Lima Jorge, Guerreiro João, Ângelo-Dias Miguel, Serra Sofia Silvério, Costa Teresa, Marto Natália, de Pinho João Feldman, Costa João, Ruano Rodrigo, Duarte Gonçalo Silva
Department of Obstetrics and Gynecology, High-Risk Pregnancy Center, Hospital da Luz Lisboa, Lisbon, Portugal.
Comprehensive Health Research Centre-CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisbon, Portugal.
Front Med (Lausanne). 2025 May 14;12:1569819. doi: 10.3389/fmed.2025.1569819. eCollection 2025.
Approximately 50% of cases of recurrent pregnancy loss (RPL) remain unexplained, and there is a lack of consensus concerning the effective treatments for idiopathic RPL. We used network meta-analyses to evaluate the efficacy of several prophylactic therapeutic interventions used in women with idiopathic RPL.
We conducted a systematic literature search using several databases from their inceptions to 20 July 2023. References from key articles were also manually searched. Randomized controlled trials assessing the efficacy and safety of any prophylactic intervention that were conducted in adult women with RPL were included. Studies with known causes of RPL were excluded. Two reviewers independently extracted data and assessed the risk of bias. Primary outcomes were live births and miscarriage rates. Secondary outcomes included serious adverse/adverse events and trial discontinuation. The network meta-analyses used a Bayesian hierarchical model with direct and indirect comparisons. Rank probabilities (assessed by surface under the cumulative ranking curve [SUCRA]) and certainty of evidence (assessed by Grading Recommendations Assessment, Development, and Evaluation [GRADE]) were also assessed.
Thirty-eight studies (6,379 participants) were evaluated. No statistically significant differences in live birth rates among the interventions were found. The three best-ranked interventions for this outcome were prednisone plus progesterone plus aspirin (83%), leukocyte immune therapy (74%), and prednisolone (65%). Women who were treated with progesterone plus human chorionic gonadotrophin (instead of a placebo) presented an increase in miscarriage odds (odds ratio [OR] 3.83, 95% credible intervals [CrIs] 1.04-14.38). The three best-ranked interventions for miscarriage rate were prednisone plus progesterone plus aspirin (SUCRA = 81%), hydroxychloroquine (SUCRA = 79%), and intralipid (SUCRA = 65%). Overall, under placebo, 59% (95% confidence interval [CI] 51-67; I = 92%) of participants underwent successful live births, and 35% (95% CI 30-42, I = 86%) underwent miscarriages. We found no evidence of statistically significant differences between interventions (the top three interventions were low-molecular-weight heparin, granulocyte colony-stimulating factor, and leukocyte immune therapy) in those who discontinued trial participation.
Our results suggest that none of the analyzed interventions led to improvements in the live birth rate or a reduction in the miscarriage rate in women with idiopathic RPL.
https://www.crd.york.ac.uk/prospero, identifier CRD42023455668.
约50%的复发性流产（RPL）病例病因不明，对于特发性RPL的有效治疗方法尚无共识。我们使用网络荟萃分析来评估几种用于特发性RPL女性的预防性治疗干预措施的疗效。
我们使用多个数据库进行了系统的文献检索，检索时间从数据库建立至2023年7月20日。还手动检索了关键文章的参考文献。纳入了评估任何预防性干预措施对成年RPL女性疗效和安全性的随机对照试验。排除已知RPL病因的研究。两名研究者独立提取数据并评估偏倚风险。主要结局为活产率和流产率。次要结局包括严重不良/不良事件和试验中止情况。网络荟萃分析采用贝叶斯分层模型进行直接和间接比较。还评估了排序概率（通过累积排序曲线下面积[SUCRA]评估）和证据确定性（通过推荐分级的评估、制定与评价[GRADE]评估）。
共评估了38项研究（6379名参与者）。各干预措施的活产率无统计学显著差异。该结局排名前三的干预措施为泼尼松联合孕酮联合阿司匹林（83%）、白细胞免疫疗法（74%）和泼尼松龙（65%）。接受孕酮联合人绒毛膜促性腺激素治疗（而非安慰剂）的女性流产几率增加（优势比[OR] 3.83，95%可信区间[CrIs] 1.04 - 14.38）。流产率排名前三的干预措施为泼尼松联合孕酮联合阿司匹林（SUCRA = 81%）、羟氯喹（SUCRA = 79%）和脂肪乳剂（SUCRA = 65%）。总体而言，在安慰剂组中，59%（95%置信区间[CI] 51 - 67；I² = 92%）的参与者成功活产，35%（95% CI 30 - 42，I² = 86%）发生流产。我们未发现干预措施（排名前三的干预措施为低分子肝素、粒细胞集落刺激因子和白细胞免疫疗法）在试验中止参与者中有统计学显著差异的证据。
我们的结果表明，对于特发性RPL女性，所分析的干预措施均未提高活产率或降低流产率。
