Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial.

ObjectiveTo estimate the efficacy and safety of mifepristone antagonization with high-dose oral progesterone.MethodsWe planned to enroll 40 patients in a double-blind, placebo-controlled, randomized trial. We enrolled patients at 44-63 days of gestation with ultrasound-confirmed gestational cardiac activity who were planning surgical abortion. Participants ingested mifepristone 200 mg and initiated oral progesterone 400 mg or placebo 24 hours later twice daily for 3 days, then once daily until their planned surgical abortion 14-16 days after enrollment. Follow-up visits were scheduled 3±1, 7±1, and 15±1 days after mifepristone intake with ultrasonography and blood testing for human chorionic gonadotropin and progesterone. Participants exited from the study when they had their surgical abortion or earlier for gestational cardiac activity absence, gestational sac expulsion, or medically indicated suction aspiration. We assessed the primary outcome of continued gestational cardiac activity at approximately 2 weeks (15±1 day), side effects after drug ingestion, and safety outcomes including hemorrhage and emergent treatment.ResultsWe enrolled participants from February to July 2019 and stopped enrollment after 12 patients for safety concerns. Mean gestational age was 52.5 days. Two (one per group) voluntarily discontinued 3 days after mifepristone ingestion for subjective symptoms (nausea and vomiting, bleeding). Among the remaining 10 patients (five per group), gestational cardiac activity continued for 2 weeks in four in the progesterone group and two in the placebo group. One patient in the placebo group had no gestational cardiac activity 3 days after mifepristone use. Severe hemorrhage requiring ambulance transport to hospital occurred in three patients; one received progesterone (complete expulsion, no aspiration) and two received placebo (aspiration for both, one required transfusion). We halted enrollment after the third hemorrhage. No other significant side effects were reported.ConclusionWe could not estimate the efficacy of progesterone for mifepristone antagonization due to safety concerns when mifepristone is administered without subsequent prostaglandin analogue treatment. Patients in early pregnancy who use only mifepristone may be at high risk of significant hemorrhage.Clinical trial registrationClinicalTrials.gov, NCT03774745

Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.

BackgroundEarly pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 μg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure.ObjectiveThis study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss.Study designWe performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment.ResultsOverall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49).ConclusionNo baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors

Gabapentin for pain management after osmotic dilator insertion and prior to dilation and evacuation: A randomized controlled trial.

ObjectiveTo evaluate if gabapentin 600 mg reduces pain after osmotic dilator placement the day before a dilation and evacuation (D&E) procedure.Study designWe conducted a double-blind, placebo-controlled, randomized (stratified by vaginal parity) trial among women undergoing osmotic dilator placement before D&E at 15-23 5/7 weeks gestation. Subjects received gabapentin 600 mg or placebo 30 min before dilator placement, with re-dosing 8 h later. We assessed pain after dilator placement using a numeric rating scale (NRS; scale 0-10) at 5 min, 2, 4, and 8 h, and at presentation for D&E. The primary outcome was median NRS pain score change from baseline to 8 h after dilator placement. Secondary outcomes included gabapentin-related side effects and analgesic use.ResultsOf 121 randomized women, we excluded three subjects (allergic reaction [placebo], randomization error, no NRS data), leaving 60 gabapentin and 58 placebo subjects. Of 110 (93%) women who provided 8-hour data, median pain score changes from baseline did not differ between gabapentin and placebo groups overall (2 vs. 2.5, p = 0.52), in vaginally nulliparous women (2 vs. 4, p = 0.10) or in parous women (2 vs. 1.5, p = 0.37). We found no statistically significant differences in median pain score change from baseline to any timepoint overall or when stratified by parity. Beginning at 2 h after dilator placement, more gabapentin than placebo users experienced dizziness (29/53[55%] vs. 11/53[21%], p = 0.001) and tiredness (34/54[63%] vs. 17/54[31%], p = 0.002). The proportion of women using narcotics did not differ between gabapentin (35/60[58%]) or placebo (40/58[69%]) users (p = 0.26).ConclusionsGabapentin does not reduce pain with overnight osmotic dilator placement prior to D&E and causes drug-related side effects.Implications statementWomen experience pain, mostly mild to moderate, with overnight cervical dilator placement at 15-23 5/7 weeks gestation. About 2/3 of women will use a limited quantity of narcotics if provided. Gabapentin does not decrease the pain with or following dilator placement and does not decrease narcotic use