Ectopic Pregnancy:

Revisiting an old foe

Disclosures

No disclosures or
conflicts of interest.
Objectives
 Current terminology
 Know the accuracy of
ultrasound for the
diagnosis of ectopic
pregnancy
  Understand the use of
beta-hCG subunit in the
context of ultrasound
 Review the data on the
last 10 years of ectopic
pregnancies diagnosed at
Kapiolani Medical Center
at Women’s and Children’s
The Basics
Definition
Any pregnancy that occurs
outside the normal location
in the uterine cavity.

Prevalence
 Occurs in ~2% of all U.S.
pregnancies and is the
leading cause of pregnancy-
related death in the 1st
trimester.

Ruptured ectopic pregnancies

account for nearly 10% of all
maternal deaths.

Location, location,
location
 Tubal
 Ampullary (70%)
 Isthmic (12%)
  Fimbrial (11%)
 Cornual (~3%)
 Cervical (<1%)
 Ovarian (<1%)
 C/S scar (<1%)
 Abdominal (<1%)

Isthmic Ectopic
Cornual Ectopic
Cornual Ectopic
Abdominal Ectopic
Location, location,
location
  Cervical

Location, location,
location
 Abdominal

Location, location,
location

 Heterotopic
The search for the best
test for the earliest
diagnosis of ectopic
pregnancy….Is it:
  Ultrasound alone?
 Serum beta-hCG alone?
 Combination of
ultrasound and beta-hCG
levels?
 What about the latest
and greatest?
New Consensus for
defining Pregnancy
of unknown location
(PUL)
 Definite EP: extrauterine gestational sac 
with yolk sac and/or embryo (with or without
cardiac activity)
  Probable EP: inhomogeneous adnexal 
mass or extrauterine saclike structure
 PUL: no signs of either EP or IUP
 Probable IUP: intrauterine echogenic 
sac­like structure
 Definite IUP: intrauterine gestational sac
with yolk sac and/or embryo (with or without
cardiac activity

Transabdominal
Ultrasound
 Ectopic pregnancies
with hemoperitoneum
  Very limited usefulness for
the diagnosis of early ectopic
pregnancy

Transvaginal
Ultrasound
 A gestational age of 5.5 weeks
has nearly 100% sensitivity in
diagnosing an intrauterine
pregnancy
 High resolution TVS detects the
gestational sac of an IUP by 32 to
35 days of gestation.
Tubal Ring Sign/
Bagel Sign
Adnexal Mass
Transvaginal
Ultrasound
 Only 20-25% of ectopic
pregnancies present with
visualization of an
extrauterine embryo.

Transvaginal
Ultrasound
 The presence of a
pseudosac does not make
ectopic pregnancy more
OR less suspicious.
 Ahmed in 2004 found
that the number of
patients with a pseudosac
did not have an ectopic
and a number of patients
with an ectopic did not
have a pseudosac.
Pseudosac or Early
IUP
Double decidual sac
Yolk Sac
Use of serum beta-
hCG alone
 Barnhart et al found
that the slowest increase
in serum beta-hCG in a
viable intrauterine
pregnancy is 53% after 48
hours rather than the
traditionally quoted 66%
rise in 48 hours.
 They also found that the
slowest rate of decline was
 21-35% in 2 days and 60-
84% in 7 days for a
spontaneous miscarriage
or tubal miscarriage.

Combination of
ultrasound with serum
beta-hCG
 Improves sensitivity to
97% and specificity to 96%
 ASSUMPTION
 If beta-hCG is above
2000 mIU/ml, without
evidence of intrauterine
pregnancy by transvaginal
 ultrasound, an ectopic or
non-viable pregnancy could
be safely and accurately
diagnosed.

Assumption put to
the test
 Retrospective review of 112
women with presumed dx of
ectopic pregnancy due to
beta-hCG above 2000 mIU/ml
without evidence of IUP by U/S
or due to an abnormal rise or
fall of serial beta-hCGs.
 Incorrect 40% esp with
beta-hCG above 2000 mIU/ml
and no IUP—they had 50/50
 chance of miscarriage or
ectopic.
 Women with plateaus in
hCG or initial hCG below 2000
mIU/ml were more likely to
have ectopic pregnancies with
the presumed dx but they
were still wrong 30% of the
time.
Diagnostic Accuracy of Ultrasound
Above and Below the Beta-hCG
Discriminatory Zone

 333 consecutive pregnant women who

presented to an ER with vaginal bleeding or
abdominal pain.
 TVS nondiagnostic in 59 (17.7%) of 333
subjects and 43 (67.2%) of 64 subjects with β-
 hCG levels below 1500 mIU/mL at presentation.
 Preliminary ultrasound diagnoses were
reported significantly more frequently when
presenting β-hCG levels were above 1500
mIU/mL (253 [94.1%] of 269 subjects) compared
with levels below 1500 mIU/mL (21 [32.8%] of 64
subjects: P < .001
 The proportion of accurate preliminary
ultrasound diagnoses was significantly higher in
subjects who presented with β-hCG levels above
1500 mIU/mL (227 [91.5%] of 248 subjects)
compared with levels below 1500 mIU/mL (18
[28.6%] of 63 subjects: P < .001

Prompt diagnosis of
ectopic pregnancy in an
emergency department
setting
 Prospectively evaluated 1263
women presenting to ER prospectively
(NOTE) 8% (99) dx’d with EP (59%
never reached hCG of 1500 mIU/mL.)

Protocol in the ER
Barnhart et al, Prompt diagnosis of Ectopic Pregnancy in an
emergency department setting, Obstet Gynecol, 1994 Dec 84
(6): 1010-5

The most important take-

home message
Cost-effective ?
approach
 Obtain transvaginal
ultrasound first on all women
who present with abdominal
pain or bleeding in the 1st
 trimester
 If U/S inconclusive, a
quantitative beta-hCG is
obtained and women were
treated according to that level.
 Strategy produced the best
outcomes in that no ectopic
pregnancies were missed and
the smallest number 1% of
potential IUPs interrupted.
 Average time to dx was
1.46 days in high and low risk
populations.

Clinical Factors
Affecting the
Accuracy of
Ultrasonography in
Symptomatic First-
Trimester Pregnancy
 There are significantly more
false negative and false-positive
diagnoses when the criteria used to
identify a gestational sac in the
uterus or adnexa do not include the
presence of a yolk sac or an
embryo. Additionally, accuracy of
the initial ultrasonography is
significantly lower when the hCG
value is low and when the patient
reports bleeding.
Serum Biomarkers
“Fundamentally, the
question of whether a serum
biomarker exists that can
accurately and specifically
detect a tubal ectopic
pregnancy is still
unanswered.
Furthermore, with the
advent of better imaging
techniques, a serum
biomarker may be
superseded by ultrasound-
related technology.”
The Data:
Kapiolani Medical
Center for Women
and Children
Study Period: 8/1/00 -
8/31/10
10 years
Conclusions
 40% of all ectopic
pregnancies in this database
had a beta-hCG level below
threshold of the ability to see
an IUP sonographically.
 74% of the total were
diagnosed sonographically—
 56% by the loosest criteria of
having an adnexal mass
present and 18% by
pregnancy signs in the
adnexa.

Conclusion
 The early diagnosis of
ectopic pregnancies
remains a significant
clinical dilemma even
though there has been
tremendous progress over
the last 20 years in
improved technologies.
 Transvaginal ultrasound
with or without the use of
serum markers or Doppler
has become the mainstay
in the first-line evaluation
of women suspected of
having an EP or in cases of
pregnancies of unknown
location.