Vaginal progesterone fares equal with cerclage for preventing preterm births in women who have a short cervix and history of previous mid-trimester miscarriage (MTM) and/or preterm labor (PTL) reports the results of an updated comparison meta-analysis published in July issue of American Journal of Obstetrics and Gynecology.
In a recent update by WHO, every year 15 million babies are born before 37 weeks of gestation and the figures continue to rise. Prematurity is the leading cause of death in children under 5 years of age and is responsible for causing about 1 million deaths worldwide.
In addition, prematurity is a major contributor towards lifelong neurological morbidities such as intellectual disability, cerebral palsy, hearing and visual impairments, and a higher risk of chronic diseases in adulthood.
Women with a previous history of PTL and a short cervix (≤25) face a 3-fold increased risk of recurrent preterm births as compared to women with a cervical length >25 mm in the midtrimester.
The efficacy of vaginal progesterone and cerclage in preventing PTL is a hotly debated topic, but to date, only 2 small RCTs have been conducted to compare these two treatment modalities. However, the sample size was too small to detect any treatment differences.
The 2016 multicenter double-blind randomized placebo-controlled OPPTIMUM trial refuted the claim that progesterone reduces the risk of PTL and helps decrease the associated neonatal morbidity and mortality.
Hence, this adjusted indirect comparison meta-analysis was performed which usually, but not always, provides results similar to head-to-head randomized controlled trials.
An updated literature search of MEDLINE, EMBASE, CINAHL, LILACS, the Cochrane Central Register of Controlled Trials, conference proceedings and research registers of ongoing trials was performed from their inception to March 31, 2018.
All the RCTs comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm was included in the meta-analysis.
The researchers looked at prevention of preterm birth <35 weeks of gestation and perinatal mortality as the primary outcomes.
Five trials comparing vaginal progesterone vs placebo (265 women), 5 comparing cerclage vs no cerclage (504 women) and the OPPTIMUM study were included in the analysis.
The daily dose of vaginal progesterone used in the trials varied from 90 to 200 mg, and the treatment was administered from 18–25 to 34–36 weeks of gestation. Thirty women in two RCTs underwent a cerclage after randomization.
In direct comparison, the use of vaginal progesterone reduced the risk of preterm birth <35 weeks by 32%, <32 weeks of gestation by 40%, neonatal sepsis by 62%, neonatal morbidity by 71%, and admission to NICU by 54%.
The use of cerclage reduced the risk of preterm birth <35 weeks by 30%, <32 weeks of gestation by 34%, composite neonatal morbidity and mortality by 36%, and birthweight <1500 g by 36%.
Both interventions together were associated with a nonsignificant ∼36% reduction in the rate of perinatal death.
Adjusted indirect comparison meta-analyses didn’t show any differences between vaginal progesterone and cerclage in preventing preterm births and perinatal deaths.
The study has several advantages such as the use of individual patient data, similar patient demographics, and low rates of bias. There were few limitations such as the absence of data on respiratory distress syndrome in the OPPTIMUM study, some women with cerclage received 17-OHPC that could have affected the results and non-reporting of maternal side effects in the individual patient data (IPD) meta-analysis.
In the absence of adequately powered, high-quality, randomized controlled trials comparing vaginal progesterone and cerclage, our indirect comparison treatment meta-analysis provides the best available evidence regarding the comparative efficacy of the 2 interventions.
This meta-analysis results have huge implications in clinical practice. Both progesterone or cerclage show similar efficacy in preventing recurrent preterm births in patients with singleton pregnancy and short cervix. Thus, besides efficacy, the decision to use one intervention over other is based on physician preferences, cost-effectiveness, and maternal side effects.
