Ectopic Pregnancy - ClinicalKey

1/14/2021 Ectopic pregnancy- ClinicalKey
CLINICAL OVERVIEW
Ectopic pregnancy
Elsevier Point of Care (see details)
Updated March 4, 2020. Copyright Elsevier BV. All rights reserved.
Synopsis Urgent Action

Key Points Patients may present with
Ectopic pregnancy occurs when a fertilized ovum implants hemorrhagic shock when there is
in a site other than the endometrial lining of the uterus, a ruptured ectopic pregnancy;
usually in the fallopian tubes resuscitation should begin
immediately with IV volume
Previous ectopic pregnancy, pelvic infection, history of replacement, supplementation of
infertility treatment, and/or history of tubal surgery oxygen if hypoxemic, and
increase risk; however, most women who experience an replacement of packed RBCs
ectopic pregnancy do not report any risk factor 1
In hemodynamically unstable
Consider ectopic pregnancy in any woman of reproductive patients with an ectopic
age presenting with vaginal bleeding and/or missed menses, pregnancy, immediate surgery
pelvic or abdominal pain, or unexplained syncope or shock either by laparoscopy or
regardless of history and examination findings; however, laparotomy is indicated 4
symptoms may be absent until rupture occurs
Transvaginal ultrasonography and serum hCG measurements are the primary diagnostic tools for
excluding viable intrauterine pregnancy 2
If hCG level is above discriminatory threshold with an indeterminate sonogram, an abnormal

pregnancy is implied, but it may be either a failed intrauterine pregnancy or an ectopic pregnancy.
Serial hCG levels can confirm an abnormal gestation if rate of rise is less than 53% every 2 days 3
Hemodynamically stable patients without suspicion for rupture can be managed in 1 of 3 ways,
depending on the situation: expectantly, medically, or surgically 2
For appropriate patients, intramuscular methotrexate has a success rate comparable to

laparoscopic salpingostomy with similar future pregnancy outcomes 4
Tubal pregnancies may be managed by either salpingectomy or salpingostomy 4
Emergency surgery is indicated for ruptured ectopic pregnancy, especially in a hemodynamically

unstable patient 2
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Pitfalls
Ectopic pregnancy may be symptomatic as early as 4 to 5 weeks of gestational age; however,
misdiagnosis may occur such as with:
Unrecognized pregnancy
Atypical pain pattern
Benign examination
Failure to consider the diagnosis (particularly with prior tubal surgery, including tubal ligation
for pregnancy prevention
In some patients with an ectopic pregnancy, ultrasonography findings will be normal or

indeterminate initially, without evidence of intrauterine or extrauterine pregnancy
Do not use a single quantitative hCG value to exclude diagnosis of ectopic pregnancy in patients
with indeterminate ultrasonography results 5
Consider acute rupture in differential diagnosis of patients with known ectopic pregnancy
undergoing treatment with methotrexate who return with increasing pain or a physical
examination consistent with hemoperitoneum 6
Methotrexate treatment results in serious and avoidable toxicity to the embryo if a viable
pregnancy is misdiagnosed as an ectopic pregnancy 3
Terminology
Clinical Clarification
Ectopic pregnancy is defined by implantation of a fertilized ovum at a site other than the
endometrial lining of the uterus
Classification
Based on location
Fallopian tube
95% of ectopic pregnancies 7
Most commonly in the ampullary region
May occur in interstitial region (portion of fallopian tube that traverses the myometrium
before ending in uterine cavity); this is sometimes erroneously described as being in cornua of
uterus
Ovary
3.2% of ectopic pregnancies 7
Abdomen
1.3% of ectopic pregnancies 7
Uterine cervix
Very rare 7
Intramural (within uterine wall)
Extremely rare
Occurs when there is implantation within the myometrium
May occur within a cesarean delivery scar
Heterotopic
Occurs when there are simultaneous intrauterine and ectopic pregnancies
Approximately 1% of pregnancies resulting from assisted reproduction are heterotopic 3
Diagnosis
Clinical Presentation
History
Consider ectopic pregnancy in any female of reproductive age who reports vaginal bleeding, a
missed menstrual period, abdominal pain, or pelvic pain
Previous ectopic pregnancy, pelvic infection, history of infertility treatment, and/or history of tubal
surgery increase risk, but most women with the diagnosis do not report any risk factor 1
Pregnancy symptoms such as nausea, breast tenderness, or weight gain usually are not yet present
at the time of ectopic pregnancy presentation
General symptoms
Vaginal spotting or bleeding
Pain
Before 6 weeks of gestation, may be absent or vague
May be crampy or steady, unilateral or bilateral
Abdominal pain during cough (when associated with tenderness to light touch on physical
examination) has a positive likelihood ratio of about 4 8
Pain specifically due to rupture
Usually occurs at 6 to 10 weeks of gestation, with pain typically unilateral, severe, and
persistent
Referred to the shoulder or flank with hemoperitoneum
Lightheadedness and/or syncope may occur
Symptoms associated with specific implantation site
Ovarian/tubal pregnancy
Abdominal pain is most common symptom
Abdominal pregnancy
Nausea and vomiting may be prominent symptoms
Vaginal bleeding is less frequent than in tubal ectopic pregnancies
Some women present with syncope due to shock from placental separation or rupture of
maternal blood vessels or viscera
Rarely, presents with symptoms of bowel obstruction
Cervical pregnancy
Lower abdominal pain or cramps may or may not be present
Pain without bleeding is rare
Intramural pregnancy (including pregnancy occurring within a cesarean delivery scar)
Clinical presentation ranges from vaginal bleeding with or without pain to uterine rupture and
hypovolemic shock
Physical examination
Distressed appearance due to pain
Pallor may be present with significant blood loss
Hypotension or orthostatic hypotension with tachycardia may be signs of impending shock

