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ª Springer Science+Business Media New York 2017 Abdom Radiol (2017) 42:1524–1542

Abdominal Published online: 31 January 2017 DOI: 10.1007/s00261-016-1020-4

Radiology

Pitfalls and tips in the diagnosis of ectopic


pregnancy
E. Mausner Geffen , C. Slywotzky, G. Bennett
Department of Radiology, NYU Langone Medical Center, 550 1st Avenue, New York, NY 10016, USA

Abstract General principles


Women of reproductive age with pelvic pain, vaginal
Obtaining a history
bleeding, and a positive pregnancy test often require When screening patients for possible ectopic pregnancy,
evaluation with pelvic ultrasound. In these situations, the it is important to document a complete history and
primary role of pelvic ultrasound is to differentiate an physical examination, including the patient’s last men-
ectopic pregnancy from either a normal or abnormal strual period (LMP). Particular attention should be paid
intrauterine pregnancy. While an accurately performed to risk factors associated with ectopic pregnancy such as
and interpreted pelvic ultrasound results in rapid diag- pelvic inflammatory disease, endometriosis, smoking,
nosis and management, numerous diagnostic pitfalls can presence of an intrauterine contraceptive device, use of
lead to negative outcomes. Therefore, familiarity with assisted reproductive techniques (ART), and a history of
the appropriate laboratory tests, sonographic technique, prior ectopic pregnancy [2]. In addition to past medical
and imaging features of ectopic pregnancy is essential for and reproductive history, a thorough surgical history
all radiologists. We present a review of ectopic pregnancy including prior tubal surgery, dilatation and curettage
cases from our institution with attention to common (D&C), and Cesarean sections should be addressed [2].
pitfalls and troubleshooting tips for physicians who However, it should be remembered that approximately
perform and interpret pelvic ultrasounds. We also pre- fifty percent of ectopic pregnancies occur in patients
sent recently published literature to aid in the manage- without any clear risk factors [1].
ment of first trimester pregnancy. Tip Patients may be unaware of pertinent details or
may not be forthcoming with sensitive information, and
Key words: Ectopic pregnancy—Pregnancy of unknown
therefore clinical suspicion for ectopic pregnancy should
location—Human chorionic gonadotropin (HCG)
not be dismissed in the absence of historical data.

Ectopic pregnancy is an increasingly common occur- Nonspecific lower abdominal/pelvic pain


rence reported in approximately 1.5–2.0% of all preg- The evaluation of a female patient with abdominal or
nancies [1]. Since ruptured ectopic pregnancy accounts pelvic pain often begins with a broad differential. We
for 6% of pregnancy-related deaths and is the leading urge clinicians to consider, and evaluate the possibility
cause of first trimester maternal death, early perfor- of, ectopic pregnancy in all women of reproductive age.
mance and accurate interpretation of pelvic ultrasonog- This includes women with a known history of gyneco-
raphy are essential [1, 2]. In this review, we demonstrate logic pathology as well as teenage girls who present with
the various types of ectopic pregnancies and the associ- right lower quadrant pain in whom alternative diagnoses
ated ultrasound findings, common diagnostic imaging such as appendicitis are favored. Because of the potential
pitfalls, and indications for further imaging with 3D danger of a delayed diagnosis and rupture of an ectopic
ultrasound or dedicated MRI of the pelvis (Fig. 1). pregnancy, a urine pregnancy test (qualitative beta-hu-
man chorionic gonadotropin test) should be obtained
prior to cross-sectional imaging with MRI or CAT scan.
In cases with a positive beta-human chorionic gonado-
tropin (beta-HCG), a pelvic ultrasound should always be
the initial test of choice. Thus, early beta-HCG testing
Correspondence to: E. Mausner Geffen; email: evm221@nyumc.org
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1525

Fig. 1. Diagram summarizing the possible locations where ectopic pregnancies may occur.

helps guide physicians to the best imaging test, and can respectively, may cause confusion if they are compared
potentially avoid inappropriate imaging (Figs. 2, 3). to one another. Additionally, the discriminatory zone
Tip In women with right lower quadrant pain and a will vary based on the beta-HCG assay used [3]. While
positive beta-HCG, the first imaging test performed much of the older literature on the discriminatory zone
should be a pelvic ultrasound to rule out ectopic preg- was written using the Second IS, most hospitals are
nancy even in cases where appendicitis was the original currently using the Third IS. The conversion between the
leading diagnosis. A graded compression ultrasound of two systems is as follows: Second IS 91.8 = Third IS.
the right lower quadrant can be performed simultane- Of note, the Third IS was originally referred to as the
ously with a pelvic ultrasound to look for appendicitis. First International Reference Preparation (IRP) and
these two terms may be used interchangeably.
Tip Always make sure that the beta-HCG discrimi-
Beta-HCG values—what do they mean?
natory zone reference range being used is correct for your
When interpreting a quantitative beta-HCG value, it is laboratory preparation as values can vary across insti-
essential to know the reference range and laboratory tutions.
preparation used at a given institution. In general,
transvaginal ultrasound is capable of detecting an
intrauterine pregnancy (IUP) when the quantitative beta-
Qualitative vs. quantitative beta-HCG
HCG level is greater than 2000 mIU/mL (discriminatory
and trending the beta-HCG level
zone, Third International Standard); however, physi- A commonly encountered problem in the clinical setting
cians should be aware that three different reference occurs when only the qualitative beta-HCG (i.e., the
ranges exist [3]. The three standards, referred to as the urine pregnancy test) is positive, but there is no quanti-
First, Second, and Third International Standard (IS), tative beta-HCG blood test available at the time of
1526 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

