Ectopic pregnancy often does not present with a standard clinical picture. This
leads to frequent delays in diagnosis and helps contribute to this being the
number one cause of maternal death during the 1 st trimester. Therefore, the
diagnosis should be considered for all reproductive patients presenting with any
clinical factors discussed below.
An ectopic pregnancy is a pregnancy outside of the uterus. 95% of ectopic
pregnancies are located within the fallopian tube, 2% are interstitial, 2% are
ovarian and the remainder are cervical or abdominal. Concomitant intrauterine
plus ectopic pregnancy (heterotopic) can occur, but it is extremely rare.
In 1992 the CDC reported the incidence of ectopic pregnancy to be
approximately 2%, a 6-fold increase over the previous 25 years. Heterotopic
implantation is rare in spontaneous pregnancy (1 in 10,000 -50,000) but more
common in women undergoing assisted reproductive technologies (0.3-1%).
Risk factors for ectopic pregnancy include a history of:
previous tubal surgery
previous ectopic pregnancy
in utero DES exposure
history of pelvic inflammatory disease
history of infertility
history of chlamydia or gonococcal cervicitis
current or past history of use of an intrauterine device
tobacco smoking either past or current
previous spontaneous or induced abortion
age 40 years and older
The diagnosis of ectopic pregnancy should be considered in any fertile woman
presenting with any of the following and a positive pregnancy test:
pelvic or lower abdominal pain
abnormal vaginal bleeding
evidence of hemodynamic instability
Patients may have any one or combination of the above. If rupture has occurred,
the symptoms will probably be more severe.
Diagnosis is made by history and physical exam in conjunction with one or serial
serum beta-HCGs and a pelvic ultrasound. The combined approach of
measurement of beta-HCG and transvaginal ultrasound detects ectopic
pregnancy with 97% sensitivity and 95% specificity, avoiding the need for further
invasive tests, such as a dilatation and curettage. Vaginal sonography is highly
accurate. If not available, transabdominal ultrasound can be done. In the
absence of obvious signs of an ectopic pregnancy, an intrauterine gestation is
usually visible on transvaginal scan at a beta-HCG concentration of 2000 IU/L. If
only transabdominal ultrasound is available, the discriminatory zone of beta-HCG
is 6500 IU/LK. In the case of multiple pregnancies, beta-HCG concentrations will
be greater than 2000 IU/L before the intrauterine gestation sacs are visible on
The diagnosis can be excluded if a pelvic ultrasound confirms the presence of an
intrauterine pregnancy (except in rare cases of heterotopic pregnancy), or if
products of conception from a spontaneous abortion or uterine curettage
examined by a pathologist confirm the presence of placental or fetal tissue.
When no intrauterine pregnancy (IUP) is visualized on ultrasound, the differential
diagnosis includes a pregnancy that is too early to be seen, a spontaneous
abortion, an abnormal intrauterine pregnancy, or an ectopic pregnancy.
Diagnosis is suggestive when ultrasonic findings include a complex adnexal
mass, fluid in the cul-de-sac, or fluid in the cul-de-sac with a cystic adnexal mass.
A small amount of fluid can be seen in both normal and abnormal pregnancies,
but the presence of a large amount of fluid or complex fluid is more consistent
with an ectopic pregnancy. Diagnosis of ectopic pregnancy is also suggested
when histological examination of the tissue from a dilatation and curettage
reveals no products of conception with a rising beta-HCG.
Problems that can complicate the diagnosis include recent elective abortion that
may have missed an ectopic pregnancy, patient report of passage of tissue that
is not products of conception, and intermittent symptoms.
As noted above, heterotopic pregnancy is extremely rare, but more common in
women undergoing assisted reproductive technologies. The following are signs
of heterotopic pregnancy:
ultrasound shows uterine and ectopic gestations
clinically suspicion of ectopic pregnancy without vaginal bleeding
rising or persistent hCG levels following D&C for abortion (induced or
uterine size is larger than expected for the gestational age
Patients must undergo a physical examination. Any signs of hemodynamic
instability or acute abdomen must be treated immediately and will probably
require surgical intervention.
A serum beta-HCG is useful to determine the possibility of seeing the pregnancy
on ultrasound. A normal intrauterine pregnancy should be accompanied by a
beta-HCG that doubles every 48 hours, through approximately the 5th week of
A low serum progesterone is indicative of an abnormal pregnancy, but cannot
distinguish between an ectopic or abnormal IUP. A pelvic ultrasound should be
Type & Rh: If an Rh(-) patient turns out to be pregnant and is bleeding or has an
ectopic, RhIG should be given (see Section 4B RhAb Screening, page 10.00).
