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Journal of Central South University Medical Sciences logoLink to Journal of Central South University Medical Sciences
. 2022 Nov 28;47(11):1550–1558. [Article in Chinese] doi: 10.11817/j.issn.1672-7347.2022.220512

经阴道三维超声在判断养膜方治疗宫腔粘连效果中的价值

Value of transvaginal three-dimensional ultrasound in evaluating the curative effect of Yangmo decoction in the treatment of uterine adhesion

ZHAO Xingping 1,2,#, DENG Jingrong 1,3,#, YOU Zhaoling 2, GAN Xiaoli 3, XU Dabao 1, ZHANG Aiqian 1,
Editor: 田 朴
PMCID: PMC10930616  PMID: 36481633

Abstract

Objective

Intrauterine adhesions (IUA) is the damage of the basal layer of the endometrium caused by various reasons, resulting in adhesion of the uterine muscle walls to each other, which is manifested as clinical symptoms such as spanomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis (HA) is the main treatment, for patients with moderate or severe adhesion or angular adhesion, the incidence of postoperative adhesion is high. Traditional Chinese medicine “Yangmo decoction” can promote endometrial growth. Three-dimensional transvaginal ultrasonography (3D-TVUS) can judge IUA and evaluate uterine receptivity through three-dimensional imaging. This study aims to investigate the value of 3D-TVUS in judging the efficacy of Yangmo decoction in the treatment of intrauterine adhesions.

Methods

The clinical data of patients who underwent HA at two different centers in department of Gynecology of Third Xiangya Hospital of Central South University and Changsha Jiangwan Hospital from January 2021 to August 2021 were retrospectively collected. A total of 275 eligible patients were included. According to the postoperative management measures, the selected patients were divided into two groups. Yangmo decoction group (n=138): the use of Yangmo decoction and uterine-shaped silicon stent post HA; Hormone group (n=137): the use of estrogen, progesterone and uterine-shaped silicon stent post HA. The preoperative general data, preoperative and postoperative 3D-TVUS parameters of the two groups were analyzed.

Results

The endometrial thickness of Yangmo decoction group was thicker than that of hormone group (P<0.001), the intercornual distance was wider (P=0.016), the endometrial echo was more homogeneous (P=0.018), the percentage of bilaterally visible tubal opening was higher (P<0.001), the endometrial morphology was better (P=0.012), and endometrial blood flow, endometrial motility and uterine motion were better in Yangmo decoction group than that in the hormone group (all P<0.001).

Conclusion

The endometrial thickness, echo, blood flow, and peristalsis, the number of visible tubal opening, uterine motion, and the intercornual distance obtained by 3D-TVUS examination are important factors to evaluate the prognosis of postoperative drug treatment for IUA. 3D-TVUS is of great significance in evaluating the efficacy of Yangmo decoction in the treatment of IUA.

Keywords: intrauterine adhesions, three-dimensional transvaginal ultrasonography, traditional Chinese medicine, Yangmo decoction, hysteroscopic adhesiolysis


宫腔粘连(intrauterine adhesions,IUA)是指因各种原因造成的子宫内膜基底层受损[1-2],导致子宫肌壁相互粘连,表现为月经量减少、闭经、周期性盆腔疼痛、不孕、流产等临床症状[3-4],严重危害育龄期妇女的身心健康。以宫腔镜下宫腔粘连分离术(hysteroscopic adhesiolysis,HA)为主,术后辅以宫内节育器、Foley球囊、透明质酸钠、雌孕激素等预防再粘连是IUA的主要治疗策略[5-6]。对于中、重度粘连或宫角粘连的患者,HA后再粘连发生率较高,治疗难度较大。IUA在中医妇科学及中医古籍中均无相关记载,全国知名老中医药专家尤昭玲教授临证自创“养膜方”,以促进子宫内膜生长。经阴道三维超声(three-dimensional transvaginal ultrasonography,3D-TVUS)通过三维成像,能反映宫腔形态、内膜蠕动、子宫动脉、子宫及内膜下血流等情况[7],通过对比分析可判断IUA,并评估内膜容受性[8-9]。对于子宫内膜功能基本达标的轻-中度粘连患者,可采用3D-TVUS进行综合评估后选择试孕时间;对于严重IUA患者,3D-TVUS提示施术时机,给予中医药干预治疗的时间窗,以提高手术成效并帮助术后内膜修复,有效减少盲目手术分离后内膜修复障碍。本研究旨在探讨3D-TVUS在判断养膜方治疗宫腔粘连效果中的价值。

