I. Epidemiology & Etiology

  1. Incidence about 20/1,000 pregnancies
  2. Accounts for about 9% of all pregnancy-related deaths
  3. Risk factors
    1. Prior pelvic inflammatory disease, particularly if due to Chlamydia
    2. Prior ectopic pregnancy
    3. Prior tubal surgery
    4. Tobacco use
    5. DES exposure
    6. Increasing age
    7. History of infertility

II. Clinical features

  1. Pelvic pain and tenderness and cervical motion tenderness, & often bleeding, usually around 7-8 weeks gestation
    1. The following were ass'd with < 10% risk of having ectopic in a retrospective study of 438 pts presenting to ER with abdominal pain or bleeding in 1st TM (Ann. Emer. Med. 33:283, 1999--AFP):
      1. No pain or only mild pain & no risk factors for ecopic pregnancy (h/o infertility, IUD use, prior BTL, h/o pelvic surgery) (5.5% prevalence)
      2. Mod-severe pain but no cervical motion tenderness, peritoneal signs, or risk factors (8.5% prevalence)
      3. Mod-severe pain & CMT but open cervical os (0% prevalence)
  2. Diagnosis
    1. Ultrasound (transvaginal)
      1. Should be able to detect IUP from 5wks or when hCG is > 2,000 mIU/ml
      2. Can identify ectopics with less than perfect sensitivity but very high specificity
      3. Note that can have IUP and ectopic simultaneously if has dizygotic twins; incidence of this is unknown but thought to be rare
    2. Serial quantitative serum beta-hCG
      1. hCG is generally lower with ectopic than with intrauterine pregnancy (IUP) for a given gestational age
      2. In IUP at 6-8 weeks, hCG should increase 66% over 48h (won't in 15% of normal IUP's and will increase that much in 17% of ectopics!)
      3. hCG decreasing over time suggests nonviable pregnancy
      4. In a study in 200 women presenting to an ED with first-trimester pain or vaginal bleeding and inconclusive initial ultrasound, eventually confirmed to have ectopic pregnancy, who also had at least 2 serial serum hCG measurements > 24h but < 7d apart, 21% had increases in hCG similar to what is considered normal witu intrauterine pregnancies
      5. After successful tx of ectopic, serum hCG decreases in two-phase distribution (initial half-life 5-9h; secondary half-life 22-32h)
    3. Serum progesterone levels--not very useful
    4. Absence of products of conception on uterine curettage, if performed, is suggestive of ectopic
  3. Spontaneous resolution
    1. 20-30% of ectopic pregnancies are ass'd with declining hCG at time of dx
    2. 88% of those with hCG < 200mIU/ml at time of dx spontaneously resolve!

III. Treatment

  1. Patient features to consider in choice of medical vs. surgical tx:
    1. These features must be present:
      1. No evidence for rupture
      2. Hemodynamically stable w/o active bleeding
      3. Diagnosed w/o laparoscopy
      4. Ability to return for f/u care
      5. No contraindications to methotrexate (see below)
    2. These features tend to favor medical as opposed to surgical tx
      1. Desire for future fertility
      2. Contraindications to general anesthesia
      3. Mass no more than 3.5cm in greatest dimension
      4. No fetal cardiac motion detected
      5. hCG < 15,000 mIU/ml
    3. Absolute contraindications to methotrexate:
      1. Breastfeeding
      2. Immunodeficiency
      3. Chronic liver disease or alcoholism
      4. Blood dyscrasia of any type
      5. Known sensitivity to methotrexate
      6. Active pulmonary disease
      7. Peptic ulcer disease
      8. Renal dysfunction
    4. Relative contraindications to mthotrexate:
      1. Gestational sac > 3.5cm in longest dimension
      2. Embryonic cardiac motion
    5. Success rate, tubal patency rates at 3mos, and subsequent pregnancy rates in pts trying to conceive were similar in one nonrandomized trial comparing surgical vs. medical (methotrexate) tx for ectopic pregnancy (Obs. Gyn 92:989, 1998--AFP)
  1. Methotrexate
    1. Interferes with DNA synthesis and hence cellular replication
    2. Associated with success in about 85% of cases with single-dose tx.
      1. Serum hCG a sig. predictor of success in a retrospective study of 350 pts--those w/hCG < 15,000 had 93% chance of success; those with hCG > 15,000 had a 66% chance of success (NEJM 341:1974, 1999--JW)
    3. Procedure
      1. Check baseline beta-hCG, BUN/Cr, LFT's, and CBC w/plats (also blood type & Rh and Ab screen)
      2. Give RhOGAM if Rh-negative
      3. Counsel pt to d/c any folic acid supplements including prenatal vitamins; avoid NSAIDs (b/c of bleeding risk?) and avoid intercourse (?why--ACOG bulletin doesn't say)
      4. Counsel re: signs/sx of tubal rupture (increased pain, bleeding, dizziness, syncope, tachycardia)
      5. Methotrexate 50mg/m2 of body surface area IM x 1
        1. Other protocols have used 75mg IM x 1 or multiple serial doses on alternate days w/alternate-day leucovorin rescue
      6. Follow quantitative hCG to determine tx response
        1. With single-dose MTX, hCG us. increases, peaking 4d after tx, starting decline by 7d post-tx
        2. Consider surgery or 2nd dose MTX if hCG doesn't decrease at least 15% from day 4 to 7 post-tx; ultrasound may be helpful in this situation
        3. Once document decline in hCG, check weekly until undetectable (can take up to 1mo!)
      7. Also consider tx failure if pain worsens or hemodynamically unstable, regardless of what hCG is doing--this may indicate rupture!
    4. Side f/x are us. mild & self-limiting
      1. Increase in abdominal pain (seen in 2/3 of pts; lasts 24-48h; us. milder than pain from rupture)
      2. Some vaginal bleeding us. seen
      3. Nausea & vomiting
      4. Stomatitis
      5. GI upset and diarrhea
      6. Dizziness
      7. Neutropenia (rare)
      8. Alopecia (rare; reversible)
      9. Pneumonitis
      10. Effects on fertility--unclear as of 1998 how compare w/surgical tx
  2. Surgery (laparoscopic or open salpingotomy or salpingectomy)

(Source: ACOG Practice Bulletin #3, 12/98)