宫腔粘连分离术后雌激素治疗的两种方案疗效比较

发布时间：2018-04-19 11:44

  本文选题：宫腔粘连(IUA) + 雌激素疗法　； 参考：《中南大学》2014年硕士论文

【摘要】：背景：宫腔粘连是指由于各种原因引起子宫内膜基底层损伤而导致子宫壁相互粘连的病理现象。其主要临床表现为月经异常(月经量过少或闭经),还可导致周期性下腹痛、不孕及习惯性流产。妊娠期宫腔手术操作是宫腔粘连最常见的原因,其它非妊娠期宫腔手术如子宫肌剥除、纵隔电切术、上环或取环术,以及宫内急慢性感染史、子宫动脉栓塞术、严重盆腔炎等也容易引起宫腔粘连。 由于宫腔手术创伤或炎症等因素的刺激,子宫内膜基底层可受到损伤,进而引发子宫壁纤维蛋白原的渗出及肉芽组织生成,最终将导致子宫壁粘连形成。病情严重者,子宫内膜可完全被破坏而被纤维组织所代替,宫腔镜下无法见到正常的子宫内膜组织。宫腔粘连患者不孕、习惯性流产、早产和胎盘位置异常的发生率较普通人群升高,对育龄妇女的生育能力危害极大。 在宫腔镜下对粘连组织进行分离后可改善子宫内膜对雌激素的反应,有助于子宫内膜恢复至正常的功能。宫腔镜下宫腔粘连分离术明显优于过去盲目的扩宫分离术,该手术不仅可选择性的分离粘连组织,而且还可以避免对正常子宫内膜组织的损伤,已被视为一种更安全有效的微创技术,成为目前治疗宫腔粘连的手术金标准。术后常采用在宫腔内留置Foley导管、置入IUD、宫腔内注入透明质酸钠凝胶等多种方法辅助治疗,但目前宫腔粘连的治疗效果仍不理想。 宫腔粘连术后的高复发率是影响宫腔粘连治疗效果的主要问题。为了预防粘连复发,目前主要从两个方面进行治疗：一是通过建立物理屏障直接阻碍前后壁子宫内膜创面的接触,而减少粘连复发；另一方面则是通过促进创伤部位子宫内膜的生长,从而利用再生的子宫内膜防止粘连部位再次粘连。在促进创伤部位子宫内膜生长方面,主要是利用大剂量外源性雌激素,另外还有报道应用小剂量阿司匹林、一氧化氮等,但是目前公认的促进子宫内膜生长的有效方法仅为应用大剂量外源性雌激素疗法。虽然大剂量雌激素对促进子宫内膜生长的有效性是公认的,但是有关应用外源性雌激素的诸多问题尚无统一的答案。比如应用雌激素的具体剂量、用法和疗程,是否联合应用孕激素以及如何联合应用等问题,是临床实践中至关重要的问题,亟待解决。 有人认为连续性大剂量外源性雌激素的治疗相比周期性的应用大剂量雌激素更能有效促进子宫内膜的生长,在目前的临床工作中,很多妇科医生往往采用连续大剂量外源性雌激素治疗的方法治疗那些子宫内膜较薄的宫腔粘连患者,但这仅是一种临床的经验性用药,目前尚无随机对照研究(Randomized controlled trial,RCT)来验证这一结论。本研究的目的是希望通过前瞻性随机对照的研究,比较两种雌激素治疗方案对宫腔粘连治疗效果的影响,重点探讨术后使用连续性或周期性雌激素的方法对宫腔粘连复发率、月经改善率及妊娠率的影响,为临床治疗提供参考依据。 资料与方法：2012年12月至2014年3月在中南大学湘雅三医院妇科因经量减少、不孕或反复自然流产而行宫腔镜检查确诊为中度宫腔粘连的81例患者被纳入本研究。所有病例均根据美国生育协会(American Fertility Society)1988年宫腔粘连分度标准进行分度。 病例分组及治疗方案：81例中度宫腔粘连患者随机分为2组。研究组：40例,采用治疗方案A：首先行宫腔镜下宫腔粘连分离术使子宫恢复正常解剖,术后留置Foley导尿管于宫腔内,球囊内注入生理盐水3m],经导尿管注入2ml透明质酸钠至宫腔内防粘连。术后第3天再次注射同剂量透明质酸钠。术后第4天拔出Foley导尿管,同时置入合适大小的宫形环。雌孕激素治疗方案：术后即开始连续服用戊酸雌二醇(3mg,bid)56天,最后6天同时加用黄体酮胶丸(200mg,QN×6天)治疗,本周期治疗完毕后,继续予以2个人工周期治疗(戊酸雌二醇3mg,bid×21天,最后6天同时加用黄体酮胶丸200mg,QNX6天)。对照组：41例,采用治疗方案B：除雌激素治疗方案外,其他处理均同研究组。雌孕激素治疗方案：术后给予4个周期的人工周期治疗(戊酸雌二醇3mg,bid×21天,最后6天同时加用黄体酮胶丸200mg,QN×6天)。 所有患者在术后完成所有雌孕激素疗程后,于月经干净2-7天内进行宫腔镜复查并了解月经情况,观察和记录粘连复发情况及子宫内膜生长情况,若本次复查情况好,则可取出宫形环,尝试受孕。若发现再次粘连则同时行第二次宫腔粘连分离术,重新进行术后辅助治疗并定期复查,直至宫腔情况良好,可取出宫形环,尝试受孕；或因宫腔粘连疗效太差而放弃治疗。 术后监测指标包括：月经情况、粘连复发情况、宫深、子宫内膜厚度及腺体密度改善的情况、术后到妊娠的时间间隔、妊娠结局(包括流产、早产、异位妊娠)。随访时间持续至2014年3月,随访期间所有的妊娠情况均通过电话随访的方式予以记录。 结果： 1.由于患者未遵医嘱规律服药和按时复查、环位置下移、失访等原因导致部分病例中途退出本研究,最后随访人数为研究组31例,对照组38例。 2.宫腔镜复查情况： (1)术后第一次宫腔镜复查时,研究组患者月经量恢复正常率显著高于对照组(P=0.04)。