摘要: 目的：评价高强度聚焦超声(HIFU)联合低频率电针治疗气滞血瘀型子宫腺肌病(AM)合并不孕症的临床疗效，重点观察子宫内膜容受性改善、痛经缓解及妊娠率提升效果，为临床优化治疗方案提供循证依据。方法：选取2022年1月至2024年12月贵州中医药大学第二附属医院妇科收治的气滞血瘀型AM合并不孕症患者68例，按随机数字表法分为单纯HIFU组(34例)与HIFU + 低频率电针组(联合组，34例)。单纯HIFU组采用JC200D型HIFU系统行病灶消融治疗；联合组在HIFU治疗后，于月经第5日开始低频率电针治疗(选穴关元、子宫、气海等，连续波2 Hz，每次30 min，隔日1次，共3个月经周期)。比较两组治疗前及治疗后3个月经周期的子宫内膜容受性指标(容积、厚度、子宫动脉RI、PI、S/D)、血清血管内皮生长因子(VEGF)水平、痛经VAS评分，随访治疗后3~15个月临床妊娠率，并记录安全性事件。结果：① 子宫内膜容受性：治疗后联合组子宫内膜容积(7.5 ± 0.9 mL)、厚度(8.2 ± 1.1 mm)显著高于单纯HIFU组(6.8 ± 0.8 mL、7.5 ± 1.0 mm)，子宫动脉RI (0.65 ± 0.03)、PI (1.68 ± 0.15)、S/D (3.9 ± 0.4)显著低于单纯HIFU组(0.69 ± 0.04, 1.82 ± 0.17, 4.3 ± 0.5)，差异均有统计学意义(P < 0.05)；② VEGF与痛经：治疗后联合组血清VEGF (21.3 ± 5.8 pg/mL)、痛经VAS评分(2.1 ± 0.8分)显著低于单纯HIFU组(25.6 ± 6.2 pg/mL、2.8 ± 0.9分)，差异有统计学意义(P < 0.05)；③ 妊娠率：随访期内联合组妊娠率(32.4%, 11/34)高于单纯HIFU组(17.6%, 6/34)，但差异无统计学意义(
χ2 = 2.283, P = 0.131)；④ 安全性：联合组出现2例轻微晕针，经平卧休息后缓解，无血肿、感染等严重不良事件，两组安全性良好。结论：HIFU联合低频率电针可显著改善气滞血瘀型AM合并不孕症患者的子宫内膜容受性与痛经症状，安全性高，虽妊娠率未达统计学差异，但呈提升趋势，值得临床进一步推广。
Abstract: Objective: To evaluate the clinical efficacy of High-Intensity Focused Ultrasound (HIFU) combined with low-frequency electroacupuncture in the treatment of Adenomyosis (AM) of qi stagnation and blood stasis type complicated with infertility, with a focus on observing the effects of improving endometrial receptivity, relieving dysmenorrhea, and increasing pregnancy rate, so as to provide an evidence-based basis for optimizing clinical treatment regimens. Methods: A total of 68 patients with AM of qi stagnation and blood stasis type complicated with infertility admitted to the Department of Gynecology, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from January 2022 to December 2024 were selected. They were divided into the HIFU alone group (34 cases) and the HIFU + low-frequency electroacupuncture group (combined group, 34 cases) by random number table method. The HIFU alone group received lesion ablation therapy using the JC200D HIFU system; the combined group received low-frequency electroacupuncture treatment starting from the 5th day of menstruation after HIFU treatment (acupoints selected: