Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis. Multiple versus single courses of antenatal corticosteroids for preterm birth: a pilot study. Double-blind controlled trial of progesterone substitution in threatened abortion. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial. Intracervical prostaglandin in postdate pregnancy. A randomized trial. Progesterone receptor modulator for emergency contraception: a randomized controlled trial.
Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth.
                This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at </= 32 weeks of gestation. The trial was analyzed using an intent-to-treat strategy.
                Baseline characteristics were similar in the two treatment groups. Progesterone did not decrease the frequency of preterm birth at </= 32 weeks. There was no difference between the groups with respect to the mean gestational age at delivery, infant morbidity or mortality or other maternal or neonatal outcome measures. Adverse events during the course of treatment were similar for the two groups.
                Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth (</= 32 weeks) in women with a history of spontaneous preterm birth. The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone (e.g. sonographic cervical length) requires further investigation.
                Copyright (c) 2007 ISUOG The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population.
                A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test.
                The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05).
                Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity. Laboratory evidence indicates that progesterone has potent neuroprotective effects. We conducted a pilot clinical trial to assess the safety and potential benefit of administering progesterone to patients with acute traumatic brain injury.
                This phase II, randomized, double-blind, placebo-controlled trial was conducted at an urban Level I trauma center. One hundred adult trauma patients who arrived within 11 hours of injury with a postresuscitation Glasgow Coma Scale score of 4 to 12 were enrolled with proxy consent. Subjects were randomized on a 4:1 basis to receive either intravenous progesterone or placebo. Blinded observers assessed patients daily for the occurrence of adverse events and signs of recovery. Neurologic outcome was assessed 30 days postinjury. The primary safety measures were differences in adverse event rates and 30-day mortality. The primary measure of benefit was the dichotomized Glasgow Outcome Scale-Extended 30 days postinjury.
                Seventy-seven patients received progesterone; 23 received placebo. The groups had similar demographic and clinical characteristics. Laboratory and physiologic characteristics were similar at enrollment and throughout treatment. No serious adverse events were attributed to progesterone. Adverse and serious adverse event rates were similar in both groups, except that patients randomized to progesterone had a lower 30-day mortality rate than controls (rate ratio 0.43; 95% confidence interval 0.18 to 0.99). Thirty days postinjury, the majority of severe traumatic brain injury survivors in both groups had relatively poor Glasgow Outcome Scale-Extended and Disability Rating Scale scores. However, moderate traumatic brain injury survivors who received progesterone were more likely to have a moderate to good outcome than those randomized to placebo.
                In this small study, progesterone caused no discernible harm and showed possible signs of benefit. Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy.
                In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581.
                Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51).
                Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy.
                Chief Scientist Office of the Scottish Government Health Directorate. (1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS), more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.
                Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS, were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.
                Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.
                A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible. Between 1983 and 1984 a double-blind randomized study with progesterone substitution in threatened abortion was carried out. Fifty-six patients with vaginal bleeding during the first trimester of pregnancy, the internal cervical os being closed, were referred to the hospital. Twenty-five women (5th and 6th week of gestation) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results. In other 25 women (7th-10th week of pregnancy) and 6 women (greater than or equal to 11th week of pregnancy) fetal heart action and movement could be demonstrated by ultrasound. The patients were prescribed bed rest and vaginal suppositories twice daily, containing either 25 mg progesterone or only polyethylene glycol. The code was not broken until after completion of the study. Serial serum determinations of beta-hCG, estradiol-17 beta (E2), progesterone, and ultrasound were performed. Four patients had to be omitted from final analysis (two tubal pregnancies, one intrauterine infection, one sectio parva). Three of 26 patients progesterone (11%) and five of 26 patients with placebo (19%) had an abortion, which represented no significant difference. Frequency of abortion was increased in women more than 30 years old, in women with previous abortions and after ovulation induction. Progesterone treatment resulted in a significant elevation of serum progesterone concentrations (p less than 0.01), while beta-hCG and E2 were unchanged. The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) Fifty-eight women with severe preeclampsia between 28-34 weeks' gestation qualified for a randomized controlled trial to establish whether elective delivery 48 hours after administration of betamethasone (aggressive-management group) or delivery later as indicated by maternal or fetal condition (expectant-management group) was more beneficial to maternal and fetal outcome. Twenty women who qualified were not randomized because they developed maternal or fetal indications necessitating delivery within 48 hours; these newborns developed most of the complications. Expectant management was not associated with an increase in maternal complications, but it significantly prolonged the gestational age (mean 7.1 days; P less than .05), reduced the number of neonates requiring ventilation (P less than .05), and reduced the number of neonatal complications (P less than .05). A study was designed to see if incorporating intracervical administration of prostaglandin could affect the outcome of postdate pregnancies. All patients with verified dates, at least 41 6/7 weeks pregnant and enrolled in an antepartum testing schedule were randomized in a double-blind fashion to receive either 0.5 mg of prostaglandin E2 (PGE2) suspended in methylcellulose or a placebo of the gel alone. The gel was inserted directly into the cervical canal after the patient had a reactive/negative contraction stress test. The patient was then observed on an external fetal monitor for an hour before going home. A total of 23 patients received PGE2, and 20 received the placebo. Results were analyzed for the following: change in the Bishop score, lag time from dosage to delivery, spontaneous versus induced labor, cesarean section rate, length of labor and neonatal outcome. There were no significant differences between the groups except in the incidence of patients going into labor within 72 hours. The results indicate that, in general, 0.5 mg of intracervical PGE administered at greater than or equal to 41 6/7 weeks without subsequent oxytocin induction of labor did not appear to significantly alter the obstetric outcome. Compare the efficacy and adverse effects of CDB-2914, a new progesterone receptor modulator, to levonorgestrel for emergency contraception.
                We performed a randomized, double-blinded noninferiority trial, enrolling healthy women seeking emergency contraception within 72 hours of unprotected intercourse. Participants were randomly assigned to receive a single dose of 50 mg of CDB-2914, plus a placebo 12 hours later or two doses of 0.75 mg of levonorgestrel taken 12 hours apart. Follow-up was scheduled 5 to 7 days after the expected onset of the next menstrual period. Posttreatment pregnancy was established by a positive urine test at follow-up and confirmed by quantitative serum beta-hCG. Daily diaries were used from the time of emergency contraception use until next menses to record adverse effects and sexual activity.
                Product efficacy was evaluable in 775 of CDB-2914 users and 774 of levonorgestrel users. Pregnancies occurred in 7 (0.9%, 95% confidence interval 0.2-1.6%) and 13 (1.7%, 95% confidence interval 0.8-2.6%) women, respectively. Based on the estimated cycle day of unprotected intercourse, 85% and 69% of anticipated pregnancies, respectively, were averted. Nausea was reported by a somewhat greater percentage of CDB-2914 than levonorgestrel users (29% compared with 24%, P=.03), but the distribution of other adverse effects was similar in both groups. Women in both groups experienced considerable variation in menstrual cycle length as compared with their reported individual normal cycle lengths.
                CDB-2914 is at least as effective as levonorgestrel in preventing pregnancies after unprotected intercourse and has a similar side effect profile.
                I.
The one small randomised controlled trial demonstrated neither evidence of benefit or harm related to the replacement of estradiol and progesterone in preterm infants less than 30 weeks gestation. A properly powered randomised controlled trial is required to determine whether or not administration of estradiol or progesterone, either alone or in combination, and at varying doses, confers any clinically significant benefits, or poses any risk, to the preterm infant.