Ectopic Pregnancy

BASICS

DESCRIPTION

Ectopic: pregnancy implanted outside the uterine cavity; subtypes include:

Tubal—pregnancy implanted in the fallopian tube
Abdominal—pregnancy implanted intra-abdominally, usually after tubal abortion or rupture of tubal ectopic pregnancy
Heterotopic pregnancy—implanted intrauterine pregnancy (IUP) and a separate pregnancy outside the uterine cavity
Ovarian—implantation of pregnancy in ovarian tissue
Cervical—implantation of pregnancy in cervix
Intraligamentary—implantation of pregnancy within the broad ligament

EPIDEMIOLOGY

Prevalence

Ectopic pregnancy occurs in about 2% of all pregnancies (1), and about 1 in 10 first-trimester pregnancies presenting to the emergency department with pain and/or bleeding. In the United States, ectopic pregnancy is the leading cause of first-trimester maternal deaths.
Heterotopic pregnancy, although very rare, occurs with greater frequency in women undergoing in vitro fertilization (IVF); increasing incidence of nontubal, and particularly cesarean scar ectopic pregnancies, due in part to more cesarean sections and more IVF

ETIOLOGY AND PATHOPHYSIOLOGY

Most ectopic pregnancies occur in the fallopian tube, followed by the ampulla, isthmus, and then the fimbria. One cause of tubal pregnancy is impaired movement of the fertilized ovum to the uterine cavity due to dysfunction of the tubal cilia, scarring, or narrowing of the tubal lumen.

RISK FACTORS

History of pelvic inflammatory disease (PID), endometritis, or current gonorrhea/chlamydia infection, pelvic adhesive disease (infection or prior surgery), tobacco use, and patients with disorders that affect ciliary motility may be at increased risk (e.g., endometriosis).
Previous ectopic pregnancy, history of tubal surgery
Use of an intrauterine device (IUD): IUD reduces absolute risk (and therefore number) of ectopic pregnancies, but in a patient with an IUD in place presenting with a pregnancy, there is an increased likelihood that the pregnancy is ectopic, compared with a patient without an IUD.
Use of assisted reproductive technologies

GENERAL PREVENTION

Screen for and treat STIs (i.e., gonorrhea, chlamydia) that can cause PID and tubal scarring that increase the risk for an ectopic pregnancy.

DIAGNOSIS

HISTORY

Classically sudden-onset of abdominal pain following cessation of/or irregular menses and acute vaginal bleeding; other common symptoms include nausea and/or vomiting, and pain referred to the shoulder (from hemoperitoneum); ectopic pregnancies can also be asymptomatic.

PHYSICAL EXAM

Abdominal tenderness ± rebound tenderness
Vaginal bleeding may be present
Palpable mass on pelvic exam (adnexal or cul-de-sac fullness), cervical motion tenderness
In cases of rupture and significant intraperitoneal bleeding, signs of shock such as pallor, tachycardia, and hypotension may be present.

DIFFERENTIAL DIAGNOSIS

Missed, threatened, inevitable, or completed abortion (miscarriage), gestational trophoblastic neoplasia (“molar pregnancy”); appendicitis; salpingitis; PID; ruptured corpus luteum or hemorrhagic cyst; ovarian tumor, benign or malignant; ovarian torsion; cervical polyp, cancer, trauma, or cervicitis

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

CBC and ABO type and antibody screen
Transvaginal ultrasound (TVUS) is the gold standard for diagnosis:
- Failure to visualize a normal intrauterine gestational sac when serum human chorionic gonadotropin (hCG) is above the discriminatory level (>1,500 to 2,000 IU/L) suggests (but is not definitively diagnostic of) an abnormal pregnancy. TVUS is often inconclusive, and the pregnancy is then called “pregnancy of unknown location” (PUL).
- An hCG level of 3,500 IU/L is associated with a 99% probability of detecting a normal intrauterine gestational sac in clinical practice.
- These values are not validated for multiple gestations.
If TVUS unavailable or inconclusive for IUP, check serial hCG levels (1). Serial quantitative serum levels normally increase by at least 35% every 48 hours. Higher initial hCG levels increase less than lower initial hCG levels(1). Abnormal rise (<35%) should prompt workup for gestational abnormalities. Clinical impression of acute abdomen/intraperitoneal bleeding concurrent with a positive hCG level is indicative of ectopic pregnancy until proven otherwise.
MRI may also be useful but costly and rarely used if TVUS is available; benefits particularly for abdominal or cesarean scar pregnancy

Follow-Up Tests & Special Considerations

HCG levels should be carefully monitored and followed. All patients should receive counseling about return precautions (severe abdominal pain, heavy vaginal bleeding, nausea or vomiting).

Diagnostic Procedures/Other

In the setting of an undesired pregnancy, uterine aspiration or D&C can identify the presence/absence of intrauterine chorionic villi. When an IUP has been evacuated, hCG levels should drop by 50% within 48 hours.

