宫内妊娠物残留的治疗进展

Advances in the treatment of retained products of conception

摘要

宫内妊娠物残留是一种常见的妊娠相关疾病，可能导致异常子宫出血、感染、继发性动静脉瘘、宫腔粘连、不孕等多种并发症。目前临床上治疗宫内妊娠物残留的常见方案包括手术治疗、药物治疗、期待治疗，必要时辅助高强度聚焦超声或子宫动脉栓塞术，但并无统一的治疗规范。药物治疗和期待治疗可以让部分患者避免手术治疗或者减少手术次数，但病程较长；而手术治疗虽然见效快，但对于病灶较大的患者，可能需要多次手术，增加子宫内膜损伤及宫腔粘连的风险。在选择最佳治疗方案或制订个体化治疗策略时，仍缺乏充分的循证医学依据。探讨宫内妊娠物残留的治疗进展，重点关注有效保护子宫内膜的方式，旨在最大程度保留患者的生育潜能，推动实现更加精准、微创和高效的个体化治疗。

Abstract

Retained products of conception (RPOC) represent a common pregnancy-related condition that may lead to complications such as abnormal uterine bleeding, infection, secondary arteriovenous fistula, intrauterine adhesions, and infertility. Currently, the main clinical treatments for RPOC include surgical intervention, medical therapy, and expectant management, sometimes supplemented by high-intensity focused ultrasound or uterine artery embolization when necessary. However, no standardized treatment guidelines exist. Medical and expectant management may help some patients avoid or reduce the need for surgery, though these approaches often involve a prolonged disease course. While surgery yields rapid results, patients with large lesions may require multiple procedures, increasing the risk of endometrial damage and intrauterine adhesions. There is still a lack of robust evidence-based guidance for selecting the optimal or individualized treatment approach. This review explores recent advances in the management of RPOC, with an emphasis on strategies that effectively preserve the endometrium, safeguard fertility, and support more precise, minimally invasive, and efficient personalized treatment.

关键词

妊娠物残留 / 宫腔镜 / 子宫内膜保护 / 宫腔粘连 / 期待治疗

Key words

retained products of conception / hysteroscopy / endometrial preservation / intrauterine adhesions / expectant management

妊娠物残留(retained products of conception，RPOC)指妊娠终止后妊娠相关组织未能完全排出，部分残留在宫腔内，或伴有肌层植入的现象，其临床症状主要为终止妊娠后出现异常的阴道流血。RPOC是一种常见妊娠相关疾病，分娩后发生率约为1%，而早中孕流产后发生率为2.3%~21.3%，若患者合并如子宫肌瘤、子宫腺肌症、子宫畸形等宫内疾病，发病率更高^[1]。结合患者分娩或流产史、阴道流血的症状、血清人绒毛膜促性腺激素(human chorionic gonadotropin，HCG)水平、多普勒超声检查^[2]等辅助检查可诊断RPOC。RPOC的近期并发症包括出血、盆腔感染、继发性动静脉瘘等，远期可能因为手术操作等原因而并发宫腔粘连、不孕^[3]等。

目前临床上对于RPOC存在手术治疗、药物治疗、期待治疗等多种方案，手术方式选择也存在多样化，对于合并胎盘植入或者大出血的患者必要时辅助高强度聚焦超声、子宫动脉栓塞等治疗^[4]，然而，这些干预措施是否会加重子宫内膜损伤，进而影响后续生育结局，仍存在一定争议。本文就RPOC的治疗现状进行相关综述，为优化RPOC管理策略提供理论支持与实践路径。

1 手术治疗

手术治疗是宫内RPOC的最有效治疗方式，能积极清除妊娠物，缩短阴道流血时间，降低潜在感染风险。对于较大病灶的RPOC或者合并胎盘植入的患者，一次常规手术可能无法完全清除，需要再次或多次宫腔镜手术。而反复的手术操作可能增加感染风险，且导致子宫内膜损伤加重，继而引起宫腔粘连甚至不孕。