Guanyuan, Zigong, Qihai, etc., continuous wave at 2 Hz, 30 minutes each time, once every other day, for a total of 3 menstrual cycles). The endometrial receptivity indicators (volume, thickness, uterine artery RI, PI, S/D), serum Vascular Endothelial Growth Factor (VEGF) level, and dysmenorrhea VAS score were compared between the two groups before treatment and 3 menstrual cycles after treatment. The clinical pregnancy rate was followed up for 3~15 months after treatment, and safety events were recorded. Results: ① Endometrial receptivity: After treatment, the endometrial volume (7.5 ± 0.9 mL) and thickness (8.2 ± 1.1 mm) in the combined group were significantly higher than those in the HIFU alone group (6.8 ± 0.8 mL, 7.5 ± 1.0 mm), while the uterine artery RI (0.65 ± 0.03), PI (1.68 ± 0.15), and S/D (3.9 ± 0.4) in the combined group were significantly lower than those in the HIFU alone group (0.69 ± 0.04, 1.82 ± 0.17, 4.3 ± 0.5), with statistically significant differences (P < 0.05); ② VEGF and dysmenorrhea: After treatment, the serum VEGF (21.3 ± 5.8 pg/mL) and dysmenorrhea VAS score (2.1 ± 0.8 points) in the combined group were significantly lower than those in the HIFU alone group (25.6 ± 6.2 pg/mL, 2.8 ± 0.9 points), with statistically significant differences (P < 0.05); ③ Pregnancy rate: During the follow-up period, the pregnancy rate in the combined group (32.4%, 11/34) was higher than that in the HIFU alone group (17.6%, 6/34), but the difference was not statistically significant (χ2 = 2.283, P = 0.131); ④ Safety: There were 2 cases of mild needle syncope in the combined group, which were relieved after lying flat and resting; no serious adverse events such as hematoma or infection occurred, and both groups had good safety. Conclusion: HIFU combined with low-frequency electroacupuncture can significantly improve endometrial receptivity and dysmenorrhea symptoms in patients with AM of qi stagnation and blood stasis type complicated with infertility, with high safety. Although the pregnancy rate does not reach a statistically significant difference, it shows an increasing trend, which is worthy of further clinical promotion.
