Methotrexate effects on trophoblast and the corpus luteum in early pregnancy

OBJECTIVE: Our purpose was to determine whether methotrexate affects the trophoblast or corpus luteum when administered for abortion. STUDY DESIGN: A randomized controlled trial was performed in women requesting an abortion up to 49 days' gestation. Twenty patients were treated with 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 serially after methotrexate administration for the first 24 hours, then every 24 hours for 7 days. On the seventh day misoprostol 800 mu g was administered vaginally. RESULTS: Serum beta-human chorionic gonadotropin increased at a lower rate than occurs in normal pregnancy. Progesterone 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 women all aborted after a single dose of misoprostol. Levels of 17-hydroxyprogesterone plateaued during the first day after methotrexate administration; both progesterone and 17-hydroxyprogesterone declined simultaneously between the third and fourth day after methotrexate. CONCLUSIONS: Methotrexate most likely primarily affects trophoblast production of human chorionic gonadotropin, as evidenced by a blunting of the expected 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 administration were inconsistent and are unlikely to represent the ultimate effect of methotrexate in abortion. The less-than-normal increase in serum beta-human chorionic gonadotropin levels after methotrexate administration is most likely a result of disruption of cytotrophoblast syncytialization. This disruption may be the true effect of methotrexate in destabilizing the implantation site of an early pregnancy.