1.1 钳刮清宫术

传统的钳刮清宫术操作方便、简单，治疗效果明确，能在短时间内清除残余妊娠物，解决患者阴道流血的症状，且清宫术对手术设备要求低，容易开展，费用相对低廉，因此在基层医院开展广泛，且仍作为主要治疗手段。但该治疗方式容易引起清宫不全，必要时需反复清宫^[5]；也可能因过度清宫损伤内膜基底层，导致内膜纤维化增生引起宫腔粘连^[6-7]，并增加后续妊娠胎盘植入的风险。随着超声技术的普及，基层医院逐渐采取超声引导下清宫，有利于减少子宫穿孔，也增加了一定的操作精确度。但由于超声监护下清宫是非直视下清宫，手术操作的精准度不够，仍避免不了子宫内膜损伤的风险。

1.2 宫腔镜手术

宫腔镜手术被认为是RPOC的首选治疗方式^[8]，宫腔镜下可视化精准操作避免了非直视下清宫对子宫内膜的损伤^[9]，同时也降低了术中发生子宫穿孔的风险。研究^[10]证实宫腔镜手术较传统清宫术具有手术时长较短、术中失血较少、术后并发症发生率较低等优点，一次手术成功率更高^[5-6]，再次手术率更低，能显著提高患者的就医体验。宫腔镜下妊娠物电切术能显著缩短手术时间，减少术中出血，提高操作精准度，避免损伤邻近部位的子宫内膜，提高手术一次清除率。对于宫腔形态异常的患者，可避免清宫不全及过度刮宫损伤子宫内膜，且术中可同时明确子宫畸形诊断，并酌情同时处理。有研究^{[9, 11]}报道宫腔镜妊娠物电切术用于RPOC患者中较清宫术创伤小，不良反应发生率较低。然而，宫腔镜妊娠物电切术对手术医生操作技术要求相对较高，在治疗的同时可能增加对内膜组织的热损伤，导致子宫内膜的纤维化增生修复(非功能性修复)，增加宫腔粘连的风险，严重时导致后续妊娠胎盘异常植入^[12]。

随着近年来对生育力保护的逐渐重视，宫腔镜下妊娠物电切术可能对后续妊娠带来的潜在影响越来越受到重视，随着宫腔镜下冷刀技术迅速发展，宫腔镜下冷刀妊娠物清除技术由于无电热损伤，有利于保护子宫内膜，降低清宫术后宫腔粘连及不孕的风险，被广泛认可^[13-14]。有研究^[15]对比电切系统与冷刀系统治疗宫内疾病，发现冷刀系统不带电操作，手术操作更安全，且无热损伤，其可视化操作精准，能有效避免电辐射损伤周围内膜组织，使得其术后宫腔粘连发生率降低90%。

传统宫腔镜技术由于微型手术机械的局限性，在处理病灶较大的RPOC时手术时间延长，水中毒发生率增加，且增加再次甚至多次手术清宫风险。目前巨型冷刀器械的应用日益广泛，比如4 mm(即12Fr)勺型钳直视下将残留组织钳出，较传统微型钳而言具有非常大的优势^[16]。宫腔镜宫内组织旋切系统是一种新型的机械性切割器械，在切除残留物的同时可通过自控负压将组织碎片排出宫腔，且可保持术中视野的清晰度，避免反复进出宫腔，缩短了手术时间，极大降低了容量负荷过重的风险，同时增加了手术一次性清除率，降低了感染风险^[17]。研究显示：美奥舒宫腔组织切除系统治疗RPOC的一次性清除率可达94%~100%^[18-19]；宫腔镜下宫内组织旋切系统利于保护子宫内膜，从而降低了宫腔粘连的发生风险，改善了生殖结局^[20]；采用美奥舒宫腔组织切除系统的宫腔镜手术操作时间更短，术中失血量更少，术后患者发生宫腔粘连的概率更低^[21]。

尽管随着宫腔镜手术技术的发展和普及，特别是宫腔镜冷刀技术的发展，宫腔镜下RPOC清除术更加微创化，宫内RPOC仍是一个棘手的临床问题，特别是积极手术清宫往往不能达到理想的妊娠物清除效果，往往需要再次甚至多次清宫，如何避免术中出血导致宫腔镜冷刀治疗的视野不清、如何确定最佳的手术时机、术中的子宫内膜损害和术后的宫腔粘连等仍是非常重要的临床问题，需要进一步研究去阐明。

