Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind, randomized clinical trial

Combs, C. Andrew; Garite, Thomas J.; Maurel, Kimberly; Das, Anita; Porto, Manuel

doi:10.1016/j.ajog.2010.06.016

Cited by 79 publications

(72 citation statements)

References 14 publications

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“…[1][2][3] However, previous trials using different progestogens in multiple pregnancies have failed to decrease the incidence of preterm birth in these women. [10][11][12][13][14]16 Our trial aimed to explore the possibility of using a higher dose of natural micronised vaginal progesterone (400 mg/day) than those previously administered (90-200 mg/day), 5,11,17,18 but we also failed to demonstrate any benefit in unselected twin pregnancies.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 In contrast, recent trials have not shown any significant effect of progestogens on the rate of preterm delivery in unselected multiple pregnancies. [10][11][12][13][14] Two different progestogens have been investigated in twin pregnancies: intramuscular 17 a-hydroxyprogesterone caproate (17P) and vaginal micronised natural progesterone. Although the dosage of the former is quite uniform (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double‐blind multicentre trial

Serra¹,

Perales²,

Meseguer³

et al. 2012

BJOG

100

110

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Objective Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90-200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies.Design Randomised controlled double-blind multicentre trial (1:1:1).Setting The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain).Population Women with dichorionic diamniotic twin pregnancies.Methods The women self-inserted two vaginal pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n = 97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention-to-treat basis.Main outcome measure Preterm birth rate.Results The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone-treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200-versus 400-mg progesterone groups. No serious adverse effects were encountered.Conclusions Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400-mg progesterone dose offered no advantages over the 200-mg regimen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double‐blind multicentre trial

Serra¹,

Perales²,

Meseguer³

et al. 2012

BJOG

100

110

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“…A significant increased risk of perinatal mortality associated with 17-OHPC use was reported in one 5 of two randomised controlled trials in which triplet gestations were allocated to receive 17-OHPC or placebo. 5,6 Moreover, the American Congress of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommended that women be counselled about the potential risks when receiving 17-OHPC (Letter to Members; Friday, 29 April 2011).Schuit et al report that vaginal progesterone did not reduce the rate of the composite perinatal outcome in unselected twins. Nevertheless, subgroup analyses showed that there was a significant~44% reduction in the risk of the primary composite outcome measure in women with a short cervix at randomisation (26.8% versus 36.7%; RR 0.57, 95% CI 0.47-0.70; four studies) or before 24 weeks of gestation (26.9% versus 37.5%; RR 0.56, 95% 0.42-0.75; four studies).…”

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confidence: 99%

Is 17α‐hydroxyprogesterone caproate contraindicated in twin gestations?

Romero

Conde-Agudelo

2014

BJOG

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Please cite this paper as: Romero R, Conde-Agudelo A. Is 17a-hydroxyprogesterone caproate contraindicated in twin gestations ? BJOG 2015;122:6-7. In this issue of BJOG, Schuit et al. 1 report the results of an important individual patient data (IPD) meta-analysis on the efficacy of progestogens for the prevention of preterm birth and neonatal morbidity in twin gestations. IPD meta-analyses are based on the raw data from each patient and are considered the 'gold standard' for summarising evidence across clinical studies.The primary outcome of the IPD meta-analysis was a composite of perinatal mortality and serious neonatal morbidity. Secondary outcomes included the individual events of the composite endpoint and fetal death or preterm birth at several gestational ages. The investigators performed subgroup analyses to explore the effect of progestogens on these outcomes according to chorionicity, sonographic cervical length at randomisation (and at <24 weeks of gestation), and a previous spontaneous preterm birth (<37 weeks of gestation). Two progestogens were studied: 17a-hydroxyprogesterone caproate (17-OHPC) and vaginal progesterone. 2The authors found that 17-OHPC did not reduce the risk of adverse perinatal outcomes in unselected women with a twin gestation. However, there was a trend towards an increase in the risk for the majority of adverse perinatal outcomes among women treated with 17-OHPC. In addition, the administration of 17-OHPC in women with a cervical length >25 mm at randomisation and before 24 weeks of gestation was associated with a significantly increased risk of the composite perinatal outcome (relative risk [RR] 2.1, 95% confidence interval [95% CI] 1.9-2.2 at randomisation and RR 1.4, 95% CI 1.26-1.5 before 24 weeks). Given that 86% 3 to 99% 4 of women with a twin gestation have a cervical length >25 mm at mid-gestation and that 17-OHPC had no beneficial effects in those with a cervical length ≤25 mm, we strongly agree with the authors of this IPD meta-analysis that 17-OHPC is contraindicated in twin gestations. These findings support a 'call for caution' when using 17-OHPC. A significant increased risk of perinatal mortality associated with 17-OHPC use was reported in one 5 of two randomised controlled trials in which triplet gestations were allocated to receive 17-OHPC or placebo. 5,6 Moreover, the American Congress of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommended that women be counselled about the potential risks when receiving 17-OHPC (Letter to Members; Friday, 29 April 2011).Schuit et al. report that vaginal progesterone did not reduce the rate of the composite perinatal outcome in unselected twins. Nevertheless, subgroup analyses showed that there was a significant~44% reduction in the risk of the primary composite outcome measure in women with a short cervix at randomisation (26.8% versus 36.7%; RR 0.57, 95% CI 0.47-0.70; four studies) or before 24 weeks of gestation (26.9% versus 37.5%; RR 0.56, 95% 0.42-0.75; four studies). Similar fin...

