Ectopic Pregnancy Treatment image

Ectopic Pregnancy Treatment


  • Once a diagnosis of ectopic pregnancy has been made, a treatment plan must be generated.
    • Per ACOG PB 193: “In 2011–2013, ruptured ectopic pregnancy accounted for 2.7% of all pregnancy-related deaths and was the leading cause of hemorrhage-related mortality”
    • Despite lay claims to the contrary, there is no surgical maneuver that can remove and ectopic and re-implant it in the uterus


  • Tubal pregnancy accounts for approximately 2% (1 in 50) of reported pregnancies 
  • The incidence of recurrence is approximately 15%; rises to 30% after (2) ectopics
  • Over half of women diagnosed with ectopic pregnancy have no risk factors
  • Among women presenting to the ER with first trimester bleeding and pain the incidence of ectopic pregnancy can be as high as 18% (ACOG PB193)
  • Vaginal bleeding with an ectopic may be light, but the cause of massive hemorrhage and death is typically tubal rupture and intra-abdominal bleeding
  • Surgical intervention is needed for the following
    • Vital signs are unstable
    • Hematoperitoneum is seen on imaging
  • Rh Status
    • Obtain blood type and Rh status on all women with suspected of ectopic pregnancy
    • All Rh-negative women with bleeding should receive RhO(D) immune globulin (RhoGam)
    • Administer regardless of the final outcome of the pregnancy
    • A 50mcg dose is appropriate for pregnancy loss < 12w0d


  • Evaluation of the pregnancy of unknown location and diagnosis of ectopic is covered in the ‘Pregnancy of Unknown Location’ chapter (see ‘Related Topics’ below)


Expectant Management

  • Expectant management is not typically offered in the US
  • However, in the UK, expectant management is permitted under certain clinical circumstances (NICE NG126)
    • Patient stable and pain free
    • Tubal ectopic measuring <35 mm with no visible heartbeat
    • hCG level ≤1000 IU/L
    • Can return for follow up
  • UK NICE recommended expectant management follow-up: hCG measurements on days 2, 4 and 7 and look for 15% drop at each measurement
    • If drop ≥15%: Draw hCG levels at weekly intervals to zero
    • If drop <15%: Alternate management should be undertaken
  • Option in the UK guidance based on literature that, among appropriate candidates, did not show a difference between expectant and medical management for the following
    • Rate of rupture or need for further treatment
    • Future fertility and pregnancy outcomes
  • Additionally, there is a small RCT (Jurkovic et al. Ultrasound Obstet Gynecol, 2017) that showed no difference in outcomes in women with hCG <1500 at diagnosis between those treated with MTX or expectantly managed
    • 80 women were consented and randomized to 50mg/m2 of MTX versus placebo injection
    • Time to resolution was comparable between arms
    • Resolution of pregnancy was 83% for methotrexate and 76% for placebo


  • Determination of Pregnancy Location Prior to Methotrexate (MTX) Use is important for many reasons
    • Prevents risk of birth defects from accidental exposure of ongoing IUP 
    • Limits MTX exposure to those patients who actually need it 
    • Confirmation/knowledge of true location may impact management of current and future pregnancies 
  • Risk of waiting for MTX administration in Pregnancy of Unknown Location (PUL) 
    • Rupture of ectopic pregnancy while making the determination 
    • Loss to follow-up
  • Patients should be given strict precautions for return and signs of rupture 
  • Consider MTX if following met 
    • Confirmed or high clinical suspicion of ectopic pregnancy 
    • Hemodynamically stable 
    • Unruptured mass 

Contraindications to MTX

  • Absolute MTX Contraindications include 
    • Intrauterine pregnancy | Breastfeeding | Immunodeficiency | Blood dyscrasias | Clinically important hepatic Dysfunction | Active pulmonary disease | Active peptic ulcer disease | Clinically important renal dysfunction | Patient sensitive to MTX | Inability to participate in follow-up 
  • Relative MTX Contraindications 
    • Gestational sac > 4 cm (TV ultrasound) | High quantitative HCG (qHCG) | Positive fetal cardiac activity | Refusal to accept blood transfusion 
  • There is a risk of rupture or abortion with hematoperitoneum after treatment with MTX 
    • This risk appears to be low if patient is closely monitored. 


  • Protocols can include single dose (most common), 2 dose, and multiple dose with leukovorin rescue doses 
    • Multiple (3+) dose protocols have not proven superior in studies 
    • 2 doses have been shown to be superior to single dose (Alur-Gupta et al. AJOG, 2019)  
      • Higher resolution of ectopic pregnancy 
      • Superior in cases where hCG was higher or there was a visible adnexal mass (which are higher risk for treatment failure) 
  • Can start with single dose and re-dose based on need 
    • MTX is dosed at 50mg/m2 (based on patient height and weight) 
    • LFTs and basic metabolic panel should be checked before administrating MTX 
  • Typical monitoring protocol
    • Check hCG levels on days 0 (administration day), 4 and 7, then weekly if level continues to fall
    • hCG level may rise on day 4 but this does not warrant retreatment
    • By day 7, the hCG level should have fallen by 15% from day 4 (PPV of 93%; Kirk et al. Human Reproduction, 2007)


  • If pregnancy location is unknown (and normally progressing IUP has been excluded)
    • Can treat surgically by evacuating the uterine cavity and checking for villi to determine if there was an early IUP loss (incomplete AB)
    • This can be done by floating products in water in Operating Room (if provider is experienced in determining this) or by frozen section by pathology
    • If negative for villi then can continue on to laparoscopy (ACOG PB 193) 
  • Surgical management of known tubal ectopic can include removal of the pregnancy from the tube (salpingostomy) or removal of the tube and pregnancy (salpingectomy) 


