Ectopic pregnancy: Zero in on these lab and imaging clues
Quantitative β-hCG measurements and transvaginal ultrasound findings interpreted in light of a β-hCG “cutoff” can reliably guide clinical decisions.
Surgical management
Laparoscopic salpingostomy is the preferred surgical treatment for ectopic pregnancy. A Cochrane review meta-analysis of 35 randomized controlled trials (RCTs) on intervention of ectopic pregnancy concluded that, compared with laparotomy, laparoscopy results in shorter operative time, less blood loss, less analgesia, shorter hospital stays, and greater cost effectiveness.28 Another meta-analysis of 15 RCTs concluded that laparoscopic salpingostomy is the most cost-effective treatment for ectopic pregnancy. 31
Medical management with methotrexate
This folic acid antagonist is highly effective in treating ectopic pregnancy, and is usually given intramuscularly for this indication. Clinicians who use this chemotherapeutic agent must be familiar with its dosing regimen, contraindications, and possible adverse effects. Multidose MTX is more effective than surgery, but more expensive.32 Single-dose MTX has a higher failure rate than laparoscopic salpingostomy, especially in patients with higher β-hCG levels.32
The best candidate for medical therapy is the woman who is asymptomatic, motivated, and compliant. Absolute contraindications to single-dose MTX include the following:
- breastfeeding
- overt or lab evidence of immunodeficiency
- alcoholism, alcoholic liver disease, or other chronic liver disease
- preexisting blood dyscrasias, such as bone marrow hypoplasia, leucopenia, thrombocytopenia, or significant anemia
- known sensitivity for methotrexate
- acute pulmonary disease
- peptic ulcer disease
- hepatic, renal, or hematologic dysfunction, and several metabolic diseases.33
Dosing regimen. The 3 general dosing schemes of single dose, 2-dose, and multidose (up to 4 doses) are shown in the TABLE. These were recommended by the American College of Obstetrician and Gynecologists (ACOG).33
Single dose vs multidose. The single-dose treatment is easier to administer and monitor and is most cost effective, but it may have a higher failure rate than the multidose regimens.28 The best prognostic indicator of successful treatment with single-dose MTX is the initial β-hCG level. The lower the initial level, the higher the success rate. The reported failure rate is 1.5% if the initial β-hCG level is <1000 mIU/mL; 5.6% with 1000 to 2000 mIU/mL; 3.8% with 2000 to 5000 mIU/mL; and 14.3% with 5000 to 10,000 mIU/mL.34 ACOG has outlined relative contraindications to single-dose MTX: ectopic pregnancy larger than 3.5 cm and the presence of fetal cardiac activity. Both correlate with an increased failure rate. Patients with PUL and low β-hCG levels are good candidates for single-dose MTX treatment.
Monitoring efficacy of treatment
Serum β-hCG levels indicate response to medical and surgical therapy. After salpingostomy, the serum β-hCG level declines rapidly within the first 4 days, and then more gradually, with mean resolution occurring at about 20 days. In contrast, after single-dose MTX, the mean serum β-hCG level increases for the first 4 days and then gradually declines, with a mean resolution at 27 days.35 The guideline for surveillance is shown in the TABLE.
CASE 1 The FP counsels Helen on the risks and benefits of surgery and MTX treatment for her ectopic pregnancy, and she elects to have a laparoscopic salpingostomy. The FP refers Helen to an OB/GYN via the emergency department on the same day. Helen does well. After the surgery, her β-hCG is monitored every 2 days until it decreases to 1000 mIU/mL, then every week until it is negative.
CASE 2 The FP advises Mary that an OB/GYN would likely recommend a D&C for her PUL, as her β-hCG level is above the discriminatory cutoff and the TVUS does not show a viable IUP. After discussing MTX treatment and manual vacuum aspiration of the uterine contents, Mary elects to have the MTX treatment and receives the 2-dose protocol. Her β-hCG level is 4210 mIU/mL on Day 1—higher than her level prior to the methotrexate treatment, but expected. Levels drop to 3635, 3102, and 2214 mIU/mL on Days 4, 7, and 10, respectively. Mary receives weekly surveillance until her level decreases to 0, which it did in a month.
TABLE
Monitoring methotrexate therapy for ectopic pregnancy
| Regimen | Surveillance |
|---|---|
| Single dose* Methotrexate, 50 mg/m2 IM | Measure β-hCG level on Days 4 and 7: If difference ≥15%, repeat weekly until undetectable
|
| 2 dose Methotrexate, 50 mg/m2 IM, Days 0, 4 | Follow up as for single-dose regimen |
| Multidose (up to 4 doses) Methotrexate, 1 mg/kg IM, Days 1, 3, 5, 7 Leucovorin, 0.1 mg/kg IM, Days 2, 4, 6, 8 | Measure β-hCG level on Days 1, 3, 5, and 7
|
| β-hCG, beta-human chorionic gonadotropin; IM, intramuscularly. *Preferred treatment if low initial β-hCG level. Adapted from: Seeber BE, et al. Obstet Gynecol. 2006.27 | |
