Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management

1st line – surgery

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ACUTE
|
tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management
|
hemodynamically stable
1st line – 

surgery

Preferred method is laparoscopy with either salpingostomy or salpingectomy, depending on the status of the contralateral tube and the desire for future fertility.[47][60][79][80][81][82][Figure caption and citation for the preceding image starts]: Surgical extraction of ectopic pregnancyFrom the collection of Dr Sina Haeri; used with permission [Citation ends].com.bmj.content.model.Caption@71231ac1[Figure caption and citation for the preceding image starts]: Surgical extraction of ectopic pregnancyFrom the collection of Dr Sina Haeri; used with permission [Citation ends].com.bmj.content.model.Caption@13580673

Salpingostomy should be considered for women with contralateral tube damage, as this is a risk factor for infertility.[63][71] There is no evidence to recommend salpingostomy over salpingectomy if the contralateral tube is normal.[71] Future fertility and tubal patency rates in laparoscopically treated women is similar to that in the medically managed group.[47][57]

Laparoscopic treatment of ectopic pregnancy in women with obesity (body mass index >30) is feasible and safe with proper patient selection and appropriate experience of the surgeon.[83]

Serial chorionic gonadotropin levels should be taken after salpingostomy until the levels are undetectable. A negative pregnancy test should be confirmed after salpingectomy.

Consider – post-surgical methotrexate

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ACUTE
|
tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management
|
hemodynamically stable
Consider – 

post-surgical methotrexate

Treatment recommended for SOME patients in selected patient group

If serum chorionic gonadotropin levels do not return to undetectable after surgery, methotrexate is given.

Primary options

methotrexate: 50 mg/square meter of body surface area intramuscularly as a single dose

Consider – Rho(D) immune globulin

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ACUTE
|
tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management
|
hemodynamically stable
Consider – 

Rho(D) immune globulin

Treatment recommended for SOME patients in selected patient group

The American College of Emergency Physicians' Clinical Subcommittee review found insufficient evidence either for or against treatment with Rho(D) immune globulin in rhesus-negative women with ectopic pregnancy.[84] However, the UK National Institute for Health and Care Excellence recommends Rho(D) immune globulin for all rhesus-negative women undergoing surgery for ectopic pregnancy, but not for those treated medically.[63]

Primary options

Rho(D) immune globulin: 50 micrograms (250 international units) intramuscularly as a single dose as soon as possible or within 72 hours of the event

1st line – fluid resuscitation

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ACUTE
|
tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management
|
hemodynamically unstable
1st line – 

fluid resuscitation

Hemodynamic instability associated with a ruptured ectopic pregnancy results from severe hypovolemia secondary to blood loss.

Rapid volume repletion with isotonic solution and blood products is of paramount importance to avoid ischemic injury and multi-organ damage.

Plus – surgery

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ACUTE
|
tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management
|
hemodynamically unstable
Plus – 

surgery

Treatment recommended for ALL patients in selected patient group

Type of surgery used depends on the experience and judgment of the surgeon and is decided on in consultation with the anesthetist.

Not unreasonable to undertake a laparotomy based on the availability of resources (including adequately trained personnel), with the specific procedure dependent on the location of the bleeding.

Consider – Rho(D) immune globulin

Back
ACUTE
|
tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management
|
hemodynamically unstable
Consider – 

Rho(D) immune globulin

Treatment recommended for SOME patients in selected patient group

The American College of Emergency Physicians' Clinical Subcommittee review found insufficient evidence either for or against treatment with Rho(D) immune globulin in rhesus-negative women with ectopic pregnancy.[84] However, the UK National Institute for Health and Care Excellence recommends Rho(D) immune globulin for all rhesus-negative women undergoing surgery for ectopic pregnancy, but not for those treated medically.[63]

Primary options

Rho(D) immune globulin: 50 micrograms (250 international units) intramuscularly as a single dose as soon as possible or within 72 hours of the event

tubal ectopic pregnancy: moderate risk or failed expectant management

1st line – methotrexate

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ACUTE
|
tubal ectopic pregnancy: moderate risk or failed expectant management
1st line – 

methotrexate

In women who are clinically stable with a nonruptured ectopic pregnancy, laparoscopic surgery and medical management are both reasonable management options and the decision should be guided by initial investigations and discussion with the woman.[47][63]

Medical management is reserved for hemodynamically stable women who have a confirmed or high clinical suspicion of ectopic pregnancy, an unruptured mass, and no absolute contraindications to methotrexate.[47][71]

It has been suggested that initial serum human chorionic gonadotropin (hCG) levels >5000 mIU/mL are predictive of an increased failure rate for medical management, particularly for single-dose regimens, and the American College of Obstetricians and Gynecologists states that high initial hCG concentration is a relative contraindication for methotrexate therapy.[47][74]

Ultrasound features that are suggestive of early gestational development or that indicate potential tubal rupture are also risk factors for treatment failure.[71] These include visualized yolk sac or embryo, and significant pelvic free fluid.[71] Ectopic pregnancy size >4 cm is considered a relative contraindication for medical management, but tubal rupture is unlikely if ectopic size is <2 cm and hCG level is <1855 mIU/mL.[47][75]

Other relative contraindications are embryonic cardiac activity on transvaginal ultrasound scan, high initial hCG concentration and refusal to accept blood transfusion.[47][60] Most practitioners use the specific clinical scenario, in addition to ultrasound findings and hCG values, to determine whether medical management is an appropriate choice for an individual woman.

