中西医联合用药对照单纯西药改善不孕症患者子宫内膜容受性疗效的系统评价及Meta分析

A Systematic Review and Meta-Analysis of the Efficacy of Traditional Chinese Medicine Combined with Western Medicine against Western Medicine Alone in Improving Endometrium Receptivity in Infertility Patients

摘要: 目的：系统评价近5年中西药联合用药与单用西药对改善不孕症患者子宫内膜容受性的临床疗效，为临床治疗不孕症提供依据。方法：电子检索中国知网、万方平台、维普官网、PubMed、Embase，查询2018年1月1日至2023年3月1日期间，上述两种用药方法的相关随机对照实验研究，根据纳入及排除标准筛选文献，采用Endnote 20.1纳入数据、RevMan 5.4.1软件进行Meta分析。结果：共有18项RCT符合纳入要求，合计1620例不孕症患者，其中治疗组808例，对照组812例。Meta分析结果显示：1) 中西药联合运用可显著增加患者子宫内膜厚度[MD = 1.32, 95%CL (1.24, 1.40), P < 0.00001]；2) 提高患者A型子宫内膜占比[RR = 1.31, 95%CL (1.18, 1.46), P < 0.00001]；3) 降低患者子宫动脉搏动指数(PI) [MD = −0.33, 95%CL (−0.37, −0.29), P < 0.00001]；4) 降低子宫动脉阻力指数(RI) [MD = −0.10, 95%CL (−0.11, −0.09)], P < 0.00001]；5) 提高血清性激素雌二醇(E2)水平[MD = 34.98, 95%CL (29.50, 40.47), P < 0.00001]；6) 提高血清性激素孕酮(P)水平[MD = 2.99, 95%CL (2.64, 3.35), P < 0.00001]；7) 提高不孕症患者临床妊娠率[RR = 1.57, 95%CL (1.40, 1.77), P < 0.00001]，疗效优于单纯西药治疗组。Meta亚组分析结果显示：1) 中药联合戊酸雌二醇(CM + EV)对子宫内膜厚度的改善更优于中药联合来曲唑(CM + LE)，CM + EV [MD = 1.52, 95% CL (1.27, 1.76), P < 0.00001]，CM + LE [MD = 0.94, 95% CL (0.54, 1.35), P < 0.00001]，Total [MD = 1.39, 95% CL (1.15, 1.63), P < 0.00001]，Test of Subgroup differences (P = 0.02, I² = 82.6%)，P < 0.05；2) 中西药联合改善薄型子宫内膜厚度的疗效更优于非薄型子宫内膜，联合改善薄型内膜[MD = 1.37, 95%CL (1.28, 1.46), P < 0.00001]，联合改善非薄型内膜[MD = 1.14, 95%CL (0.97, 1.31), P < 0.00001]，Total [MD = 1.32, 95%CL (1.24, 1.40), P < 0.00001]，Test of Subgroup differences (P = 0.02, I² = 82.5%)，P < 0.05；3) 西药联合运用补肾填精益气养血方与联合补肾活血化瘀方两亚组对改善临床妊娠率无显著性差异(P = 0.20)，联合补肾填精益气养血方剂改善效果[RR = 1.49, 95%CL (1.29, 1.71), P < 0.00001]，联合补肾活血化瘀方时[RR = 1.57, 95%CL (1.42, 2.17), P < 0.00001]，Total [RR = 1.57, 95%CL (1.40, 1.77), P < 0.00001]。结论：中西药联合改善子宫内膜容受性的疗效优于纯西药治疗，对薄型子宫内膜厚度的改善优于非薄型，CM + EV对子宫内膜厚度的改善效果优于CM + LE。并且中西药联合运用未见不良反应发生，整体调整患者体质，对提高临床妊娠率、减少孕后流产率有效。但该结论尚需更多高质量研究进一步加以验证，结论仅供参考。

