Methotrexate versus laparoscopic salpingostomy. In 1 randomized clinical comparison,29 100 women with laparoscopy-confirmed ectopic pregnancy were randomized to methotrexate or laparoscopic salpingostomy. Of the 51 patients treated medically, 7 (14%) required surgical intervention for active bleeding and/or tubal rupture. An additional course of methotrexate was required in 2 patients (4%) for persistent trophoblasts.
Of the 49 patients in the salpingostomy group, 4 women (8%) failed therapy and required salpingectomies, and 10 patients (20%) were treated with methotrexate for persistent trophoblasts.
Tubal patency was present in 23 of 42 women (55%) in the methotrexate group, compared with 23 of 39 (59%) in the salpingostomy group.
Overall, this randomized study29 and previous meta-analysis demonstrate that systemic multiple-dose methotrexate is comparable in efficacy to laparoscopic salpingostomy.
TABLE 2
Multiple-dose methotrexate protocol
Discontinue treatment when there is a decline in 2 consecutive ß-hCG titers or after 4 doses, whichever comes first.
| DAY | INTERVENTION | DOSE (MG) |
|---|---|---|
| 1 | Baseline studies ß-hCG titer, CBC, and platelets Methotrexate | 1.0 |
| 2 | Leucovori | 0.1 |
| 3 | Methotrexate | 1.0 |
| 4 | Leucovorin ß-hCG titer | 0.1 |
| 5 | Methotrexate ß-hCG titer | 1.0 |
| 6 | Leucovorin ß-hCG titer | 0.1 |
| 7 | Methotrexate ß-hCG titer | 1.0 |
| 8 | Leucovorin ß-hCG titer CBC and platelets Renal and liver function tests | 0.1 |
| Weekly | ß-hCG titer until negative |
TABLE 3
Treatment outcomes for ectopic pregnancy
| METHOD | NUMBER OF STUDIES | NUMBER OF PATIENTS | NUMBER WITH SUCCESSFUL RESOLUTION | TUBAL PATENCY RATE | SUBSEQUENT FERTILITY RATE | |
|---|---|---|---|---|---|---|
| INTRAUTERINE PREGNANCY | ECTOPIC PREGNANCY | |||||
| Conservative laparoscopic surgery | 32 | 1,626 | 1,516 (93%) | 170/223 (76%) | 366/647 (57%) | 87/647 (13%) |
| Variable-dose methotrexate | 12 | 338 | 314 (93%) | 136/182 (75%) | 55/95 (58%) | 7/95 (7%) |
| Single-dose methotrexate | 7 | 393 | 340 (87%) | 61/75 (81%) | 39/64 (61%) | 5/64 (8%) |
| Direct-injection methotrexate | 21 | 660 | 502 (76%) | 130/162 (80%) | 87/152 (57%) | 9/152 (6%) |
| Expectant management | 14 | 628 | 425 (68%) | 60/79 (76%) | 12/14 (86%) | 1/14 (7%) |
| Reprinted with permission from Elsevier (The Lancet, 1998, vol 351, 1115–1120). | ||||||
Fine points of treatment
During methotrexate therapy, examine the patient only once to avoid triggering a rupture, and counsel her to avoid intercourse for the same reason.30 Do not perform repeat vaginal ultrasound examination. Also inform her that transient pain (“separation pain”) from tubal abortion frequently occurs 3 to 7 days after the start of therapy, lasts 4 to 12 hours, and then resolves.31 This is perhaps the most difficult aspect of methotrexate therapy, as it is not always easy to differentiate the pain of tubal abortion from the pain of rupture.
If ß-hCG titers continue to rise rapidly between methotrexate doses, rupture is more likely and surgery should proceed.32
Overall, isthmic ectopic pregnancies (12.3% of ectopics) appear to be at a particularly high risk for rupture and comprise nearly half of methotrexate failures.32 Unfortunately, there is no way to identify isthmic pregnancies without surgery.
Avoid NSAIDs and GI-“unfriendly” foods. Counsel the patient to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) because they may impair natural hemostasis. Gasforming foods such as leeks, corn, and cabbage can cause distension, which may be mistaken for rupture.
Also instruct the patient to avoid folic acid, which impairs the efficacy of methotrexate.
Ultrasound surveillance is unnecessary. If an adnexal mass was identified at initial imaging, there is no need to view it again, since these masses tend to enlarge and form hematomas and can cause undue anxiety in both physician and patient. In properly selected patients, multidose methotrexate with monitoring of ß-hCG levels should suffice.
When surgery is indicated
Surgical intervention is necessary when pain is severe, persists beyond 12 hours, and is associated with orthostatic hypotension, falling hematocrit, or persistently elevated ß-hCG levels after methotrexate therapy.
Laparoscopy is the preferred approach. Advantages include less blood loss and analgesia,33 shortened postoperative recovery, and lower costs.
Technique. For unruptured ampullary ectopic pregnancy, salpingostomy is preferred. Make a linear incision over the bulging antimesenteric border of the fallopian tube using electrocautery, scissors, or laser. Remove the products of conception using forceps or suction, and leave the incision to heal by secondary intention.
For isthmic pregnancies, use segmental excision followed by delayed microsurgical anastomosis.34 The isthmic tubal lumen is narrower and the muscularis thicker than in the ampulla. Thus, the isthmus is predisposed to greater damage after salpingostomy and greater rates of proximal obstruction.33
An increased risk of persistent ectopic pregnancy has been a criticism of salpingostomy. However, when 1 dose of systemic methotrexate is combined with salpingostomy, the risk of persistent pregnancy is virtually eliminated.35
When rupture occurs, salpingectomy is the first choice for treatment, as it arrests hemorrhage and shortens the procedure. Either laparoscopy or laparotomy is appropriate.
The authors report no financial relationships relevant to this article.