17-alpha-hydroxyprogesterone caproate for maintenance tocolysis: a systematic review and metaanalysis of randomized trials

We sought to evaluate the efficacy of maintenance tocolysis with 17-alpha-hydroxyprogesterone caproate (17P) compared to control (either placebo or no treatment) in singleton gestations with arrested preterm labor (PTL), in a metaanalysis of randomized trials. Electronic databases (MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials) were searched from 1966 through July 2014. Key words included "progesterone," "tocolysis," "preterm labor," and "17-alpha-hydroxyprogesterone caproate." We performed a metaanalysis of randomized trials of singleton gestations with arrested PTL and treated with maintenance tocolysis with either 17P or control. Primary outcome was preterm birth (PTB) <37 weeks. This metaanalysis was performed following the Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) statement. The protocol was registered with PROSPERO (registration no: CRD42014013473). Five randomized trials met inclusion criteria, including 426 women. Women with a singleton gestation who received 17P maintenance tocolysis for arrested PTL had a similar rate of PTB <37 weeks (42% vs 51%; relative risk [RR], 0.78; 95% confidence intervals [CI], 0.50-1.22) and PTB <34 weeks (25% vs 34%; RR, 0.60; 95% CI, 0.28-1.12) compared to controls. Women who received 17P had significantly later gestational age at delivery (mean difference, 2.28 weeks; 95% CI, 1.46-13.51), longer latency (mean difference, 8.36 days; 95% CI, 3.20-13.51), and higher birthweight (mean difference, 224.30 g; 95% CI, 70.81-377.74) as compared to controls. Other secondary outcomes including incidences of recurrent PTL, neonatal death, admission to neonatal intensive care unit, neonatal respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal sepsis were similar in both groups. Maintenance tocolysis with 17P after arrested PTL is not associated with prevention of PTB compared to placebo or no treatment in a metaanalysis of the available randomized trials. As 17P for maintenance tocolysis is associated with a significant prolongation of pregnancy, and significantly higher birthweight, further research is suggested

Vaginal progesterone for maintenance tocolysis: A systematic review and metaanalysis of randomized trials

OBJECTIVE: We sought to evaluate the efficacy of maintenance tocolysis with vaginal progesterone compared to control (placebo or no treatment) in singleton gestations with arrested preterm labor (PTL) in a metaanalysis of randomized controlled trials. STUDY DESIGN: Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of key words and text words related to "progesterone," "tocolysis," and "preterm labor" from 1966 through November 2014. We included all randomized trials of singleton gestations that had arrested PTL and then were randomized to maintenance tocolysis treatment with either vaginal progesterone or control (either placebo or no treatment). All published randomized studies on progesterone tocolysis were carefully reviewed. Exclusion criteria included maintenance tocolysis in women with preterm premature rupture of membrane, maintenance tocolysis with 17-alpha-hydroxyprogesterone caproate, and maintenance tocolysis with oral progesterone. The summary measures were reported as relative risks (RRs) with 95% confidence interval (CI). The primary outcome was preterm birth (PTB) <37 weeks. RESULTS: Five randomized trials, including 441 singleton gestations, were analyzed. Women who received vaginal progesterone maintenance tocolysis for arrested PTL had a significantly lower rate of PTB <37 weeks (42% vs 58%; RR, 0.71; 95% CI, 0.57-0.90; 3 trials, 298 women). Women who received vaginal progesterone had significantly longer latency (mean difference 13.80 days; 95% CI, 3.97-23.63; 4 trials, 368 women), later gestational age at delivery (mean difference 1.29 weeks; 95% CI, 0.43-2.15; 4 trials, 368 women), lower rate of recurrent PTL (24% vs 46%; RR, 0.51; 95% CI, 0.31-0.84; 2 trials, 122 women), and lower rate of neonatal sepsis (2% vs 7%; RR, 0.34; 95% CI, 0.12-0.98; 4 trials, 368 women). CONCLUSION: Maintenance tocolysis with vaginal progesterone is associated with prevention of PTB, significant prolongation of pregnancy, and lower neonatal sepsis. However, given the frequent lack of blinding and the generally poor quality of the trials, we do not currently suggest a change in clinical care of women with arrested PTL. We suggest instead well-designed placebo-controlled randomized trials to confirm the findings of our metaanalysis

Pessary versus cerclage versus expectant management for cervical dilation with visible membranes in the second trimester.

OBJECTIVE: We evaluated pessary for dilated cervix and exposed membranes for prolonging pregnancy compared to cerclage or expectant management. METHODS: Multicenter retrospective cohort study of women, 15-24 weeks, singleton pregnancies, dilated cervix ≥2 cm and exposed membranes. Women received pessary, cerclage or expectant management. Primary outcome was gestational age (GA) at delivery. Secondary outcomes were time until delivery, preterm premature rupture of membranes (PPROM) and neonatal survival. RESULTS: About 112 women met study criteria; 9 - pessary, 85 - cerclage and 18 - expectant management. Mean GA at delivery was 22.9 ± 4.5 weeks with pessary, 29.2 ± 7.5 weeks with cerclage and 25.6 ± 6.7 weeks with expectant management (p = 0.015). Time until delivery was 16.1 ± 18.9 days in the pessary group, 61.7 ± 48.2 days in the cerclage group and 26.8 ± 33.4 days in the expectant group (p \u3c 0.001). PPROM occurred less frequently and neonatal survival increased in women with cerclage. There was a significant difference in all the perinatal outcomes with cerclage compared with either pessary or expectant management. CONCLUSIONS: Perinatal outcomes with pessary were not superior to expectant management in women with dilated cervix with exposed membranes in the second trimester in this small retrospective cohort

Prior Ultrasound-Indicated Cerclage: Comparison of Cervical Length Screening or History-Indicated Cerclage in the Next Pregnancy

