Up to 3% of pregnancies in the second trimester are nonviable and require delivery due to myriad complications including stillbirth, preterm prelabor rupture of membranes (PPROM) at a previable gestational age, fetal anomalies, or risk to maternal life. Stillbirth complicates in 1 in 160 deliveries, with over half of these occurring in the second trimester. Additionally, the rate of preterm previable PPROM is estimated to complicate up to 1% of all pregnancies. The rate of neonatal survival after previable PPROM after expectant management is reported to be as low as 20% due to complications from premature delivery, inadequate fetal lung development, and infectious complications. On the other hand, pregnancy continuation in the setting of previable PPROM increases maternal risk of bleeding, infection, sepsis, and even death. Most fetal anomalies including those that are lethal or associated with severe morbidity are diagnosed after 20 weeks' gestation which is the standard time for the ultrasound assessment of fetal anatomy. Lastly, at any time in pregnancy maternal medical complications can arise or worsen that make continuation of pregnancy contraindicated due to threat to maternal life. Patients in these and other complex situations are counseled on options for the pregnancy, and many make the decision to proceed with induction of labor with the understanding that the fetus will not survive to hospital discharge.

The standard of care for labor induction of a nonviable second trimester pregnancy is the use of misoprostol. However, mifepristone's adjunctive use to shorter time to delivery in the second trimester has become a topic of interest. Mifepristone, also known as RU-486, is a well-tolerated competitive progesterone receptor antagonist. Data has demonstrated the safety and efficacy of mifepristone administration followed by misoprostol 1-2 days later in medical management of first-trimester pregnancy loss and in first-trimester medication abortion. Newer data suggests that mifepristone administration prior to labor induction with misoprostol in nonviable pregnancies decreases total time in labor, with optimal time interval between mifepristone and misoprostol administration thought to be 24-48 hours. However, when considering the time from first medication administration to delivery, the time is longer in those patients receiving mifepristone, owing to the delay from mifepristone administration to induction of labor. A retrospective review of our patients undergoing induction of labor for nonviable second trimester pregnancies from 2018 to 2021 revealed an average length of time from first medication administration to placental delivery of 13.8 hours in patients receiving misoprostol alone, compared to 43.3 hours in those receiving mifepristone at least 24 hours prior to induction of labor (p\<0.01). In the setting of many second trimester pregnancies requiring delivery, shortening the time from diagnosis of pregnancy complication and initiation of labor induction to delivery is of utmost importance to decrease the risk of maternal morbidity with a continuing pregnancy. Currently, given need to expedite delivery, these patients are generally induced with misoprostol without adjunctive mifepristone as mifepristone's effectiveness given concurrently with labor induction is unknown. However, pharmacokinetic studies of mifepristone demonstrate that peak concentrations are reached within 60-120 minutes and remain elevated for at least 48 hours, thus it is reasonable to suspect that mifepristone administered at the initiation of labor induction could offer some benefit to patients needing urgent delivery. Thus, the investigators are conducting a randomized controlled trial investigating the utility of simultaneous mifepristone administration at the time of complicated nonviable labor induction with misoprostol in the second trimester.