associated with rupture
Abdominal tenderness is present in most patients
Signs of peritoneal irritation (eg, guarding, rebound pain, hypoactive bowel sounds) are commonly
associated with hemoperitoneum
Vaginal bleeding is often observed, but there is no visible tissue extruded into the vagina
On bimanual examination, adnexal tenderness and a palpable adnexal mass may be present or
absent 8
Cervical motion tenderness is highly suggestive 8
Cervical os may be open or closed
Causes and Risk Factors

Causes
Anatomic blockage or altered motility of reproductive tract prevents ovum from implanting in
uterine cavity
Risk factors and/or associations

Age
May occur in any sexually active female of reproductive age
Risk increases with advancing maternal age 1
Ethnicity/race
In the United States, nonwhite women have a higher incidence 2
Other risk factors/associations

Intrauterine device (both copper and progestogen-releasing)
Progestin-only oral contraception
Infertility treatment (ie, pharmacologic ovulation induction, in vitro fertilization) 1
History of:
Ectopic pregnancy 1
Infertility
Tubal sterilization procedures and previous tubal surgeries, which can cause damage to fallopian
tubes 1
Endometriosis, which can cause disruption and scarring of pelvic anatomy
Pelvic inflammatory disease with fallopian tube involvement
First sexual intercourse at an early age
Multiple sexual partners
Smoking 7
Exposure to diethylstilbestrol in utero
Diagnostic Procedures
Primary diagnostic tools
History and physical examination lack specificity; diagnosis requires a positive pregnancy test
result with ancillary diagnostic testing including transvaginal ultrasonography and quantitative
hCG 2
Ectopic pregnancy may be symptomatic as early as 4 to 5 weeks of gestational age, but many
cases are misdiagnosed because of unrecognized pregnancy, atypical pain, benign examination,
or failure to consider the diagnosis; failure to consider pregnancy in a patient with prior tubal
ligation is a concern
First, perform a urine or serum pregnancy test (qualitative hCG) on any woman of
reproductive age presenting with pain (abdominal or pelvic) or vaginal bleeding to confirm
pregnancy 2
For patients with a positive pregnancy test result, perform transvaginal ultrasonography. The
primary purpose of imaging is to identify intrauterine pregnancy, as many ectopic pregnancies
will not be visualized at presentation 5
Imaging results will place the patient into 1 of 4 categories:
Intrauterine pregnancy: if seen, an ectopic pregnancy is essentially ruled out
However, heterotopic pregnancy (ectopic pregnancy coexisting with an intrauterine

pregnancy) is still a remote possibility (extremely rare in natural conceptions but occurs
in 1% of in vitro fertilizations) 3
Definite ectopic pregnancy: a gestational sac, fetal pole, or beating heart is seen in an
ectopic location; these definitive ultrasonographic findings are present in a minority of
patients at presentation
Suggestive of ectopic pregnancy: other sonographic findings (eg, cul-de-sac fluid collection,
adnexal mass) suggest diagnosis, but definitive sonographic findings are absent
Indeterminate: transvaginal sonogram is negative for intrauterine pregnancy and does not
suggest ectopic pregnancy
For patients with a positive pregnancy test result and indeterminate transvaginal sonogram,
obtain baseline quantitative hCG; follow with serial measurements in a stable patient who can
be observed on an outpatient basis 2
Discriminatory threshold (usually 1500-2000 mIU/mL) is the level at which an intrauterine

