Progesterone-mediated reversal of mifepristone-induced pregnancy termination in a rat model: an exploratory investigation

Globally, a substantial proportion of pregnancies end in induced (particularly medication) abortion. However, data also indicates a percentage of women who seek assistance in potentially reversing the medication abortion process. While previous literature has suggested the potential for progesterone-mediated reversal of mifepristone-induced abortion, this process has not been effectively investigated pre-clinically. Our study explored the potential reversal of mifepristone-induced pregnancy termination using progesterone in a rat model, following a clear initiation of pregnancy termination. Female Long-Evans rats were divided into three groups (n = 10-16/group): Pregnant control (M-P-), mifepristone-only/pregnancy termination (M+P-) and mifepristone + progesterone (M+P+). Drug/vehicle administration occurred on day 12 of gestation (first-trimester human equivalent). Rat weight was measured throughout gestation. Uterine blood, collected post-drug/vehicle administration, was analyzed spectrophotometrically to measure blood loss. Additionally, at the end of gestation (day 21), ultrasound was utilized to confirm pregnancy and measure fetal heart rate. Number of gestational sacs, uterine weights and diameters were obtained following tissue collection. Our results indicate that progesterone administration following initiation of mifepristone-induced pregnancy termination (indicated by weight loss and uterine bleeding) reversed the process in 81% of rats in the M+P+ group. Following the initial weight loss, these rats proceeded to gain weight at a similar rate to the M-P- group, in contrast to the continued decrease displayed by the M+P- group (and unsuccessful reversals). Moreover, while uterine blood loss was similar to that of the M+P- group (confirming pregnancy termination initiation), number of gestational sacs, uterine weights, diameters, approximate fetal weights and fetal heart rates were similar to the M-P- group. Thus, our results indicate a clear progesterone-mediated reversal of an initiated mifepristone-induced pregnancy termination in a rat model at first-trimester human equivalent, with resultant fully developed living fetuses at the end of gestation, clearly indicating the necessity for further pre-clinical investigation to assist in better informing the scientific/medical communities of the potential implications in humans.