Colombo G E, Leonardi M, Armour M, Di Somma H, Dinh T, da Silva Costa F, Wong L, Armour S, Condous G
School of Medicine, Medical Sciences, and Nutrition, University of Aberdeen, Aberdeen AB24 3FX, UK.
Acute Gynaecology, Early Pregnancy, and Advanced Endosurgery Unit, Nepean Hospital, Kingswood, 2747 NSW, Australia.
Hum Reprod Open. 2020 Oct 25;2020(4):hoaa044. doi: 10.1093/hropen/hoaa044. eCollection 2020.
Is expectant management (EM) of tubal ectopic pregnancy (EP) an effective and safe treatment strategy when compared to alternative interventions?
There is insufficient evidence to conclude EM yields a difference in the resolution of tubal EP, the avoidance of surgery or time to resolution of tubal EP when compared to intramuscular methotrexate in stable patients with β-hCG <1500 IU/l.
The utilisation of medical and surgical management for EP is well established. EM aims to allow spontaneous resolution of the EP without intervention.
We performed a systematic review and meta-analysis, searching Ovid MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, OpenGrey.eu, Google Scholar, cross-referencing citations and trial registries to 15 December 2019. There were no limitations placed on language or publication date. Search terms included tubal EP and EM as well as variations of these terms.
PARTICIPANTS/MATERIALS SETTING AND METHOD: We considered studies that included patients with tubal EP, EM as a comparator, and that were randomised controlled trials (RCTs). The primary outcome was resolution of tubal EP. Secondary outcomes included avoidance of surgery and the time to resolution of EP. Two reviewers independently selected the studies, assessed bias and extracted data. Relative risk (RR) and mean difference with 95% CI were assessed using a random effects model. The certainty of evidence was scored according to Grading of Recommendations Assessment, Development and Evaluation guidelines.
In total, 920 studies were screened. Five studies were eligible for inclusion in the systematic review. Two RCTs comparing methotrexate to EM were identified as being eligible for inclusion in meta-analysis. No RCTs comparing surgery to EM were identified. Compared with EM, there was insufficient evidence that methotrexate yields a difference on resolution of tubal EP (RR 1.04, 95% CI 0.88-1.23, = 0.67; two RCTs, moderate-certainty evidence), avoiding surgery (RR 1.10, 95% CI 0.94-1.29, = 0.25; two RCTs, low-certainty evidence) or the time to resolution of tubal EP (-2.56 days (favouring EM), 95% CI -7.93-2.80, = 0.35; two RCTs, low-certainty evidence).
Only two RCTs with a total of 103 patients were eligible for inclusion in this meta-analysis. Further RCTs comparing EM to medical and surgical management are needed and these should also report adverse events. Patient preference should also be evaluated.
We found insufficient evidence of differences in terms of resolution, avoidance of surgery and time to resolution between expectant and medical management. Given the imprecision in the effect estimates as demonstrated by the wide CIs, resulting in the downgrading of certainty of evidence for all outcomes in this meta-analysis, larger RCTs comparing interventions for tubal EP are needed. Caution should be exercised when trying to decide between EM and methotrexate to treat tubal EP.
STUDY FUNDING/COMPETING INTERESTS: There was no funding for this study. NICM receives funding from various sources; none specifically supported this research. M.L. reports grants from Australian Women and Children's Research Foundation, outside the submitted work. M.A.: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies and industry. Sponsors and donors provide untied and tied funding for work to advance the vision and mission of the Institute. This systematic review was not specifically supported by donor or sponsor funding to NICM. M.A. reports a partnership grant with Metagenetics outside the submitted work. G.C. reports grants from Australian Women and Children's Research Foundation, personal fees from Roche and GE Healthcare, outside the submitted work. The remaining authors report no conflicts of interest.
CRD42020142736.
与其他干预措施相比，输卵管异位妊娠（EP）的期待治疗（EM）是否是一种有效且安全的治疗策略？
与肌内注射甲氨蝶呤治疗β-hCG<1500IU/L的稳定患者相比，没有足够的证据得出期待治疗在输卵管EP的消退、避免手术或输卵管EP消退时间方面存在差异的结论。
EP的药物和手术治疗方法已得到充分确立。期待治疗旨在使EP在无干预的情况下自然消退。
研究设计、规模和持续时间：我们进行了一项系统评价和荟萃分析，检索了Ovid MEDLINE、Embase、PsycINFO、CINAHL、Web of Science、OpenGrey.eu、Google Scholar，并交叉引用了截至2019年12月15日的文献和试验注册信息。对语言或出版日期没有限制。检索词包括输卵管EP和期待治疗以及这些术语的变体。
参与者/材料、设置和方法：我们纳入了包括输卵管EP患者、以期待治疗作为对照且为随机对照试验（RCT）的研究。主要结局是输卵管EP的消退。次要结局包括避免手术和EP消退时间。两名研究者独立选择研究、评估偏倚并提取数据。使用随机效应模型评估相对风险（RR）和95%置信区间的均值差。根据推荐分级评估、制定和评价指南对证据的确定性进行评分。
共筛选了920项研究。5项研究符合纳入系统评价的条件。两项比较甲氨蝶呤与期待治疗的RCT被确定符合纳入荟萃分析的条件。未发现比较手术与期待治疗的RCT。与期待治疗相比，没有足够的证据表明甲氨蝶呤在输卵管EP消退方面存在差异（RR 1.04，95%CI 0.88-1.23，I²=0.67；两项RCT，中等确定性证据）、避免手术方面（RR 1.10，95%CI 0.94-1.29，I²=0.25；两项RCT，低确定性证据）或输卵管EP消退时间方面（-2.56天（有利于期待治疗），95%CI -7.93-2.80，I²=0.35；两项RCT，低确定性证据）。
局限性、谨慎的原因：本荟萃分析仅纳入了两项共103例患者的RCT。需要进一步进行比较期待治疗与药物和手术治疗的RCT，并且这些研究还应报告不良事件。还应评估患者偏好。
我们发现，在消退、避免手术和消退时间方面，期待治疗与药物治疗之间没有差异的证据不足。鉴于宽置信区间表明效应估计不精确，导致本荟萃分析中所有结局的证据确定性降低，需要进行更大规模的比较输卵管EP干预措施的RCT。在决定采用期待治疗还是甲氨蝶呤治疗输卵管EP时应谨慎。
研究资金/利益冲突：本研究没有资金支持。NICM从各种来源获得资金；没有专门支持本研究的资金。M.L.报告在提交的工作之外从澳大利亚妇女和儿童研究基金会获得资助。M.A.：作为一个医学研究所，NICM健康研究所从基金会、大学、政府机构和行业获得研究资助和捐赠。赞助商和捐赠者为推进研究所的愿景和使命的工作提供无附加条件和有附加条件的资金。本系统评价未得到NICM捐赠者或赞助商的专门资助。M.A.报告在提交的工作之外与Metagenetics有合作资助。G.C.报告在提交的工作之外从澳大利亚妇女和儿童研究基金会获得资助，从罗氏和通用电气医疗集团获得个人费用。其余作者报告无利益冲突。
PROSPERO注册号：CRD42020142736。