Certain conditions preclude a woman from undergoing treatment with methotrexate, including evidence of immunodeficiency, liver disease (with transaminases more than double normal), renal disease (creatinine >1.5 mg/dL), active peptic ulcer disease, significant pulmonary disease, or hematologic abnormalities (e.g., significant anemia, thrombocytopenia, or leukopenia).[47][57][71] Other contraindications include intrauterine pregnancy, breast-feeding, sensitivity to methotrexate, and the inability to participate in follow-up.[47][60][63][71]

Once methotrexate has been administered, hCG levels should be serially monitored until they reach a nonpregnancy level.[47][63] This usually takes 2-4 weeks but can be up to 8 weeks.[76]

During methotrexate treatment, vigorous activity and sexual intercourse should be avoided as this may potentially cause a rupture of ectopic pregnancy; pelvic and ultrasound scans should be limited; and women should avoid folic acid and nonsteroidal anti-inflammatory drugs as these reduce the efficacy of methotrexate. Gas-forming foods should also be avoided as they may produce pain that can be confused with symptoms of rupture. Sunlight exposure may risk methotrexate dermatitis.[47] Once methotrexate treatment is complete, it may be advisable for women to delay attempts to conceive for 12 weeks or more to allow for maximum clearance.[71]

At any given point in time, if a woman becomes clinically unstable, surgical intervention is indicated.[47] Unsuccessful medical management is also managed surgically. However, a case-control series found that ultrasound-guided injection of methotrexate into the ectopic pregnancy, in addition to systemic methotrexate, may be a safe alternative to surgery in cases where there is a higher risk of treatment failure (e.g., higher hCG levels or fetal cardiac activity).[78]

Primary options

two-dose regimen

methotrexate: 50 mg/square meter of body surface area intramuscularly as a single dose on day 1 and day 4

More

OR

single-dose regimen

methotrexate: 50 mg/square meter of body surface area intramuscularly as a single dose on day 1

More

Secondary options

multiple-dose regimen

methotrexate: 1 mg/kg intramuscularly once daily on days 1, 3, 5, and 7

More

and

leucovorin: 0.1 mg/kg intramuscularly once daily on days 2, 4, 6, and 8

1st line – surgery

Back
ACUTE
|
tubal ectopic pregnancy: moderate risk or failed expectant management
1st line – 

surgery

In women who are clinically stable with a nonruptured ectopic pregnancy, laparoscopic surgery and medical management are both reasonable management options and the choice should be guided by initial investigations and discussion with the individual woman.[47][63]

If a woman shows signs of hemodynamic instability, symptoms of a ruptured ectopic mass, or signs of intraperitoneal bleeding then surgical intervention is required. It is also necessary if the woman has absolute contraindications to medical therapy.[47][63]

The preferred method is laparoscopy with either salpingostomy or salpingectomy, depending on the status of the contralateral tube and the desire for future fertility.[47][60][79][80][81][82] Salpingostomy should be considered for women with contralateral tube damage, as this is a risk factor for infertility.[63][71] There is no evidence to recommend salpingostomy over salpingectomy if the contralateral tube is normal.[71]

Laparoscopic treatment of ectopic pregnancy in women with obesity (body mass index >30) is feasible and safe with proper patient selection and appropriate experience of the surgeon.[83]

Serial chorionic gonadotropin levels should be taken after salpingostomy until the levels are undetectable. A negative pregnancy test should be confirmed after salpingectomy.

Consider – postsurgical methotrexate

Back
ACUTE
|
tubal ectopic pregnancy: moderate risk or failed expectant management
Consider – 

postsurgical methotrexate

Treatment recommended for SOME patients in selected patient group

If serum chorionic gonadotropin levels do not return to undetectable after surgery, methotrexate is given.

Primary options

methotrexate: 50 mg/square meter of body surface area intramuscularly as a single dose

Consider – Rho(D) immune globulin

Back
ACUTE
|
tubal ectopic pregnancy: moderate risk or failed expectant management
Consider – 

Rho(D) immune globulin

Treatment recommended for SOME patients in selected patient group

The American College of Emergency Physicians' Clinical Subcommittee review found insufficient evidence either for or against treatment with Rho(D) immune globulin in rhesus-negative women with ectopic pregnancy.[84] However, the UK National Institute for Health and Care Excellence recommends Rho(D) immune globulin for all rhesus-negative women undergoing surgery for ectopic pregnancy, but not for those treated medically.[63]

Primary options

Rho(D) immune globulin: 50 micrograms (250 international units) intramuscularly as a single dose as soon as possible or within 72 hours of the event

tubal ectopic pregnancy: low risk

1st line – expectant management

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ACUTE
|
tubal ectopic pregnancy: low risk
1st line – 

expectant management

Appropriate for low risk, hemodynamically stable, asymptomatic women (or with minimal pain) where there is objective evidence of resolution - usually demonstrated by a plateau or decrease in human chorionic gonadotropin (hCG) levels.[47][60][71] In women with an initial hCG <200 mIU/mL, 88% will have spontaneous resolution, with a lower rate expected with higher hCG levels.[47][72] The UK National Institute for Health and Care Excellence (NICE) has therefore made a strong recommendation for expectant management if serum hCG is ≤1000 IU/L but a conditional recommendation for expectant management if serum hCG is >1000 and <1500 IU/L.[63][Evidence C] 

One randomized controlled trial (RCT) of women with pregnancy of unknown location or ectopic pregnancy reported a success rate of 59% with expectant management compared with 76% following single-dose methotrexate.[73] A 2021 RCT of women with persisting pregnancy of unknown location reported a success rate of 51.5% with active management versus 36.0% with expectant management.[65]

Serial hCG levels should be taken until levels are undetectable.

Failed expectant management is followed by medical treatment, if eligible, or surgical treatment. Expectant management should be ceased if a woman has increasing pain, hCG levels are not decreasing, or there are signs of tubal rupture.[47]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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