Women with preterm premature rupture of the membranes do not benefit from weekly progesterone.

OBJECTIVE: We sought to determine if 17-alpha-hydroxyprogesterone (17P) extends gestation vs placebo in women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: Women with vertex presentations with PPROM, 20-30 weeks' gestation, were randomized to receive weekly 17P or placebo in an attempt to prolong the pregnancy. A total of 69 patients (17P, n = 33; placebo, n = 36) were randomized into this study. RESULTS: Initial cervical dilatation, gestational age at enrollment, and interval to delivery were not different between the 2 groups (P = .914, .424, and .146, respectively). Time of randomization to delivery (P = .250), mode of delivery (relative risk, 1.16; 95% confidence interval, 0.66-2.06), and the neonatal outcome statistics of morbidity (P = .820) and mortality (relative risk, 1.28; 95% confidence interval, 0.59-2.75) were similar between the 2 groups. CONCLUSION: In patients with PPROM, 17P did not extend gestation vs placebo and cannot be recommended for treatment in such women.

History- or ultrasound-based cerclage placement and adverse perinatal outcomes.

OBJECTIVE: To determine whether cerclage based on serial transvaginal ultrasound (STVUS) vs. cerclage based on obstetric history (prior multiple midgestation losses) is superior for treatment of cervical insufficiency. STUDY DESIGN: This retrospective study evaluated all history-based or ultrasound-based cerclages in singleton pregnancies over a 5-year period at the University of Mississippi Medical Center. Demographic statistics, interval from cerclage placement to delivery, and gestational age at delivery were recorded, as were neonatal factors such as birthweight, morbidity, and mortality. RESULTS: No significant difference was found in regard to gestational age at delivery between the history-based cerclage and the ultrasound-based groups. The number of patients delivered before 24 weeks or after 34 weeks was similar. Birth weights, Apgar scores, and the number with growth restriction were similar between the two groups, as were perinatal loss and significant morbidity. In the ultrasound-based cerclage group, 52.1% did not require cerclage placement despite a history consistent with cervical insufficiency. CONCLUSION: There were no statistical differences between history-based and ultrasound-based cerclage in regard to obstetric or neonatal outcome. Using STVUS instead of cerclage procedures based on obstetric history, unnecessary procedures can be avoided in more than half the patients.

17-Hydroxyprogesterone blunts the hypertensive response associated with reductions in uterine perfusion pressure in pregnant rats.

OBJECTIVE: Reduction in uteroplacental perfusion (RUPP) in pregnant rats is associated with hypertension, elevated cytokines, and activation of the endothelin (ET-1) system. Our objective was to determine whether the antiinflammatory properties of 17-alpha-hydroxyprogesterone caproate (17 OHP) reduce cytokine-stimulated vasoactive pathways that are associated with hypertension in response to placental ischemia. STUDY DESIGN: Mean arterial pressure (MAP), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and renal ET-1 were measured in the following: pregnant controls, pregnant controls plus 17 OHP (6.6 mg/kg), RUPP rats, and RUPP rats plus 17 OHP. RESULTS: MAP increased 29 mm Hg in RUPP rats compared with pregnant controls (P < .001), whereas in RUPP plus 17 OHP rats, MAP increased only 19 mm Hg (P < .05). TNF-alpha and IL-6 increased 2- to 3-fold, respectively, in response to placental ischemia but was normalized in RUPP rats treated with 17 OHP. ET-1 increased 3-fold in RUPP rats but was markedly less in RUPP plus 17 OHP rats. CONCLUSION: 17 OHP blunts hypertension associated with RUPP, possibly via suppression of cytokine-stimulated ET-1 activation.

Progesterone does not prevent preterm births in women with twins.

OBJECTIVE: To compare preterm birth rate and neonatal outcome in twin gestations randomized to either 17 alpha-hydroxyprogesterone caproate (17P) or placebo. MATERIALS AND METHODS: Women with twin gestations between 20-30 weeks were randomized to receive weekly injections of either 250 mg 17P injection (Group I), or placebo (Group II). Maternal and neonatal outcome data was recorded. RESULTS: Thirty twin intrauterine pregnancies were randomized; 16 received 17P and 14 received placebo. Demographic data as well as past history and gestational age at randomization were equivalent between groups (P = 0.286-0.847). All patients in both groups were Medicaid recipients. The incidence of preterm labor (P = 0.980), and premature rupture of the membranes (P = 0.525) were the same between groups. Gestational age at delivery was also similar between 17P (33.9 weeks) versus placebo (33.1 weeks, P = 0.190) as was the incidence of preterm birth <35 weeks (44% vs 79%, P = 0.117). Infant weight (P = 0.641), Apgar score at 5 minutes (P = 0.338) as well as neonatal morbidity such as respiratory distress syndrome (P = 0.838), patent ductus arteriosus (P = 0.704), intraventricular hemorrhage (P = 0.851) and necrotizing enterocolitis (P = 0.946) showed no difference. Days spent in the NICU among 17P (18.4) versus placebo (17.3, P = 0.155), neonatal death (P = 0.359) and those infants discharged with neurologic handicap (P = 0.594) were not different between groups. CONCLUSION: Amongst this group of twin gestations weekly 17HP injections did not reduce the incidence of preterm birth or the complications associated with prematurity.

Effects of 17-hydroxyprogesterone on tumor necrosis factor-alpha-induced hypertension during pregnancy.

BACKGROUND: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) may be an important link between placental ischemia and hypertension in preeclampsia. We examined the effect of 17-hydroxyprogesterone caproate (17-OHP) on TNF-alpha-stimulated endothelin (ET) production and hypertension during pregnancy. METHODS: TNF-alpha-stimulated ET was examined from endothelial cells cultured in the presence and absence of progesterone. Blood pressure and tissue ET-1 were measured in the following groups of pregnant rats: controls, 17-OHP (3.32 mg/kg), TNF-alpha treated (50 ng/day), TNF-alpha treated+17-OHP. RESULTS: Progesterone abolished TNF-alpha-stimulated ET-1 from endothelial cells. TNF-alpha-induced hypertension was associated with significant increases in renal and placental ET-1. Administration of 17-OHP attenuated TNF-alpha-induced hypertension and decreased renal ET-1. CONCLUSION: Progesterone directly abolished TNF-alpha-stimulated ET-1 and attenuated TNF-alpha-induced hypertension, possibly via suppression of the renal ET-1 system. These data suggest that treatment with progesterone of hypertension associated with elevated cytokines during pregnancy may be worthy of further consideration.