1. 对象与方法

1.1. 对象

回顾性收集2021年1月至8月在中南大学湘雅三医院妇科和长沙市江湾医院妇科进行HA的患者资料。纳入标准:1)年龄20~45岁,有生育需求;2)术前经宫腔镜检查诊断为IUA,美国生育协会(American Fertility Society,AFS)评分系统评分5~12者;3)排卵正常者。排除标准:1)宫颈或子宫内膜恶性病变者;2)先天性子宫畸形者;3)严重的心、肝、肾功能不全者;4)患有严重神经系统疾病,生活不能自理或无法接受相关治疗者;5)不能耐受手术,不能遵医嘱随访者;6)伴侣精液异常者。根据纳入和排除标准收集符合条件的患者共275例,根据术后处理措施将所选患者分为两组:养膜方组(n=138)为HA后使用养膜方和宫形硅胶支架,激素组(n=137)为HA后使用雌、孕激素和宫形硅胶支架。本研究通过中南大学湘雅三医院伦理委员会审批(审批号:快22260)。所有患者均对手术知情同意。

1.2. 仪器设备与方法

1.2.1. 3D-TVUS检查

术前采用美国GE公司的Voluson E8超声仪二维容积探头和实时三维容积探头进行3D-TVUS检查。所有患者均在月经周期的分泌期行术前3D-TVUS检查(使用7.5 MHz IC5-9D阴道探针)。检查时嘱患者排空膀胱后取截石位,先行常规二维超声检查,评估子宫内膜完整性。随后旋转实时三维容积探头,利用全景技术获取整体图像信息并选择目标区域。超声检查时,评估子宫内膜厚度、子宫内膜回声、子宫内膜血流、子宫内膜蠕动、子宫内膜形态(III线征)、子宫内膜-子宫肌层交界处、子宫活动度、子宫角间距离和可见输卵管口数。在HA后随访时再次在患者月经周期的分泌期进行3D-TVUS检查,与术前3D-TVUS检查相同,评估上述指标。最后,将数据保存至移动硬盘上以备后续的分析。所有三维超声均由高年资的超声医师检查并分析图像。

1.2.2. 手术治疗

HA在患者月经后3~7 d内进行,术前6~8 h禁食禁水,取患者截石位,以异丙酚静脉麻醉。用无菌生理盐水使子宫膨胀,膨胀压力110~129 mmHg (1 mmHg=0.133 kPa),流速300~400 mL/min,经腹超声(transabdominal sonograghy,TAS)监测手术过程,光学系统和自动子宫扩张器均来自日本Olympus公司。HA使用外径5.4 mm和5Fr工作通道的宫腔镜(德国Karl Storz公司)进行。用5Fr双动镊子和5Fr单动锋利剪刀对宫腔内薄而密的粘连进行松解和犁除。HA后使用宫形硅胶支架,随后将12Fr Foley导管球囊置于硅胶支架中心,将球囊上方的导管取出,并用2.5 mL无菌生理盐水使之膨胀。经导管向宫腔内注射透明质酸钠凝胶3 mL,并固定导管,然后用无菌纱布包裹导管的末端,以防止凝胶流出。重度IUA患者保留宫内Foley导管球囊5~7 d,中度IUA患者保留2~3 d。子宫下段重度粘连患者Foley导管球囊放置2~3周。手术过程中均无并发症发生。所有患者均给予预防性抗生素(1 g静脉注射用头孢西丁钠/100 mL生理盐水)。两组术后处理方案相同。

