17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial.

The objective of the study was to evaluate the efficacy of 17 alpha-hydroxyprogesterone caproate (17OHP-C) in prolonging gestation in patients with a short cervix and other risk factors for preterm delivery, such as previous preterm birth, cervical surgery, uterine anomalies, or prenatal diethylstilbestrol (DES) exposure. This open-label, multicenter, randomized controlled trial included asymptomatic singleton pregnancies from 20(+0) through 31(+6) weeks of gestation with a cervical length less than 25 mm and a history of preterm delivery or cervical surgery or uterine malformation or prenatal DES exposure. Randomization assigned them to receive (or not) 500 mg of intramuscular 17OHP-C weekly until 36 weeks. The primary outcome was time from randomization to delivery. After enrolling 105 patients, an interim analysis demonstrated the lack of efficacy of 17OHP-C in prolonging pregnancy. The study was discontinued because of futility. The groups were similar for maternal age, body mass index, parity, gestational age at inclusion, history of uterine anomalies, DES syndrome, previous preterm delivery or midtrimester abortion, and cervical length at randomization. The enrollment-to-delivery interval did not differ between patients allocated to 17OHP-C (n = 51) and those allocated to the control group (n = 54) (median [interquartile range] time to delivery: 77 [54-103] and 74 [52-99] days, respectively). The rate of preterm delivery less than 37 (45% vs 44%, P > .99), less than 34 (24% vs 30%, P = .51), or less than 32 (14% vs 20%, P = .44) weeks was similar in patients allocated to 17OHP-C and those in the control group. 17OHP-C did not prolong pregnancy in women with singleton gestations, a sonographic short cervix, and other risk factors of preterm delivery (prior history, uterine malformations, cervical surgery, or prenatal DES exposure).

Winer N ，Bretelle F ，Senat MV ，Bohec C ，Deruelle P ，Perrotin F ，Connan L ，Vayssière C ，Langer B ，Capelle M ，Azimi S ，Porcher R ，Rozenberg P ，Groupe de Recherche en Obstétrique et Gynécologie ... -  《-》

17-hydroxyprogesterone caproate for preterm rupture of the membranes: a multicenter, randomized, double-blind, placebo-controlled trial.

Preterm rupture of membranes (PROM) is associated with an increased risk of preterm birth and neonatal morbidity. Prophylactic 17-hydroxyprogesterone caproate (17OHP-C) reduces the risk of preterm birth in some women who are at risk for preterm birth. We sought to test whether 17OHP-C would prolong pregnancy or improve perinatal outcome when given to mothers with preterm rupture of the membranes. This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. The study included singleton pregnancies with gestational ages from 23(0/7) to 30(6/7) weeks at enrollment, documented PROM, and no contraindication to expectant management. Consenting women were assigned randomly to receive weekly intramuscular injections of 17OHP-C (250 mg) or placebo. The primary outcome was continuation of pregnancy until a favorable gestational age, which was defined as either 34(0/7) weeks of gestation or documentation of fetal lung maturity at 32(0/7) to 33(6/7) weeks of gestation. The 2 prespecified secondary outcomes were interval from randomization to delivery and composite adverse perinatal outcome. The planned sample size was 222 total women. From October 2011 to April 2014, 152 women were enrolled; 74 women were allocated randomly to 17OHP-C, and 78 were allocated randomly to placebo. The trial was stopped when results of a planned interim analysis suggested that continuation was futile. The primary outcome was achieved in 3% of the 17OHP-C group and 8% of the placebo group (P = .18). There was no significant between-group difference in the prespecified secondary outcomes, randomization-to-delivery interval (17.1 ± 16.1 vs 17.0 ± 15.8 days, respectively; P = .76) or composite adverse perinatal outcome (63% vs 61%, respectively; P = .93). No significant differences were found in other outcomes, which included rates of chorioamnionitis, postpartum endometritis, cesarean delivery, individual components of the composite outcome, or prolonged neonatal length of stay. Compared with placebo, weekly 17OHP-C injections did not prolong pregnancy or reduce perinatal morbidity in patients with PROM in this trial.

Combs CA ，Garite TJ ，Maurel K ，Abril D ，Das A ，Clewell W ，Heyborne K ，How H ，Huang W ，Lewis D ，Lu G ，Miller H ，Nageotte M ，Porreco R ，Sheikh A ，Tran L ，Obstetrix Collaborative Research Network ... -  《-》

Prevention of preterm delivery by 17 alpha-hydroxyprogesterone caproate in asymptomatic twin pregnancies with a short cervix: a randomized controlled trial.

