( ). In (b), the fluid-filled area of the scar defect (1.7 × 1.0 cm) is visible in the anterior wall of
the uterus; the uterine wall defect (measurement 1) was 0.42 cm in length. (c) Rendered sagittal image showing the cervix (cx), the
endocervical canal ( ), the scar defect in the anterior uterine wall (arrow) and the bladder (bl).
Copyright  2008 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound Obstet Gynecol 2008; 31: 245–251.
Editorial
intervention to stop hemorrhage. Having recently gained
acceptance in gynecological surgery4 , UAE, which aims to
slow hemorrhage by limiting blood supply to the uterus,
has been applied in the management of cervical pregnancy
as adjunctive treatment to control hemorrhage following
local or systemic MTX administration, and as primary
intervention in missed cervical pregnancies to prevent
excessive bleeding as the pregnancy resolves5 .
Cesarean scar pregnancy
Case presentation
A 39-year-old woman was diagnosed with a uterine
wall defect of 4 mm at the Cesarean scar site during
routine pelvic ultrasound examination (Figure 4). She
was later referred for investigation of suspected Cesarean
scar pregnancy, which revealed a non-viable 5-cm
gestational sac located within the isthmic area of the
lower anterior wall of the uterus, protruding toward
the vesicouterine junction (Figure 5, Videoclip S2).
Conservative management was planned; however, on the
development of severe vaginal bleeding the patient was
readmitted and D&C performed. Bleeding continued and
disseminated intravascular coagulation developed. The
patient received repeated blood transfusions, laparotomy
was performed and the gestational sac was resected
(Videoclip S2, online). Refractory uterine bleeding
necessitated intracavitary Foley balloon tamponade.
Analysis
Sonographic evidence of a defect in the area of a Cesarean
scar can theoretically be diagnosed in all women who have
undergone this procedure, whether they are symptomatic
or asymptomatic13 – 15 . There are no strict diagnostic
249
criteria for uterine wall defect at the Cesarean scar site,
although fluid collection in the scar area14 or detectable
myometrial thinning at the scar site15 have been proposed.
Criteria for the sonographic diagnosis of Cesarean scar
pregnancy have been proposed16 .
The spectrum of management strategies for Cesarean
scar pregnancy is broad, and has been presented in
several case series and recent reviews17 – 21 . Expectant
management has been described, but it carries a
considerable risk of uterine rupture and hemorrhage19 ,
perhaps as high as 50%.
Asymptomatic and hemodynamically stable patients
are candidates for medical management. Systemic therapy
consists of different regimens (single or repeated doses)
of MTX treatment. This has been described for
asymptomatic patients with unruptured pregnancies of
less than 8 weeks and β-hCG < 5000 mIU/mL17,19 . The
success rate of this approach is difficult to determine,
partly due to publication bias of case reports and also due
to the tendency to resort to surgery on the first suspicion of
complications22 , but it has been estimated at between 44
and 80%19 . The actual success rate is probably somewhat
more modest.
Local therapy involves injection of MTX directly into
the gestational sac. This may be appropriate when β-hCG
levels are high. Additional doses may be needed if the
gestational sac persists or excessive bleeding ensues. In
some cases, systemic and local MTX may be combined19 .
Surgical interventions that have been applied include
endoscopic methods (hysteroscopy or laparoscopy) and
laparotomy, which involves a wedge-shaped excision
of the gestational tissue and repair of the uterine wall
defect23 . This may be advantageous for subsequent
pregnancies. The procedure has a short immediate
follow-up period, but full recovery to disappearance of
residua may be lengthy. Endoscopic surgical methods
have the advantage of being minimally invasive while
still providing a definitive treatment. However, this
approach is most suitable when experienced surgical and
support systems are available, for example angiography
for prompt and effective hemostasis. No formal data
are available on the role of angiography in the
armamentarium of scar pregnancy treatment procedures.
D&C should not be considered, as it has been
shown to have a high failure rate and may result in
severe hemorrhage19 , necessitating urgent complimentary
treatment procedures.
Discussion
Figure 5 Cesarean scar pregnancy in the same woman as in
Figure 4. The gestational sac (sac) was located within the isthmic
area of the lower anterior wall of the uterus, protruding towards
the vesicouterine junction. The endometrium is indicated ( ), as are
the uterine–bladder interface (arrow), the cervix (cx) and the uterus
(u). (See also supplementary material online: Videoclip S2).
Copyright  2008 ISUOG. Published by John Wiley & Sons, Ltd.