gestational sac should be visible with transvaginal ultrasonography 2
If the hCG level is above the discriminatory threshold with an indeterminate sonogram, an
abnormal pregnancy is implied, but it may be either a failed intrauterine pregnancy or an
ectopic pregnancy. Serial hCG levels can confirm an abnormal gestation if rate of rise is less
than 53% every 2 days 3
Do not use a single quantitative hCG value to exclude diagnosis of ectopic pregnancy in
patients with indeterminate ultrasonography results 5
Progesterone level measurement is occasionally used as a diagnostic aid, although not common;
level less than 5 ng/mL is associated with higher probability of abnormal pregnancy 2
If pregnancy is clearly abnormal based on pattern of serial hCG results, but its location
(intrauterine versus ectopic) cannot be determined by repeated transvaginal sonography:
Laparoscopic visualization of uterine adnexa is considered the gold standard in investigating

ectopic pregnancy. 7 It is not routine, but is helpful when there is diagnostic uncertainty after
other testing and in all patients with hemodynamic instability
Dilation and curettage may be performed; if products of conception are revealed, this
confirms intrauterine pregnancy and nearly eliminates possibility of ectopic pregnancy
(except in patients undergoing assisted reproduction techniques) 2
If no chorionic villi are visualized in removed tissue, intrauterine pregnancy is not present
(93% accurate) 2
Routine laboratory tests for all patients include CBC, comprehensive metabolic panel, and type
and screen (with crossmatch for suspected rupture with large-volume blood loss)
Laboratory
Qualitative hCG
Urine
Done in women of reproductive age presenting with vaginal bleeding, hypotension,

abdominal pain, or syncope
Test result is nearly always positive by the time patient presents with acutely ruptured
ectopic pregnancy
False-negative result may be produced by testing very dilute urine
Serum
May be done as an alternative to a urine pregnancy test
Quantitative hCG
Measure in all patients with history or symptoms suggestive of ectopic pregnancy
There is no specific hCG level associated with ectopic versus intrauterine pregnancy 5
Used diagnostically to determine if discriminatory threshold has been reached, and to

identify a normal versus abnormal rate of rise
Discriminatory threshold
In a normal pregnancy, a level of 1500 to 2000 mIU/mL causes gestational sac to

become visible via transvaginal ultrasonography 2
Rate of rise
In a stable patient, serial measurements to assess rate of rise may be necessary if there is
a positive pregnancy test result but gestational sac is not visualized with ultrasonography
2
Minimum rise in hCG for a viable intrauterine pregnancy is 53% over 48 hours (occurs
in 99% of viable pregnancies) 9
If gestation is abnormal, most patients will show less than 53% increase after 48 hours
2
Also used to guide therapy in patients being treated medically with methotrexate 2
Do not use a single quantitative hCG value to exclude diagnosis of ectopic pregnancy in
patients with indeterminate ultrasonography results 5
Progesterone 2
Occasionally used as alternative or additional diagnostic aid, although not common
Level less than 5 ng/mL is associated with higher probability of abnormal pregnancy
Levels in normal intrauterine pregnancies are 10 ng/mL or above
Hematology
Measure baseline hematocrit for all patients, and serially for hemodynamically unstable
patients
CBC is recommended before beginning methotrexate therapy 3
Chemistry
Measuring electrolyte, serum creatinine, and hepatic transaminase levels in all

hemodynamically unstable patients and before beginning methotrexate therapy is
recommended 6
Blood bank
Recommended before medical and surgical treatment
Type and screen, including Rh antigen 3
Type and crossmatch for patients with large-volume blood loss
Imaging
Transvaginal ultrasonography
Obtained for symptomatic pregnant patients
Discriminatory threshold for visualization of gestational sac in a normal intrauterine

