Progesterone-Mediated Reversal of Mifepristone-Induced Pregnancy Termination in an Animal Model: An Exploratory Investigation

Abstract

Abstract Background A substantial proportion of pregnancies end in induced abortion globally, with drug-induced abortion increasing in availability and use. However, data also indicates a percentage of women who, following mifepristone administration, seek assistance in potentially reversing the 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, with only one rat model indicating the potential based on simultaneous mifepristone/progesterone administration. Thus, our study explored the potential reversal of mifepristone-induced pregnancy termination using progesterone in an animal model (administered at a human equivalent of ~ 6–9 hours post-mifepristone), where the process of pregnancy termination was clearly initiated. Methods Female Long-Evans rats were divided into three groups (n = 10–16/group): Pregnant control (M-P-), mifepristone-only/abortion (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. Results Our results indicate that progesterone administration following mifepristone-induced initiation of abortion (indicated by weight loss and uterine bleeding) reversed the process in 81% of rats in the M + P + group. Furthermore, following the initial weight loss, rats in this group proceeded to gain weight at a similar rate to those in 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 abortion initiation), number of gestational sacs, uterine weights, diameters, approximate fetal weights and fetal heart rates were similar to the M-P- group. Conclusions Thus, our results indicate a clear progesterone-mediated reversal of an initiated mifepristone-induced pregnancy termination in an animal model (i.e., pre-clinical level) 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 and medical communities of the potential implications in humans.