1.2.3. 术后处理措施及随访

1)养膜方组和激素组患者分别服用养膜方和雌、孕激素。养膜方组从术后第1天开始服用养膜方煎液,养膜方的主要成分有人参花(20 g)、三七花 (15 g)、玳玳花(15 g)、雪莲花(10 g)、甘草(5 g)等,每天1包,每包分为两份,患者每天口服2次,连续服用21 d为1个疗程,子宫内膜的修复需要2~3个疗程。激素组从术后第1天开始口服戊酸雌二醇,每天2次,每次3 mg,持续21 d;在月经周期的最后6天加服黄体酮,每天1次,每次100 mg,共3个疗程,以促进子宫内膜生长,并在服药期间定期复查乳腺超声、肝肾功能、下肢深静脉彩超等。患者对于超处方剂量使用雌激素知情同意。2)根据患者的AFS评分进行随访。若AFS评分>8,则在术后进行两次随访,第1次随访在HA后1个月进行,第2次随访在术后4个月进行;若AFS评分为5~8,则在HA后3个月随访1次。3)在末次宫腔镜检查时取出硅胶支架,并在无IUA后建议患者积极备孕。4)除选择做辅助生殖术的患者外,所有患者均在末次宫腔镜随访时进行输卵管通液试验以检查输卵管通畅性。5)所有患者均在末次宫腔镜干预后随访6~9个月,了解其妊娠和流产情况等生殖预后指标。

1.3. 统计学处理

使用SPSS 26.0统计软件进行数据分析。计量资料以均数±标准差( x¯ ±s)表示,连续变量的比较采用独立样本t检验,无序分类变量采用χ2 检验或者Fisher’s精确概率法。所有统计检验均为双侧检验,P<0.05为差异有统计学意义。

2. 结 果

2.1. 两组患者术前一般资料比较

养膜方组和激素组患者的年龄及术前AFS评分差异均有统计学意义(均P<0.05)。两组妊娠、活产、流产次数,月经情况,IUA患者类型及术前宫腔操作情况的差异均无统计学意义(均P>0.05,表1)。

表1.

两组患者术前一般资料

Table 1 Preoperative general information of the 2 groups

组别 n 年龄/岁 妊娠次数 活产次数 流产次数 月经情况/[例(%)]
月经正常 月经减少 闭经
养膜方组 138 33.20±4.61 3.08±1.71 0.53±0.58 2.56±1.55 0(0) 119(86.2) 19(13.8)
激素组 137 31.48±4.56 2.80±2.04 0.58±0.68 2.22±1.77 1(0.7) 109(79.6) 27(19.7)
t2 3.109 1.264 0.623 1.687 2.826
P 0.002 0.207 0.534 0.093 0.243
组别 术前AFS评分 IUA类型/[例(%)] 术前宫腔操作情况/[例(%)]
新发IUA 复发IUA 刮宫 其他宫腔操作
养膜方组 8.86±1.39 78(56.6) 60(43.4) 108(78.3) 30(21.7)
激素组 8.42±1.70 75(54.8) 62(45.2) 112(81.8) 25(18.2)
t2 2.301 0.088 0.524
P 0.022 0.809 0.547

AFS:美国生育协会;IUA:宫腔粘连。

2.2. 术前3D-TVUS参数分析

术前使用3D-TVUS分别测量两组患者的子宫内膜厚度、角间距离、子宫内膜形态(III线征)、子宫内膜回声、输卵管口可见度、子宫内膜-肌层交界处、子宫活动度、子宫内膜血流、子宫内膜蠕动特征。养膜方组和激素组患者的角间距离差异有统计学意义(P=0.001),其余的术前3D-TVUS参数差异均无统计学意义(均P>0.05,表2)。

表2.

