1、子宫内膜异位症不孕的中医临床研究思路与方法 Clinical study Approaches on TCM of Endometriosis-related Infertility,广州中医药大学妇科欧阳惠卿Ouyang Huiqing Gynecological Department, Guangzhou University of TCMMarch.22.2009New York . USA,子宫内膜异位症不孕Endometriosis-related Infertility,子宫内膜异位症（内异症）是指有生长功能的子宫内膜组织在子宫腔以外的组织和器官生长，并因异位内膜病灶的存在引发一系
2、列临床症状和体征的疾病。Endometriosis is a disorder in which abnormal growths of tissue, histologically resembling the endometrium, are present in locations other than the uterine lining.,子宫内膜异位症不孕Endometriosis-related Infertility,结婚2年，同居、性生活正常，未避孕而不孕者称之为不孕症A couple is said to be infertile if pregnancy does not
3、 result after 1 year of normal sexual activity without contraceptives.,子宫内膜异位症不孕Endometriosis-related Infertility,与内异症共存的不孕症称为内异症不孕.It has been suggested that endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it
4、is preferable to speak of endometriosis-related infertility in such cases.,子宫内膜异位症不孕,患内异症的妇女中合并不孕的约有3050，不孕症患者约有3058同时患有内异症。 According to medical statistics it is estimated that 30-40% of women with endometriosis are also infertile. 30-58% of infertile women are found to have endometriosis.,内异症不孕发病机
5、理 (一) Pathogenesis ,1、盆腔器官解剖结构改变 1.The implication of endometrial adhesions 内异症的盆腔存在程度不同的粘连 ，使输卵管的拾卵以及在输卵管内的输送障碍 ；内膜异位病灶，直接影响受孕 ；If the Endometriosis related adhesions obstruct or close off the fallopian tube, they could obstruct the pathway of the egg and sperm and thus prevent conception;,内异症不孕发病机
6、理 (一) Pathogenesis ,卵巢周围粘连影响排卵； 盆腔腹膜的痛性结节造成的性交痛，可使性交频率减少甚至拒绝性交，从而减少了受孕机会 ；子宫后倾固定，宫颈向前变位难以接触精液池，影响了精子的输入 ；Adhesions around the ovary could influence ovulation;Endometriosis also leads to dyspareunia due to some tender nodules in the posterior vaginal fornix;Sperm motility may also be influenced by th
7、e cul-de-sac adhesions of the uterus.,内异症不孕发病机理 (二) Pathogenesis ,2、盆腔局部免疫环境的改变 2.Endometriosis causes reduced immune function in the Pelvic Cavity盆腔内异位内膜病灶的病理生长和发展过程，使腹腔液量增加和细胞成分的改变，激活了盆腔局部免疫系统并引起了一系列效应是造成内异症不孕的重要环节 。巨噬细胞 ，细胞因子 （白细胞介素1 、白细胞介素6 、肿瘤坏死因子 等），前列腺素（PGS）Women with endometriosis appear to
8、display immunologic defects or dysfunctions; (Macrophage ,Cytokines(IL-1,IL-6, TNF-), Prostaglandins),内异症不孕发病机理 (三) Pathogenesis ,3、卵泡功能异常 3.Endometriosis results in the dysfunction of the Ovum可能与腹腔液中前列腺素的含量增高有关；Prostaglandins are released into the abdomen instead of the uterus; 促卵泡成熟素(FSH)含量偏低，泌乳素（
