甲氨蝶呤注射后 hCG 的变化，能作为治疗宫外孕成功的指标?

近期《Human Reproduction》杂志发表了一篇题为《Early (Days 1–4) post-treatment serum hCG level changes predict single-dose methotrexate treatment success in tubal ectopic pregnancy》的文章，旨在探讨甲氨蝶呤单剂量注射后第 1-4 天血清人绒毛膜促性腺激素 (hCG) 水平的变化能否成为药物治疗输卵管妊娠成功与否的预后指标？

本篇内容由翻译志愿者康针珍医生翻译，蔡贺博士审校，供大家学习交流！

STUDY QUESTION

研究问题

What is the capacity of the change between Day 1 and Day 4 post-treatment serum human chorionic gonadotropin (hCG) levels for predicting single-dose methotrexate treatment success in tubal ectopic pregnancy?

甲氨蝶呤单剂量注射后第 1-4 天血清人绒毛膜促性腺激素 (hCG) 水平的变化能否成为药物治疗输卵管妊娠成功与否的预后指标？

SUMMARY ANSWER

结论

Any fall in Days 1–4 serum hCG signified an 85% (95% CI 76.8–90.6) likelihood of treatment success for women with tubal ectopic pregnancy (initial hCG of ≥1000 and ≤5000 IU/l) managed with single-dose methotrexate.

对于接受单剂量甲氨蝶呤治疗的输卵管妊娠（治疗前 hCG 为 1000-5000 IU/L）的女性，第 1-4 天血清 hCG 任何程度的下降都预示治疗成功，其可能性为 85%（95%置信区间为76.8-90.6）。

WHAT IS KNOWN ALREADY

已知情况

For those with tubal ectopic pregnancy managed by single-dose methotrexate, current guidelines advocate intervention if Days 4–7 hCG fails to fall by >15%. The trajectory of hCG over Days 1–4 has been proposed as an early indicator that predicts treatment success, allowing early reassurance for women. However, almost all prior studies of Days 1–4 hCG changes have been retrospective.

目前的指南建议，若接受单剂量甲氨蝶呤治疗的输卵管妊娠女性第4-7天hCG下降幅度若未超过15%，则需要进一步干预。有学者提出第1-4日hCG发展轨迹可作为预测治疗成功的早期指标。然而，几乎所有以往关于第1-4天hCG变化的研究都是回顾性的。

STUDY DESIGN, SIZE, DURATION

研究设计、样本量和持续时间

This was a prospective cohort study of women with tubal ectopic pregnancy (pre-treatment hCG of ≥1000 and ≤5000 IU/l) managed with single-dose methotrexate. The data were derived from a UK multicentre randomized controlled trial of methotrexate and gefitinib versus methotrexate and placebo for treatment of tubal ectopic pregnancy (GEM3). For this analysis, we include data from both treatment arms.

这是一项前瞻性队列研究，研究对象为接受单剂量甲氨蝶呤治疗的输卵管妊娠(治疗前hCG为1000-5000 IU/l)女性。这些数据来自英国一项多中心随机对照试验（GEM3），该试验比较了甲氨蝶呤联合吉非替尼与甲氨蝶呤联合安慰剂治疗输卵管妊娠的效果。本研究中，我们纳入了这2个治疗组的数据。

PARTICIPANTS/MATERIALS, SETTING, METHODS

研究对象/材料、设定、方法

Participants were categorized according to single-dose methotrexate treatment success or failure. Treatment success for this analysis was defined as complete and uneventful resolution of tubal ectopic pregnancy to serum hCG <30 IU/l following single-dose methotrexate treatment without additional treatment. Patient characteristics of the treatment success and failure groups were compared. Changes in Days 1–4, 1–7, and 4–7 serum hCG were evaluated as predictors of treatment success through receiver operating characteristic curve analysis. Test performance characteristics were calculated for percentage change ranges and thresholds including optimal classification thresholds.

受试者根据单剂量甲氨蝶呤治疗成功或失败进行分组。单剂量甲氨蝶呤治疗输卵管妊娠成功的标准：给药后无额外干预，患者血清hCG消退至30 IU/l以下。比较治疗成功组和失败组的患者特征，通过对受试者特征曲线的分析，评估第1-4、1-7和4-7天血清hCG的变化作为治疗成功的预测因素。计算百分比变化范围和阈值，包括最优分类阈值。

MAIN RESULTS AND THE ROLE OF CHANCE

主要结果和机会性概率

A total of 322 women with tubal ectopic pregnancy were treated with single-dose methotrexate. The overall single-dose methotrexate treatment success rate was 59% (n = 189/322). For any fall in serum hCG on Days 1–4, likelihood ratios were >3, while for any fall of serum hCG >20% on Days 1–7, likelihood ratios reached 5. Any rise of serum hCG on Days 1–7 and 4–7 strongly reduced the chance of success. Any fall in Days 1–4 hCG predicted single-dose methotrexate treatment success with a sensitivity of 58% and specificity 84%, resulting in positive and negative predictive values of 85% and 57%, respectively. Any rise in Days 1–4 serum hCG <18% was identified as an optimal test threshold that predicted treatment success with 79% sensitivity and 74% specificity, resulting in 82% positive predictive value and 69% negative predictive value.

共有322名输卵管妊娠妇女接受了单剂量甲氨蝶呤治疗。其总成功率为59%（n = 189/322）。对于第1-4天血清hCG值任何程度的下降，似然比均大于3，而对于第1-7天而言，血清hCG的任何下降在20%以上者，似然比达到5。血清hCG在第1-7天和第4-7天的任何升高都会大大降低成功的几率。第1-4天hCG的任何程度下降都可以预测单剂量甲氨蝶呤治疗的成功，敏感性为58%，特异性为84%，阳性和阴性的预测值分别为85%和57%。第1-4天血清hCG的任何升高幅度不到18%都被定义为预测治疗成功的最佳检测阈值，具有79%的敏感性和74%的特异性，阳性预测值为82%和阴性预测值为69%。

LIMITATIONS, REASONS FOR CAUTION

局限性、需谨慎原因

Our findings may be limited by intervention bias resulting from existing guidelines which influences evaluation of hCG changes reliant on Day 7 serum hCG levels.

我们的研究结果可能受到现有指南的干预偏倚的限制，该指南影响了依赖于第7天的血清hCG水平的hCG变化评估。

WIDER IMPLICATIONS OF THE FINDINGS

研究结果的更深层次意义

Examining a large prospective cohort, we show the value of Days 1–4 serum hCG changes in predicting single-dose methotrexate treatment success in tubal ectopic pregnancy. We recommend that clinicians provide early reassurance to women who have a fall or only a modest (<18%) rise in Days 1–4 serum hCG levels, that their treatment will likely be effective.

通过对一个大型前瞻性队列进行研究，我们指出了第1-4天血清hCG变化在预测单剂量甲氨蝶呤治疗输卵管妊娠成功中的价值。对于第1-4日血清hCG水平下降或仅小幅(<18%)升高的女性，我们建议临床医师尽早让她们放心，她们的治疗可能是有效的。

文章来源：

Scott C Mackenzie, Catherine A Moakes, Ann M Doust, Ben W Mol, W Colin Duncan, Stephen Tong, Andrew W Horne, Lucy H R Whitaker, Early (Days 1–4) post-treatment serum hCG level changes predict single-dose methotrexate treatment success in tubal ectopic pregnancy, Human Reproduction, Volume 38, Issue 7, July 2023, Pages 1261–1267, https://doi.org/10.1093/humrep/dead089