对照组发现6/29例月经量未得到改善(含1例减少),研究组有4/28例(P0.05)。 (2)两组患者术后第一次宫腔镜复查时的经期比较,研究组患者的经期明显长于对照组,差异有统计学意义(研究组：4.94±1.16天,对照组：4.20±1.19天,P=0.03)。 (3)术后第一次宫腔镜复查时研究组患者的宫腔粘连平均AFS评分比对照组低,差异无统计学意义(研究组：1.23±1.99,对照组：0.87±1.66,P0.05)。 (4)术后第一次宫腔镜复查中有61例患者宫腔恢复了满意的解剖形态(宫腔镜检查示宫腔粘连完全消失并未见再粘连现象)。其中研究组有28/31例(90.3%),对照组有33/38例(89.5%),差异无统计学意义(P0.05)。术后研究组中有3例需要进行多次宫腔粘连分离术,对照组有5例。两组差异无统计学意义(P0.05)。术后子宫内膜腺体密度及子宫内膜厚度改善情况两组无明显差异(P0.05)。 3.术后妊娠及妊娠结局： (1)69例患者中有64例(研究组29例,对照组35例)尝试受孕,另外5位病人暂无受孕计划。平均随访7.18±2.23月,妊娠率分别为研究组27.6%(8/29)、对照组34.3%(12/35)。两组差异无统计意义(P0.05)。 (2)研究组的受孕时间距最后一次行宫腔粘连分离术的平均时间为8.37±2.44月,对照组为8.25±2.01月,差异无统计学意义(P0.05)。 (3)对照组术后的产科并发症(如自然流产、稽留流产、异位妊娠)发生率略高于研究组。研究组为25%(2/8),对照组为50%(6/12),但差异无统计学意义(P0.05)。 结论：初步研究提示中度宫腔粘连分离术后采用连续性雌激素治疗效果并不优于周期性雌激素治疗。
[Abstract]:Background: intrauterine adhesion is the pathological phenomenon of the adhesion of the uterine wall caused by the damage of the endometrium basal layer for various reasons. Its main clinical manifestation is abnormal menstruation (excessive menstruation or amenorrhea), and it can also lead to periodic lower abdominal pain, infertility and habitual abortion. Uterine cavity operation in pregnancy pregnancy is the most common intrauterine adhesion. Reasons, other non pregnancy uterine surgery, such as uterine muscle stripping, mediastinal electrocision, upper ring or ring removal, and the history of acute and chronic intrauterine infection, uterine artery embolization, severe pelvic inflammation, may also cause intrauterine adhesions.
The basal layer of the endometrium can be damaged by the stimulation of the surgical trauma or inflammation of the uterine cavity, which may lead to the exudation of fibrinogen and the formation of granulation tissue, which will eventually lead to the formation of the adhesions of the uterus. The endometrium can be completely destroyed and replaced by the fibrous tissue. The hysteroscopy can not be seen in the uterus. The incidence of infertility, habitual abortion, preterm birth and abnormal placental position in patients with uterine cavity adhesion is higher than that of the general population, which is very harmful to the fertility of women of childbearing age.
