BSA = body surface area; �-hCG =�-human chorionic gonadotropin; MTX = methotrexate; NA = not applicable. Data from American Society for Reproductive Medicine, 2013.
Of precautions, MTX is bound primarily to albumin, and its displacement by other medications such as phenytoin, tetracyclines, salicylates, and sulfonamides can increase MTX serum drug levels. Moreover, renal clearance of MTX may be impaired by nonsteroidal antiinlammatory drugs including aspirin, probenecid, or penicillins (Stika, 2012). Last, vitamins containing folic acid may lower MTX eicacy.
For ease and eicacy, intramuscular MTX administration is used most often for ectopic pregnancy medical resolution, and single-dose and multidose MTX protocols are available (see Table 19-1). As noted, MTX can lead to bone marrow depression. his toxicity can be blunted by early administration of leucovorin, which is olinic acid and has activity equivalent to folic acid. Thus, leucovorin, which is given within the multidose protocol, allows for some purine and pyrimidine synthesis to bufer side efects.
In comparing these two protocols, trade-ofs are recognized.
For example, single-dose therapy ofers simplicity, less expense, and less intensive posttherapy monitoring and does not require leucovorin rescue. However, some but not all studies report a higher success rate for the multidose regimen (Alleyassin, 2006; Barnhart, 2003a; Lipscomb, 2005). At our institution, we use single-dose MTX.
The best candidate for medical therapy is the woman who is asymptomatic, motivated, and compliant. With medical therapy, some classic predictors of success include a low initial serum 3-hCG level, small ectopic pregnancy size, and absent fetal cardiac activity. Of these, initial serum 3-hCG level is the single best prognostic indicator of successful treatment with single-dose MTX. Speciically, reported failure rates are 1.5 percent if the initial serum 3-hCG concentration is < 1000 mID/mL; 5.6 percent at 1000 to 2000 mID/mL; 3.8 percent at 2000 to 5000 mID/mL; and 14.3 percent when levels range between 5000 and 10,000 mID/mL (Menon, 2007). Interestingly, the initial serum 3-hCG value is not a valid indicator of the number of doses needed for successful resolution (NowakMarkwitz, 2009).
Many early trials also used "large size" as an exclusion criterion, although these data are less precise. Lipscomb and colleagues (1998) reported a 93-percent success rate with single-dose MTX when the ectopic mass was <3.5 cm. This compared with success rates between 87 and 90 percent when the mass wasi> 3.5 cm. Last, failure rates rise if cardiac activity is seen, with an 87 -percent success rate in such cases.
hese regimens are associated with minimal laboratory changes and symptoms, although occasional toxicity may be severe. Kooi and Kock (1992) reviewed 16 studies and reported that adverse efects resolved by 3 to 4 days ater MTX was discontinued. he most common were liver involvement-12 percent; stomatitis6 percent; and gastroenteritis-1 percent. One woman had bone marrow depression. Fortunately, MTX treatment does not diminish ovarian reserve (Boots, 2016; Dyar, 2013). Moreover, conceptions within the irst 6 months after MTX treatment for this indication are not associated with elevated rates of miscarriage or fetal malformations and growth restriction (Svirsy, 2009).