9、PRL）含量偏高也是影响卵巢排卵功能的因素之一 ；low level of FSH and high level of PRL;常有黄体功能不足 ；Occasional luteal insufficiency;黄素化未破裂卵泡综合症（LUFS）。 Luteinized unruptured follicle syndrome;,内异症不孕发病机理 (四) Pathogenesis,4、子宫内膜功能的改变 4.Dysfunction of Endometrium子宫内膜自身抗体及炎症改变 ；Endometrial antibody;Inflammatory responses ;白细胞介素2(
10、IL-2) ，可以促进淋巴细胞增生影响有效封闭抗体形成，使母体对胚胎产生免疫攻击，抑制胚胎的发育 ；IL-2;,内异症不孕发病机理 (四) Pathogenesis,一氧化氮合酶 ，持续过高的分泌可能降低精子活动度，过量或不足会破坏胚胎早期发育而影响妊娠率 ；Nitric Oxide Synthase ；整合素； Integrin； 芳香化酶 ，局部过高水平的芳香化酶所导致的E2水平升高可增加子宫肌收缩性和引起子宫内膜的微环境变化而影响胚胎的种植促成不孕 ；Aromatase; 基质金属蛋白酶（MMPS）及其抑制物（TIMPS）。 MMPS/TIMPS。,内异症的病理类型 (一)Patholo
11、gy ,内异症在组织学上是良性表现，但由于在疾病发展中可引起局部浸润、播散，造成盆腔器官或组织的广泛损害，因而导致内异症的病理形态表现为多形性和不一致性。Endometriosis is a benign lesion, but can be invasive; widely implanted and recurrent， causing multi-formations按异位病灶发生的部位 可分为：Manifestations of the pathology differ according to locations:,内异症的病理类型 (二)Pathology,1、腹膜内异症 1. P
12、eritoneal Endometriosis 镜下病变 Lesions under the microscope早期临床病变或活动性病变，又称红色病变red lesions 典型病变或进展活动性、晚期病变，又称黑色病变black typical lesions 愈合病变或非活动性病变，又称白色病变 white lesions,内异症的病理类型 (三)Pathology ,2、卵巢内异症 (又稱卵巢朱古力囊腫) 2. Ovarian Endometrial Cysts or Endometrioma - chocolate cysts due to the large amount of bl
13、ood and debris they contain; 3、结节性或阴道直肠子宫内膜异位症 3.Deep Nodular Endometriosis - ectopic tissue infiltrates into the rectovaginal septum or fibromuscular pelvic structures (e.g. uterosacral and utero-ovarian ligaments).,内异症不孕的临床诊断 (一)Diagnosis,1、症状 1.Symptoms 不孕；Infertility痛经为内异症患者的常见症状，多为继发性和渐进性；Dysme
14、norrhea;或痛经发作时伴有腰骶部疼痛、肛门下坠感；Lower back pain and Dyschezia ;部分患者表现为持续性下腹部疼痛、性交痛等；Dyspareunia (painful intercourse);部份患者表现为月经量增多或经期延长。Heavy or long menstrual periods.,内异症不孕的临床诊断 (二)Diagnosis,2、体征 2.Signs典型的内异症多表现为子宫后倾固定；Fixed and retroverted uterus;子宫直肠陷窝、宫骶韧带或子宫后壁下段等部位可扪及大小不等的触痛性结节；Tender nodules in
15、the posterior vaginal fornix and pain on gynaecological examination;宫颈或阴道壁可见点状或结节状紫蓝色病灶；Indigo nodules;可在一侧或双侧附件区扪及与子宫有粘连的囊性包块；Adnexal masses;重度者可触及“冰冻骨盆”。internal organs may fuse together, causing a condition known as a frozen pelvis” (advanced stages);,内异症不孕的临床诊断 (三)Diagnosis,3、影像学检查 3.Imaging tes
16、ts 阴道B超对卵巢内膜异位囊肿的诊断准确率较高。肠道浸润的深部内异症，经直肠超声是一种较准确的诊断方法。核磁共振（MRI)对卵巢囊肿、宫骶韧带独立结节和阴道直肠膈结节的敏感性又高于阴道B超。但對盆腔广泛性病变的诊断性不高。UltrasoundMagnetic resonance imaging,内异症不孕的临床诊断 (四)Diagnosis,4、腹腔镜检查腹腔镜检查及术中活组织检查是诊断内异症的“金标准”4. Laparoscopy 能直接观察到腹膜表面各病理类型的病灶和卵巢朱古力囊肿；卵巢和输卵管的形态和解剖关系，输卵管注入美蓝液尚可觀察到输卵管的通畅度，以评估其对生育能力的影响；但对阴道
17、直肠膈深部浸润的内异症（病灶向腹膜下浸润达到5mm以上的内异症）则容易漏诊。,内异症不孕的临床诊断 (五)Diagnosis,5、生化检测 5.Marker-CA125 血清CA125对诊断深部内异症和卵巢内异症参考价值较高，作为内异症诊断以及治疗后复发的参考依据。may predict the response to medical and surgical treatment; may also be helpful in differentiating endometriomas from non-endometriotic benign cysts.,TCM VIEW,祖国医学对内异症