The separation of adhesive tissue under hysteroscopy can improve the response of endometrium to estrogen and help to restore the endometrium to normal function. Hysteroscopic adhesions separation is obviously superior to that of the past blind dilation of uterus. This operation can not only selectively separate the tissue, but also avoid the normal uterus. The damage of membrane tissue has been considered as a safer and more effective minimally invasive technique. It has become the gold standard for the treatment of intrauterine adhesions at present. After the operation, the Foley catheter was retained in the uterine cavity, IUD was inserted into the uterine cavity, and sodium hyaluronate gel was injected into the intrauterine, but the therapeutic effect of the intrauterine adhesions was still not ideal.
The high recurrence rate of adhesion after intrauterine adhesion is the main problem affecting the effect of intrauterine adhesions. In order to prevent adhesion and recurrence, it is mainly treated from two aspects: one is to prevent the contact of the anterior and posterior wall of the endometrium through the establishment of a physical barrier, and reduce the recurrence of adhesion; on the other hand, it is to promote the trauma position by promoting the trauma position. The growth of the endometrium can prevent the adhesion of adhesions from the regenerated endometrium. In promoting the growth of the endometrium in the wound site, it is mainly the use of large doses of exogenous estrogen, and the use of small dose aspirin, nitric oxide, etc., but it is recognized that the effective methods to promote the growth of the endometrium are only the only effective methods before the eyes. While large dose of estrogen therapy is used. Although the effectiveness of large doses of estrogen is recognized to promote the growth of endometrium, there are no unified answers to the problems relating to the application of exogenous estrogen. For example, the specific dosage, usage and course of estrogen application, the combination of progestin and how to combine the use of progestin, etc. The problem is a crucial problem in clinical practice, which needs to be solved urgently.
Some people think that the treatment of continuous large dose of exogenous estrogen is more effective in promoting the growth of endometrium than the periodic use of large doses of estrogen. In the current clinical work, many gynecologists often treat patients with thin endometrium with continuous large dose of exogenous estrogen therapy. But this is only a clinical empirical drug, and there is no randomized controlled study (Randomized controlled trial, RCT) to verify this conclusion. The purpose of this study is to compare the effect of two kinds of estrogen therapy on the effect of intrauterine visco therapy through prospective randomized controlled study, and to focus on the continuity of postoperative use or The effect of periodic estrogen on the recurrence rate, menstrual improvement rate and pregnancy rate of uterine cavity adhesions can provide reference for clinical treatment.
Data and methods: from December 2012 to March 2014, 81 patients with moderate intrauterine adhesions diagnosed by gynecologic reduction, infertility or recurrent spontaneous abortion at Xiangya Third Hospital, Central South University, were included in this study. All cases were based on the 1988 American Fertility Society. It must be divided.
Case group and treatment scheme: 81 patients with moderate intrauterine adhesions were divided into 2 groups randomly. The study group: 40 cases, using the treatment scheme A: first, the uterus cavity adhesion separation was performed to restore normal anatomy. After the operation, the Foley catheter was indwelling in the uterine cavity, the physiological salt water 3m] was injected into the balloon, and 2ml hyaluronate sodium was injected into the uterus through the catheter. Intraluminal anti adhesion. The same dose of sodium hyaluronate was injected again third days after operation. Foley catheter was extracted fourth days after operation, and the proper size of uterine ring was placed. Estrogen and progesterone therapy program: after 56 days, 3mg (bid) was taken continuously for 56 days, and the last 6 days were treated with Progesterone Soft Capsules (200mg, QN x 6 days), and this period was treated. After completion, 2 artificial cycles were continued (estradiol valerate 3mg, bid x 21 days, and Progesterone Soft Capsules 200mg, QNX6 days at the last 6 days). Control group: 41 cases, treatment regimen B: except for estrogen therapy, other treatments were treated with estrogen and progesterone therapy: valerate (valerate) was given after 4 cycles (valerate) after operation Estradiol 3mg, bid * 21 days, the last 6 days at the same time with the Progesterone Soft Capsules 200mg, QN * 6 days).
After the treatment of all estrogen and progesterone after the operation, all the patients were reexamined by hysteroscopy within 2-7 days of menstruation, to observe and understand the situation of menstruation, to observe and record the recurrence of adhesion and the growth of the endometrium. If this reexamination was good, we could take out the palace ring and try to get pregnant. If again, second times of adhesions were found at the same time. Separation, re - operation and periodic review until the palace is good, can take out the palace ring, try to be pregnant, or because the effect of uterine cavity adhesion is too poor and give up treatment.
The postoperative monitoring indexes include: menstruation, recurrence of adhesion, uterine depth, endometrial thickness and density of glands, the interval of postoperatively to pregnancy, pregnancy outcome (including abortion, premature delivery, ectopic pregnancy). The follow-up time lasted until March 2014, and all the pregnancy conditions during the follow-up period were recorded by telephone follow up. Book.
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