ultrasound interpretation. In this situation, an indeter- With only a qualitative result, it is unknown whether the
minate ultrasound showing that there is no ectopic beta-HCG value is above the discriminatory zone and in
pregnancy or IUP visualized is of unclear significance. a range where an IUP could reliably be identified [4].
When this occurs, radiologists should request a quanti-
tative beta-HCG blood test; if the quantitative beta-
HCG value is below the discriminatory zone, close fol-
low-up with serial beta-HCGs and ultrasounds is re-
quired to determine pregnancy viability.
A second common problem is seen when patients
present emergently with a single isolated beta-HCG va-
lue. The difficulty in this scenario is that an indetermi-
nate ultrasound in a patient with a single beta-HCG
value above the discriminatory zone (in one series as high
as 4336 mIU/mL Third IS) does not preclude an IUP [5].
As such, a similar conservative management strategy
with serial beta-HCGs and ultrasounds should be em-
ployed in a stable patient with a desired pregnancy, as
per the recommendations of the Society of Radiologists
in Ultrasound (SRU). [6].
A common misconception is that ectopic pregnancies
are only visible when the beta-HCG level is above the
discriminatory zone of 2000 mIU/mL. This is dangerous
as either high or low beta-HCGs can be seen at the time
Fig. 2. Teenage female presented to ED with abdominal
pain and a CT scan was performed to evaluate for appen-
of diagnosis of an ectopic pregnancy (Fig. 4). In fact,
dicitis. Beta-HCG found to be positive only after the CT scan more than 50% of patients with a visible ectopic preg-
was performed. Axial CT with oral contrast demonstrates nancy on ultrasound have a beta-HCG less than
heterogeneous complex fluid collection and hemorrhage in 2000 mIU/mL [7].
the pelvis with a left adnexal mass (arrow). At surgery, this Tip Though a pelvic ultrasound is unlikely to
was found to represent a ruptured ectopic pregnancy. Normal demonstrate an IUP if the beta-HCG is below the dis-
appendix (not shown). criminatory zone, a low beta-HCG should not deter

Fig. 3. 34-year-old female with known uterine fibroids was ovary (black arrow) (A). Post-contrast T1 GRE images (con-
referred to MRI for lower abdominal pain and continuous trast was given as the patient was not known to be pregnant)
uterine bleeding for one month. MRI was intended for surgical demonstrated peripheral enhancement in the adnexal mass
planning prior to myomectomy. Axial T2 TSE image demon- (B). Surgical pathology revealed a right adnexal ectopic
strated a right adnexal mass (white arrow) separate from the pregnancy.
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1527