Test Interpretation

Products of conception (POC; especially chorionic villi) outside the uterine cavity

TREATMENT

GENERAL MEASURES

Management of ectopic pregnancy usually requires medical management or surgery with comparable efficacy from either in appropriately chosen candidates. A very few patients with low and declining HCG levels and meeting other criteria may be managed expectantly (2)[A]. Patients who are diagnosed early can often be managed with medication. However, those who have concern for tubal rupture with signs of hemodynamic instability, will require surgical intervention.

MEDICATION

First Line

Medication therapy with methotrexate is the preferred treatment if the patient is hemodynamically stable and is able to comply with follow-up.
- Methotrexate: treatment for unruptured tubal pregnancy or for remaining POCs after laparoscopic salpingostomy. If TVUS is suggestive but not diagnostic, in the hemodynamically stable patient who qualifies for medical management, confirm suspected US findings with 2 hCG levels drawn 48 hours apart. Rise <35% is consistent with nonviable pregnancy. Methotrexate is most effective when pregnancy is <3 cm diameter, hCG <5,000 mIU/mL, and no fetal heart activity is seen. Success rate is 88% if hCG <1,000 mIU/mL, 71% if hCG 1,000 to 2,000 mIU/mL, 38% if 2,000 to 5,000 mIU/mL. All regimens require following quant hCG to 0. Contraindications: hemodynamic instability or any evidence of rupture, moderate to severe anemia, severe hepatic or renal dysfunction, immunodeficiency; relative contraindications: fetal heart activity seen, large gestational sac (>3 to 4 cm), noncompliance or limited access to hospital or transportation, hCG >5,000 mIU/ml; precautions: immunologic, hematologic, renal, GI, hepatic, and pulmonary disease, or interacting medications
Three main dosage regimens exist and require a reliable, hemodynamically stable patient (1).
- Single: IM methotrexate 50 mg/m² of body surface area (BSA); may repeat once if <15% decline in hCG between days 4 and 7; if there is a decrease in hCG by at least 15% between days 4 and 7, adequate treatment occurred; follow hCG weekly. The single-dose regimen is preferred for simplicity, safety, lower adverse effect rate, and comparable effectiveness to multidose regimens (3).
- Two dose: methotrexate 50 mg/m² of BSA once and then repeated on day 4; if <15% decline in hCG between days 4 and 7, may repeat third dose on day 7 (not needed if hCG decrease is >15%). Repeat hCG as needed on days 11 and 14 until decreases >15% in the interval and then weekly. If not dropping by day 14, refer for surgical management; may be somewhat more effective for higher initial hCG levels than in the single dose regimen
- Multidose (fixed dose with frequent injections): methotrexate 1 mg/kg IM/IV every other day, on days 1, 3, 5, and 7, with leucovorin 0.1 mg/kg IM rescue in between, on days 2, 4, 6, and 8 (counteracts effects of methotrexate); maximum 4 doses until hCG drop below 15%; course may be repeated 7 days after last dose if necessary.
- Pretreatment testing: serum hCG, CBC, liver and renal function tests, blood type and screen
- Patient counseling: During therapy, refrain from use of alcohol, aspirin, NSAIDs, and folate supplements (decreases efficacy of methotrexate); avoid excessive sun exposure due to risk of sensitivity. Adherence to scheduled follow-up appointments is critical. Increased abdominal pain may occur during treatment; however, severe pain, nausea, vomiting, bleeding, dizziness, or light-headedness may indicate treatment failure and require urgent evaluation. Rupture of ectopic pregnancy during methotrexate treatment ranges from 7% to 14%.
- Adverse reactions of methotrexate include nausea, diarrhea, abdominal cramping, cough and the rare risk of neutropenia and leukopenia.
- Systemic methotrexate may be offered in some kinds of nontubal ectopic pregnancies, but data is limited.

ISSUES FOR REFERRAL

Consider gynecologic consultation if not experienced in medical management, and for surgical care.

ADDITIONAL THERAPIES

Physician or patient may elect for surgical treatment as primary method and then postop hCG should guide need for supplemental methotrexate.
After evidence of medical failure or tubal rupture, surgery is necessary.
Treatment of cervical, ovarian, abdominal, or other ectopic pregnancy is complicated and requires immediate specialist referral.
Offer anti-D Rh prophylaxis at a dose of 50 μg to all Rh-negative women who have a surgical procedure to manage an ectopic pregnancy or if there has been significant bleeding or abdominal pain.
Expectant management to allow for spontaneous resolution of PUL is acceptable in asymptomatic patients with no evidence of rupture or hemodynamic instability coupled with an appropriately low and decreasing hCG levels (<200 to 1,500 mIU/mL) and no extrauterine mass suggestive of ectopic. Ruptured tubal pregnancies may occur even with extremely low hCG levels (<100 mIU/mL) (4).
With expectant management of PUL, repeat TVUS weekly (or when hCG above discriminatory zone) until location is confirmed or clinical picture is unstable.