OBJECTIVE: To evaluate outcomes of women with prior ultrasound-indicated cerclage, who in their subsequent pregnancy were either followed by transvaginal ultrasound cervical length screening or received a planned history-indicated cerclage. METHODS: Multicenter cohort study of singleton gestations with a prior ultrasound-indicated cerclage performed from 1994 to 2014. We evaluated three pregnancies in the study participants: first pregnancy with prior spontaneous preterm birth at less than 37 weeks of gestation; second pregnancy with ultrasound-indicated cerclage for cervical length 25 mm or less; and the third index pregnancy managed with either transvaginal ultrasound cervical length screening with ultrasound-indicated cerclage for cervical length 25 mm or less or planned history-indicated cerclage. The primary outcome was incidence of spontaneous preterm birth at less than 37 weeks of gestation. We planned a subgroup analysis for women who delivered at less than 32 weeks of gestation compared with 32 weeks of gestation or greater in their prior ultrasound-indicated cerclage pregnancy. RESULTS: Of 102 singleton gestations included, 38 (37.3%) were followed with transvaginal ultrasound cervical length screening and 64 (62.7%) underwent history-indicated cerclage. Of 38 women in the transvaginal ultrasound group, 18 (47.4%) underwent ultrasound-indicated cerclage for cervical length 25 mm or less. After adjusting for confounders, the rate of spontaneous preterm birth at less than 37 weeks of gestation was similar between transvaginal ultrasound cervical length screening and history-indicated cerclage groups (36.8% compared with 43.8%; adjusted odds ratio 0.77, 95% confidence interval 0.47-1.45). Secondary outcomes were also similar in both groups. All women (n=7) who delivered at less than 32 weeks of gestation in their prior pregnancy and subsequently had transvaginal ultrasound screening received ultrasound-indicated cerclage in the index pregnancy compared with only 35.5% of women who delivered at 32 weeks of gestation or greater in their prior pregnancy. CONCLUSION: Women with prior ultrasound-indicated cerclage have similar outcomes if they receive either transvaginal ultrasound cervical length screening with ultrasound-indicated cerclage for cervical length 25 mm or less or planned history-indicated cerclage in the subsequent pregnancy. Less than 50% of the transvaginal ultrasound cervical length screening group require a repeat ultrasound-indicated cerclage in the subsequent pregnancy

Trends in cerclage use

INTRODUCTION: The indications of placement of cerclage have recently changed, and so it is important to evaluate how many women are undergoing this procedure. With the recent completion of clinical trials, it is plausible that obstetricians and perinatologists may have become more selective in terms of the best candidates for cerclage. MATERIAL AND METHODS: We conducted a retrospective cohort study of women who underwent cerclage for prevention of preterm birth in the Division of Maternal and Fetal Medicine of Thomas Jefferson University Hospital (Philadelphia, USA) over a 16-year period, from 1998 to 2013. We included women with singleton gestations who had a history-indicated (HIC) or ultrasound-indicated cerclage (UIC). Physical examination-indicated cerclage and transabdominal cerclage were excluded. We planned to compare data before and after 2005. RESULTS: From 1998 to 2013, there were 33 353 deliveries, of which 16 871 occurred from 1998 to 2005 and 16 482 from 2006 to 2013. Of all deliveries, 328 women (1.0%) received HIC or UIC, and were therefore included in the analysis. Between 1998-2005 and 2006-2013 there were significant decreases in the overall rate of cerclage (1.4% to 0.6%; p < 0.001), as well as the rate of HIC (0.8% to 0.2%; p < 0.001) and UIC (0.6% to 0.3%; p < 0.001). CONCLUSIONS: During the last 16 years, the overall rate of HIC and UIC cerclage at Thomas Jefferson University Hospital significantly declined from 1.4% to 0.6%; significant decreases were seen for both HIC and UIC. The reason for the lower rate of cerclages may be the recently published evidence

Recent Change in the Incidence of Cervical Cerclage

Conclusions: More selective indications for cervical cerclage based on recent randomized studies were associated with decreased cerclage placement. The decrease in incidence of history-indicated cerclage may be due to the fact that more women with prior PTB are being followed by transvaginal cervical length measurements. The decrease in incidence of ultrasound-indicated cerclage may be due to the use of 17-hydroxy progesterone caproate in women with PTB

Prior ultrasound-indicated cerclage: what should the management be in next pregnancy?

Abstract Objective: To evaluate pregnancy outcomes of women with prior history of ultrasound-indicated cerclage (UIC) for short cervix who in subsequent pregnancy either were followed by transvaginal ultrasound cervical length(TVU CL)screening or received a history-indicated cerclage (HIC). Materials and Methods: Retrospective cohort study was performed from 1993-2012, involving women with an index singleton pregnancy and history of UIC. Prior UIC was defined as cerclage placed for CLinstitution, women with prior history of UIC were managed in their subsequent pregnancy either by TVU CL screening or by HIC, at the physician\u27s discretion(Figure). In the TVU CL group, if CL became24wks, an UIC was performed. In the HIC group, HIC was placed around 12-15wks. Primary outcome was spontaneous PTB (sPTB) at \u3c35wks. Results: 28 women met the inclusion criteria. Of these 28 women, 13 were in TVU CL group and 15 in HIC group. Demographics were similar in both the groups, except earliest GA of prior sPTB (Table). The odds of sPTB(OR 0.54, 95%CI 0.04-6.77). Secondary outcomes were also similar in two groups except birth weight (Table). Conclusion: Women with prior UIC have similar outcomes if they are managed in the next pregnancy by either TVU CL screening and UIC placement if CL is24wks, or by HIC. Our study results are limited by small sample size. There are currently no other studies evaluating this clinical dilemma