Methotrexate (MTX) Treatment for Ectopic Pregnancy – Systemic vs Local Injection
M. Pansky
Gynecologic Endoscopy Unit,Assaf Harofe Medical Center Zerifin
Affiliated Sackler School of Medicine, Tel-Aviv University, Israel
Summary
We conducted a thorough review of the literature, including the 26 largest series reporting on MTX Treatment for ectopic pregnancy. The purpose of this review was to reach a conclusion as to which is the superior method to treat unruptured ectopic pregnancy: local or systemic. Since there are extensive differences between the selection criteria for each method, and the dosage used and there is a lack of fertility long term outcome, it is difficult to reach a definite conclusion on this issue. It appears that systemic administration of MTX is more beneficial, however additional prospective randomized trials are needed in order to reach a final conclusion and better data-based decision.
Introduction
The dramatic change in the clinical picture of ectopic pregnancies, and the drive to adjust the management to the newer form of the disease, has recently stimulated many investigators to design various new non surgical methods of treatments for early unruptured ectopic pregnancy. Certain drugs, (MTX, Actinomycin-D, KCL, Hypertonic Glucose, PGF2 a, and RU-486) are capable of acting on the trophoblastic cells, arresting their growth and thus stopping the development of the ectopic pregnancy. Since MTX, a folinic antagonist, is the most popular and widely used, and is the only drug that has been administrated locally and/or systemically, this review will concentrate on it.Materials and Methods
In order to avoid bias from very small series or case reports, we limited our review to clinical studies which reported a series of more than 10 cases, which were treated either systemically or locally, guided by U/S or laparoscopy, and using the single MTX injection protocol. In our survey (26 series, 1990-1999) MTX has been administered systemically to 772 patients and locally to 559 patients. In 353 patients the procedure was guided by U.S. and in 206 by laparoscopy.
Results
Analyzing the inclusion and exclusion criteria for MTX treatment, hemodynamic stability and lack of severe abdominal pain were common to all reviews. Definite proof of pregnancy viability by means of rising titers of B-hCG levels was mandatory in only 38% of protocols. Upper limit of B-hCG level on admission was used as a selection criteria in only 11% of the series (range 5000-15000 miU/ml).
Pregnancy diameter as demonstrated by Ultrasound or laparoscopy, was used as an exclusion criteria in 57% of the series (range 3-6 cm). Fetal pulse was used as an exclusion criteria in 23% of series; endometrial biopsy for the absence of chorionic villi was mandatory in 12% of series and the amount of blood in the Douglas Pouch was used as an exclusion criteria in 18% of studies (range 100-500cc). The overall success rate, comparing different treatment modes and different dosage protocols, is summarized in Table 1. By analyzing Table 1, it appears that the use of the systemicadministration of MTX gives a slightly higher success rate. Since only few studies reported on side effects, it was very difficult to compare the two methods on this issue.
Unfortunately, only a few series reported on their fertility follow up, and from the small number of cases it appears that tubal patency, after systemic and local treatment with MTX, was 83.5% and 65.6% respectively, intrauterine pregnancy rate was 52.6% and 42% respectively and ectopic pregnancy rate was 8.3% and 3.7%.
Conclusion
1.It seems that the systemic route, of using MTX as treatment for ectopic pregnancy has advantages over local injection in terms of simplicity of use, applicability to more patients, success rate and fertility outcome.
2.Large prospective randomized trials are needed in order to establish common selection criteria, dosage of MTX and a longer follow up, all of which will aid in selecting the superior method.