18、不孕研究思路的启示 中医古籍无内异症的病名记载，西医关于内异症的病理机制研究经血倒流内膜种植学说，恰好是王清任提出的离经之血即是瘀血的现代临床研究。 There were no records of endometriosis in the ancient books of Chinese Medicine;The theory of Wang Qingren, a famous Chinese physician of ancient times, views extravasated blood as stasis is in accord with Western theories of
19、 retrograde menstruation and transplantation;,TCM VIEW,中医认为，不循正常通道即阴道排出而逆流入盆腔的经血为“离经之血”，即是瘀血，瘀血聚结胞中，导致冲任二脉失调，或瘀血占住胞宫均可致不能摄精成孕，因此认定内异症以瘀血为基本病机。 根据内异症以血瘀为本的研究思路，临床上的治疗研究以活血化瘀为基本方法 。According to current TCM views, Endometriosis is considered as blood stasis in the Chong and Ren channels that subsequent
20、ly leads to infertility; Therefore the TCM treatment principle is to remove the stasis by promoting circulation;,内异症不孕的中医治疗 TCM Therapy,治療原則：活血祛瘀選藥原則：活血化瘀不動血，散結消癥不 破血，調經止血不歛濇，通調經脈以助孕，補血慎用益精藥，益氣少用壅補劑。Treatment principle: remove the blood stasis and promote the circulation;Selecting the right herbs:Av
21、oid herbs which strongly move blood Avoid astringent herbs Do not use too many tonifying herbs,内异症不孕的中医治疗 TCM Therapy,1、活血化瘀消癥法 Method -1: Herbs to move blood and remove stasis司徒仪报道，用丹参、赤芍、当归、郁金、水蛭活血化瘀，三棱、莪术、鸡内金、浙贝、鳖甲化癥散结，枳壳理气，治疗内异症不孕15例，受孕8例（妊娠率53.3%）。本方用水蛭配伍三棱、莪术会加强活血消癥之力。 Salvia , Red Peony Root
22、, Angelica Sinensis , Curcuma Longa , Leech - to activate blood circulation. Rhizoma Sparganii, Zedoary Turmeric , Galli Corium Stomachium, Fritillary Bulb, Trio Nyx Sinensis - to disperse mass.Citrus aurtantium to regulate blood condition. Source: study by Situ Yi - Pregnancy rate achieved: 53.3%,内
23、异症不孕的中医治疗 TCM Therapy,2、化瘀通腑法 Method 2: Disperse blood stasis by Purging 王祖倩报道以醋制大黄、醋制炙鳖甲、琥珀按221比例制成丸剂，治疗内异症不孕患者25例，受孕8例（妊娠率32）。本方用大黄化瘀通腑逐邪为特点。Pills composed of Da huang (Rhubarb processed with vinigar) , Trio Nyx Sinensis (processed with vinigar) , Amber - to cure the patients with endometriosis re
24、lated infertility;Pregnant rate was 32%.Reported by Wang Zuqian.,内异症不孕的中医治疗 TCM Therapy,3、化瘀祛痰消癥法 Method 3: Remove blood stasis, phlegm and mass 周元荣报道用大黄、血竭、三七、穿山甲、鳖甲、怀牛膝、地鳖虫化瘀消癥，海藻、薏苡仁、川贝母利湿祛痰。治疗内异症不孕17例，受孕4例（妊娠率23.55%）。本方痰瘀分消，据报道纳入治疗60例，其中巧克力囊肿患者占26例。从组方分析，本资料比较有针对性的治疗卵巢巧克力囊肿。 Rhubarb, Daemonorops
25、 draco , Panax Notoginseng, Pangolin , Trio Nyx Sinensis, Achyranthes Bidentata Bl., Eupolyphaga - to remove blood stasis and mass; Varec, Semen Coicls, Bulbus Fritillariae Cirrhosae - to promote diuresis to eliminate damp and phlegm; Pregnant rate was 23.55%Reported by Zhou Yuanrong.,内异症不孕的中医治疗 TCM