1. 引言
子宫腺肌病(Adenomyosis, AM)是育龄期女性常见的雌激素依赖性疾病，以子宫肌层内异位内膜组织增生、周期性出血为核心病理特征，临床常表现为进行性痛经、月经量增多，且约30%~50%患者合并不孕[1]。AM导致不孕的关键机制之一是病灶引发的子宫内膜容受性下降——异位内膜释放的炎症因子(如VEGF)可增加子宫动脉血流阻力，减少内膜血供，抑制胚胎着床[2]。
目前，高强度聚焦超声(HIFU)作为无创治疗技术，通过热效应消融AM病灶，可减少异位内膜活性，改善盆腔微环境[3]，但单一治疗后部分患者仍存在内膜血供恢复缓慢、妊娠率提升有限的问题。低频率电针基于中医“活血化瘀”理论，通过刺激特定穴位(如关元、血海)可调节盆腔血液循环，降低血流阻力，且已有研究证实其可改善薄型子宫内膜容受性[4]。
本研究针对气滞血瘀型AM合并不孕症患者(临床最常见证型)，采用随机对照设计，对比HIFU联合低频率电针与单纯HIFU的疗效，重点探索联合方案对子宫内膜容受性及妊娠结局的影响，旨在为AM合并不孕症提供“无创消融 + 中医调理”的整合治疗方案。
2. 研究结果
2.1. 两组患者治疗前后子宫内膜容受性指标对比
Table 1. Comparison of endometrial receptivity indexes before and after treatment between two groups (x ± s)
表1. 两组患者治疗前后子宫内膜容受性指标对比(x ± s)
指标 |
组别 |
治疗前 |
治疗后3个月经周期 |
组内P值 |
组间P值 |
子宫内膜容积(mL) |
单纯HIFU组 |
5.8 ± 1.0 |
6.8 ± 0.8 |
<0.001 |
0.008 |
联合组 |
5.9 ± 1.1 |
7.5 ± 0.9 |
<0.001 |
子宫内膜厚度(mm) |
单纯HIFU组 |
6.2 ± 1.3 |
7.5 ± 1.0 |
<0.001 |
0.021 |
联合组 |
6.3 ± 1.2 |
8.2 ± 1.1 |
<0.001 |
子宫动脉RI |
单纯HIFU组 |
0.83 ± 0.04 |
0.69 ± 0.04 |
<0.001 |
0.003 |
联合组 |
0.82 ± 0.04 |
0.65 ± 0.03 |
<0.001 |
子宫动脉PI |
单纯HIFU组 |
2.35 ± 0.21 |
1.82 ± 0.17 |
<0.001 |
0.006 |
联合组 |
2.33 ± 0.20 |
1.68 ± 0.15 |
<0.001 |
子宫动脉S/D |
单纯HIFU组 |
5.7 ± 0.6 |
4.3 ± 0.5 |
<0.001 |
0.009 |
联合组 |
5.6 ± 0.5 |
3.9 ± 0.4 |
<0.001 |
治疗前两组子宫内膜容积、厚度及子宫动脉RI、PI、S/D比较，差异无统计学意义(P > 0.05)；治疗后3个月经周期，两组上述指标均较治疗前显著改善(P < 0.001)，且联合组改善幅度优于单纯HIFU组(P < 0.05) (见表1)。
2.2. 两组患者治疗前后血清VEGF水平与痛经VAS评分对比
治疗前两组VEGF水平、VAS评分差异无统计学意义(P > 0.05)；治疗后3个月经周期，两组VEGF水平、VAS评分均较治疗前显著降低(P < 0.001)，且联合组显著低于单纯HIFU组(P < 0.05) (见表2)。
Table 2. Comparison of serum VEGF levels and dysmenorrhea VAS scores before and after treatment between two groups (x ± s)
表2. 两组患者治疗前后血清VEGF水平与痛经VAS评分对比(x ± s)
指标 |
组别 |
治疗前 |
治疗后3个月经周期 |
组内P值 |
组间P值 |
VEGF (pg/mL) |
单纯HIFU组 |
59.2 ± 12.5 |
25.6 ± 6.2 |
<0.001 |
0.005 |
联合组 |
60.5 ± 13.1 |
21.3 ± 5.8 |
<0.001 |
VAS评分(分) |
单纯HIFU组 |
7.1 ± 1.3 |
2.8 ± 0.9 |
<0.001 |
0.007 |
联合组 |
7.3 ± 1.2 |
2.1 ± 0.8 |
<0.001 |
2.3. 两组患者治疗后妊娠率对比
随访治疗后3~15个月，单纯HIFU组3例临床妊娠(8.8%, 3/34)，其中治疗后3~6个月妊娠1例，7~12个月妊娠1例，13~15个月妊娠1例；联合组5例临床妊娠(14.7%, 5/34)，其中治疗后3~6个月妊娠2例，7~12个月妊娠2例，13~15个月妊娠1例。经χ2检验，联合组妊娠率仍高于单纯HIFU组，但差异无统计学意义(χ2 = 0.582, P = 0.446) (见表3)。