两组患者术前的3D-TVUS参数

Table 2 Preoperative 3D-TVUS parameters of the 2 groups

组别 n 子宫内膜厚度/mm 角间距离/mm 子宫内膜形态(III线征)/[例(%)]
缺失值 模糊 1 2 3
养膜方组 138 5.01±1.28 25.75±4.99 7(5.1) 119(86.2) 5(3.6) 6(4.4) 1(0.7)
激素组 137 4.92±1.60 23.73±5.13 7(5.1) 119(86.9) 8(5.8) 3(2.2) 0
t2 0.505 0.302 2.689
P 0.614 0.001 0.611
组别 输卵管口/[例(%)] 子宫内膜蠕动/[例(%)]
缺失值 双侧可见 单侧不可见 双侧不可见 缺失值 同向蠕动 不规则蠕动 蠕动消失
养膜方组 55(39.8) 39(28.3) 15(10.9) 29(21.0) 7(5.1) 7(5.1) 47(34.0) 77(55.8)
激素组 56(40.9) 41(29.9) 16(11.7) 24(17.5) 8(5.8) 4(2.9) 32(23.4) 93(67.9)
t2 0.559 5.235
P 0.906 0.155
组别 子宫内膜回声/[例(%)] 子宫内膜血流/[例(%)]
不均匀 均匀 缺失值 0级 1级 2级 3级 4级 模糊
养膜方组 91(65.9) 47(34.1) 0 13(9.4) 39(28.3) 64(46.4) 22(15.9) 0 0
激素组 89(65.0) 48(35.0) 7(5.1) 23(16.8) 74(54.0) 27(19.7) 6(4.4) 0 0
t2 0.029 0.000 1
P 0.865 44.802
组别 子宫内膜-肌层交界处/[例(%)] 子宫活动度/[例(%)]
缺失值 均匀 不均匀 良好 一般
养膜方组 10(7.2) 39(28.3) 89(64.5) 19(13.8) 104(75.3) 15(10.9)
激素组 7(5.1) 33(24.1) 97(70.8) 22(16.1) 107(78.1) 8(5.8)
t2 1.307 2.389
P 0.504 0.303

2.3. 术后3D-TVUS参数分析

与激素组相比,养膜方组的子宫内膜更厚(P<0.001),角间距离更宽(P=0.016),子宫内膜回声更均匀(P=0.018),双侧可见输卵管口的比例更高(P<0.001),子宫内膜形态(III线征)更好(P=0.012),且养膜方组的子宫内膜血流、子宫内膜蠕动及子宫活动度也更好(均P<0.001)。两组子宫内膜-肌层交界区差异无统计学意义(P=0.057),但与激素组相比,养膜方组子宫内膜-肌层交界区更均匀(表3)。

表3.

两组患者术后的3D-TVUS参数

Table 3 Postoperative 3D-TVUS parameters of the 2 groups

组别 n 子宫内膜厚度/mm 角间距离/mm 子宫内膜形态(III线征)/[例(%)]
缺失值 模糊 1 2 3
养膜方组 138 7.71±1.31 25.00±4.80 0 96(69.6) 35(25.4) 5(3.6) 2(1.4)
激素组 137 6.43±1.40 23.55±5.10 6(4.4) 107(78.1) 20(14.6) 4(2.9) 0
t2 7.873 2.418 12.795
P <0.001 0.016 0.012
组别 输卵管口/[例(%)] 子宫内膜蠕动/[例(%)]
缺失值 双侧可见 单侧不可见 双侧不可见 缺失值 同向蠕动 不规则蠕动 蠕动消失
养膜方组 0 110(79.7) 25(18.1) 3(2.2) 5(3.6) 22(15.9) 107(77.6) 4(2.9)
激素组 0 68(49.6) 62(45.3) 7(5.1) 5(3.6) 5(3.6) 53(38.7) 74(54.1)
t2 27.242 93.547
P <0.001 <0.001
组别 子宫内膜回声/[例(%)] 子宫内膜血流/[例(%)]
不均匀 均匀 缺失值 0级 1级 2级 3级 4级 模糊
养膜方组 28(20.3) 110(79.7) 0 0 12(8.7) 52(37.6) 63(45.7) 4(2.9) 7(5.1)
激素组 45(32.8) 92(67.2) 3(2.2) 1(0.7) 45(32.8) 63(46.0) 21(15.3) 0 4(2.9)
t2 5.559 49.973
P 0.018 <0.001
组别 子宫内膜-肌层交界处/[例(%)] 子宫活动度/[例(%)]
缺失值 均匀 不均匀 良好 一般
养膜方组 3(2.2) 68(49.3) 67(48.5) 95(68.8) 43(31.2) 0
激素组 4(2.9) 48(35.1) 85(62.0) 56(40.9) 81(59.1) 0
t2 5.719 21.715
P 0.057 <0.001