26、 Therapy,4、温阳化瘀法 Method 4:Warm the yang and remove blood stasis朱兰等报道用良方温经汤加味，以当归、川芎、白芍、牛膝、莪术、丹皮活血化瘀，桂心温补元阳，人参温补中焦，治疗内异症不孕15例，治疗后妊娠12例，(妊娠率80)。Angelica, Rhizoma Ligustici Chuanxiong, Radix Paeoniae Alba, Achyranthes Bidentata, Cortex Moutan - to remove blood stasis;Cinnamon and Panax - to warm the ya
27、ng.Pregnant rate was 80 (Reported by Zhu Lan),Method4,张予宛报道用少腹逐瘀汤加味以当归、川芎、蒲黄、五灵脂、赤芍、没药、元胡索活血理气化瘀，肉桂、干姜、小茴香温阳，治疗内异症不孕94例，受孕57例，(妊娠率60.63)。以上两报道均以肉桂温阳通脉散瘀配伍辛温之归芎，非寒实证不可轻用。Angelica, Rhizoma Ligustici Chuanxiong, Radix Paeoniae Rubra, Typha orientalis , Faeces Trogopterori, Rhizoma Corydalis, Myrrh - to
28、 promote blood circulation and regulate qi to remove blood stasis; Cinnamon, Dried Ginger, fennel can warm yang. Pregnant rate was 60.63.(Reported by Zhang yuwan),内异症不孕的中医治疗 TCM Therapy,5、化瘀补肾法 Method-5:Nourish Kidneys and Remove Blood Stasis王宁以当归、桃仁、石打穿、蒲黄、五灵脂、皂角刺活血化瘀散结，肉桂、淫羊藿、地黄、制首乌补肾益精治疗内异症不孕15例，
29、受孕9例（妊娠率60）。另外，不孕症并自然流产者15例，用該方治疗后已分娩11人，孕期大于4个月4人（妊娠率88.2）。本研究主要探讨活血化瘀佐以补肾方药对内异症不孕与内异症自然流产的免疫调节作用。本組病例中， 29例血清子宫内膜抗体阳性患者治疗2个月复查子宫内膜抗体，结果28例呈阴性反应，阴转率达96.5%。Angelica, Peach Kernel, Faeces Trogopterori, Rhizoma Corydalis, Zaojaoci, Shidachuan - to remove blood stasis and mass;Cinnamon, Barrenwort, Reh
30、manniae, Polygonum - to invigorate the kidney.Pregnant rate was 60. (Reported by Wang Ning),Method 5,张丽君以丹参、川芎、三棱、莪术、血竭末、茺蔚子活血化瘀，续断、枸杞子、菟丝子补肾益精，治疗内异症不孕30例，经13疗程治疗后，受孕5例，(妊娠率17)。本法以化瘀消癥为主，补肾药性平和，不偏温通滋而不膩。Salvia, Rhizoma Ligustici Chuanxiong, Rhizoma Ligustici Chuanxiong, Rhizoma Sparganii, Zedoary Tu
31、rmeric, Daemonorops draco, Motherwort Seed - to remove blood stasis and promote the circulation. Teasel,Wolfberry, Cuscuta Chinensis - to invigorate the kidney.Pregnant rate was17.(Reported by Zhang Lijun),Method 5,李祥云以三棱、莪术、水蛭、地鳖虫、穿山甲活血化瘀，菟丝子、仙灵脾补肾气治疗内异症不孕109例，68例受孕，治愈率为63.39%。本法消癥通络力稍强，经量多或经期长者，要注
32、意服药时间、配伍及剂量调节。 Rhizoma Sparganii, Zedoary Turmeric, Leech, Eupolyphaga Sinensis, Pangolin - to remove blood stasis and promote the circulation;Cuscuta Chinensis, Xianlingpi - to supplement the kidney;Pregnant rate was 63.39%.(Reported by Li Xiangyun),内异症不孕的中医治疗 TCM Therapy,6、益气化瘀法 Method-6: Tonify Q
33、i and Remove Blood Stasis 陈晓平等报道以补阳还五汤原方运用，以当归尾、川芎、赤芍、桃仁、红花活血化瘀，地龙通络，黄芪补气，治疗内异症不孕16例，受孕12例（妊娠率75）。Angelica, Peach Kernel, Rhizoma Ligustici Chuanxiong, Safflower, Radix Paeoniae Alba - to remove the stasis.Di long (Earthworm) to unblock the channels;Huang qi (Astragalus) to supplement Qi.Pregnant ra