pregnancy is between 1500 and 2000 mIU/mL (usually occurs by gestational age 5.5
weeks) 2 3
Threshold varies institutionally and by operator; may also vary depending on which
ultrasonographic criteria are used to define intrauterine pregnancy 5
Considered the single best diagnostic modality for suspected ectopic pregnancy in a
hemodynamically stable patient 8
Ultrasonogram findings place patients into the following categories of suspicion for ectopic
pregnancy when intrauterine pregnancy is not seen: 10
Definite
Ectopic gestational sac
Ectopic fetal pole
Ectopic fetal heart activity
Highly suspicious
Moderate or large amount of fluid in the cul-de-sac without intrauterine pregnancy
Adnexal mass (may be cystic or complex, but a complex mass is more suggestive)
Indeterminate scan
No intrauterine or extrauterine pregnancy is seen with a quantitative pregnancy test

result higher than the discriminatory level
In some patients with an ectopic pregnancy, ultrasonography findings will be normal or

indeterminate initially, without evidence of intrauterine or extrauterine pregnancy
Differential Diagnosis
Most common
Conditions that may occur in

the setting of a positive Threatened or incomplete abortion
pregnancy test Symptoms include profuse vaginal bleeding and uterine
cramping
Products of conception may be passed or seen in cervical os or

vagina during physical examination; may also be seen in
uterine cavity on transvaginal ultrasonography
Consider heterotopic pregnancy and use transvaginal

ultrasonography to evaluate for concomitant intrauterine and
ectopic pregnancy
Ruptured corpus luteal cyst
Symptoms initially include dull ache or sharp pain in lower

abdomen, lower back pain, and discomfort during sexual
intercourse
Acute pain may indicate ruptured cyst with hemoperitoneum
Transvaginal ultrasonography may be diagnostic, but

laparoscopy or laparotomy may be required for diagnosis and
to maintain hemostasis in severe cases
Ovarian cyst torsion
Symptoms include abrupt onset of moderate to severe pelvic

pain, which is usually unilateral unless there is associated
peritonitis
Associated nausea and vomiting may be present
Ultrasonography with Doppler or CT is diagnostic
Pelvic inflammatory disease
Infection is most commonly chlamydial or gonococcal
May result in salpingitis, salpingo-oophoritis, tubo-ovarian

abscess, or pelvic peritonitis
Symptoms include lower abdominal pain, vaginal spotting,

and adnexal and cervical motion tenderness on physical
examination, which can be confused with ectopic pregnancy
when pregnancy test result is positive
Differentiating features include fever and purulent

cervicovaginal discharge
Acute appendicitis (Related: Appendicitis)
Symptoms/signs include periumbilical pain (which later

migrates to right lower quadrant), anorexia, rebound
abdominal tenderness, and sometimes fever
Nausea, vomiting, and diarrhea may also occur
Leukocyte count is commonly elevated
Transvaginal ultrasonography can be used to identify

intrauterine pregnancy and may reveal thickening of appendix
wall
Additional diagnostic imaging may be helpful; laparotomy or

laparoscopy may be required for definitive diagnosis
Treatment
Goals
Provide relief of symptoms
Prevent serious morbidity or death
Preserve future fertility
Disposition
Admission criteria
Patients with suspected ruptured ectopic pregnancy
Patients with hemodynamic instability should be taken to surgery for immediate diagnostic
laparoscopy or laparotomy
Criteria for ICU admission

Postoperative hemodynamic instability
Recommendations for specialist referral

All patients with an ectopic pregnancy, including those managed expectantly or with medical
management, should be evaluated by an obstetrician/gynecologist before discharge from the
emergency department and should have timely outpatient obstetrician/gynecologist follow-up
arranged
Treatment Options
Management of tubal ectopic pregnancy
Unruptured
Hemodynamically stable patients without suspicion for rupture can be managed in 1 of 3 ways,
depending on the situation: expectantly, medically, or surgically 2
Expectant management
No medical intervention, but close follow-up as outpatient
Not a preferred plan of management, but some ectopic pregnancies may resolve without
treatment 2
Usually reserved for asymptomatic women with hCG titers that plateau but do not rise 2
Overall success rate of 69% has been reported for expectant management; the lower the
initial hCG level, the greater the success with spontaneous resolution 2
Medical management
For appropriate patients, intramuscular methotrexate has success rate comparable to

laparoscopic salpingostomy with similar future pregnancy outcomes 4
Recommended for patients meeting the following criteria:
Sonographically confirmed (or high clinical suspicion of) ectopic pregnancy 2
Hemodynamically stable 3
Minimal symptoms with no persistent or severe abdominal pain 3
Pretreatment serum hCG concentration levels less than 5000 mIU/mL (likely to fail if
level is higher) 4
Gestational sac less than 4 cm 2
No fetal cardiac activity on ultrasonographic examination (likely to fail if activity is seen) 3
Low volume of free intraperitoneal fluid on ultrasonography 7
No medical contraindications to methotrexate, including:
Clinically important abnormalities in baseline hematologic, renal, or hepatic laboratory

