Vaginal compared with intramuscular progestogen for preventing preterm birth in high‐risk pregnant women (VICTORIA study): a multicentre, open‐label randomised trial and meta‐analysis

Abstract

Objective To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. Design A multicentre, randomised, open‐label, equivalence trial and a meta‐analysis. Setting Tertiary referral hospitals in South Korea. Population Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). Methods Eligible women were screened and randomised at 16‒22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α‐hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at https://ClinicalTrials.gov (NCT02304237). Main outcome measure Preterm birth (PTB) before 37 weeks of gestation. Results A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention‐to‐treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI −7.6 to 13.8%), which was within the equivalence margin of 15%. The meta‐analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. Conclusion Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. Tweetable abstract Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

17-alpha hydroxyprogesterone caproate for the prevention of recurrent preterm birth among singleton pregnant women with a prior history of preterm birth: a systematic review and meta-analysis of six randomized controlled trials

“…Moreover, they studied the majority of patients for 15 weeks assessing cervical length changes and found no significant difference between both the interventions. Moreover, Choi et al [ 25 ] conducted recent RCT comparing vaginal micronized progesterone to intramuscular 17OHPC and concluded equal efficacy for preventing PTB before 37 weeks of gestation.…”

A Comparison of Vaginal and Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth

“…Other studies that have been published comparing the two forms of progesterone are similarly limited by either small sample size or lack of generalizability. 9,10,12,13 One of our hypotheses at the outset of the study was that the association between route of progesterone administration and PTB might be modified by maternal BMI. Among women receiving 17OHP-C for prevention of recurrent PTB, lower plasma concentrations of 17OHP-C are associated with higher rates of prematurity, 26 and prior research has suggested that there may be an inverse relation between maternal BMI and plasma 17OHP-C concentrations.…”

“…These studies found either a reduction in PTB rates with vaginal progesterone 8,9 or no clinically relevant difference. [10][11][12][13] Yet, the quality of this evidence is low, owing in part to the small sample sizes, 14 and lack of generalizability to women in the United States. 15 Given the limitations of the prior studies, further research directly comparing vaginal progesterone and 17OHP-C is needed to better determine the optimal route of administration of progesterone in women with a prior PTB.…”

A Propose of Effective Model For Prediction of Spontaneous Preterm Delivery With Quadruple Serum Biomarkers of Aneuploidy Screening.

“…When earlier models to predict sPTD using serum biomarkers were evaluated, they generally indicated that the association of maternal characteristics with serum biomarkers increased the ability to predict preterm delivery [21,36]. Previous preterm delivery had a strong association with preterm delivery in many previous studies, which also recommended the administration of progesterone to reduce the risk of preterm delivery [10,[60][61][62][63]. Thus, combining a history of previous preterm with serum biomarkers can increase the rate of prediction of sPTD, as found in our study.…”

“…The impact of such preterm delivery costs can create serious nancial burdens, especially in developing countries [6,7]. There is a method available to prevent preterm births in at-risk pregnant women, such as progesterone administration but indicated only in women who had history of spontaneous preterm delivery (sPTD) [8][9][10][11][12]. Currently there is no effective universal screening method for predicting preterm delivery [13,14] .…”