• American College of Obstetricians and Gynecologists (ACOG). Medical management of ectopic pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2008 Jun. 7 p. (ACOG practice bulletin; no. 94). [29 references]

This is the current release of the guideline.

This guideline updates a previous version: American College of Obstetricians and Gynecologists (ACOG). Medical management of tubal pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 1998 Dec. 7 p. (ACOG practice bulletin; no. 3).

Tubal ectopic pregnancy

Counseling
Diagnosis
Management
Treatment

Obstetrics and Gynecology

Physicians

• To aid practitioners in making decisions about appropriate obstetric and gynecologic care
• To review the risks and benefits of the use of methotrexate in the management of ectopic pregnancy

Pregnant women presenting with signs and symptoms of ectopic pregnancy

Diagnosis

1. Clinical signs, physical symptoms
2. Serial human chorionic gonadotropin (hCG) levels
3. Transvaginal ultrasonography
4. Serum progesterone levels

Management/Treatment

1. Determining if a patient is a candidate for methotrexate therapy
2. Methotrexate
   • Single-dose regimen protocol
   • Two-dose regimen protocol
   • Fixed multidose regimen protocol
3. Surveillance after methotrexate therapy
   • Serial hCG levels
4. Patient counseling and education concerning side effects of methotrexate
5. Expectant management of ectopic pregnancy

• Sensitivity and specificity of diagnostic tests
• Incidence of heterotopic pregnancy
• Success rate of methotrexate regimen
• Methotrexate-associated morbidity
• Tubal preservation
• Tubal patency
• Repeat ectopic pregnancy
• Future pregnancies
• Patient satisfaction

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

The MEDLINE database, the Cochrane Library, and the American College of Obstetricians and Gynecologists' (ACOG's) own internal resources and documents were used to conduct a literature search to locate relevant articles published between January 1985 and May 2007. The search was restricted to articles published in the English language. Priority was given to the articles reporting results of original research although review articles and commentaries also were consulted. Abstracts of research presented at symposiums and scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were located by reviewing bibliographies of identified articles.

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force.

I Evidence obtained from at least one properly designed randomized controlled trial.

II-1 Evidence obtained from well-designed controlled trials without randomization.

II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.

II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.

III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Review of Published Meta-Analyses
Systematic Review

Not stated

Expert Consensus

Analysis of available evidence was given priority in formulating recommendations. When reliable research was not available, expert opinions from obstetrician-gynecologists were used. See also the "Rating Scheme for the Strength of Recommendations" field regarding Grade C recommendations.

Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:

Level A — Recommendations are based on good and consistent scientific evidence.

Level B — Recommendations are based on limited or inconsistent scientific evidence.

Level C — Recommendations are based primarily on consensus and expert opinion.

A formal cost analysis was not performed and published cost analyses were not reviewed.

Internal Peer Review

Practice Bulletins are validated by two internal clinical review panels composed of practicing obstetrician-gynecologists generalists and sub-specialists. The final guidelines are also reviewed and approved by the American College of Obstetricians and Gynecologists (ACOG) Executive Board.

The grades of evidence (I-III) and levels of recommendations (A-C) are defined at the end of "Major Recommendations" field.

The following conclusion is based on good and consistent evidence (Level A):

• In comparing systemic methotrexate with tube-sparing laparoscopic surgery, randomized trials have shown no difference in overall tubal preservation, tubal patency, repeat ectopic pregnancy, or future pregnancies.

The following recommendations and conclusions are based on limited or inconsistent evidence (Level B):

• An increase in serum human chorionic gonadotropin (hCG) of less than 53% in 48 hours confirms an abnormal pregnancy.
• With an hCG level of 5,000 mIU/mL or higher, multiple doses of methotrexate may be appropriate.
• Methotrexate can be considered in those women with a confirmed, or high clinical suspicion of, ectopic pregnancy who are hemodynamically stable with an unruptured mass.
• Failure of the hCG level to decrease by at least 15% from day 4 to day 7 after methotrexate administration is considered treatment failure requiring therapy with either additional methotrexate administration or surgical intervention.
• Post-treatment hCG levels should be monitored until a nonpregnancy level is reached.

The following conclusion is based primarily on consensus and expert opinion (Level C):

• If the initial hCG level is less than 200 mU/mL, 88% of patients experience spontaneous resolution.

Definitions:

Grades of Evidence

I Evidence obtained from at least one properly designed randomized controlled trial.

II-1 Evidence obtained from well-designed controlled trials without randomization.

II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.

II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this type of evidence.

III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Levels of Recommendations

Level A — Recommendations are based on good and consistent scientific evidence.

Level B — Recommendations are based on limited or inconsistent scientific evidence.

Level C — Recommendations are based primarily on consensus and expert opinion.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Improved treatment of tubal ectopic pregnancies with methotrexate

Adverse Effects Associated with Methotrexate Treatment

• Because methotrexate affects all rapidly dividing tissues within the body, including bone marrow, the gastrointestinal mucosa, and the respiratory epithelium, it should not be given to women with blood dyscrasias or active gastrointestinal and respiratory disease. Methotrexate is directly toxic to the hepatocytes and is cleared from the body by renal excretion; therefore, it should not be used in women with liver or kidney disease.
• Methotrexate morbidity usually is dose and treatment duration dependent. Because methotrexate affects rapidly dividing tissues, gastrointestinal side effects, such as nausea, vomiting, and stomatitis, are the most common. Therefore, women treated with methotrexate should be advised not to use alcohol and nonsteroidal anti-inflammatory drugs (NSAIDs). Elevation of liver enzymes usually is seen only with multidose regimens and resolves after discontinuing methotrexate use or increasing the rescue dose of folinic acid. Alopecia is a rare side effect with the doses used to treat ectopic pregnancy.
• It is not unusual for women treated with methotrexate to experience abdominal pain 2–3 days after administration, presumably from the cytotoxic effect of the drug on the trophoblast tissue, causing tubal abortion.

Absolute Contraindications to Methotrexate Therapy

• Breastfeeding
• Overt or laboratory evidence of immunodeficiency
• Alcoholism, alcoholic liver disease, or other chronic liver disease
• Preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia
• Known sensitivity to methotrexate
• Active pulmonary disease
• Peptic ulcer disease
• Hepatic, renal, or hematologic dysfunction

Relative Contraindications to Methotrexate Therapy

• Gestational sac larger than 3.5 cm
• Embryonic cardiac motion

These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.

An implementation strategy was not provided.

Getting Better

Effectiveness
Patient-centeredness

• American College of Obstetricians and Gynecologists (ACOG). Medical management of ectopic pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2008 Jun. 7 p. (ACOG practice bulletin; no. 94). [29 references]

Not applicable: The guideline was not adapted from another source.

1998 Dec (revised 2008 Jun)

American College of Obstetricians and Gynecologists - Medical Specialty Society

American College of Obstetricians and Gynecologists (ACOG)

American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins- Gynecology

Not stated

Not stated

This is the current release of the guideline.

This guideline updates a previous version: American College of Obstetricians and Gynecologists (ACOG). Medical management of tubal pregnancy. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 1998 Dec. 7 p. (ACOG practice bulletin; no. 3).

Proposed performance measures are included in the original guideline document.

This NGC summary was completed by ECRI on January 14, 2005. This summary was updated by ECRI Institute on July 29, 2008. The updated information was verified by the guideline developer on August 20, 2008.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.