the surrounding anatomy and lead to misinterpretation


of the location of the gestational sac. In one such case at
our institution, a patient presented for initial TVUS,
which documented an apparent IUP and seemingly
normal circumferential endometrial tissue. However, on
further transabdominal imaging, the sac was noted to be
anteroinferiorly displaced within a thinned-out Cesarean
section scar (Fig. 6). The patient was diagnosed with a
scar ectopic implantation. In light of this, we believe that
both transabdominal and transvaginal ultrasound should
be routinely performed on all patients in whom ectopic
pregnancy is suspected [9]. We recommend first per-
forming a transabdominal ultrasound for a global view
of the abdomen and pelvis. This should include imaging
of both Morrison’s pouch and the paracolic gutters to
evaluate for hemorrhage. It is helpful if the bladder is
moderately distended to allow for an optimal acoustic
window; however, scanning should not be delayed until
Fig. 4. 41-year-old female with a beta-HCG of 1330 mIU/mL the bladder is full. Indeed, a scan without a distended
who presented with vaginal bleeding. Transvaginal ultrasound bladder may still yield valuable information. Subsequent
showed a heterogeneous left adnexal mass (calipers) with scanning with a transvaginal ultrasound should then be
associated hemoperitoneum, which was suspicious for a performed (after the patient has voided) for higher res-
ruptured tubal ectopic pregnancy. This diagnosis was con- olution images.
firmed at surgery.
Tip Both transabdominal and transvaginal ultra-
sound should be routinely performed on all patients in
performance of a pelvic ultrasound if there is a concern whom ectopic pregnancy is suspected.
for an ectopic pregnancy. Ectopic pregnancies are often
visible when the beta-HCG is well below the discrimi-
natory zone. The transducer
Tip Not all ectopic pregnancies require immediate Prior to beginning the pelvic ultrasound, the appropriate
medical or surgical management. Watchful waiting may transducer must be selected. Images with a curvilinear
be the best course of action for a stable patient with a low abdominal probe (1–6 MHz) should be obtained for
beta-HCG level (£200 mIU/mL) that is down trending transabdominal scanning first, with the patient’s bladder
[8]. distended to allow optimal visualization. Then, the pa-
tient is asked to void, and transvaginal images are ob-
Sonographic technique tained. Transvaginal ultrasound should be performed
Approach with a high-frequency transducer (7.5–10 MHz) in order
to obtain high-resolution images and allow for better
Choosing the scanning approach is the first step in a visualization of early pregnancy structures. Using a low-
properly performed pelvic ultrasound examination. We frequency transvaginal transducer may cause the inter-
have found that it is a common mistake for practitioners preting physician to miss key imaging findings.
to rely solely on transvaginal ultrasound (TVUS) in the
diagnosis of an ectopic pregnancy. In one case at our
institution, a woman presented with vaginal spotting, A comprehensive scan
right-sided abdominal pain, and a beta-HCG of When scanning the female pelvis, is it important to en-
153 mIU/mL. On transvaginal ultrasound, no IUP or sure visualization of the entire uterus from the cervix to
ectopic pregnancy was seen. Note was also made that the the cornua as well as the adnexa. Obtaining images only
right adnexa was not well visualized at TVUS. Upon in the plane of the endometrial cavity is insufficient to
further imaging with a transabdominal approach, a tubal confidently exclude an ectopic pregnancy. It is our
ring was visualized in the right adnexa and confirmed to practice to routinely include cine clips of the entire uterus
be an ectopic pregnancy (Fig. 5). The patient received and adnexa as part of a complete pelvic ultrasound.
immediate treatment as opposed to a watchful surveil- These clips are also useful through areas of clinical
lance approach for a pregnancy for unknown location. concern, especially for radiologists reading remotely. In
A different problem arises when the gestational sac is addition to scanning the entire pelvis, it is important to
first identified by TVUS. In this setting, the coned-down consider the abdomen as a site for a possible ectopic
field of view provided by TVUS may exclude portions of pregnancy [10]. This is particularly important when the
1528 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Fig. 5. Female patient presenting with vaginal spotting, TVUS (B). Upon further transabdominal imaging, a tubal ring
right-sided abdominal pain, and a beta-HCG of 153 mIU/mL. (arrow) was visualized in the right adnexa adjacent to the right
On transvaginal ultrasound, no IUP or ectopic pregnancy was ovary (star) and confirmed to be a tubal ectopic pregnancy
seen (A). The right adnexa was incompletely visualized by (C).

patient can localize pain to a specific quadrant within the evidence of an ectopic pregnancy. In such instances, the
abdomen. In one case, a patient presented with a positive patient needs a follow-up beta-HCG blood level and
beta-HCG and left upper quadrant abdominal pain. pelvic ultrasound to monitor for an occult ectopic
Initial transabdominal and transvaginal sonography pregnancy. Detailed guidelines for follow-up of these
failed to show an IUP or ectopic pregnancy. Further cases are addressed in the Society of Radiologists in
dedicated ultrasound images of the left upper quadrant Ultrasound (SRU) recommendations (Fig. 8) [6].
over the area of maximal tenderness documented a
splenic ectopic pregnancy (Fig. 7). Indirect imaging findings
Tip In order to achieve the best diagnostic accuracy, it
Intrauterine fluid
should be standard practice to ask the patient to localize
her discomfort and dedicated images should be obtained The examination of a patient with pelvic pain and a
in this region. positive beta-HCG always begins by evaluating for the
presence of an IUP [11–15]. The earliest documented
No imaging findings (a normal pelvic sonographic finding of an IUP is the intradecidual sign
ultrasound) (IDS) first seen at 4.5 weeks after the patient’s LMP [3].
The IDS is a round, eccentrically located, anechoic fluid
Pregnancy of unknown location collection surrounded by an echogenic ring within the
This scenario occurs when there is no IUP demonstrated, decidua of the endometrium [12]. The double sac sign
no definite evidence for recent pregnancy loss, and no (DSS) is another indicator of an IUP and first appears
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1529

Fig. 6. 34-year-old female presented for routine evaluation Additionally, a thin endometrium was noted which is atypical
of a desired pregnancy. Initial transvaginal ultrasound for an IUP (B). Three week follow-up transvaginal ultrasound
demonstrated a gestational sac with apparent normal demonstrated the gestational sac in direct contact with the
intrauterine location (A). Subsequent transabdominal images bladder without overlying myometrium (C). The pregnancy
showed that the sac was actually in the lower uterine segment was carried to term, and hysterectomy was performed at the
consistent with a Cesarean section niche ectopic pregnancy. time of delivery.

