Vaginal progesterone vs intramuscular 17α‐hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta‐analysis of randomized controlled trials (original) (raw)
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OBJECTIVE: Randomized controlled trials (RCTs) have recently compared intramuscular 17-alpha-hydroxy-progesterone caproate (17-OHPC) to vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singletons with prior SPTB. The aim of this systematic review with meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB. METHODS: Searches were performed in electronic databases. No restrictions for language or geographic location were applied. We included all RCTs of asymptomatic singleton gestations with prior SPTB who were randomized to prophylactic treatment with either vaginal progesterone (i.e. intervention group) or intramuscular 17-OHPC (i.e. comparison group). The primary outcome was SPTB<34 weeks. Secondary outcomes were SPTB<37 weeks, <32 weeks, <28 weeks and <24 weeks, maternal adverse drug reaction and neonatal outcomes. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). RESULTS: Three RCTs (680 women) were included. The mean gestational age at randomization was about 16 weeks. Women were given progesterone until 36 weeks or delivery. Regarding vaginal progesterone, one study used 90 mg gel daily; one 100 mg suppository daily; and the other one 200 mg suppository daily. All the included trials used 250 mg 17-OHPC weekly as comparison group. Women who received vaginal progesterone had a significantly lower rate of SPTB<34 weeks (17.5% vs 25.0%; RR 0.71, 95% CI 0.53 to 0.95; low quality of evidence) and SPTB<32 weeks (8.9% vs 14.5%; RR 0.62, 95% CI 0.40 to 0.94; low quality of evidence) compared to women who received 17-OHPC. There were no significant differences in the rate of SPTB<37 weeks, SPTB<28 weeks and SPTB<24 weeks. The rate of women who reported adverse drug reactions was significantly lower in the vaginal compared to 17-OHPC group (7.1% vs 13.2%; RR 0.53, 95% CI 0.31 to 0.91; very low quality of evidence). Regarding neonatal outcomes, vaginal progesterone was associated with a lower rate of neonatal intensive care unit admission compared to 17-OHPC (18.7% vs 23.5%; RR 0.63, 95% CI 0.47 to 0.83; low quality of evidence). QUALITY OF EVIDENCE: For comparison of 17-OHPC vs vaginal progesterone, the quality of evidence was downgraded for all outcomes by at least one degree due to imprecision (the optimal information size was reached) and by at least one degree due to indirectness (different interventions). CONCLUSIONS: Daily vaginal progesterone started at about 16 weeks (either suppository or gel) is a reasonable, if not better, alternative to weekly 17-OHPC for prevention of SPTB in women with singleton gestations and prior SPTB. However, the quality level of the summary estimates was low/very low as assed by GRADE, indicating that the true effect may, or is even likely to, be substantially different from the estimate of the effect.
The effects of progesterone therapy in pregnancy: vaginal and intramuscular administration
The Journal of Maternal-Fetal & Neonatal Medicine, 2019
This study was performed to evaluate the effects of vaginal versus intramuscular progesterone supplementations on the mood, quality of life, and metabolic changes in pregnant women with history of previous preterm birth. Methods: This study was conducted as a prospective, randomized, open label, clinical trial evaluated 100 pregnant women who referred for prenatal visit, with 16-17 weeks of gestation from September 2014 through October 2015. The mothers were then randomly allocated into two groups: the vaginal progesterone group to receive 400mg Cyclogest vaginal suppositories (Actavis, UK limited, England) once daily, and the intramuscular progesterone group to receive weekly intramuscular injections of 250mg of 17-Hydroxyprogesterone Caproate (17-HPC) (Bayer Schering Pharma, Germany), starting from the 16th to the 35th weeks of pregnancy. demographics, medical and obstetrical history, sleeping disturbances, alteration in sexual desire, nausea/vomiting, serum levels of fasting blood sugar (FBS), high density lipoprotein (HDL), and low density lipoprotein (LDL) were evaluated, first and 8 weeks later. Results: 11 (11.2%) screened positive for psychosocial disorders; 25 (25.5%) had sleep disturbance, 11 (11.2%) had alteration in sexual desire, and 29 (29.6%) had nausea/vomiting upon enrolment. after two months of receiving daily vaginal progesterone there was a significant increase in the GHQ-28 score (p<0.001), and rates of positive screening for psychosocial disorders (p=0.001) in this group. No
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 2016
To compare the efficacy of intramuscular hydroxyprogesterone caproate with that of vaginal progesterone for prevention of recurrent preterm birth. A prospective randomized controlled trial was conducted at a US tertiary care center between June 1, 2007, and April 30, 2010. Women with singleton pregnancies (16-20 weeks) and a history of spontaneous preterm birth were randomly allocated using a computer-generated randomization sequence to receive either a weekly intramuscular injection of hydroxyprogesterone caproate (250 mg) or a daily vaginal progesterone suppository (100 mg). Participants, investigators, and assessors were not masked to group assignment. The primary outcome was birth before 37 weeks of pregnancy. Per-protocol analyses were performed: participants who completed follow-up were included. Analyses included 66 women given intramuscular progesterone and 79 given vaginal progesterone. Delivery before 37 weeks was recorded among 29 (43.9%) women in the intramuscular proges...
