A reproductive‑age woman presents with pelvic pain, vaginal bleeding, a positive pregnancy test, and risk factors (prior tubal surgery, pelvic inflammatory disease, infertility treatment, prior ectopic pregnancy). How should I evaluate (quantitative serum β‑human chorionic gonadotropin level, transvaginal ultrasound) and manage (medical with methotrexate versus surgical) a suspected ectopic pregnancy?

Evaluation and Management of Suspected Ectopic Pregnancy

In a reproductive-age woman with pelvic pain, vaginal bleeding, positive pregnancy test, and risk factors for ectopic pregnancy, immediately obtain quantitative serum β-hCG and perform transvaginal ultrasound regardless of β-hCG level—then manage medically with methotrexate if hemodynamically stable with β-hCG ≤10,000 mIU/mL and adnexal mass ≤5 cm, or surgically if unstable, β-hCG >10,000 mIU/mL, or contraindications to methotrexate exist. 1

Initial Diagnostic Evaluation

Immediate Laboratory Testing

• Obtain quantitative serum β-hCG immediately when ectopic pregnancy is suspected, as a negative test essentially excludes both intrauterine and ectopic pregnancy (becomes positive approximately 9 days after conception). 2
• Do not rely on urine pregnancy tests alone—qualitative urine tests can miss very early pregnancies or remain positive for weeks after pregnancy termination. 2
• A single β-hCG measurement has limited diagnostic value; the level alone cannot distinguish between viable intrauterine pregnancy (mean 1,300 mIU/mL), embryonic demise (1,600 mIU/mL), or ectopic pregnancy (~1,150 mIU/mL). 2

Transvaginal Ultrasound Protocol

• Perform transvaginal ultrasound (TVUS) immediately, regardless of β-hCG level—this is the single best diagnostic modality with 99% sensitivity and 84% specificity when β-hCG is elevated. 3
• Never defer ultrasound based on "low" β-hCG levels: approximately 22% of ectopic pregnancies occur with β-hCG <1,000 mIU/mL, and rupture can occur at very low levels. 2, 3
• The traditional discriminatory threshold of 3,000 mIU/mL has virtually no diagnostic utility (positive likelihood ratio 0.8, negative likelihood ratio 1.1) and should not be used to exclude ectopic pregnancy or delay imaging. 2

Key Ultrasound Findings

Definitive intrauterine pregnancy:

• Gestational sac in upper two-thirds of uterus with yolk sac or embryo visible—this essentially excludes ectopic pregnancy in spontaneous conceptions. 2

Definitive ectopic pregnancy:

• Adnexal mass without intrauterine pregnancy (positive likelihood ratio 111 for ectopic). 2, 3
• Classic "tubal-ring" sign: 1-3 cm adnexal mass with 2-4 mm echogenic rim surrounding hypoechoic center. 3
• Extraovarian adnexal mass with or without embryo/cardiac activity. 2

Pregnancy of unknown location (PUL):

• Positive pregnancy test but no intrauterine or ectopic pregnancy visible on ultrasound—7-20% ultimately prove to be ectopic. 2

Risk Stratification Based on Findings

High-Risk Features Requiring Immediate Surgical Consultation

• Hemodynamic instability (hypotension, tachycardia, syncope). 1, 4
• Peritoneal signs on examination (rebound tenderness, guarding). 2
• Moderate to large amount of free fluid or echogenic fluid in pelvis suggesting hemoperitoneum. 2
• β-hCG ≥3,000 mIU/mL without visible intrauterine gestational sac (57% ectopic risk). 2
• Fetal cardiac activity detected outside uterus on ultrasound. 4

Intermediate-Risk: Pregnancy of Unknown Location

• β-hCG <3,000 mIU/mL with no intrauterine or ectopic pregnancy visible. 2
• Hemodynamically stable with minimal symptoms. 1
• Requires serial monitoring protocol (see below). 2

Serial Monitoring Protocol for Pregnancy of Unknown Location

β-hCG Monitoring Algorithm

1. Obtain baseline quantitative serum β-hCG when pregnancy location cannot be confirmed. 2
2. Repeat β-hCG exactly 48 hours later—this interval is evidence-based for characterizing ectopic risk and viable intrauterine pregnancy probability. 2
3. Interpret the 48-hour change:
   • Rise >53-66%: suggests viable intrauterine pregnancy. 2
   • Rise <53% or plateau (<15% change): suspect abnormal pregnancy (ectopic or failing intrauterine). 2
   • Decline: suggests spontaneous resolution of nonviable pregnancy. 2
4. Continue serial measurements until β-hCG rises to 1,000-3,000 mIU/mL (when ultrasound becomes more definitive) or reaches zero. 2