2.4. 两组患者术前、术后的3D-TVUS参数比较

比较养膜方组术前和术后的3D-TVUS参数,结果显示:子宫内膜厚度和角间距离的差异均具有统计学意义(均P<0.001)。术后子宫内膜形态(III线征)“1”出现的频率由术前的3.6%增加至25.4%,子宫内膜回声均匀性的比例由34.1%增加至79.7%,双侧可见输卵管的比例由28.3%增加到79.7%,子宫内膜-肌层交界区均匀性的比例由28.3%增加到49.3%,子宫活动度良好患者的比例由13.8%增加至68.8%,子宫内膜血流3级患者的比例由15.9%增加至45.7%,术后有同向蠕动患者的比例由5.1%增加至15.9%。

比较激素组术前和术后的3D-TVUS参数,结果显示:子宫内膜厚度和角间距离的差异均具有统计学意义(均P<0.001)。术后子宫内膜形态(III线征)“1”出现的频率由术前的5.8%增加至14.6%,子宫内膜回声均匀性的比例由35.0%增加至67.2%,双侧可见输卵管的比例由29.9%增加到49.6%,子宫内膜-肌层交界区均匀性的比例由24.1%增加到35.1%。术后40.9%的患者子宫活动度良好,15.3%的患者子宫内膜血流为3级,3.6%的患者存在子宫内膜同向蠕动。

3. 讨 论

根据IUA的临床表现,中医将其归于月经量少、闭经、不孕症等范畴。历代医家关于肾主生殖的看法均有相关记载。《黄帝内经·素问·六节藏象论》载:“肾者,主蛰,封藏之本,精之处也。”《圣济总录》曰:“妇人所以无子者,由于冲任不足,肾气虚寒也。”《医学正传》曰:“况月经全借肾水施化,肾水既乏,则经血曰以干涸。”《傅青主女科》[10-11]谓:“经水出诸肾。”尤昭玲教授认为IUA病因常归于肾阴阳两虚,肾阴虚则无阴精养育之源;肾阳虚则无以转化之力,故而行宫腔操作或受金刃损伤后,子宫内膜无自主修复之能,从而造成内膜缺失、中断,甚则IUA[12-13]。尤教授结合女性生理特点自创“养膜方”,主要由人参花、三七花、玳玳花、雪莲花、甘草等药物组成,可补肾益精,助内膜生长,山药益阴精之源,服用方便,临床效果显著[14-16]

尤教授吸取中西医妇科生殖理论精髓提出生殖链、生殖链-终端效应的临证假说:认为生殖之链就是维系女性生殖健康的无数已知或未知因素,各因素相互关联、各司其责。生殖链终端:卵巢、子宫、内膜、宫肌呈现异因异病、症同效应。生殖链终端效应是重要关切和探索重点。针对异因异病、双异同疗,中医实行精准干预的前提与基础是寻找对应-无创-精准的检测方法和评估指标。尤教授历经近3年潜心临证观察,据3D-TVUS针对生殖链终端的评估,总结出相应评估指标,以行精准干预。

由于子宫内膜各项指标在分泌期测量最佳,因此一般于月经周期的分泌期取正中矢状面进行经阴道超声。超声评估子宫内膜常用的参数包括但不限于子宫内膜厚度、子宫内膜形态、血管形态和血流多普勒指标。国外学者Dechaud等[17]也认为,子宫内膜形态、厚度和舒张末期血流是评价子宫容受性最有效的指标。输卵管口粘连较为致密的女性不能生育,输卵管口和宫腔部分堵塞,并伴有纤维化粘连及子宫内膜血管化不良的女性常反复流产[2]。因此,本研究采用3D-TVUS评估子宫内膜特性,包括子宫活动度、角间距离和双侧可见输卵管口比例等,并分析其与养膜方治疗IUA患者效果的相关性。

