The Evolution of Methotrexate as a Treatment for Ectopic Pregnancy and Gestational Trophoblastic Neoplasia: A Review

Abstract

Methotrexate was developed in 1949 as a synthetic folic acid analogue to compete with folic acid and thus interfere with cell replication. While initially developed as a potential treatment for acute lymphoblastic leukaemia, a serendipitous observation led to methotrexate's use to effect the dramatic cure of a case of advanced choriocarcinoma. This prompted the exploration for the potential of methotrexate to treat other conditions involving disordered trophoblastic tissue. Methotrexate has subsequently revolutionized the treatment of two pregnancy-related conditions—gestational trophoblastic neoplasia and ectopic pregnancy. This article reviews the development of modern treatment protocols that use methotrexate to medically treat these two important gynaecological conditions.

Multidose Methotrexate Treatment of Ectopic Pregnancies with High initial β-Human Chorionic Gonadotropin: Can Success Be Predicted?

“…No difference was found between the success and the failures by means of side effects. On the other hand, the success rate (88.5%) was comparable with the reports of patients with lower initial βhCG and higher than those reported on patients with high βhCG values in the literature [1,2,4,6].…”

“…Mtx is also given in a multidose regimen of daily 1 mg/kg intramuscularly, alternating with 0.1 mg/kg of folinic acid intramuscularly for up to 4 doses or 2 dose regimen where 2 doses of Mtx was injected on day 0 and day 4 while continuing the same surveillance of human chorionic gonadotropin (hCG) with a single-dose protocol (on days 4 and 7) without folic acid. All these regimes are effective and safe with reported success rates of 65-94% and have minimal side effects [2][3][4].…”

“…Data about the Mtx treatment in patients with (βhCG) > 5,000 mIU/mL in the literature is relatively scarce because majority of those patients undergo surgery [2,3,7,8]. In this study, to the selected patients with high initial serum (βhCG; between 5,042 and 31,114 mIU/mL) who asked medical therapy, multiple doses of Mtx (1 mg/kg) with folinic acid rescue were given on an individualized basis.…”

“…Use of other drugs such as Ru-486, gefitinib and Actinomycine D is still in the experimental stage. There are 3 widely used protocols of Mtx treatment, namely, single, double, and multiple dose regimens, but debate still exits as to which regimen is more appropriate for the ectopic pregnancy patients [2,3].…”

Ameliorative Effect of Quercetin on Methotrexate Induced Toxicity in Sprague-Dawley Rats: A Histopathological Study

“…1 In addition to its enlarged spectrum of clinical use, a well-defined toxicity profile has been identified and has a growing body of evidence which suggest significant toxic effect associated with its dose and duration. Methotrexate may cause mild to severe life threatening side effects which may cause reversible or irreversible adverse effect to the host.…”