around 5 weeks. The DSS appears as two echogenic rings IDS and DSS from the intrauterine fluid of an ectopic
around an anechoic round fluid collection. The etiology pregnancy (pseudogestational sac) can be quite difficult
of these echogenic rings is controversial. One common (Fig. 9). Though it raises concern for an ectopic preg-
theory suggests that they represent two layers of decid- nancy, a nonspecific centrally located intrauterine fluid
ua—the inner decidua capsularis and the outer decidua collection without an IUP remains an equivocal finding.
vera [12]. Soon after the double decidual reaction begins, In fact, nonspecific intrauterine fluid is seen in approxi-
the yolk sac develops within the gestational sac mately 0.2% of normal intrauterine pregnancies. Based
(5.5 weeks) [3]. The presence of a yolk sac within the on the greater prevalence of IUPs compared to ectopic
endometrial cavity is 100% specific for the diagnosis of pregnancies, the finding of nonspecific intrauterine fluid
an IUP [3]. is statistically more likely to represent an IUP rather than
While the IDS or DSS strongly suggests the presence a pseudogestational sac [15].
of an IUP, the absence of these signs does not exclude the Tip The possibility of an early IUP should always be
possibility of an IUP [12]. In addition, differentiating suggested in cases of nonspecific intrauterine fluid col-
1530 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Fig. 7. Female patient presented with left upper quadrant (SPL) (A). Left kidney (LT KID) for anatomic reference. Fol-
pain. No IUP or pelvic ectopic identified (not shown). Addi- low-up axial contrast-enhanced CT confirmed the splenic
tional ultrasound images in the left upper quadrant in the area gestational sac (B). Case courtesy of Ushma Patel, MD,
of concern demonstrated a gestational sac in the spleen University of Medicine and Dentistry of New Jersey.

Fig. 8. 29-year-old G3P1011 female at 5 weeks and 5 days a pregnancy of unknown location, and follow-up ultrasound
by LMP presented with left-sided pelvic pain for 1 week. The was recommended. Repeat pelvic ultrasound performed
initial transvaginal ultrasound demonstrated a thickened en- 10 days later showed a left adnexal mass consistent with a
dometrium without an intrauterine gestational sac (A). The tubal ectopic pregnancy (arrow) (B). Star denotes left ovary in
bilateral adnexa were normal. The patient was diagnosed with (B).

lections [13, 15]. Conservative management (rather than Extrauterine fluid


upfront methotrexate) with close follow-up should be
In addition to assessing the uterus for fluid collections,
offered to all patients who are stable and desire a preg-
nancy. evaluation for extrauterine fluid, particularly in the cul-
Tip In cases where intrauterine fluid is not well de- de-sac, is a key component of the pelvic ultrasound [2].
fined on standard two-dimensional ultrasound, three- Hemoperitoneum may be seen in the setting of an ectopic
dimensional ultrasound can be utilized to more clearly pregnancy, though this finding is also seen with hemor-
depict the IDS and increase interpreter confidence rhagic corpus luteum cysts, endometriomas, and spon-
regarding the presence of an IUP (Fig. 10). taneous abortions. Hemoperitoneum may present as
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1531

Fig. 9. 40-year-old G5P2022 female presented with right was found to have a tubal ectopic pregnancy. In contrast, a
lower quadrant pain and spotting for 2 days. Beta-HCG on reproductive age patient with an early IUP demonstrating the
admission was 687 mIU/mL. Transabdominal ultrasound intradecidual sign (IDS). Here, there is an eccentrically lo-
demonstrated hypoechoic fluid centrally within the endome- cated fluid collection separate from the endometrial cavity and
trial canal concerning for a pseudogestational sac (arrow) (A). within the decidua of the endometrium (B).
There was no intrauterine yolk sac or embryo. The patient

Fig. 10. Example of two-dimensional sonogram (A) with surrounding echogenic rim eccentrically located within the
accompanying three-dimensional volume rendered imaging endometrium, consistent with the intradecidual sign (arrow).
(B). 3D ultrasound nicely demonstrates a fluid collection with

focal clot with a heterogeneous collection in the pelvis low sensitivity, specificity, and positive predictive value
(Fig. 11). This collection may obscure vital structures [16]. If a patient with hemoperitoneum becomes hemo-
and confound diagnosis of an ectopic pregnancy. When dynamically unstable, emergent surgical intervention is
hemoperitoneum is present in the pelvis, the upper ab- typically warranted regardless of the cause (Fig. 12; Ta-
domen should be scanned to assess the extent of bleeding ble 1). The ultrasound should be quickly terminated and
[2]. The key places in the abdomen to evaluate include the referring clinician must be notified.
the paracolic gutters and Morrison’s pouch. The pres- Tip Extrauterine hemoperitoneum may be seen in a
ence of complex echogenic fluid in these regions indicates patient with an ectopic pregnancy; however, the differ-
a large peritoneal bleed (greater than 500 cc) and raises ential diagnosis is broad. Additionally, the upper abdo-
concern for a tubal rupture; however, this finding has a
1532 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Tip The peripheral trophoblast of the tubal ring is


often more echogenic than the ovarian stroma whereas
the corpus luteum is more hypoechoic, which can also
help differentiate the two [17] (Fig. 15).