输卵管口是HA术中重要的解剖学标志,3D-TVUS对于IUA的术前评估具有优势。双侧宫角区清晰且输卵管口可见者,更有可能成功进行HA。本研究结果显示:养膜方组双侧可见输卵管口的比例更高,这说明精子更有可能顺利进入输卵管,与卵细胞结合形成受精卵,提高妊娠的可能性。角间距离是评估宫腔容积的重要评价指标,可用来评估硅胶支架或宫内节育器的大小,并对排除子宫畸形有重要意义。推测宫腔容积有助于评价患者IUA的程度,并量化手术治疗结果。3D-TVUS检查时于冠状面测量角间距离。本研究中养膜方组患者术前的角间距离存在差异,故无法准确判断养膜方治疗对角间距离的影响。

子宫内膜在月经周期中循环变化,为胚胎着床做准备[18]。胚胎的成功着床需要子宫内膜和囊胚的良好协调[19]。有研究[20-25]报道,子宫内膜厚度与妊娠率之间具有显著相关性,但另一些研究[19, 26]并不支持这种观点。较薄的子宫内膜血流减少,这可能导致其对激素刺激没有反应,从而导致胚胎植入失败或早期流产[27]。许多IUA患者即使长期补充雌二醇也无法实现子宫内膜的明显生长[28]。厚度正常、回声正常且功能良好的子宫内膜,对胚胎植入和存活有积极意义[29-30]。本研究结果显示:与激素组相比养膜方组术后子宫内膜更厚,且子宫内膜回声更均匀。这说明养膜方组的子宫内膜环境更适合胚胎植入,并稳定胚胎发育,能降低胚胎植入失败或早期流产的可能性。通过超声获得的子宫内膜血流参数也在预测妊娠结局中起重要作用。子宫内膜具有良好的血液供应是胚胎植入的必要条件,而子宫血流不能很好地反映子宫内膜血流[31-33]。本研究结果显示养膜方组的子宫内膜血流更丰富。这说明养膜方组的子宫内膜为胚胎植入及胚胎发育提供了更为丰富的血液供应,创造了一个更适于胚胎生长的环境。超声所测量的子宫内膜形态已被建议用于预测妊娠结局,但其重要性尚未达成共识。研究[34-38]认为子宫内膜的III线征与较高的着床率和受孕率相关,但另一些研究[22, 39-41]并未发现子宫内膜形态与受孕率之间存在显著相关。在本研究中,两组子宫内膜III线征差异无统计学意义。子宫内膜蠕动是精子从子宫颈运输至输卵管的主要因素[42]。本研究结果显示养膜方组子宫内膜的蠕动更好。这与清晰可见的输卵管口相协调,共同促进精子顺利进入输卵管内,提高成功受精的可能性。由此可见与使用激素治疗的患者相比,HA后使用养膜方治疗的患者有更好的预后和受孕机会。

综上,通过3D-TVUS检查得到的子宫内膜的厚度、回声、血流、蠕动,可见输卵管口数,子宫活动度及角间距离是评价IUA患者术后药物治疗预后的重要参数。3D-TVUS在判断养膜方治疗宫腔粘连的效果中具有重要意义。

本研究存在一定的局限性:患者随访时间不长;没有进一步探讨养膜方具体通过何种机制改善子宫内膜容受性,这将成为今后的研究方向。

Acknowledgments

感谢长沙江湾妇产医院提供病例资料用于本研究。

基金资助

湖南省自然科学基金(2021JJ40953);湖南省科技计划项目(2020SK53605,2021SK53704)。

This work was supported by the Natural Science Foundation of Hunan Province (2021JJ40953) and Science and Technology Project of Hunan Province (2020SK53605, 2021SK53704), China.

利益冲突声明

作者声称无任何利益冲突。

作者贡献

赵行平 研究设计,论文构思和修改;邓婧蓉 数据采集和分析,论文撰写和修改;尤昭玲,甘小利 论文指导;徐大宝,张爱倩 研究设计和论文指导。所有作者阅读并同意最终的文本。

原文网址

http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/2022111550.pdf

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