Kabiri Doron, Hamou Yael, Gordon Gali, Ezra Yosef, Matok Ilan
Department of Obstetrics and Gynecology, Hadassah Hebrew Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
The Division of Clinical Pharmacy, School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Front Pharmacol. 2023 Jul 12;14:1153013. doi: 10.3389/fphar.2023.1153013. eCollection 2023.
To evaluate the effectiveness of vaginal progesterone in preventing preterm birth in women with a singleton gestation and short cervical length and to determine which of the two formulations, micronized progesterone vaginal capsule versus vaginal gel containing micronized progesterone, is more effective for preventing preterm birth. A systematic search was performed in the following databases: EMBASE, PubMed (MEDLINE), The Cochrane Library, and the Clinical Trials Registry (clinicaltrials.gov). Randomized controlled trials (RCTs), prospective and retrospective observational studies were included. We searched for progesterone administration to prevent preterm birth in asymptomatic women with a shortened cervix (<25 mm) measured by ultrasound in the second trimester of singleton pregnancy. Assessments of the risk of bias of RCTs were performed by applying the Cochrane Collaboration's Risk of Bias Tool; non-randomized control trials were evaluated with the Newcastle-Ottawa Scale (NOS). The primary outcome was preterm birth ≤33 weeks of gestation. Pooled relative risks (RR) and 95% CI's were calculated for dichotomous outcomes. Heterogeneity of treatment effect was assessed with the I statistic. We pooled results of the primary outcome for individual studies using a random-effect model. We then performed a network meta-analysis to pool indirect comparisons between the two formulations (gel vs capsule). This analysis was performed using the network meta-analysis package within the R environment. Five studies met the inclusion criteria (4 RCTs, one cohort study) including 1,048 women. The meta-analysis demonstrated that vaginal micronized progesterone significantly reduces preterm birth risk, Risk Ratio = 0.63; 95% CI, 0.48-0.82; = 0.0006; with no heterogeneity between the studies: = 0%. In the network meta-analysis, no significant difference was demonstrated (OR = 0.85; 95% CI, 0.43-1.69) between the effect of the two formulations of vaginal micronized progesterone (vaginal gel versus vaginal capsules) on the risk of PTB. Vaginal progesterone is associated with a decreased risk of premature birth in women with a shortened cervix in the second trimester of pregnancy. No differences were found between vaginal micronized progesterone in gel or capsule formulations. PROSPERO, identifier CRD42020165198.
评估阴道用黄体酮预防单胎妊娠且宫颈长度短的女性早产的有效性，并确定两种制剂（微粉化黄体酮阴道胶囊与含微粉化黄体酮的阴道凝胶）中哪种在预防早产方面更有效。在以下数据库中进行了系统检索：EMBASE、PubMed（MEDLINE）、Cochrane图书馆和临床试验注册库（clinicaltrials.gov）。纳入随机对照试验（RCT）、前瞻性和回顾性观察性研究。我们检索了在单胎妊娠中期通过超声测量宫颈缩短（<25mm）的无症状女性中使用黄体酮预防早产的情况。通过应用Cochrane协作网偏倚风险工具对RCT的偏倚风险进行评估；使用纽卡斯尔-渥太华量表（NOS）对非随机对照试验进行评估。主要结局为妊娠≤33周的早产。对二分结局计算合并相对风险（RR）和95%置信区间（CI）。用I统计量评估治疗效果的异质性。我们使用随机效应模型汇总各研究主要结局的结果。然后我们进行了网络荟萃分析，以汇总两种制剂（凝胶与胶囊）之间的间接比较。该分析使用R环境中的网络荟萃分析软件包进行。五项研究符合纳入标准（4项RCT，1项队列研究），共纳入1048名女性。荟萃分析表明，阴道用微粉化黄体酮显著降低早产风险，风险比=0.63；95%CI，0.48-0.82；P=0.0006；各研究之间无异质性：I²=0%。在网络荟萃分析中，两种阴道用微粉化黄体酮制剂（阴道凝胶与阴道胶囊）对早产风险的影响之间未显示出显著差异（OR=0.85；95%CI，0.43-1.69）。阴道用黄体酮与妊娠中期宫颈缩短的女性早产风险降低相关。凝胶或胶囊剂型的阴道用微粉化黄体酮之间未发现差异。PROSPERO标识符：CRD42020165198。