There have been no prospective studies to compare
outcomes of medical and surgical management strategies
for ectopic pregnancies of unusual location. Conservative
management approaches have been proposed in recent
years. The published case reports and case series describe
women observed in the authors’ centers and treated with
various regimens of MTX, KCl or other agents. Patient
selection is not standardized regarding level of β-hCG,
gestational age, size of gestational sac or mass, or presence
Ultrasound Obstet Gynecol 2008; 31: 245–251.
Valsky and Yagel
250
Figure 6 A large Cesarean scar defect in the anterior wall ( ) of a non-gravid uterus, as demonstrated by: two-dimensional sagittal
transvaginal ultrasound (a); multiplanar imaging (b); and the rendered image of the defect, enlarged (c). The patient presented for
investigation of persistent uterine bleeding 2 months following Cesarean delivery.
or absence of cardiac activity. The definitions of treatment
success or failure are not uniform; nor are the approaches
to treatment failure. Follow-up periods also vary greatly,
since conservative management often requires lengthy
follow-up until the disappearance of sonographic evidence
of the gestational tissue.
Data regarding the future obstetric success of medically
treated patients are also lacking. This is particularly
important regarding patients with interstitial or cornual
pregnancy. It is unknown how the management of these
pregnancies will affect their future risks at delivery, or,
if they are managed surgically, whether they should be
delivered by elective Cesarean in subsequent pregnancies,
or whether they could be delivered vaginally.
Many questions surround each type of ectopic
pregnancy of unusual location. In interstitial pregnancy,
for example, is intervention necessary in a missed
abortion? How long is too long for a wait-and-see
approach? What is the risk of bleeding if the sac is not
developing? Can we base the decision on the size of the
mass, gestational age or β-hCG?
As laparoscopy becomes more commonly employed,
what is its real-world success rate? How should we regard
the post-laparoscopic uterus? Is the uterus scarred, and
if so should these women be considered at high risk
of rupture and delivered by Cesarean? No study has
compared outcomes of laparoscopy and laparotomy with
respect to immediate outcome or long-term follow-up and
risks. While our skills in diagnosis and follow-up have
increased, our ability to counsel the patient, especially
regarding her obstetric future, has not kept pace.
In cervical ectopic pregnancy, our surgical management
options are more limited because of the problematic
location. D&C can be very dangerous and hysteroscopy
is not feasible. These baseline limitations place much
more weight on alternative treatments, such as UAE,
but there are no clear-cut criteria for patient selection
for this procedure. Should UAE be considered as a firstline treatment option in cervical pregnancy, or reserved
as a rescue procedure in cases of hemorrhage? When
do we intervene surgically in these cases? If a cervical
pregnancy is non-viable and the patient is asymptomatic,
can we wait? Where there are no clear criteria, should the
Copyright  2008 ISUOG. Published by John Wiley & Sons, Ltd.
decision be based on gestational age, β-hCG levels or the
size of the mass?
In the case of Cesarean scar pregnancies, it is possible
to diagnose a uterine scar defect in the non-gravid uterus
(Figure 6). In this instance should the defect be repaired? Is
the defect’s size of any significance in taking this step? Will
repair prevent some or any Cesarean scar pregnancies?
Many cases of conservative management of ectopic
pregnancies have been described in the literature. It is time
to move forward with the tools that we have to develop
strategies to address the management dilemmas described
here. The time has come for structured studies that will
allow for the objective comparison of surgical and medical
approaches to these cases. As the conditions described
here are rare, no single center can collect sufficient cases
for a well-powered study. We propose that management
protocols be developed, so that in time it will be possible
to collect, analyze and compare successfully managed
and complicated cases, to create an evidentiary basis for
patient counseling and management.
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SUPPLEMENTARY MATERIAL ON THE INTERNET
The following material is available from the Journal homepage: http://www.interscience.wiley.com/jpages/
0960–7692 (restricted access)
Videoclip S1 Video obtained during laparoscopy showing a protrusion of the ectopic gestational sac with active
bleeding.
Videoclip S2 Video showing the gestational sac located within the isthmic area of the lower anterior wall of
the uterus, protruding towards the vesicouterine junction. The empty uterine cavity, disrupted anterior wall,
gestational sac and bladder are marked.
Published online in Wiley InterScience (www.interscience.wiley.com) DOI:10.1002/uog.5289.
Copyright  2008 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound Obstet Gynecol 2008; 31: 245–251.