American Journal of Obstetrics and Gynecology, 2003
Recent studies have shown that an increase in the number of uterine contractions precedes the onset of preterm labor, and the frequency of uterine contractions in pregnancies with preterm delivery is higher than in women with term and postterm delivery. Progesterone is useful in allowing pregnancy to reach its physiologic term because at sufficient levels in the myo-OBJECTIVE: The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population. STUDY DESIGN: 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 χ 2 analysis and Fisher exact test. RESULTS: 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). CONCLUSION: Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity. (Am J Obstet Gynecol 2003;188:419-24.)
Lancet (London, England), 2016
Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child. We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22-24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primar...
Prevention of preterm birth: a randomized trial of vaginal compared with intramuscular progesterone
Acta Obstetricia et Gynecologica Scandinavica, 2013
Objective. To assess efficacy and tolerability of vaginal compared with intramuscular progesterone in reducing the rate of recurrent preterm birth before 34 weeks of gestation. Design. Prospective randomized study. Setting. Obstetrics and Gynecology Department, Armed Forces Hospital Southern Region, Kingdom of Saudi Arabia. Sample. Five-hundred and eighteen women with a prior history of preterm birth. Methods. Women were randomized to receive either 90 mg of vaginal progesterone gel once daily or 250 mg of intramuscular progesterone weekly. Treatment began between 14 and 18 weeks of gestation and continued until 36 complete weeks of gestation, delivery or the occurrence of premature rupture of membranes. Main outcome measures. The primary outcome measure was delivery before 34 weeks of gestation. The secondary outcome measures were PTB between 34 and 37 weeks of gestation and neonatal outcomes including birthweight, neonatal death, and the need for admission to the neonatal intensive care unit. Results. The baseline characteristics of the study participants were similar. Two-hundred and thirty-eight (94.1%) patients in the vaginal group and 226 (90.8%) patients in the intramuscular group were compliant with their medications. Vaginal progesterone was associated with a lower percentage of deliveries before 34 weeks of gestation than the intramuscular preparation (p = 0.02). This association was also observed at 28 and 32 weeks of gestation (p = 0.04). Adverse effects were reported in 14.1% of patients in the intramuscular group, but in only 7.5% of patients in the vaginal group (p = 0.017). Conclusions. Vaginal progesterone was more effective than intramuscular progesterone for the prevention of preterm birth and had fewer adverse effects.
Abstract: Introduction: Progesterone is a hormone of paramount importance in the reproductive physiology. Its multiple physiological roles and pharmacology have been extensively studied throughout the years. However, the use of progesterone in the pathophysiology of pregnancy as well as in its other indications remains arguable for diverse reasons. One of these reasons concerns the fact that there have been few large randomised controlled trials, which are not easily comparable because of the different dosages, populations and routes of administration used. Regarding this last issue, the route of progesterone administration may have a strong influence on the efficacy of the treatment since the distribution and concentration of the hormone at the tissutal level varies considerably. Objective: To review the literature concerning the efficacy of progesterone in its diverse indications in correlation to the different routes of administration used. Methods: The search strategy included a literature search of PubMed, MEDLINE and the Cochrane Database from 1949 to April 2005, as well as a review of reference lists of identified studies and a hand search of relevant textbooks and reference works. Search terms used included: progesterone, pregnancy, preterm birth, preterm labor, threatened miscarriage, recurrent miscarriage, menopause, contraception, pharmacology, route of administration. Study designs included experimental studies, observational studies, case control studies, reviews, letters, and editorials. Results: The search on MEDLINE identified approximately 3800 articles. We found only limited literature relating to some of the administration route of progesterone (transnasal, transdermic, sublingual, rectal). Conclusion: Many routes of progesterone administration have been studied, but the only routes of administration used in the clinical practice are the i.m., oral and vaginal one. Among these options, the intramuscular administration is the only one that ensures adequate and verifiable plasmatic levels of progesterone.
Acta Obstetricia et Gynecologica Scandinavica, 2017
Introduction. Progesterone is becoming universally accepted for preventing recurrent spontaneous preterm delivery. There is, however, poor consensus on the effective types and doses of progesterone to be used. Despite the encouraging available research, the role of oral micronized progesterone has not yet been thoroughly investigated. Material and methods. We randomized 212 singleton pregnancies with past history of spontaneous preterm delivery at <37 weeks, into a progesterone group (receiving 100 mg oral micronized progesterone, six-hourly, starting at 14-18 weeks until 37 weeks or delivery) and an identical placebo group. The rate of spontaneous preterm delivery was the primary outcome. Secondary outcomes included gestational age at birth and admission to neonatal intensive care units. Results. The progesterone group delivered at a later gestational age, and needed longer tocolysis-todelivery intervals (35.4 weeks vs. 33.9 weeks, p = 0.01, and 87 days vs. 36 days, p < 0.001, respectively). The relative risk of spontaneous preterm delivery was 0.7 (95% confidence interval 0.54-0.92, p = 0.01), and the number needed-totreat to prevent one case of spontaneous preterm delivery was 5 (95% confidence interval 3-20). The two groups had similar rates of operative delivery and postpartum complications. Progesterone was associated with mild maternal dizziness (29.1% vs. 9.8%, p = 0.002), somnolence (41.6% vs. 19.7%, p = 0.002), and vaginal dryness (20.8% vs. 8.7%, p = 0.03), lower neonatal mortality rates (7.3% vs. 25.2%, p < 0.001), and shorter neonatal intensive care unit admissions (p = 0.008). Conclusion. Oral micronized progesterone is effective in preventing spontaneous preterm delivery. The additional advantages of oral administration, affordability, and high safety profile make it worth recommending, at least for further research.