2 药物治疗

由于手术有不可完全避免的相关风险，包括近期风险如感染、损伤等，远期风险如宫腔粘连、不孕等，RPOC的药物治疗越来越受到重视。2019年发布的不全流产专家共识^[22]确定了药物保守治疗的适应证，包括：残留妊娠组织在宫腔内时间≤14 d；彩色多普勒超声提示宫内异常回声，且直径≤2.5 cm；HCG升高但水平较低。目前常用的药物治疗方式为米非司酮配伍前列腺素类药物。具体的用药方案包括：1)米索前列醇单药应用，米索前列醇400 μg阴道上药或600 μg口服；2)米索前列醇或米非司酮联合缩宫素，米索前列醇600 μg单次口服或米非司酮50 mg口服+缩宫素10 U静滴，1 d 1次连续治疗3 d；3)米非司酮联合米索前列醇：米非司酮50 mg口服，1 d 1次连续治疗3 d+米索前列醇600~800 μg单次口服^[22]。研究显示：采用米索前列醇代替清宫手术的有效率达到93%，重复清宫率降低了79.6%^[23]；使用米非司酮联合缩宫素治疗RPOC的有效率为81.8%^[24]。尽管药物治疗对部分患者有效，然而疗效存在不确定性，且病程较长。研究^[25-27]认为当残余妊娠组织直径<2.5 cm时，药物治疗RPOC的成功率较高。但是关于药物治疗的适应证和药物治疗方法仍有争议，值得临床进一步研究探索。

此外，中药也可用于宫内RPOC的治疗，以活血化瘀、行气通络为主，常用方药包括生化汤、四物汤、益母草、当归等。加减生化汤辅助治疗早孕药物流产不全能缩短患者阴道出血时间，调节性激素水平，促进机体恢复^[28]；米非司酮联合桃红四物汤治疗产后胎盘残留疗效更佳，可更好地减少胎盘残留，促进子宫恢复，减少盆腔感染，减轻患者机体应激反应^[29]。益母草有促进子宫收缩^[30]和排出残留物的作用^[31]。根据病情可配伍桃仁、红花、蒲黄等，增强化瘀止血效果^[32]。治疗应结合辨证施治，如气滞血瘀者加行气药，血热者加清热凉血药^[33]。中药治疗需在医生指导下进行，结合病情动态调整。

3 期待治疗

RPOC的期待治疗是指既不采取手术治疗，也不采取药物治疗。越来越多的研究^[34-36]表明在一定条件下期待治疗是有效的，也是安全的。一项荟萃分析^[37]表明当宫腔内残留组织直径<2.0 cm时，期待治疗与药物治疗疗效无明显差异。一项回顾性队列研究^[38]纳入了54例RPOC患者，其中44例患者选择进行期待治疗，34例(77%)患者在无干预的情况下残留妊娠组织自行排出体外并无需接受手术治疗，其他10例(23%)患者因“持续阴道流血”接受宫腔镜手术治疗，这表明期待治疗有效且能减少宫腔操作的次数。与清宫术比较，期待治疗更加安全有效，可替代部分手术治疗且不会增加大出血的风险^[39]。一项荟萃分析^[40]认为期待治疗是有效的治疗方式，并认为残余妊娠物直径<50 mm且生命体征平稳的患者适宜接受期待治疗，但接受手术治疗的患者能在短时间内完全清除残留的妊娠物，较期待治疗更有效。

在临床工作中，为避免残留妊娠物持续存在引起大出血或感染等并发症，医生多倾向于采用积极的手术治疗来避免并发症的发生。但有研究^[41]显示期待治疗过程中患者出现大出血并需急诊处理的风险与直接手术治疗相当，而反复进出宫腔的操作不仅增加术后感染风险，还会加重子宫内膜损伤，导致宫腔粘连^[5]。早孕流产清宫术后发生宫腔粘连的概率约为29.6%，而当RPOC一次清宫不全需反复清宫时，发生宫腔粘连的概率可升高至40%，且其中75%的患者为中重度宫腔粘连^[42]。67.5%~83.1%的重度宫腔粘连与妊娠清宫相关^[43-45]。

实际上，宫腔粘连的发病率可能被低估，由于宫腔粘连典型的临床表现为月经量减少，严重者伴有继发不孕，主要影响患者生育力，而对日常生活无明显影响，致使部分患者未因此而就诊或接受相关治疗。因此，对于有生育要求的患者，期待治疗不失为一个安全有效的选择，可能避免或减少宫腔操作且不会增加大出血的风险。