The objective of the study was to evaluate the use of 17 alpha-hydroxyprogesterone caproate (17P) to reduce preterm delivery in women with a twin pregnancy and short cervix. This open-label, multicenter, randomized controlled trial included women with a twin pregnancy between 24(+0) and 31(+6) weeks of gestation who were asymptomatic and had a cervical length of 25 mm or less measured by routine transvaginal ultrasound. Women were randomized to receive (or not) 500 mg of intramuscular 17P, repeated twice weekly until 36 weeks or preterm delivery. The primary outcome was time from randomization to delivery. Analysis was performed according to the intent-to-treat principle. The 17P and control groups did not differ significantly for median [interquartile range] time to delivery: 45 (26-62) and 51 (36-66) days, respectively. However, treatment with 17P was associated with a significant increase in the rate of preterm delivery before 32 weeks. Twice-weekly injections of 17P did not prolong pregnancy significantly in asymptomatic women with a twin pregnancy and short cervix.

Senat MV ，Porcher R ，Winer N ，Vayssière C ，Deruelle P ，Capelle M ，Bretelle F ，Perrotin F ，Laurent Y ，Connan L ，Langer B ，Mantel A ，Azimi S ，Rozenberg P ，Groupe de Recherche en Obstétrique et Gynécologie ... -  《-》

Efficacy of midtrimester short cervix interventions is conditional on intraamniotic inflammation.

Midtrimester ultrasound is a valuable method for identifying asymptomatic women at risk for spontaneous preterm delivery (PTD). However, response to various treatments (cerclage, progestogen) has been variable in the clinical setting. It remains unclear how other biomarkers may be used to guide intervention strategies. We applied an amniotic fluid inflammatory scoring system to determine if the degree of inflammation is associated with intervention efficacy in patients with midtrimester short cervix. Women carrying a singleton fetus between 16-24 weeks' gestation with a short cervix (≤25 mm) on transvaginal ultrasound underwent amniocentesis and were assigned to McDonald cerclage, no cerclage, or weekly 17-alpha hydroxyprogesterone caproate (17OHP-C). Our previously described inflammatory risk score (comprised of 14 inflammatory markers) was used to classify patients as high (score ≥8) or low (score <8) risk for inflammation. Gestational age at delivery was compared for each intervention and risk score status. Risk of delivering as a function of the remaining gestation was evaluated using modified Cox proportional hazards models with incorporation of methods to account for both left and right truncation bias. Ninety patients were included: 24 were in the nonintervention control group, 51 received cerclage, and 15 received 17OHP-C. Inflammation status at time of sampling influenced the efficacy of the treatment (P < .001). Compared to the nonintervention control group, in patients with low inflammation (score < 8), both cerclage (adjusted hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.28-6.37) and 17OHP-C (HR, 3.11; 95% CI, 1.04-9.30) were associated with increased hazard of PTD. In contrast, in patients with high inflammation (score ≥8) both cerclage (HR, 0.22; 95% CI, 0.08-0.65) and 17OHP-C (HR, 0.20; 95% CI, 0.05-0.81) were associated with lower hazard of delivering preterm. Cerclage placement or administration of 17OHP-C therapy for midtrimester short cervix for PTD prevention appears beneficial only in the subset of patients with high inflammation. Knowledge of the amniotic fluid inflammatory status may aid in guiding the appropriate therapy for women presenting with midtrimester short cervix who are at increased risk of PTD.

Kiefer DG ，Peltier MR ，Keeler SM ，Rust O ，Ananth CV ，Vintzileos AM ，Hanna N ... -  《-》

Prevention of preterm delivery after successful tocolysis in preterm labor by 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial.

The objective of the study was to evaluate the use of 17 alpha-hydroxyprogesterone caproate (17P) to reduce preterm delivery. This open-label, multicenter, randomized controlled trial included women with singleton pregnancies admitted at 24-31 weeks' gestation and cervical length less than 25 mm for preterm labor successfully arrested by tocolytic treatment. Randomization assigned them to receive (or not) 500 mg of intramuscular 17P after tocolysis ended, repeated semiweekly until 36 weeks or preterm delivery. The primary outcome was the time from randomization to delivery. Outcome data were available for 184 of 188 women randomized. The 17P and control groups (similar for most baseline characteristics) did not differ significantly for median [interquartile range] time to delivery (64 [42-79] and 67 [46-83] days, respectively) or rates of delivery before 37, 34, or 32 weeks of gestation or adverse perinatal outcomes. Semiweekly injections of 17P did not prolong pregnancy significantly in women with tocolysis-arrested preterm labor.

Rozenberg P ，Chauveaud A ，Deruelle P ，Capelle M ，Winer N ，Desbrière R ，Perrotin F ，Bohec C ，Connan L ，Vayssière C ，Langer B ，Mantel A ，Azimi S ，Porcher R ，Azria E ，Groupe De Recherche En Obstétrique et Gynécologie ... -  《-》