values
Immunodeficiency, active pulmonary disease, or peptic ulcer disease
Alcohol use disorder or chronic liver disease
Current breastfeeding
Hypersensitivity to methotrexate
Understands and is willing to comply with treatment regimen and posttreatment

monitoring until ectopic pregnancy is resolved 3
Requires multiple follow-up visits; complete resolution of ectopic pregnancy usually

takes between 2 and 3 weeks, but can take 6 to 8 weeks if pretreatment hCG levels are
in higher ranges 3
Must understand that surgical treatment is required if signs of treatment failure or

impending rupture are present (ie, pain increases or hCG does not decrease by
appropriate amount) 3
2 commonly used protocols: single dose or 2 doses
Outcomes are comparable (83% success for single-dose regimen versus 79% for 2-dose
regimen); single dose may be preferable for simplicity 11
Methotrexate may be administered to appropriate patients in the emergency department

after consultation with obstetrician/gynecologist if appropriate follow-up as an outpatient
is assured 6
Single-dose regimen
When describing this method to patients, single-dose regimen may be misleading

because additional doses are required in a minority of patients started on this protocol
Administer methotrexate intramuscularly on day 0 2 11
Measure serum hCG level on days 4 and 7
If level falls by 15% or more between days 4 and 7, continue to measure hCG on
weekly basis until it returns to baseline (nonpregnant) level
If level falls by less than 15% between days 4 and 7 after first dose, this is considered
treatment failure. Give a second dose of methotrexate and repeat hCG level on days 4
and 7 after second dose. If the level falls by less than 15%, give a third dose
2-dose protocol
Administer methotrexate intramuscularly on days 0 and 4 11
Measure serum hCG level on days 4 and 7
If hCG does not decline at least 15% between days 4 and 7, a third dose of
methotrexate is administered
Patients who receive a third dose of methotrexate return on day 11 for another hCG
measurement
If hCG level decreases by at least 15% between days 7 and 11, weekly hCG
measurements are performed until a negative result is obtained; otherwise, a fourth
dose of methotrexate is administered, and another hCG level is obtained on day 14
If there is at least a 15% decrease between days 11 and 14, weekly hCG measurements
are performed until a negative result is obtained; if at least a 15% decrease does not
occur, the patient is referred for surgical management
Surgical management 12
Recommended when: 2
There are symptoms of impending ectopic mass rupture (ie, severe or persistent
abdominal pain)
There is a coexistent viable intrauterine pregnancy (heterotopic pregnancy)
Methotrexate treatment is unlikely to be successful (ie, gestational sac larger than 4 cm)
Patient is unable or unwilling to adhere to methotrexate therapy and follow-up or there

are medical contraindications to methotrexate
Tubal pregnancies may be managed by either salpingectomy or salpingostomy (conserving

fallopian tube and removing trophoblast only)
Salpingostomy is often preferred because preservation of both tubes may offer increased
future fertility 13
A 2014 meta-analysis questions this preference; it found that in women with a healthy
contralateral tube, salpingostomy does not significantly improve fertility prospects
compared with salpingectomy 13
Persistent trophoblast occurs more frequently with salpingostomy 14
Risk of future ectopic pregnancy is similar for both types of treatment 13
Ruptured
Patients may present with hemorrhagic shock when there is a ruptured ectopic pregnancy;
resuscitation should begin immediately with IV volume replacement, oxygen supplementation if
hypoxemic, and packed RBC replacement
Emergency surgery is indicated for ruptured ectopic pregnancy, especially in a hemodynamically

unstable patient 2 12
Surgical procedures
For tubal ectopic pregnancy, salpingostomy or salpingectomy may be carried out by either
laparoscopy or laparotomy 4
Laparoscopic surgery is the most effective treatment in most patients with ruptured tubal
ectopic pregnancy 14
Especially after salpingostomy, postoperative serum hCG monitoring should be done