34、te was 75%.(Reported by Chen Xiaoping).,Method 6,傅友丰等以失笑散、生贯众、鬼见羽、益母草、制香附、元胡索活血理气化瘀，皂角刺祛痰散结，黄芪、人参补气治疗内异症不孕22例，受孕9例（40.9%）。本法黄芪重用，意在补气以行血、补为通用。 Typha orientalis , Faeces Trogopterori, Cyrtomium Fortunei, Motherwort, Aconite, Rhizoma Corydalis - to regulate Qi and promote the circulation;Zaojiaoci - t
35、o disseminate mass and Huang qi (Astragalus) and ren shen (Panax) - to supplement Qi.Pregnant rate was 40.9%.(Reported by Fu Youfeng),西医药物治疗Western Medication,醋酸炔诺酮 5mg/D*6个月Ethyl nortestosterone 5mg/D,6months甲羟孕酮2050mg/D*6个月Medroxyprogesterone 2050mg/D，6 months达那唑0.2 BidTid*6个月Danazol 0.2 BidTid，6
36、months孕三烯酮2.5mg/次 每周2次*3-6个月Gestrinone 2.5mg/each time and two times per week, 3-6 months亮丙瑞林3.75mg 皮下注射 每28天一次Leuprorelin(GnRH-) 3.75mg Subcutaneous injection, every 28 days. 戈舍瑞林3.6mg 皮下注射 每28天一次Goserelin Acetate Leuprorelin(GnRH-) 3.6mg Subcutaneous injection, every 28 days.,手术治疗Surgical Treatmen
37、t,卵巢异位内膜囊肿剔除术盆腔粘连松解术盆腔腹膜病灶去除术盆腔深部结节去除术Excision (endometrioma ,deeper lesions )Pelvic adhesion lysis Electrosurgical Ablation,治疗选择的建议 (一)Treatment Suggestions,1、首先了解盆腔病变情况对生育功能的影响，根据患者的证候、病理类型的不同，制定个体化的治疗方案。盆腔器官无解剖变异因素存在，中药治疗可作为首选。若卵巢被粘连包裹、输卵管阻塞，則药物治疗难以奏效，不宜作为内异症不孕的中药治疗研究对象。1.According to clinical ma
38、nifestation individual therapeutic strategies are established, depending on how the disease may influence the reproductive function:Chinese medication may be the first choice if no anatomical structures change in pelvic cavity;Chinese medication is used only in support of WM if the patient suffers f
39、rom severe adhesions that obstructs the fallopian tubes;,治疗选择的建议 (二)Suggestions of treatment,2、中、重度内异症不孕，但输卵管通畅，手术松解盆腔粘连或剔除较大的卵巢巧克力囊肿后，施以中药治疗，临床观察表明，可缩短疗程提高疗效。 2. Clinical studies show that Chinese medicine can shorten the healing process and increase the chances of fertility in women with severe ad
40、hesions, but patent fallopian tubes.,治疗选择的建议 (三)Suggestions of treatment ,3、年龄大于35岁，双侧输卵管阻塞者，宜施行人工受精或试管婴儿。辅助生育手术前，中药治疗36个月，改善盆腔微环境，可提高妊娠率。 3.Infertile women with endometriosis who are older(35), or who have fallopian tube obstructions, can undergo assisted reproduction (in vitro fertilization, gamet
41、e intra-fallopian transfer,etc). Chinese medicine will be used to assist conception and improve successful pregnancy rate.,治疗选择的建议 (四)Suggestions of treatment,4、伴有月经量多，经期延长或月经先期者，非经时用药宜选用祛瘀不动血药，经时用药宜祛瘀止血药如失笑散、三七、大黄、血竭、没药、茜草、大蓟、小蓟等；4. Infertile women with endometriosis who suffer from menorrhagia, or
