Ectopic pregnancy: Histopathology and assessment of cell proliferation with and without methotrexate treatment

Objective: To evaluate tubal morphology, trophoblast proliferation, and inflammatory reaction in response to methotrexate (MTX) treatment of ectopic pregnancy (EP). Design: Nonrandomized controlled study. Setting: Academic hospital. Patients: Archival specimens from 10 EP unsuccessfully treated with MTX and 10 cases primarily treated by surgery. Interventions: Ki67/hCG and Ki67/human placental lactogen double immunohistochemical methods were used to examine trophoblastic spread, placentation, hormone production, decidualization, vascular invasion, hemorrhage, rupture, and proliferative index of the cytotrophoblast. B and T-lymphocyte responses were evaluated by CD3 and CD20. Results: Trophoblastic spread and placentation were confined to the tubal mucosa after MTX treatment, whereas invasion of the muscularis and subserosa was common in the controls. The proliferative index was reduced (19% versus 93%), although a high proliferative index was found in two of three cases complicated by rupture. Polar proliferation of Ki67-positive cytotrophoblast toward the implantation site was abolished in MTX-treated cases. Decidual reaction was not observed. No correlation was observed between the above-mentioned findings and gestational age, level of beta-hCG, dose of MTX, or interval to surgery. Conclusion: Trophoblastic spread, differentiation, and invasion were compromised by MTX treatment. Methotrexate seems to decrease cytotrophoblast proliferation. Whether a missing decrease in proliferation index reflects treatment failure awaits a larger population-based study.