  • Not shown to improve future fertility if the patient’s other tube is present and appears normal (Mol et al. Lancet, 2014)
  • Could theoretically increase risk of future ectopic due to internal damage or previous damage and/or abnormality
    • However, in the RCT by Mol et al (Lancet, 2014) this was not shown to be the case and confirmed in a meta-analysis of previous retrospective publications 
    • Non-significant higher risk of continued trophoblastic tissue after surgery (Mol et al. Lancet, 2014)
  • Typical monitoring protocol
    • QHCG should be checked at post-operative visit (4 to 6 weeks) for salpingostomy or patients whose tissue was aborted at the time of surgery and at risk for implantation in the peritoneal cavity
    • Checking qHCG at the 4 to 6-week visit for all surgically managed ectopic pregnancies is a valid protocol
  • Surgical treatment of tubal pregnancy should be laparoscopic unless patient is too unstable or there is concern that hematoperitoneum is too large 

Cornual Pregnancy

  • Cornual pregnancy surgical treatment is higher risk for bleeding complications
    • While sometimes able to be removed laparoscopically, patient should be counseled on high risk of conversion to open surgery 
  • Cornual, abdominal and other ectopic pregnancies not in the tube should be managed by a provider with experience as they are at higher risk of complications and morbidity/mortality

Cervical Ectopic

  • 1 in 9000 pregnancies
  • Tamponade with size 26-Foley catheter may be used to temporize bleeding (30cc)
  • Methotrexate is first line for cervical ectopic
  • Ligation of blood vessels: vaginal of cervical branches, uterine artery ligation or embolization of cervical, uterine or internal iliac arteries, usually in preparation for D&C, or alongside chemotherapy.  Limited data on fertility following UAE for cervical ectopic. Cervical artery ligation (3 and 9 o’clock with 2-0 vicryl) and tamponade. 
  • Surgical excision usually involves curettage, but risks severe hemorrhage.  Consider vasopressin prior to curettage (20 to 30 mL of vasopressin (0.5 units/mL).  Can consider primary hysterectomy if patient not desiring future fertility.  In a review, 100% of cervical ectopic > 12 weeks required hysterectomy
  • Ultrasound guided intra-amniotic instillation of KCl (20-gauge needle with 1 to 5 mL of 20% KCl )solution and/or methotrexate if FCA present; resorption can take 1-3 months


Hsu et al. AJOG, 2017

Retrospective Cohort Study of a Prospective Dataset  (2006-2015) that assessed management trends and associations in ectopic pregnancy | 62,588 women were included

  • Overall, 78.4% of women were treated surgically vs 21.6% who were treated with MTX
  • From 2006-2015
    • MTX use increased from 14.5% to 27.3% (P<.001)
    • Salpingostomy decreased from 13.0% to 6.0% (P<.001)
  • Teaching hospital and higher volume centers were associated with the increased use of methotrexate (P<.05)
  • Medicaid recipients were less likely to receive MTX (adjusted risk ratio [ARR] 0.92; 95% CI, 0.87 to 0.98)
  • Uninsured women were less likely to receive MTX (ARR 0.87; 95% CI, 0.82 to 0.93)
  • Among those who underwent surgery, compared to white women, Black and Hispanic women were less likely to undergo salpingostomy
    • Black women: ARR 0.76 (95% CI, 0.69 to 0.85)
    • Hispanic women: ARR 0.80 (95% CI, 0.66 to 0.96)
  • Among those who underwent surgery and were analyzed for insurance status, compared to commercial insurance
    • Women with Medicaid were less likely to undergo salpingostomy ARR 0.69 (95% CI, 0.64 to 0.75)
    • Uninsured women were less likely to undergo salpingostomy ARR 0.60 (95% CI, 0.55 to 0.6)
  • Conclusions
    • The authors conclude that there are significant race and insurance related disparities in management of ectopic pregnancy
    • However, the study did not assess outcomes and they were unable to compare clinical parameters at entry to care (such as weeks’ gestation at presentation)



  • The recommendations in this chapter refer to treatment of ectopic pregnancy in a tubal location
  • However, 90% of ectopic pregnancies are tubal and the ACOG Practice Bulletin states

However, implantation in the abdomen (1%), cervix (1%), ovary (1–3%), and cesarean scar (1–3%) can occur and often results in greater morbidity because of delayed diagnosis and treatment

An ectopic pregnancy can also co-occur with an intrauterine pregnancy, a condition known as heterotopic pregnancy

The risk of heterotopic pregnancy among women with a naturally achieved pregnancy is estimated to range from 1 in 4,000 to 1 in 30,000, whereas the risk among women who have undergone in vitro fertilization is estimated to be as high as 1 in 100


ACOG Practice Bulletin 193: Tubal Ectopic Pregnancy

NICE Guideline [NG126] Ectopic pregnancy and miscarriage: diagnosis and initial management

Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial (Jurkovic et al. Ultrasound Obstet Gynecol, 2017)

Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis (Alur-Gupta et al. AJOG, 2019)

Diagnosis and management of cervical ectopic. (Singh. J Hum Reprod Sci, 2013)

A validation of the most commonly used protocol to predict the success of single-dose methotrexate in the treatment of ectopic pregnancy (Kirk et al. Human Reproduction, 2007)

Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial (Mol et al. Lancet, 2014)

Disparities in the management of ectopic pregnancy (Hsu et al. AJOG, 2017)