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“…Some studies like Comb's et al [16] reported that prophylactic treatment with 17-OH progesterone did not reduce the neonatal morbidity in triplet pregnancy and also even the studies not recommending the use of prophylactic cerclage in multiple pregnancies pointed to some advantages of cerclage in 3 aspects the 1 st aspect is that avoidance of the emergency need for cerclage which proved to be of no value [17] [18], 2nd aspect is that cerclage allowed patient free activity and minimized bed rest with its psychological and economical aspects [19], the 3rd aspect is allowing corticosteroid therapy to be given if preterm labour or PROM occurred [19].…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Cervical Cerclage versus Vaginal Progesterone in Triplet Pregnancy—A Randomized Prospective Comparative Study

Al-Gergawy¹,

Gamal²

2017

OJOG

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Objective: To compare the effect of prophylactic cervical cerclage with vaginal progesterone in triplet (with normal cervical measurements) to evaluate its efficacy in improving pregnancy outcome and prolonging gestation. Design: A randomized prospective comparative study. Setting: At Tanta university hospitals and outpatient clinics. Patients: 51 selected cases of triplet pregnancy were recruited and classified into 2 groups randomly, progesterone group (n = 28 cases) and cerclage group (n = 23 cases). Interventions: Transvaginal ultrasound was done for number of fetuses, viability, cervical measurements, vaginal progesterone for progesterone starting at 20 weeks, and applying McDonald cerclage at 14 -16 weeks for cerclage group. Main Outcome Measures: Time of occurrence of preterm labor, premature rupture of membranes (PROM), stitch removal, gestational age at delivery, mode of delivery, and neonatal complications. Results: Preterm labor occurred in 9, 8 cases and PROM in 4, and 3 cases in progesterone and cerclage groups respectively. The mean gestational age was 33.57 ± 2.97 and 31.74 ± 3.21 weeks in progesterone and cerclage groups; mean birth weight was 2049 ± 591 gm, and 1686 ± 512 gm in progesterone and cerclage groups respectively; Apgar score 7 or more was found in 52 (60.8%), and 39 (56.3%) newborn in progesterone and cerclage group respectively. Perinatal mortality was lower in progesterone group 26.1% (3 IUFD+19 neonatal) than in cerclage group 30.4% (2 IUFD + 19 neonatal). Respiratory distress syndrome (RDS) occurred in 43.9%, 49.76%, while need of mechanical ventilation occurred in 12.2%, 16.41% of progesterone and cerclage groups respectively and neonatal jaundice was found in 49.38%, 53.7% of progesterone and cerclage groups respectively. Conclusion: Vaginal progesterone seems to be more effective than prophylactic cerclage in reducing preterm delivery in triplet pregnancies with normal cervical measurements even in those with prior history of preterm labour and minimizing neonatal morbidity and mortality.

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Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind, randomized clinical trial

Cited by 79 publications

References 14 publications

Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double‐blind multicentre trial

Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double‐blind multicentre trial

Is 17α‐hydroxyprogesterone caproate contraindicated in twin gestations?

Prophylactic Cervical Cerclage versus Vaginal Progesterone in Triplet Pregnancy—A Randomized Prospective Comparative Study

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