Interstitial and cornual pregnancies


An interstitial pregnancy refers to an ectopic pregnancy
located in the portion of the fallopian tube that passes
through the uterine wall. Interstitial pregnancies are rare,
making up 2–4% of cases [19]. In addition to being rare,
they are difficult to diagnose and easily confused with
intrauterine pregnancies. As a result, they tend to be
diagnosed late and are associated with an increased risk
Fig. 11. Reproductive age female with positive qualitative of rupture. On ultrasound, an interstitial pregnancy is
beta-HCG presented with abdominal pain and vaginal seen as an eccentric gestational sac (greater than 1 cm
bleeding. Transvaginal ultrasound in the sagittal plane from the lateral wall of the uterine cavity) surrounded by
demonstrated echogenic clot and debris (arrrow) surrounding an asymmetric thin myometrial mantle [20]. A sono-
the uterus (star) concerning for a ruptured ectopic pregnancy graphic marker of an interstitial pregnancy is the inter-
with hemoperitoneum. No intrauterine pregnancy identified. stitial line sign (ILS), defined as an echogenic line
extending from the gestational sac into the cornua of the
uterus (Fig. 16A, B). When present, the ILS is highly
men should be evaluated to gauge the extent of possible sensitive and specific for interstitial pregnancy [21]. The
bleeding and help direct patient management. term cornual pregnancy is frequently used inappropri-
ately and interchangeably with interstitial pregnancy.
Direct imaging findings Unlike interstitial pregnancies, cornual pregnancies are
Tubal pregnancy intrauterine and occur when a gestational sac implants in
one horn of a bicornuate or septate uterus (Fig. 15C, D)
The most common location of an ectopic pregnancy is in [19].
the fallopian tube, most frequently in the ampullary Tip On routine two-dimensional ultrasound, a cor-
portion of the tube. Ultrasound findings in tubal preg- nual pregnancy and interstitial pregnancy may be indis-
nancy include a live extrauterine pregnancy, tubal ring, tinguishable if the uterine anatomy is indeterminate.
heterogeneous adnexal mass, hematosalpinx, and a ring Therefore, it is our recommendation that when ultra-
of fire on color Doppler (Fig. 13). Diagnostic confidence sound findings are equivocal, all interstitial and cornual
increases significantly if a yolk sac or cardiac activity can pregnancies should be further evaluated with three-di-
be demonstrated within the adnexal mass. The ring of mensional ultrasound or pelvic MRI (Fig. 16B, D). Ad-
fire seen on color Doppler is a measure of the hyper- vanced imaging allows for characterization of variant
vascularity of the ectopic gestational sac. This sign is uterine anatomy and clarification of the location of the
useful for locating a potential ectopic pregnancy, par- gestational sac.
ticularly if the adnexa is obscured by surrounding he-
matoma [14] (Fig. 14). The tubal ring sign is defined by
the presence of a round hypoechoic adnexal collection Cervical pregnancy
with a well-defined hyperechoic rim [17]. This represents A cervical pregnancy occurs when a blastocyst implants
a gestational sac (hypoechoic center) with surrounding in the endocervical canal. Cervical implantation is seen in
trophoblast (hyperechoic rim) and is present in up to less than 1% of all ectopic pregnancies. This type of ec-
71% of tubal ectopic pregnancies (Fig. 15A). Tubal topic pregnancy most frequently occurs in patients who
pregnancies can be confused with ovarian findings such have undergone prior D&C or those using ART [2, 14].
as corpus luteum cysts and ovarian follicles due to the A cervical ectopic may result in a figure of eight (hour-
similarity of the greyscale and color Doppler appear- glass) uterine shape formed by a distended cervical canal
ances. In all cases, it is important to demonstrate that the at one end and the uterine fundus at the other (Fig. 17).
tubal ring is extraovarian—moving separately from the The presence of cardiac activity within a cervical gesta-
ovary during real-time examination. The use of gentle tional sac provides a definitive diagnosis of cervical
pressure with the transvaginal probe may help to move pregnancy [22]. For this reason, cardiac motion should
the tubal ectopic pregnancy away from the ovary and be documented whenever possible (Fig. 18). Addition-
confirm the diagnosis. This finding is known as the ally, color Doppler imaging of the gestational sac doc-
sliding organ sign [18]. umenting prominent peritrophoblastic vascularity should
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1533

Fig. 12. 30-year-old G5P3013 female presented with pelvic echogenic soft tissue and complex free fluid (A, B). Transab-
pain and vaginal bleeding. Beta-HCG was 5596 mIU/mL. dominal images of the upper abdomen showed large volume
Transabdominal midline longitudinal and transverse ultrasound echogenic fluid consistent with massive hemoperitoneum (C).
through the pelvis showed an empty uterus surrounded by The patient was taken emergently to the operating room.

be obtained, and can help distinguish a spontaneous products of an ongoing spontaneous abortion. In both
abortion from a live ectopic pregnancy. In cases of sus- cases, a gestational sac can be seen within the cervical
pected cervical ectopic pregnancy, the internal and canal. One key difference is that a cervical ectopic
external cervical os should be routinely imaged. If either pregnancy will have a round shape and remain adherent
os are open, this favors an abortion in progress over a to the cervix during the ultrasound (Fig. 18A, B).
cervical ectopic pregnancy. Alternatively, an abortion in progress may show an
Tip A common pitfall occurs when attempting to irregular-shaped sac extending from the uterine cavity
differentiate a cervical ectopic pregnancy from the into the cervix with an open internal and/or external os.
1534 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Fig. 13. 34-year-old G3P2002 female at 7 weeks by LMP complex fluid in the endometrial cavity. No intrauterine gesta-
presented with lower abdominal pain. Pelvic ultrasound through tion was identified (A). A live tubal ectopic pregnancy was
the uterus showed an irregularly thickened endometrium and identified in the region of the right adnexa (B, C).