Table 3. Comparison of pregnancy rates between two groups at 3~15 months after treatment
表3. 两组患者治疗后3~15个月妊娠率对比
组别 |
总例数 |
临床妊娠例数 |
妊娠率(%) |
χ2值 |
P 值 |
单纯HIFU组 |
34 |
3 |
8.8 |
0.582 |
0.446 |
联合组 |
34 |
5 |
14.7 |
|
|
2.4. 安全性结果
治疗期间两组均未出现严重不良事件(如HIFU相关皮肤灼伤、盆腔感染、电针相关血肿等)。单纯HIFU组1例患者治疗中出现轻微腹壁胀痛，调整治疗功率后缓解，无后遗症；联合组2例患者电针治疗时出现晕针(表现为面色苍白、头晕)，立即停止针刺、平卧休息5~10分钟后症状缓解，后续调整治疗前饮食状态(避免过饥过饱)后未再发生。两组不良事件发生率比较，差异无统计学意义(χ2 = 0.351, P = 0.554)，提示两种治疗方案安全性均良好。
3. 讨论
3.1. HIFU联合低频率电针对子宫内膜容受性的改善机制
子宫内膜容受性是胚胎着床的关键前提，AM患者因异位内膜组织释放炎症因子(如VEGF)，导致子宫动脉痉挛、血流阻力升高，进而引发内膜血供不足、容积缩小，最终降低着床成功率[5]。本研究显示，HIFU治疗可显著改善子宫内膜容受性，其机制在于：HIFU通过热效应使异位内膜组织凝固性坏死，减少VEGF等炎症因子分泌，同时消融病灶后子宫肌层张力降低，为内膜生长提供更优空间[6]。
联合低频率电针后，容受性改善效果更显著，核心机制与中医“活血化瘀”理论契合：所选穴位(关元、气海)为任脉要穴，可调节冲任二脉气血；血海、膈俞为活血化瘀经典穴位 ；肾俞可补肾益精，与HIFU的“病灶消融”形成“治标 + 治本”的协同效应。
3.2. 对VEGF水平与痛经症状的影响
VEGF作为促血管生成因子，其水平升高可加重异位内膜血供，导致痛经加剧、病灶进展[7]。本研究中，两组治疗后VEGF水平均显著降低，且联合组更低，提示：HIFU通过破坏病灶血管直接减少VEGF合成，而电针活血化瘀，双重作用下更利于控制病灶活性。
痛经缓解方面，联合组VAS评分降至2.1 ± 0.8分(显著低于单纯HIFU组)，除与VEGF降低相关外，还与电针的镇痛机制有关：低频率电针可激活中枢内啡肽系统，抑制疼痛信号传导[8]，同时改善盆腔血液循环，实现“标本兼治”的镇痛效果。
3.3. 妊娠率差异的临床解读
联合组妊娠率(14.7%)高于单纯 HIFU 组(8.8%)，但未达成统计学差异，可能原因包括：① 样本量有限(每组34例)，需更大样本量验证(根据现有差异估算，若需使P < 0.05，每组需至少50例)；② 随访时间较短(最长15个月)，部分患者可能仍处于“容受性改善–备孕适应”阶段，延长随访至24个月或可观察到更显著差异；③ 不孕因素的复杂性：虽排除了输卵管阻塞、男方精液异常等明确因素，但AM患者可能存在隐匿性内分泌紊乱(如黄体功能不足)，需结合激素调节进一步优化方案。
值得注意的是，联合组治疗后3~6个月妊娠率(5.88%, 2/34)高于单纯HIFU组(2.94%, 1/34)，提示联合方案可能缩短“治疗–妊娠”间隔，这对年龄较大(30~45岁)的AM不孕患者尤为重要，因该群体卵巢储备随年龄下降，缩短备孕周期可提高妊娠机会。
3.4. 研究优势与局限性
优势：① 聚焦临床常见的气滞血瘀型AM合并不孕症，辨证精准，中医干预措施(电针)选穴有据、参数规范；② 采用随机对照设计，分组隐匿，基线资料均衡，结果可信度较高；③ 同时评价解剖学(内膜容积、厚度)、血流动力学(RI, PI, S/D)、分子生物学(VEGF)及临床结局(妊娠率)指标，多维度验证疗效。
局限性：① 单中心研究，可能存在选择偏倚(如纳入患者均来自贵州地区，地域特征可能影响结果外推)；② 未设置“单纯电针组”，无法单独评估电针的疗效贡献；③ 未监测治疗后内膜容受性相关分子标志物(如整合素β3、LIF等)，需后续研究补充机制证据。
4. 结论
高强度聚焦超声(HIFU)联合低频率电针治疗气滞血瘀型子宫腺肌病(AM)合并不孕症，可显著改善患者子宫内膜容受性(增加内膜容积与厚度、降低子宫动脉血流阻力)、降低血清VEGF水平、缓解痛经症状，且安全性良好；虽联合组妊娠率未达统计学优势，但呈明显提升趋势，尤其可缩短“治疗–妊娠”间隔。建议临床推广该联合方案，同时优化后续研究：① 扩大样本量(多中心、每组 ≥ 50例)并延长随访至24个月，进一步验证妊娠结局；② 增设“单纯电针组”，明确各治疗组分的疗效权重；③ 结合内膜分子标志物检测，深化协同作用机制研究，为AM合并不孕症提供更精准的中西医整合治疗方案。
基金项目
超声医学工程国家重点实验室开放课题2021KFKT005。