在期待治疗的同时加入雌孕激素序贯治疗，可提高期待治疗的效果、减少阴道流血量及缩短持续时长，治疗成功率为66.7%~96%^[46-48]，其原理主要是通过雌激素促进子宫内膜增生和修复^[49-50]。使用雌孕激素序贯疗法治疗RPOC，停用孕激素后子宫内膜发生撤退性出血。与此同时残留组织随剥脱的内膜一起排出体外，同时建立起正常的月经周期^[51]。中成药可以促进子宫收缩及残留妊娠物自行排出。然而当病灶较大时，期待治疗效果不理想，研究^[52]认为病灶径线越大，雌孕激素序贯治疗的成功率越低，当残留妊娠物径线超过2.5 cm时，药物治疗成功率不到50%。

4 其他辅助治疗

4.1 高强度超声聚焦疗法

高强度超声聚焦疗法(high-intensity focused ultrasound，HIFU)目前可用于某些RPOC患者的辅助治疗。其原理是通过具有穿透性的超声波将能量聚焦在特定的靶区，使病灶部位瞬间达到高温，局灶组织发生凝固性坏死^[53]。HIFU治疗适合于RPOC合并植入，且未发生感染和无活动出血的患者，这类患者辅助HIFU治疗可降低治疗过程中出血风险，缩短病程，增加手术清除率，且安全有效^[54]。研究^[55]显示HIFU治疗联合宫腔镜手术治疗胎盘植入是安全有效的，不仅能显著降低术后清宫难度，同时避免严重并发症发生，最大程度保留了患者的生育功能。尽管HIFU很好地遵循了微创理念，但是否能降低出血风险的证据不足，且可能对子宫内膜造成热损伤，治疗前需要慎重评估，尚不推荐HIFU作为常规疗法。

4.2 经皮子宫动脉栓塞术

经皮子宫动脉栓塞术(uterine artery embolization，UAE)临床上用于RPOC合并活动性出血特别是危及生命的大出血的辅助治疗，以挽救患者生命，对于年轻患者是尽可能保留子宫的有效治疗手段，一般推荐临时性栓塞^[56]。UAE治疗RPOC伴出血是一种有效且安全的一线疗法^[57]。无论RPOC患者是否接受经皮UAE，再次妊娠时发生产后出血或胎盘植入的风险是相当的^[3]。经皮UAE治疗RPOC伴出血后并不会降低患者的生育能力^[58]。经皮UAE相对于HIFU，创伤较大，费用也更贵，但对于降低治疗过程中出血效果相对可靠，因此对于出血高危人群，尽管目前没有大出血，经评估后也可采用UAE辅助治疗^[59]，但是需优化UAE技术(可逆性栓塞技术)，从而可以在栓塞后7 d左右复通子宫动脉，保护子宫血供。

5 结 语

目前临床上宫内妊娠残留的治疗方案多样，但缺乏统一的流程或规范。药物治疗和期待治疗在一定条件下是安全有效的，可以避免或降低患者宫腔操作次数，但病程长，并非对所有患者有效；手术治疗是最为有效的方法，超声引导下清宫简单易行，适合于基层医院，但容易造成清宫不全，增加子宫内膜损伤风险；宫腔镜下妊娠物清除术可在直视下准确定位病灶，显著减少对子宫内膜的盲目损伤。然而，在病灶体积较大、子宫明显增大、血清 β-HCG水平升高及病灶血运丰富的情况下，术中清除难度显著增加，术后残留风险上升，患者可能需接受重复甚至多次清宫操作。这不仅加重经济负担，也显著增加子宫内膜损伤、宫腔粘连及继发不孕的风险。对于这类患者先予期待治疗，待病灶缩小到一定程度、血清HCG水平下降到一定水平后再行宫腔镜妊娠物清除术是明智之举。至于期待治疗过程中如何个体化确定最佳手术时机及选择何种手术方式需要进一步研究和探索。

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基金资助

芙蓉实验室科技攻关项目(2023SK2109┫。This work was supported by Furong Laboratory’s Key Science and Technology Research Project)

芙蓉实验室科技攻关项目(China ┣2023SK2109)

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