Table 1. Ultrasound findings and contraindications to medical man-


agement of ectopic pregnancy
Scar pregnancy
Hemoperitoneum in patient who is hemodynamically unstable A scar pregnancy refers to implantation within the uterus
Embryo with cardiac activity (relative contraindication) at the site of a prior Cesarean section incision. This type
Gestational sac ‡3.5 cm (relative contraindication)
of ectopic pregnancy has become increasingly common
Adapted from ACOG Practice Bulletin No. 94 with rising rates of Cesarean sections (roughly 1/3 of all
deliveries in the US are by Cesarean section) [23]. It is
also a particularly dangerous type of ectopic pregnancy
An abortion in progress may also change shape and because of the high risk for uterine rupture [24]. Addi-
location during the ultrasound (Fig. 18C, D). If the tionally, recent literature suggests that some morbidly
distinction between residual products of conception and adherent placentas originate from scar pregnancies, fur-
cervical ectopic cannot be made, short-term follow-up thering the importance of early diagnosis and manage-
can be performed to assess for interval change. If a cer- ment [25]. Scar pregnancies are outside of the
vical ectopic pregnancy is favored, dilatation and curet- endometrial cavity and are only surrounded by a thin rim
tage (D&C) should be avoided in order to prevent life- of myometrium and fibrous tissue. On ultrasound, the
threatening hemorrhage. gestational sac is typically found at the anterior lower
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1535

uterine segment along the enlarged scar. To confidently band of myometrial tissue should remain between the
diagnose a scar pregnancy at sonography, several criteria bladder and the sac [24] (Fig. 19). Another clue is that
should be met: both the endometrial cavity and cervical the gestational sac may be triangular in shape as it
canal should be empty; a gestational sac should be seen conforms to the shape of the preexisting Cesarean scar
within the anterior lower uterine segment; and a thin niche (Fig. 20). It is important to remember that D&C is
contraindicated in scar pregnancies due to an increased
risk of uterine perforation.
Tip In cases of suspected scar pregnancy, three-di-
mensional ultrasound can be used to reconstruct the
pelvic anatomy and increase diagnostic accuracy.

Intra-abdominal pregnancy
In an intra-abdominal ectopic pregnancy, implantation
occurs within the peritoneal cavity. This type of ectopic is
extremely rare (less than 1% of cases) and typically oc-
curs after the rupture of a tubal ectopic with resultant
implantation in the peritoneal cavity. Intra-abdominal
ectopic pregnancies are most commonly found on the
broad ligament and in the pouch of Douglas [26]. Other
sites include the liver, spleen, omentum, lesser sac, and
bowel (Fig. 7). Diagnosis of an intra-abdominal preg-
nancy requires the absence of an intrauterine sac, tubal
Fig. 14. Reproductive age female patient presented with
dilatation, or adnexal mass. In rare cases, visualization of
vaginal bleeding, pain, and a positive beta-HCG. At pelvic
ultrasound, the patient was found to have a large right ad- a gestational sac surrounded by loops of bowel can help
nexal hematoma obscuring visualization of anatomic detail. improve diagnostic accuracy. Intra-abdominal pregnan-
Further transabdominal imaging of the right adnexa with cies can grow significantly before becoming symptomatic
power Doppler demonstrated the ring of fire appearance of a [10]. When finally brought to the attention of a clinician,
tubal ectopic within the large pelvic hematoma. distorted anatomy can make the diagnosis difficult.

Fig. 15. 27-year-old G4P2012 female presented with pain hyperechoic relative to the ovary (star). Additional transvagi-
and spotting for 2 days. Beta-HCG on admission was nal ultrasound images demonstrated an ovarian corpus lu-
20,375 mIU/mL. Transvaginal ultrasound of the right adnexa teum cyst (black arrow), which is hypoechoic relative to the
demonstrated a round echogenic paraovarian mass consis- surrounding ovarian stroma (star) (B).
tent with a tubal ring (white arrow) (A). The tubal ring is
1536 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Fig. 16. 22-year-old G2P0010 female presented with vagi- identified and confirmed the presence of the left interstitial
nal bleeding and abdominal cramping. Beta-HCG on admis- ectopic pregnancy (B). For comparison, transvaginal pelvic
sion was 6860 mIU/mL. Two-dimensional transvaginal ultrasound performed in a 27-year-old G1P0 with beta-HCG of
ultrasound demonstrated an eccentrically located ectopic 2300 mIU/mL again shows an eccentrically located ectopic
gestational sac. The differential diagnosis for this finding in- gestational sac. In this case, there was an incomplete uterine
cluded a cornual pregnancy and an interstitial ectopic preg- septum, and the diagnosis of cornual pregnancy was favored
nancy (A). Follow-up imaging with three-dimensional (C). Coronal Haste pelvic MRI was performed to confirm the
transvaginal ultrasound was performed to exclude a con- presence of an incomplete uterine septum with a gestational
genital uterine duplication. The interstitial line sign was also sac in the left cornua (D).