SURGERY/OTHER PROCEDURES

Indications include hemodynamic instability, ruptured ectopic pregnancy, inability to comply with medical follow-up, previous tubal ligation, known tubal disease, current heterotopic pregnancy, and desire for permanent sterilization at time of diagnosis.
Laparoscopy is the first-line surgical management (4).
Salpingectomy (tubal removal) is preferred and is indicated for uncontrolled bleeding, recurrent ectopic pregnancy, severely damaged tube, large gestational sac, or patient’s desire for sterilization (4). Salpingostomy (preservation of tube) is considered in patients who wish to maintain fertility particularly if contralateral tube is damaged/absent. No difference in recurrence rate compared to salpingectomy.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Admission if a patient does not meet criteria for methotrexate management, if there is a high suspicion of rupture, or signs/symptoms of hemodynamic instability including orthostasis, shock, and severe abdominal pain or inability to tolerate oral intake.
Inpatient observation in the setting of an uncertain diagnosis, particularly with an unreliable patient, may be appropriate.
Surgical emergency: Two large-bore IV access lines should be placed in case immediate aggressive resuscitation as needed; blood product transfusion if necessary en route to the operating room; in cases of shock, pressors and cardiac support may be necessary.
Strict input/output, hourly vitals, orthostatics if mobile, frequent abdominal exams, serial hematocrit, pad counts if heavy vaginal bleeding
Discharge criteria: afebrile, abdominal pain resolving or resolved, diagnosis established, surgical treatment, and recovery is complete

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

Serial serum quantitative hCG until level drops to zero. After methotrexate administration, strict monitoring protocol should be followed. Following salpingostomy, weekly hCG levels are appropriate.
Pelvic US for persistent or recurrent masses
Pain control: brief course of narcotics usually necessary with medical or surgical management
Liver and renal function tests weekly following methotrexate administration if repeat dosing is required
Some clinicians recommend delaying subsequent pregnancy for at least 3 months after treatment with methotrexate due to risk for teratogenicity (4)

DIET

During treatment, avoid alcohol and foods and vitamins high in folate due to interaction with methotrexate efficacy.

PATIENT EDUCATION

Signs and symptoms of ectopic pregnancy should be reviewed.
Patients should be encouraged to plan subsequent pregnancies and seek early medical care on discovery of future pregnancies.

PROGNOSIS

Chronic ectopic pregnancies are rare and treated with surgical removal of the fallopian tube.
Future fertility depends on fertility prior to ectopic pregnancy and degree of tubal compromise. In women with normal fertility, treatment options make no differences in future fertility rates. In women with subfertility, expectant or medical treatments confer better future fertility (4).
If infertility persists beyond 12 months, the fallopian tubes should be evaluated.

COMPLICATIONS

Hemorrhage and hypovolemic shock, persistent trophoblastic tissue after medical or surgical management, infection, infertility, blood transfusions with associated infections/transfusion reaction, disseminated intravascular coagulation in the setting of massive hemorrhage

Authors

Kristina Gracey, MD, MPH
Rana Mehdizadeh, MD, MS

REFERENCES

Tonick S, Conageski C. Ectopic pregnancy. Obstet Gynecol Clin North Am. 2022;49(3):537–549. [PMID:36122984]
Al Wattar BH, Solangon SA, de Braud LV, et al. Effectiveness of treatment options for tubal ectopic pregnancy: a systematic review and network meta-analysis. BJOG. 2024;131(1):5–14. [PMID:37443463]
Yuk JS, Lee JH, Park WI, et al. Systematic review and meta-analysis of single-dose and non-single-dose methotrexate protocols in the treatment of ectopic pregnancy. Int J Gynaecol Obstet. 2018;141(3):295–303. [PMID:29485731]
Diagnosis and management of ectopic pregnancy: Green-top Guideline No. 21. BJOG. 2016;123(13):e15–e55. [PMID:27813249]

CODES

ICD10

O00.9 Ectopic pregnancy, unspecified
O00.1 Tubal pregnancy
O00.0 Abdominal pregnancy
O00.2 Ovarian pregnancy
O00.8 Other ectopic pregnancy

SNOMED

34801009 Ectopic pregnancy (disorder)
79586000 tubal pregnancy (disorder)
82661006 Abdominal pregnancy
9899009 ovarian pregnancy (disorder)
17433009 ruptured ectopic pregnancy (disorder)

CLINICAL PEARLS

Diagnosis requires high clinical suspicion in the setting of abdominal pain and a positive pregnancy test until IUP is confirmed.
Monitoring patients carefully with a combination of transvaginal ultrasounds, serial hCG levels, and clinical status is essential to help prevent poor outcomes in patients with suspected or confirmed ectopic pregnancy.

Last Updated: 2026