A complete blood count with platelets should be obtained. If considering
treatment with methotrexate, baseline LFTs can be obtained.
Other conditions should be considered in patients who are pregnant where an
accurate ultrasound has ruled out ectopic.
The patient may have a ruptured corpus luteum with ultrasound possibly showing
a cyst and intraperitoneal blood along with an intrauterine pregnancy. As many
as half of these patients may require surgery for bleeding control. (3) Discuss with
an OB consultant.
Other conditions include adnexal torsion and appendicitis – see Section 6B
Appendicitis in Pregnancy, page 56.00.
Patients with evidence of tubal rupture or hemodynamic instability must be
treated immediately and often require surgical intervention. The type of surgery
performed will depend upon the individual situation and the desires of the patient.
Patients who are hemodynamically stable with an unclear clinical picture may be
followed closely as an outpatient until a sure diagnosis can be made. They may
require serial beta-HCGs and follow up ultrasounds.
Once a diagnosis of ectopic pregnancy is made, treatment can either be surgical
or medical. This decision should be based on the individual's situation and
desires. Surgical management consists of laparoscopy or laparotomy depending
on the clinical situation, future fertility desires of the patient, and availability of
OR. Surgical decisions include salpingectomy versus salpingostomy. Medical
management consists of methotrexate use. The administration of methotrexate
is dependent upon the size of the ectopic mass, desire for future fertility, ability of
the patient to follow up, and hemodynamic stability.(1) If there is a question about
the patient's ability to follow up (e.g., poor compliance pattern, geographical
limitations), the laparoscopic approach may be safer.
ACOG has outlined absolute and relative indications and contraindications to
receiving methotrexate in their Practice Bulletin form 1998.
Absolute Indications Include:
patient desires future fertility
general anesthesia poses a significant risk
patient is able to return for follow up care
patient has no contraindications to methotrexate
Relative Indications Include:
unruptured mass to 3.5cm at its greatest dimension
no fetal cardiac motion seen
patients whose beta-HCG level does not exceed a predetermined value
(6,000 to 15,000 mIU/mL)
Absolute Contraindications Include:
overt or laboratory evidence of immunodeficiency
alcoholism, alcoholic liver disease, or other chronic liver disease
preexisting blood dyscrasias
known sensitivity to methotrexate
active pulmonary disease
peptic ulcer disease
hepatic, renal, or hematologic dysfunction
Relative Contraindications Include:
gestational sac to 3.5cm
embryonic cardiac motion
Patients receiving methotrexate should receive close follow up and serial beta-
HCGs. These patients should be counseled to avoid folic acid supplements,
sexual intercourse, and alcohol while receiving treatment. Some early
unruptured ectopic pregnancies have been seen to resolve spontaneously
without treatment. The best candidates for expectant management have beta-
HCGs less than 2000IU/L upon initial presentation. These patients need close
follow up with serial beta-HCGs and ultrasounds.
The chance on having a normal live-born infant with a subsequent pregnancy is
85%. After 2 ectopic pregnancies, the risk of having a 3rd ectopic pregnancy is
Distribute the pink patient education sheet 6B(1) Abdominal Pain in Pregnancy
and 6B(5) Ectopic Pregnancy to anyone being sent home for outpatient follow up.
Risks to Mother
The most immediate risk is shock and death. Ectopic pregnancies are the
leading cause of pregnancy-related death during the 1st trimester. There is
increased risk for future fertility problems and recurrent ectopics.
Risks to Fetus
The risks include nonviability.
If the diagnosis is made, add to area 31 of the Flow Sheet: tubal ectopic
1. The American College of Obstetricians and Gynecologists: Medical management of tubal
pregnancy. ACOG Practice Bulletin. Number 3, (ACOG, 409 12 St., SW, PO Box 96920,
Washington, DC 20090-6920), December 1998.
2. Seeber BE, Barnhart KT: Suspected ectopic pregnancy. Obstet Gynecol, 107:399-413,
3. Murray H, Baakdah H, Bardell T, Tulandi T: Diagnosis and treatment of ectopic pregnancy.
CMAJ, 173:905-912, 2005.
4. Farquhar CM: Ectopic pregnancy. Lancet; 366:583-591, 2005.