Ectopic pregnancy happens when the fertilized ovum implants outside the endometrial lining of the uterus.
Accurate early diagnosis is life-saving, reduces invasive diagnostic procedures & allows conservative treatment that can preserve fertility.
Ectopic pregnancy must be excluded in women of reproductive age w/ a positive pregnancy test, abdominal pain & vaginal bleeding.
Ruptured ectopic pregnancy remains to be the leading cause of maternal mortality in the first trimester.

Principles of Therapy

  • Treatment decision should be made on an individual basis
  • For heterotopic pregnancy, the IUP must be considered when planning management 

Surgical Management

  • Surgical treatment remains the preferred approach for most ectopic pregnancies

Surgical management is indicated if:

  • The patient’s condition deteriorates
  • β-hCG levels are rising or plateaued and ectopic mass >3-4 cm
  • Unreliable patient who may not be available for close follow-up

Medical Management

  • Success is greatest if gestation <6 weeks and tubal mass <3.5 cm in diameter
  • Serial measurements of β-hCG are necessary in patients being managed medically

Medical management may be an option if:

  • Patient is hemodynamically stable with normal hemogram and normal liver and renal function
  • Ectopic pregnancy has been confirmed by US
  • Ectopic mass has not ruptured and is <3-4 cm in diameter by US
  • Absence of active bleeding or signs of hemoperitoneum
  • Patients with β-hCG levels <5000 IU/L (5000 mIU/mL) are more likely to respond to therapy
  • Patient is willing to comply with close follow-up

Medical management is contraindicated if:

  • Breastfeeding
  • Presence of fetal cardiac activity
  • Presence of fluid in the cul-de-sac
  • Immunodeficiency
  • β-hCG levels >5000 IU/L (5000 mIU/mL)
  • Presence of contraindications related to Methotrexate use
  • Ruptured ectopic pregnancy
  • Active pulmonary or peptic ulcer disease

Expectant Management

  • May be considered if the patient remains stable, is reliable and is willing to accept the potential risk of tubal rupture
  • Evidence of resolution eg declining β-hCG levels
  • 68-77% of ectopic pregnancies resolve without intervention but clinical markers to identify these patients have not been defined
  • Spontaneous resolution is more likely in patients with β-hCG levels <1000 IU/L (1000 mIU/mL)
  • Risk of rupture will remain until pregnancy is completely resolved
  • Serial measurements of β-hCG are necessary in patients being managed expectantly

Expectant management may be an option if:

  • β-hCG levels are <1000 IU/L (1000 mIU/mL) and are declining
  • Vaginal sonography shows no evidence of intra-abdominal rupture or bleeding
  • Patient is willing to comply with close follow-up



  • Action: Methotrexate is a folic acid antagonist that interferes with DNA synthesis in rapidly dividing cells like the trophoblastic tissue
  • Effects: Reported success rates are between 65-95%
    • Treatment success rates following Methotrexate therapy are comparable to surgery
    • Failure rates are higher with larger ectopic pregnancies, evidence of fetal cardiac activity and higher β-hCG levels
    • Studies have shown that a single-dose protocol may have similar efficacy to a multidose protocol
      • Failure rate is lower with multidose Methotrexate
  • Patients for Methotrexate therapy must be hemodynamically stable with serum β-hCG level of <5000 IU/L, has no demonstrated US evidence of fetal cardiac activity or IUP and no abdominal pain that is severe or persistent
  • Methotrexate treatment of tubal ectopic pregnancy has no effect on ovarian reserve  
  • Muscle relaxation training may be of help to patients on Methotrexate therapy 
  • Patients treated with Methotrexate may experience self-limiting abdominal pain which may mimic acute ectopic rupture, a transient rise in β-hCG levels, and vaginal spotting or bleeding
  • Side effects are infrequent with short regimen but can also be mitigated by co-administration of Leucovorin
  • Patient must be willing and available for close follow-up which may take as long as 7 weeks
    • β-hCG level should be followed up until it becomes undetectable or decreases to <15 IU/L
      • If hCG level increases or plateaus, patient may be given another dose of Methotrexate
    • Patient should also be made aware that medical therapy fails in approximately 5-10% of patients and will lead to surgery
  • Patients who underwent Methotrexate therapy must wait for at least 3 months before attempting to become pregnant again

Expectant Management

  • Expectant management with close observation may be undertaken in an attempt to increase possible future tubal patency in carefully selected patients
  • This option should be offered only when transvaginal US fails to locate the gestational sac and the serum levels of β-hCG and progesterone are low and declining
    • Candidates must be asymptomatic and clinically stable with declining β-hCG levels, initially <1500 IU/L
  • Serum β-hCG should be monitored on weekly basis while transvaginal US is done on weekly interval to confirm reduction in hCG level and decrease in the adnexal mass size in 7 days
    • Thereafter, serum β-hCG and transvaginal US monitoring are done on a weekly basis until serum hCG concentration is no longer detectable since there are reports of tubal rupture at low levels of β-hCG
  • This method of treatment tends to be discouraged due to persistence of the risk of rupture until the pregnancy has been completely resolved

Anti-D Immunoglobulin

  • Based on expert opinion, anti-D immunoglobulin is recommended in nonsensitized patients who are rhesus negative and who have ectopic pregnancy
  • Anti-D prophylaxis may be offered to women who had surgical removal of an ectopic pregnancy or if bleeding is heavy, repeated or with abdominal pain 
  • Suggested dose is 250 IU (50 mcg)
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