42、 menostaxis, or prolonged menstrual cycle may choose different herbs in different phases of their cycle.,治疗选择的建议 (四)Suggestions of treatment,气虚证者宜益气摄血如白术、黄芪、人参等；阳虚肾虚者宜温补肾阳如艾叶、续断、鹿角霜等。 Treat Qi deficiency with herbs that can tonify vital energy and nourish blood, such as Atractylodes, Huang qi (Astra
43、galus), ren shen (Panax),etc.Treat deficiency of kidney-yang with herbs that can warm kidney-yang, such as mugworf leaf, Teasel etc.,病案分析Case,黄某，36岁因“痛经10年余，不孕3年”于2006年12月28日初诊。Ms Huang, Aged 36.She first came to clinic for her 10-year dysmenorrhea and 3-year infertility on Dec.28th,2006.,患者因“痛经、不孕”
44、2002年3月经腹腔镜检查诊断为盆腔子宫内膜异位症，并行病灶剔除术。术后痛经减轻，月经正常，经量中等。2004年1月右输卵管妊娠行右输卵管切除术。此后未避孕未再孕。末次月经月2006年12月12日，7天干净，经色暗红挟血块。经前乳房胀痛，经行小腹痛甚，伴四肢冷，恶心欲吐。卧床2日，服止痛药3天。舌质紫黯有瘀斑，苔黄，脉弦。She was diagnosed endometriosis by Laparoscopy and lesions was ablated at the same time in March, 2002. Dysmenorrhea was improved with nor
45、mal period. Salpingectomy (right side) was done due to tubal pregnency in Jan.,2004. LMP Dec. 12th,2006. Period bleeding was dark with gore. Breast felt pain before period and low abdomen felt pain during period with cold extremities and nausea. Dark purple tongue with ecchymosis and yellow coating.
46、Wiry pulse.,证属气滞血瘀，拟祛瘀消癥，行气止痛。Qi stagnation and blood stasis, Remove blood stasis and mass and promote qi to relieve pain.,方药：鸡内金9克，蒲黄（包）12克，五灵脂9克，延胡索15克，乌药15克，三七9克，大黄9克，土鳖虫12克，益母草15克，莪术9克，三棱9克，丹皮12克，醋鳖甲20克，猫爪草15克，赤芍12克。Precription:Jineijin 9g, Puhuang 12g, Wanglingzhi 9g, Yanhusuo 15g, Wuyao 15g, S
47、anqi 9g, Dahuang 9g, Tubiechong 12g, Yimucao 15g, Ezhu 9g, Sanleng 9g, Danpi 12g, Biejia 20g, Maozhuacao 20g, Chishao 12g.,治疗2月，痛经明显减轻，继以补肾活血法调治，上方加菟丝子15克，续断15克，熟地15克，治疗近4个月怀孕，但妊娠6周因工作操劳至流产。本例先拟化瘀理气治疗，痛经减轻，生活质素得以改善后，在活血化瘀为主佐以补肾治疗而获妊娠。但患者于妊娠后未注意调摄，伤损胎气以至流产。Dysmenorrhea relieved obviously after 2-mont
48、h treatment. Then nourishing kidney was added. Tusizi(15g), Xuduan(15g) , Shudi(15g) was used. The patient was expecting after 4-month treatment. Miscarriage was happened after 6 weeks pregnancy because of swink.,内异症术后妊娠率可达5373左右。随着距离手术时间愈长，临床观察到部分患者妊娠率有逐渐下降的趋势。本例活血化瘀中药止痛调经疗效较显著。目前研究的结果表明，主要是调低前列腺的活
49、性作用，对前列腺素的细胞介素、肿瘤坏死因子以及对卵巢子宫内膜免疫损伤的调节被认为是促进内异症不孕的可能因素。The pregnancy rate after surgical treatment may reach to 53-73% of the endometriosis, but it may decrease with the passage of time.The studies showed that the herbs that can move blood and remove stasis may relieve pain and regulate menstruation because the activities of prostaglandins were decreased.,
