随机试验发现阴道孕酮和17-α-羟孕酮己酸酯在预防复发性早产方面均有益处。先前直接比较两者的荟萃分析受到低质量证据的限制,关于建议预防复发性早产的孕激素制剂,国家和国际社会的指导方针仍然存在冲突。这项更新的系统评价与荟萃分析的目的是评估阴道孕酮与17-α-羟基孕酮己酸酯在预防单胎妊娠和先前自发性早产患者自发性早产中的疗效。
在MEDLINE中进行搜索,奥维德,Scopus,ClinicalTrials.gov,国际前瞻性系统审查登记册(PROSPERO),SciELO,Embase,和Cochrane中央对照试验登记册(CENTRAL),使用与“早产”相关的关键字和文本词的组合,\"\"早产,\"\"单身人士,“\”宫颈长度,\"\"孕酮,\“\”孕激素,\"\"阴道,“”17-α-羟基孕酮己酸酯,从每个数据库开始到2021年9月的“肌肉内”。没有对语言或地理位置的限制。
我们纳入了所有无症状单胎妊娠合并先前自发性早产的随机对照试验,这些试验被随机分配到阴道孕酮的预防性治疗(即,干预组)或肌内注射己酸17-α-羟孕酮(即,比较组)。对低偏倚风险研究和方案注册研究进行了事后敏感性分析。
主要结局是早产<34孕周。汇总措施报告为95%置信区间的相对风险。
包括1910例患者在内的7项随机对照试验被纳入荟萃分析。接受阴道孕酮的患者在<34周时的早产率明显较低(14.7%vs19.9%;相对风险,0.74;95%置信区间,0.57-0.96),<37周时早产(36.0%vs46.6%;相对危险度,0.76;95%置信区间,0.69-0.85),和<32周妊娠早产(7.9%vs13.6%;相对风险,0.58;95%置信区间,0.39-0.86),与接受肌内注射17-α-羟孕酮己酸酯的女性相比。妊娠<28周时早产率无显著差异。阴道孕酮组的药物不良反应明显低于17-α-羟孕酮己酸酯组(15.6%vs22.2%;相对危险度,0.71;95%置信区间,0.54-0.92)。阴道孕酮组的围产期死亡率低于17-α-羟孕酮己酸酯组(2.2%vs4.4%;相对风险,0.51;95%置信区间,0.25-1.01)。在敏感性分析中,包括使用至少4种Cochrane工具进行的低偏倚风险试验,包括4项试验(N=575),妊娠<34周时,阴道孕酮和己酸17-α-羟孕酮在早产方面不再有显著差异(12.2%vs13.9%;相对风险,0.87;95%置信区间,0.57-1.32)。
总的来说,阴道孕酮在预防妊娠<34周时的早产方面优于17-α-羟孕酮己酸酯。尽管高保真研究的敏感性分析显示出相同的趋势,研究结果不再具有统计学意义.
Randomized trials have found benefits of both vaginal progesterone and 17-alpha-hydroxyprogesterone caproate in the prevention of recurrent preterm birth. A previous meta-analysis directly comparing the two was limited by low-quality evidence, and national and international society guidelines remain conflicting regarding progestin formulation recommended for prevention of recurrent preterm birth. The aim of this updated systematic review with meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-alpha-hydroxyprogesterone caproate in the prevention of spontaneous preterm birth in patients with singleton gestations and previous spontaneous preterm birth.
Searches were performed in MEDLINE, Ovid, Scopus, ClinicalTrials.gov, the International Prospective Register of Systematic Reviews (PROSPERO), SciELO, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) with the use of a combination of keywords and text words related to \"preterm birth,\" \"preterm delivery,\" \"singleton,\" \"cervical length,\" \"progesterone,\" \"progestogens,\" \"vaginal,\" \"17-alpha-hydroxy-progesterone caproate,\" and \"intramuscular\" from inception of each database to September 2021. No restrictions for language or geographic location were applied.
We included all randomized controlled trials of asymptomatic singleton gestations with previous spontaneous preterm birth that were randomized to prophylactic treatment with either vaginal progesterone (ie, intervention group) or intramuscular 17-alpha-hydroxyprogesterone caproate (ie, comparison group). Post hoc sensitivity analysis was performed for studies with low risk of bias and studies with protocol registration.
The primary outcome was preterm birth <34 weeks\' gestation. The summary measures were reported as relative risks with 95% confidence intervals.
Seven randomized controlled trials including 1910 patients were included in the meta-analysis. Patients who received vaginal progesterone had a significantly lower rate of preterm birth at <34 weeks (14.7% vs 19.9%; relative risk, 0.74; 95% confidence interval, 0.57-0.96), preterm birth at <37 weeks (36.0% vs 46.6%; relative risk, 0.76; 95% confidence interval, 0.69-0.85), and preterm birth at <32 weeks of gestation (7.9% vs 13.6%; relative risk, 0.58; 95% confidence interval, 0.39-0.86), compared with women who received intramuscular 17-alpha-hydroxyprogesterone caproate. There were no significant differences in the rate of preterm birth at <28 weeks\' gestation. Adverse drug reactions were significantly lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (15.6% vs 22.2%; relative risk, 0.71; 95% confidence interval, 0.54-0.92). Perinatal mortality was lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (2.2% vs 4.4%; relative risk, 0.51; 95% confidence interval, 0.25-1.01). In sensitivity analysis including trials rated with at least 4 Cochrane tools as of \"low risk of bias,\" 4 trials were included (N=575), and there was no longer a significant difference in preterm birth at <34 weeks\' gestation between vaginal progesterone and 17-alpha-hydroxyprogesterone caproate (12.2% vs 13.9%; relative risk, 0.87; 95% confidence interval, 0.57-1.32).
Overall, vaginal progesterone was superior to 17-alpha-hydroxyprogesterone caproate in the prevention of preterm birth at <34 weeks\' gestation in singleton pregnancies with previous spontaneous preterm birth. Although sensitivity analysis of high-fidelity studies showed the same trend, findings were no longer statistically significant.