Tip If there is concern for an intra-abdominal preg- concurrently. Heterotopic pregnancies account for 1–3%
nancy, an MRI of the abdomen and pelvis is the imaging of all ectopic pregnancies but are more common in wo-
modality of choice (Fig. 21). men using assisted reproductive technology [27]
(Fig. 22). While a history of in vitro fertilization should
prompt particular attention to the possibility of multiple
Heterotopic pregnancy
intra- and extrauterine pregnancies, heterotopic preg-
Heterotopic pregnancy is an unusual situation in which nancies also occur spontaneously in women without risk
extrauterine (ectopic) and intrauterine gestations occur factors (Fig. 23). Therefore, a thorough pelvic ultra-
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1537

Fig. 17. 33-year-old female presented with vaginal bleeding cervix. The intrauterine fluid and cervical gestational sac
and a positive qualitative beta-HCG. Transabdominal and create a figure of eight appearance (A, B).
transvaginal pelvic ultrasound showed a gestational sac in the

Fig. 18. 26-year-old G6P0050 female presented with vagi- a 25-year-old G1P0 at 7 2/7 weeks presented with a gesta-
nal bleeding and a beta-HCG of 12,814 mIU/mL. Transvagi- tional sac in the cervix (arrow) on initial prevoid transvaginal
nal pelvic ultrasound demonstrated a gestational sac at the ultrasound (C). Follow-up postvoid transvaginal ultrasound
internal cervical os (arrow) (A). M-mode ultrasound through image obtained 15 min later showed hematocolpos and ab-
the embryo demonstrated a heart rate of 65 bpm, which is sence of the endocervical sac (arrow). This is diagnostic of a
diagnostic of a live cervical ectopic pregnancy (B). In contrast, spontaneous abortion.
1538 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Fig. 19. Reproductive age female with history of prior Ce- tified a gestational sac in the anterior lower uterine segment
sarean section presented with pelvic pain, bleeding, and a consistent with a Cesarean scar ectopic pregnancy. Both the
positive qualitative beta-HCG. Transvaginal ultrasound iden- uterine cavity and cervical canal were empty.

by ultrasound, the presence of a molar or heterotopic


pregnancy must be reevaluated. Likewise, if the beta-
HCG remains persistently elevated after elective termi-
nation of pregnancy or spontaneous abortion, the
physician should have a high index of suspicion for
heterotopic pregnancy (Table 2).

Ovarian pregnancy
An ovarian ectopic pregnancy refers to a pregnancy that
remains within the ovary itself and is the least common
type of ectopic pregnancy (Fig. 24). Sonographically, an
ovarian ectopic pregnancy appears as a gestational sac
surrounded by ovarian tissue in a patient with normal
fallopian tubes [28]. Based on the extremely low inci-
dence of ovarian ectopic pregnancies, a thorough search
Fig. 20. 32-year-old female with a history of a prior Cesar-
ean section presented with pelvic pain. Sagittal T2 TSE MRI
for an alternative site of ectopic pregnancy should be
of the pelvis demonstrated a triangular fluid-filled Cesarean performed. Even when an ovarian abnormality is visible,
scar niche (arrow). This niche serves as a potential reservoir likelihood would favor an alternate ovarian process such
for ectopic pregnancy implantation. as a corpus luteum cyst, which can be an incidental
finding in the setting of an ectopic pregnancy.
Tip The absence of the sliding organ sign between the
ectopic pregnancy and the ovary should heighten con-
sound should always include an assessment of the adnexa cern for an intra-ovarian ectopic pregnancy. To test for
even when an IUP is initially identified. the sliding organ sign, gentle pressure should be applied
Tip It is important to remember that the presence of with the tip of the transvaginal probe in the direction of
an IUP never obviates the need to examine the adnexa. the ovary in question; failure to separate the gestational
Tip A common pitfall in the diagnosis of a hetero- sac from the ovary can be viewed as evidence that the
topic pregnancy lies in the failure to correlate the gestational sac is within the ovary.
quantitative beta-HCG with the intrauterine ultrasound
findings. Physicians should be aware of the approximate
values for serum beta-HCG at various gestational ages.
Multimodal approach—pelvic MRI and three-
For example, a peak beta-HCG level of greater than
dimensional ultrasound
100,000 mIU/mL is expected at a gestational age of As mentioned within this review, both three-dimensional
8–11 weeks. If the beta-HCG value is higher than that ultrasound and noncontrast pelvic MRI can be used as
expected for the gestational age of an IUP documented safe and effective problem-solving tools in the evaluation
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1539