for the early detection of residual trophoblastic tissue after laparoscopic salpingectomy
Methotrexate can be administered if hCG does not return to undetectable level
Laparotomy may be preferred for unstable, volume-depleted patients
Management of ectopic pregnancy in nontubal locations
Surgery is the primary treatment for most 15
Methotrexate or cervical artery embolization are sometimes used for cervical pregnancies 3
There have been reports of successful nonsurgical management of pregnancies that occur within
a cesarean-delivery scar using local (injected) or systemic administration of methotrexate with
dilation and curettage 3
Administer Rh₀(D) immune globulin to Rh-negative women
United States guidelines (American College of Obstetricians and Gynecologists) recommend use of
Rh₀(D)-immunoglobulin therapy for all cases of ectopic pregnancy in Rh-negative women,
regardless of treatment provided (ie, surgical or medical) 16
United Kingdom guidelines recommend Rh₀(D) immunoglobulin therapy only for Rh-negative
women undergoing a surgical treatment for ectopic pregnancy 17
Drug therapy
Rh isoimmunization prophylaxis (United States standard)
Rh₀(D) immunoglobulin 3 16
Rh-negative women with ectopic pregnancy occuring at or before 12 weeks of gestation

(HyperRHO S/D Mini-Dose dose and MICRhoGAM only)
Rho(D) Immune Globulin (Human) Solution for injection; Adult and adolescent females: 50
mcg (250 international units) IM as soon as possible. Give within 3 hours of spontaneous or
surgical removal of aborted tissues, if possible, and within 72 hours of exposure.
Rh-negative women with ectopic pregnancy occuring at or after 13 weeks of gestation

(HyperRHO S/D Full dose and RhoGAM only)
Rho(D) Immune Globulin (Human) Solution for injection; Adult and adolescent females:
300 mcg (1500 international units) IM as soon as possible and within 72 hours of the
event.Rho(D) Immune Globulin (Human) Solution for injection; Adult and adolescent
females: 300 mcg (1500 international units) IM as soon as possible and within 72 hours of
the event.
Dihydrofolate reductase inhibitor
Methotrexate 12
Methotrexate treatment results in serious and avoidable toxicity to the embryo if a viable
pregnancy is misdiagnosed as an ectopic pregnancy 3
Single-dose regimen
Methotrexate Sodium Solution for injection; Adult Females: 50 mg/m2 IM as a single dose
on day 1. Measure hCG level on posttreatment day 4 and 7. If hCG decreases by 15% or more
between days 4 and 7, measure hCG weekly until at nonpregnant level. If hCG decreases by
less than 15% between days 4 and 7, give a repeat dose of 50 mg/m2 IM and repeat hCG
levels. If hCG does not decrease after 2 doses, consider surgical management. Refer to
published guidelines for proper patient selection and clinical management.Methotrexate
Sodium Solution for injection; Adult Females: 50 mg/m2 IM as a single dose on day 1.
Measure hCG level on posttreatment day 4 and 7. If hCG decreases by 15% or more between
days 4 and 7, measure hCG weekly until at nonpregnant level. If hCG decreases by less than
15% between days 4 and 7, give a repeat dose of 50 mg/m2 IM and repeat hCG levels. If hCG
does not decrease after 2 doses, consider surgical management. Refer to published
guidelines for proper patient selection and clinical management.
Two-dose regimen
Methotrexate Sodium Solution for injection; Adult Females: Give 50 mg/m2 IM on day 1.
Give a second dose of 50 mg/m2 IM on day 4 and measure the hCG level. On day 7, repeat
the hCG level. If hCG decreases by 15% or more between days 4 and 7, continue to measure
hCG weekly until at nonpregnant level. If the decrease in hCG between days 4 and 7 is less
than 15%, give another dose of methotrexate 50 mg/m2 IM on day 7 and recheck hCG on
day 11. If hCG decreases by 15% or more between days 7 and 11, continue to monitor hCG
weekly until at nonpregnant level. If hCG decreases by less than 15% between days 7 and 11,
give another dose of methotrexate 50 mg/m2 IM on day 11 and measure hCG on day 14. If
hCG does not decrease after 4 doses, consider surgical management. Refer to published
guidelines for proper patient selection and management; data suggest hCG level resolution
is significantly faster in patients successfully treated with this 2-dose regimen vs. the single-
dose regimen.Methotrexate Sodium Solution for injection; Adult Females: Give 50 mg/m2
IM on day 1. Give a second dose of 50 mg/m2 IM on day 4 and measure the hCG level. On
day 7, repeat the hCG level. If hCG decreases by 15% or more between days 4 and 7, continue
to measure hCG weekly until at nonpregnant level. If the decrease in hCG between days 4
and 7 is less than 15%, give another dose of methotrexate 50 mg/m2 IM on day 7 and
recheck hCG on day 11. If hCG decreases by 15% or more between days 7 and 11, continue to
monitor hCG weekly until at nonpregnant level. If hCG decreases by less than 15% between
days 7 and 11, give another dose of methotrexate 50 mg/m2 IM on day 11 and measure hCG
on day 14. If hCG does not decrease after 4 doses, consider surgical management. Refer to
published guidelines for proper patient selection and management; data suggest hCG level
resolution is significantly faster in patients successfully treated with this 2-dose regimen vs.
the single-dose regimen.
Monitoring
For patients managed expectantly:
Serially monitor serum hCG until level is undetectable (American Congress of Obstetricians and
Gynecologists does not recommend a specific monitoring schedule 1 )
Typical monitoring schedule is every 2 days for 2 to 3 weeks to ensure downward trend; may
then monitor at longer intervals until serum level of hCG is immeasurable
For patients managed medically with methotrexate:
Extended follow-up for several weeks after therapy is needed 2
Monitor serum hCG level at day 4 and day 7 after methotrexate
If the level does not fall by at least 15% between days 4 and 7, an additional dose of
methotrexate may be required, with further follow-up of hCG level as described
If after 3 doses of methotrexate hCG levels do not fall by 15% weekly, surgical management is
indicated
Complications and Prognosis

