Medical Therapy for Ectopic Pregnancy

Gary H Lipscomb M.D.


Semin Reprod Med. 2007;25(2):93-98. 

In This Article

Complications Of Methotrexate Therapy

It is common for patients to experience an episode of increased abdominal pain during medical treatment for an ectopic pregnacny.[15] Although the true cause of this pain is unknown, it is likely that the pain results from either tubal abortion or tubal stretching from hematoma formation. Fortunately, the pain is generally self-limiting and controlled with nonsteroidal anti-inflammatory agents such as ibuprofen, 800 mg by mouth. Interesting, nonsteroidal anti-inflammatory agents appear to be more effective for this type of pain than many narcotic-containing oral analgesics. The prescription of narcotic oral medications for use at home should be avoided because the drug might mask a true tubal rupture. At our institution, patients are advised take ibuprofen for any increased pain and to rest for 1 hour. If significant relief does not occur, they are instructed to return to the office or hospital for evaluation. Hemodynamically stable patients with severe pain are admitted and observed with serial hematocrits. An ultrasound can also be obtained to document the presence of blood outside the pelvis, indicating probable tubal rupture. As noted previously, the presence of presumed blood confined to the pelvis is not an indication for surgical intervention.

In an earlier review of our first 258 ectopic pregnancies treated with single-dose methotrexate, 34 patients required hospitalization for severe unrelieved pain and 22 other patients were evaluated as outpatients and released.[16] Twenty-seven of these 34 hospitalized patients (79%) did not require surgery during this hospitalization. Two hospitalized patients and one outpatient ultimately underwent surgery at a time remote from evaluation. Two of these surgeries were in patients who refused additional medical therapy and requested surgery.

In many centers, patients with separation pain requiring evaluation undergo surgical therapy. Extrapolating from the above data, our success rate would have decreased to 82.5% if those patients hospitalized for separation pain underwent surgery, and 74% if all patients with pain severe enough to require evaluation underwent surgery. We believe early surgical intervention in patients experiencing separation pain may be one reason for the lower success rate reported with single-dose methotrexate therapy by other institutions.

Following treatment with methotrexate, 56% of ectopic masses will increase in size if followed by ultrasound.[10] We have observed hematomas 7 to 8 cm in size develop after treatment with methotrexate. Interestingly, most of these patients are asymptomatic. These masses frequently will persist for some time; the longest documented time to resolution was 108 days.[10] Persistence after the disappearance of hCG is also common. These masses should not be interpreted as a treatment failure, given that they probably represent resolving hematomas rather than trophoblastic tissue.

Potentially serious side effects, including marrow suppression, pulmonary fibrosis, nonspecific pneumonitis, liver cirrhosis, renal failure, and gastric ulceration, can occur with methotrexate. However, these invariably are seen when methotrexate is given in high doses with frequent dosing intervals (i.e., chemotherapeutic protocols for malignancy). Such side effects rarely are seen with the doses, dosing intervals, or treatment duration used for medical management of ectopic pregnancy. None of the ~600 patients treated at our institution have experienced serious side effects.

The most common side effect observed with the single-dose methotrexate protocol is excessive flatulence and bloating due to intestinal gas formation. This problem is usually self-limited and handled as described previously. Transient mild elevation of liver-function tests can occur but rarely exceed twice the upper limit of normal. These tests invariably return to normal within 2 weeks. Stomatitis may also be seen in patients receiving more than one methotrexate injection and is generally self-limited. If needed, viscous lidocaine can be used for symptomatic relief.

The natural history of ectopic pregnancy is highly variable. At one extreme, there is acute pain, hemorrhage, shock, and even death. At the other, in an asymptomatic patient, the implantation may undergo resorption or tubal abortion. When hCG titers are decreasing and there is no evidence of tubal rupture, nonintervention offers freedom from chemotherapy toxicity and surgical morbidity. Success rates have been reported to be from 70 to 100%.[17] At our institution, we examine at least two hCG levels in all tubal ectopic pregnancies without cardiac activity before treatment with methotrexate. Patients with decreasing levels are observed conservatively as long as hCG levels decrease appropriately. However, because decreasinf hCG levels are no guarantee against rupture, many physicians prefer to treat all diagnosed ectopic pregnancies with methotrexate regardless of the status of the hCG levels.


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