Abstract: Objective: To systematically evaluate the clinical efficacy of traditional Chinese combined with Western medicine against Western medicine alone in improving endometrial receptivity in infertility patients over the past 5 years, and provide a basis for clinical treatment of infertility. Methods: Electronic searches were conducted on China National Knowledge Infrastructure, Wanfang Platform, VIP official website, PubMed, and Embase to search for relevant randomized controlled trials and studies of the two medication methods from January 1, 2018 to March 1, 2023. Literature was screened based on inclusion and exclusion criteria, and meta-analysis was conducted using Endnote 20.1 inclusion data and RevMan 5.4.1 software. Results: A total of 18 RCTs met the inclusion requirements, with a total of 1620 infertility patients, including 808 in the treatment group and 812 in the control group. The meta-analysis results showed that: 1) The combination of Chinese and Western medicine can significantly increase the thickness of the patient’s endometrium [MD = 1.32, 95%CL (1.24, 1.40), P < 0.0001]; 2) It can increase the proportion of type A endometrium in patients [RR = 1.31, 95%CL (1.18, 1.46), P < 0.0001]; 3) It can reduce the patient’s uterine artery pulsatility index (PI) [MD = −0.33, 95%CL (−0.37, −0.29), P < 0.0001]; 4) It can reduce the uterine artery resistance index (RI) [MD = −0.10, 95%CL (−0.11, −0.09), P < 0.0001]; 5) It can increase the level of serum sex hormone estradiol (E2) [MD = 34.98, 95%CL (29.50, 40.47), P < 0.00001]; 6) It can increase the level of serum sex hormone progesterone (P) [MD = 2.99, 95%CL (2.64, 3.35), P < 0.00001]; 7) It can increase clinical pregnancy rate in infertility patients [RR = 1.57, 95%CL (1.40, 1.77), P < 0.00001], with better efficacy than the group treated with Western medicine alone. The meta-subgroup analysis results show that: 1) The combination of traditional Chinese medicine and estradiol valerate (CM + EV) has a better effect on improving endometrial thickness than the combination of traditional Chinese medicine and letrozole (CM + LE). CM + EV [MD = 1.52, 95%CL (1.27, 1.76), P < 0.0001], CM + LE [MD = 0.94, 95%CL (0.54, 1.35), P < 0.0001], Total [MD = 1.39, 95%CL (1.15, 1.63), P < 0.0001], Test of subgroup differences [(P = 0.02, I2 = 82.6%), P < 0.05]; 2) The combination of Chinese and Western medicine has a better therapeutic effect on improving the thickness of thin endometrium than non-thin endometrium. The combination improves thin endometrium [MD = 1.37, 95%CL (1.28, 1.46), P < 0.0001], and improves non-thin endometrium [MD = 1.14, 95%CL (0.97, 1.31), P < 0.0001], Total [MD = 1.32, 95%CL (1.24, 1.40), P < 0.0001], Test of subgroup differences (P = 0.02, I² = 82.5%), P < 0.05; 3) There was no significant difference (P = 0.20) in the improvement of clinical pregnancy rate between the two subgroups of Western medicine combined with the tonifying kidney, filling essence, nourishing qi, and nourishing blood formula and tonifying kidney, promoting blood circulation, and removing stasis formula. The improvement effect of the combination of tonifying kidney, filling essence, nourishing qi, and nourishing blood formula (RR = 1.49, 95%CL (1.29, 1.71), P < 0.0001). When combined with the tonifying kidney, promoting blood circulation, and removing stasis formula [RR = 1.57, 95%CL (1.42, 2.17), P < 0.0001], and the total effect [RR = 1.57, 95%CL (1.40, 1.77), P < 0.0001]. Conclusion: The efficacy of combining Chinese and Western medicine in improving endometrial receptivity is superior to that of Western medicine alone. Medical treatment has a better effect on improving the thickness of thin endometrium than non-thin endometrium, and CM + EV has a better effect on improving endometrial thickness than CM + LE. Moreover, the combination of traditional Chinese and Western medicine did not cause any adverse reactions, and the overall adjustment of the patient’s physical condition was effective in improving clinical pregnancy rates and reducing post-pregnancy miscarriage rates. However, this conclusion still needs further verification through more high-quality research, and the conclusion is for reference only.