Complications
Acute complications due to ruptured ectopic pregnancy
Especially consider acute rupture in the differential diagnosis of patients with known ectopic
pregnancy undergoing treatment with methotrexate who return with increasing pain or physical
examination findings consistent with hemoperitoneum 6
Hemorrhage requiring transfusion
Hemorrhagic shock
Disseminated intravascular coagulation
Death
Persistent ectopic pregnancy (persistent trophoblast)
Complete resolution of an ectopic pregnancy usually takes between 2 and 3 weeks but can take
up to 6 to 8 weeks when pretreatment hCG levels are in higher ranges
Declining hCG level that rises again is diagnostic of persistent ectopic pregnancy
Secondary infertility due to loss of reproductive organs or scarring
Increased risk of recurrent ectopic pregnancy
Risk varies with location of pregnancy and with treatment method
Prognosis
In patients who receive appropriate and timely treatment before rupture, prognosis is good
Some ectopic pregnancies spontaneously resolve without treatment, although difficult to predict
Closely monitor those patients who meet criteria for expectant management
Overall, case fatality rate is 3.8 deaths per 10,000 ectopic pregnancies 18
Interstitial (cornual) pregnancies are highly morbid, with 2.2% maternal mortality 3
Reproductive potential of patients who have had an ectopic pregnancy may be compromised
Surgical treatment: cumulative pregnancy rate of 60.7% after salpingostomy and 56.2% after
salpingectomy with higher rate of persistent trophoblast with salpingostomy 13
2007 Cochrane review found no significant difference in long-term pregnancy rate or recurrent
ectopic pregnancy rate when comparing laparoscopic salpingostomy with medical treatment 4
Screening and Prevention

Screening
At-risk populations
At time of pregnancy recognition or confirmation, women at higher risk for ectopic pregnancy
should be carefully evaluated to assure that pregnancy is intrauterine:
History of ectopic pregnancy
History of tubal surgery, including sterilization procedures
Pregnancy occuring despite having an intrauterine device
Women undergoing infertility treatment
Screening tests
Begin evaluation with first missed menses
Transvaginal ultrasonography to visualize extrauterine gestation
Serial quantitative serum hCG levels if ultrasonography results are nondiagnostic
Prevention
Safer sex practices to decrease risk of sexually transmitted infections, which can result in pelvic
inflammatory disease and fallopian tube scarring
Early diagnosis and treatment of sexually transmitted infections
American College of Obstetricians and Gynecologists states that use of an intrauterine device does
not increase the absolute risk of ectopic pregnancy; however, if pregnancy does occur with an
intrauterine device in place, it is more likely to be ectopic 19
Counsel patients on this risk when considering an intrauterine device
Inform women about higher risk of ectopic pregnancy before any procedure involving the fallopian
tubes, including tubal ligation
REFERENCES
1: American Congress of Obstetricians and Gynecologists: Early Pregnancy Complications. In:

