METHOTREXATE EFFECTS ON TROPHOBLAST AND THE CORPUS-LUTEUM IN EARLY-PREGNANCY

OBJECTIVE: Our purpose was to determine whether methotrexate affects t he trophoblast or corpus luteum when administered for abortion. STUDY DESIGN: A randomized controlled trial was performed in women requestin g an abortion up to 49 days' gestation. Twenty patients were treated w ith intramuscular methotrexate 50 mg/m(2) (10 women) or 60 mg/m(2) (10 women). Serum beta-human chorionic gonadotropin, progesterone, and 17 -hydroxyprogesterone levels were determined at baseline and then seria lly after methotrexate administration for the first 24 hours, then eve ry 24 hours for 7 days. On the seventh day misoprostol 800 mu g was ad ministered vaginally. RESULTS: Serum beta-human chorionic gonadotropin increased at a lower rate than occurs in normal pregnancy. Progestero ne levels averaged 56.9 +/- 19.8 nmol/L at baseline and 45.5 +/- 20.5 nmol/L (P=.01) 1 week after methotrexate. Progesterone decreased in 16 women over the 7 days and increased in the other 4; these latter wome n all aborted after a single dose of misoprostol. Levels of 17-hydroxy progesterone plateaued during the first day after methotrexate adminis tration; both progesterone and 17-hydroxyprogesterone declined simulta neously between the third and fourth day after methotrexate. CONCLUSIO NS: Methotrexate most likely primarily affects trophoblast production of human chorionic gonadotropin, as evidenced by a blunting of the exp ected increase in serum beta-human chorionic gonadotropin resulting in less support for the production of progesterone by the corpus luteum. However, changes in progesterone levels after methotrexate administra tion were inconsistent and are unlikely to represent the ultimate effe ct of methotrexate in abortion. The less-than-normal increase in serum beta-human chorionic gonadotropin levels after methotrexate administr ation is most likely a result of disruption of cytotrophoblast syncyti alization. This disruption may be the true effect of methotrexate in d estabilizing the implantation site of an early pregnancy.