Fig. 21. Reproductive age female presented for pelvic MRI Alampady Shanbhogue, MD, New York University Langone
for further evaluation of ectopic pregnancy. Sagittal T2 pelvic Medical Center. This is in contrast to a cornual pregnancy
MRI showed an advanced extrauterine gestation (arrow) (arrow), which is surrounded by endometrial tissue and con-
displacing the empty uterus (star) (A). This was consistent tained within one horn of a septate uterus (B).
with an abdominal ectopic pregnancy. Case courtesy of

Fig. 22. Reproductive age female with known first trimester YS2) and two embryos (1, 2) surrounded by hypoechoic fluid
pregnancy presented with pelvic pain. Initial transvaginal (B). This was diagnostic of a heterotopic abdominal preg-
ultrasound images demonstrated a live intrauterine pregnancy nancy with a single intrauterine pregnancy and two abdominal
(A). Additional transabdominal ultrasound images through the ectopic gestations in the rectouterine pouch.
cul-de-sac demonstrated two extrauterine yolk sacs (YS1 and

of ectopic pregnancy. This is particularly useful when the makes it difficult to decipher between an IUP and an
pelvic anatomy is distorted or an ectopic pregnancy is ectopic pregnancy (Fig. 21) [10, 29]. Three-dimensional
suspected in an atypical location. MRI is most com- ultrasound offers the advantage over MRI of being easily
monly used when there is a question of an intra-ab- accessible and rapidly performed. Three-dimensional
dominal ectopic pregnancy or when a uterine anomaly ultrasound is especially helpful for the evaluation of
1540 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Fig. 23. 29-year-old female at 9 2/7 weeks with no prior risk the region of the right adnexa showed a second tubal gesta-
factors presented with right lower quadrant pain and vaginal tion (C). These findings were consistent with a heterotopic
bleeding. Midline transabdominal and transvaginal ultrasound pregnancy.
revealed a live IUP (A, B). Further transabdominal images in

interstitial ectopic pregnancies (Figure 16), cervical ectopically located pregnancy from a failed (avascular)
pregnancies, and scar pregnancies [30, 31]. Additionally, aborting IUP [32]. Given the complexity of ectopic
three-dimensional ultrasound with power Doppler is pregnancy cases, radiologists should recommend and
being increasingly used to differentiate a live but perform advanced imaging when possible.
E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy 1541

Table 2. Beta-HCG levels and common pelvic ultrasound differentials


Beta-HCG level (mIU/mL) Considerations

0–6000+ May be an early intrauterine pregnancy without gestational sac seen or could be in ectopic location.
>100,000 If no IUP, consider molar pregnancy or abdominal ectopic
Persistently elevated following termination Consider heterotopic pregnancy or retained products of conception
or spontaneous abortion

Fig. 24. 29-year-old G1P0 at 9 0/7 by dates presented with mass was also noted (arrow) (B, C). The mass was insepa-
pelvic pain and vaginal bleeding. Greyscale transvaginal rable from the ovary (star) despite attempts to elicit the sliding
ultrasound demonstrated a normal uterus without an organ sign. The findings were suspicious for an ovarian ec-
intrauterine gestational sac (A). A large vascular left adnexal topic pregnancy and were confirmed by surgical pathology.

Conclusion be comfortable obtaining a focused history, reviewing


laboratory tests, and performing a transabdominal and
It is our hope that the cases we have presented and the transvaginal ultrasound. Improved understanding of the
tips we have provided in this article will enable physi- spectrum of imaging findings associated with ectopic
cians at all levels of training to more readily and accu- pregnancies, the common diagnostic pitfalls, and the
rately diagnose an ectopic pregnancy. It is of paramount limitations of two-dimensional sonography will ensure
importance that radiologists continue to improve their that reproductive age women with pelvic pain receive
diagnostic skills in this area in order to prevent damage appropriate and timely management.
to a potentially normal early IUP. Radiologists should
1542 E. Mausner Geffen et al.: Pitfalls and tips in the diagnosis of ectopic pregnancy

Compliance with ethical standards 16. Frates MC, Doubilet PM, Peters HE, Benson CB (2014) Adnexal
sonographic findings in ectopic pregnancy and their correlation
Funding No funding was received for this study. with tubal rupture and human chorionic gonadotropin levels.
J Ultrasound Med 33(4):697–703. doi:10.7863/ultra.33.4.697
Conflict of interest The authors declare that they have no conflict of 17. Frates MC, Visweswaran A, Laing FC (2001) Comparison of tubal
interest. ring and corpus luteum echogenicities: a useful differentiating
characteristic. J Ultrasound Med 20(1):27–31; quiz 33
18. Jurkovic D, Hacket E, Campbell S (1996) Diagnosis and treatment
Ethical approval This article does not contain any studies with human
of early cervical pregnancy: a review and a report of two cases
participants or animals performed by any of the authors.
treated conservatively. Ultrasound Obstet Gynecol 8(6):373–380.
doi:10.1046/j.1469-0705.1997.08060373.x
Informed consent Statement of informed consent was not applicable 19. Malinowski A, Bates SK (2006) Semantics and pitfalls in the
since the manuscript does not contain any patient data. diagnosis of cornual/interstitial pregnancy. Fertil Steril 86(6):
e1711–e1764. doi:10.1016/j.fertnstert.2006.03.073
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