Guidelines for Women's Health Care. 4th Ed. American College of Obstetricians and Gynecologists;
2014
2: Kho RM et al: Ectopic pregnancy In: Lobo RA et al, eds: Comprehensive Gynecology. 7th ed.
Philadelphia, PA: Elsevier; 2017:348-69.e3
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3: Practice Committee of American Society for Reproductive Medicine: Medical treatment of ectopic
pregnancy: a committee opinion. Fertil Steril. 100(3):638-44, 2013
| Cross Reference (https://pubmed.ncbi.nlm.nih.gov/23849842)
4: Hajenius PJ et al: Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev.
2:CD000324, 2007
5: American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee)

on Early Pregnancy et al: Clinical policy: critical issues in the initial evaluation and management of
patients presenting to the emergency department in early pregnancy. Ann Emerg Med. 69(2):241-
50.e20, 2017
6: Hahn SA et al: Clinical policy: critical issues in the initial evaluation and management of patients
presenting to the emergency department in early pregnancy. Ann Emerg Med. 60(3):381-90.e28,
2012
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Reprod. 17(12):3224-30, 2002
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Ectopic Pregnancy - ClinicalKey

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Ectopic Pregnancy - ClinicalKey

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1/14/2021 Ectopic pregnancy- ClinicalKey

Synopsis Urgent Action

If hCG level is above discriminatory threshold with an indeterminate sonogram, an abnormal

For appropriate patients, intramuscular methotrexate has a success rate comparable to

Tubal pregnancies may be managed by either salpingectomy or salpingostomy 4

Emergency surgery is indicated for ruptured ectopic pregnancy, especially in a hemodynamically

Atypical pain pattern

In some patients with an ectopic pregnancy, ultrasonography findings will be normal or

95% of ectopic pregnancies 7

Most commonly in the ampullary region

3.2% of ectopic pregnancies 7

1.3% of ectopic pregnancies 7

Intramural (within uterine wall)

Occurs when there is implantation within the myometrium

May occur within a cesarean delivery scar

Occurs when there are simultaneous intrauterine and ectopic pregnancies

Approximately 1% of pregnancies resulting from assisted reproduction are heterotopic 3

Vaginal spotting or bleeding

Before 6 weeks of gestation, may be absent or vague

May be crampy or steady, unilateral or bilateral

Pain specifically due to rupture

Referred to the shoulder or flank with hemoperitoneum

Lightheadedness and/or syncope may occur

Symptoms associated with specific implantation site

Abdominal pain is most common symptom

Nausea and vomiting may be prominent symptoms

Vaginal bleeding is less frequent than in tubal ectopic pregnancies

Rarely, presents with symptoms of bowel obstruction

Lower abdominal pain or cramps may or may not be present

Pain without bleeding is rare

Intramural pregnancy (including pregnancy occurring within a cesarean delivery scar)

Pallor may be present with significant blood loss

Hypotension or orthostatic hypotension with tachycardia may be signs of impending shock

Abdominal tenderness is present in most patients

Cervical motion tenderness is highly suggestive 8

Cervical os may be open or closed

Causes and Risk Factors

Risk factors and/or associations

Risk increases with advancing maternal age 1

Other risk factors/associations

Progestin-only oral contraception

Infertility treatment (ie, pharmacologic ovulation induction, in vitro fertilization) 1

Endometriosis, which can cause disruption and scarring of pelvic anatomy

Pelvic inflammatory disease with fallopian tube involvement

First sexual intercourse at an early age

Multiple sexual partners

Exposure to diethylstilbestrol in utero

Imaging results will place the patient into 1 of 4 categories:

Intrauterine pregnancy: if seen, an ectopic pregnancy is essentially ruled out

However, heterotopic pregnancy (ectopic pregnancy coexisting with an intrauterine

Discriminatory threshold (usually 1500-2000 mIU/mL) is the level at which an intrauterine

Laparoscopic visualization of uterine adnexa is considered the gold standard in investigating

Done in women of reproductive age presenting with vaginal bleeding, hypotension,

False-negative result may be produced by testing very dilute urine

May be done as an alternative to a urine pregnancy test

Measure in all patients with history or symptoms suggestive of ectopic pregnancy

Used diagnostically to determine if discriminatory threshold has been reached, and to

In a normal pregnancy, a level of 1500 to 2000 mIU/mL causes gestational sac to

Occasionally used as alternative or additional diagnostic aid, although not common

Levels in normal intrauterine pregnancies are 10 ng/mL or above

CBC is recommended before beginning methotrexate therapy 3

Measuring electrolyte, serum creatinine, and hepatic transaminase levels in all

Recommended before medical and surgical treatment