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.

Figure 1

The mechanism by which methotrexate inhibits cellular proliferation. Active transporter includes the reduced folate carrier and an endocytic pathway activated by a folate receptor; dUMP: deoxyuridine monophosphate; CH₂FH₄: methylenetetrahydrofolate.