Follow-Up Ultrasound Timing

• If β-hCG rises appropriately and patient remains stable, schedule repeat TVUS in 7-10 days. 2
• At β-hCG 1,000-2,000 mIU/mL, gestational sac typically becomes visible; at 3,000 mIU/mL, 99% of intrauterine pregnancies show visible sac. 2

Medical Management with Methotrexate

Inclusion Criteria (All Must Be Met)

• Hemodynamically stable with no peritoneal signs. 1
• β-hCG ≤10,000 mIU/mL (though success decreases as levels rise). 1, 5
• Adnexal mass ≤5 cm on ultrasound. 1
• No fetal cardiac activity detected. 4
• No contraindications to methotrexate (renal/hepatic dysfunction, immunodeficiency, blood dyscrasias, active pulmonary disease, peptic ulcer disease, breastfeeding). 4
• Patient able to comply with close follow-up and monitoring. 1

Methotrexate Protocol

• Single-dose regimen: 50 mg/m² intramuscularly on day 1. 1
• Measure β-hCG on days 4 and 7:
  • Expect initial rise on day 4, then decline by day 7. 1
  • If β-hCG fails to decline ≥15% between days 4 and 7, administer second dose (occurs in ~12% of patients). 1
• Weekly β-hCG monitoring until levels reach zero. 1
• Success rate: 91-94% when inclusion criteria properly followed; only 3-6% require surgery for rupture. 1

Critical Patient Instructions

• Return immediately for:
  • Worsening or severe abdominal pain (especially unilateral). 1
  • Shoulder pain (suggests diaphragmatic irritation from hemoperitoneum). 2
  • Heavy vaginal bleeding. 1
  • Dizziness, syncope, or signs of hemodynamic instability. 1
• Avoid:
  • Folic acid supplements (interferes with methotrexate). 4
  • Sexual intercourse until β-hCG reaches zero. 4
  • Nonsteroidal anti-inflammatory drugs. 4

Surgical Management

Indications for Immediate Surgery

• Hemodynamic instability or peritoneal signs. 1, 4
• Failed medical management or rising β-hCG after methotrexate. 1
• β-hCG >10,000 mIU/mL or adnexal mass >5 cm. 1
• Fetal cardiac activity detected outside uterus. 4
• Contraindications to methotrexate. 4
• Patient unable to comply with follow-up. 1

Surgical Approach

• Laparoscopy is preferred over laparotomy when patient is stable—offers economic and aesthetic advantages. 6
• Salpingectomy (removal of affected tube) if contralateral tube is healthy. 6
• Salpingostomy (linear incision with ectopic removal, tube conservation) if contralateral tube is unhealthy or absent. 6
• Laparotomy reserved for hemodynamically unstable patients or when laparoscopy is not feasible. 6

Common Pitfalls to Avoid

• Never use β-hCG level alone to exclude ectopic pregnancy—ectopic can occur at any β-hCG level, including very low values. 2, 3
• Never defer ultrasound based on "low" β-hCG—22% of ectopics present with β-hCG <1,000 mIU/mL and can rupture at these levels. 2, 3
• Never diagnose pregnancy failure based on single low β-hCG value—serial measurements are essential. 2
• Never initiate treatment based solely on absence of intrauterine pregnancy without positive findings of ectopic pregnancy. 2
• Do not assume negative urine pregnancy test rules out ectopic—obtain quantitative serum β-hCG if clinical suspicion remains high. 3
• Avoid using discriminatory threshold of 3,000 mIU/mL as sole decision point—it has no diagnostic utility for predicting ectopic pregnancy. 2

Risk Factors to Document

• Prior ectopic pregnancy (7.8% of cases). 7
• Pelvic inflammatory disease or tubal surgery (including sterilization). 4, 7, 8
• Infertility or assisted reproductive technology (23.6% of cases). 7
• Current intrauterine device. 7, 8
• History of tubal ligation or reversal. 4
• Cigarette smoking. 4
• Previous cesarean section or dilation and curettage. 7

Note: Ectopic pregnancy should be suspected in every woman of reproductive age presenting with unexplained abdominal pain, regardless of whether amenorrhea, vaginal bleeding, or risk factors are present. 7