ADDITIVE EFFECT OF RU-486 AND ANORDRIN ON PREGNANCY INTERRUPTION IN THE MOUSE

The effect of various doses of anordrin and RU 486, alone or combined, on serum progesterone (P) levels, fetal resorption, and recovery of ovulation was studied in mice. Each drug was given as a single sc injection on day 7 of pregnancy and autopsy was performed on days 8, 9, or 11. Serum P was normal at 24 h but fell significantly 48 h after treatment with anordrin (0.05 mg). Doses of 0.05 or 0.2 mg anordrin were effective in interrupting pregnancy in 30% and 70% of pregnant mice, respectively. RU 486, 0.01 mg per mouse, induced a pronounced decrease of P levels 24 h after treatment and interrupted pregnancy in 50% of pregnant mice. The combined treatment with submaximal doses of anordrin plus RU 486 did not further decrease P levels, but increased the proportion of mice with fetal resorptions to 90%. The combination of small doses of anordrin with RU 486 had an additive effect on pregnancy termination. The additive effect required a dose of RU 486 above the threshold level. Direct observation of aborted fetuses indicated that the resorptive process occurred earlier with RU 486 than with anordrin. Recovery of ovulation was associated with pregnancy termination in a high proportion of mice treated with either drug or their combination.