本文選題：宮腔粘連(IUA) + 雌激素療法��； 參考：《中南大學(xué)》2014年碩士論文

【摘要】：背景：宮腔粘連是指由于各種原因引起子宮內(nèi)膜基底層損傷而導(dǎo)致子宮壁相互粘連的病理現(xiàn)象。其主要臨床表現(xiàn)為月經(jīng)異常(月經(jīng)量過(guò)少或閉經(jīng)),還可導(dǎo)致周期性下腹痛、不孕及習(xí)慣性流產(chǎn)。妊娠期宮腔手術(shù)操作是宮腔粘連最常見(jiàn)的原因,其它非妊娠期宮腔手術(shù)如子宮肌剝除、縱隔電切術(shù)、上環(huán)或取環(huán)術(shù),以及宮內(nèi)急慢性感染史、子宮動(dòng)脈栓塞術(shù)、嚴(yán)重盆腔炎等也容易引起宮腔粘連。 由于宮腔手術(shù)創(chuàng)傷或炎癥等因素的刺激,子宮內(nèi)膜基底層可受到損傷,進(jìn)而引發(fā)子宮壁纖維蛋白原的滲出及肉芽組織生成,最終將導(dǎo)致子宮壁粘連形成。病情嚴(yán)重者,子宮內(nèi)膜可完全被破壞而被纖維組織所代替,宮腔鏡下無(wú)法見(jiàn)到正常的子宮內(nèi)膜組織。宮腔粘連患者不孕、習(xí)慣性流產(chǎn)、早產(chǎn)和胎盤(pán)位置異常的發(fā)生率較普通人群升高,對(duì)育齡婦女的生育能力危害極大。 在宮腔鏡下對(duì)粘連組織進(jìn)行分離后可改善子宮內(nèi)膜對(duì)雌激素的反應(yīng),有助于子宮內(nèi)膜恢復(fù)至正常的功能。宮腔鏡下宮腔粘連分離術(shù)明顯優(yōu)于過(guò)去盲目的擴(kuò)宮分離術(shù),該手術(shù)不僅可選擇性的分離粘連組織,而且還可以避免對(duì)正常子宮內(nèi)膜組織的損傷,已被視為一種更安全有效的微創(chuàng)技術(shù),成為目前治療宮腔粘連的手術(shù)金標(biāo)準(zhǔn)。術(shù)后常采用在宮腔內(nèi)留置Foley導(dǎo)管、置入IUD、宮腔內(nèi)注入透明質(zhì)酸鈉凝膠等多種方法輔助治療,但目前宮腔粘連的治療效果仍不理想。 宮腔粘連術(shù)后的高復(fù)發(fā)率是影響宮腔粘連治療效果的主要問(wèn)題。為了預(yù)防粘連復(fù)發(fā),目前主要從兩個(gè)方面進(jìn)行治療：一是通過(guò)建立物理屏障直接阻礙前后壁子宮內(nèi)膜創(chuàng)面的接觸,而減少粘連復(fù)發(fā)；另一方面則是通過(guò)促進(jìn)創(chuàng)傷部位子宮內(nèi)膜的生長(zhǎng),從而利用再生的子宮內(nèi)膜防止粘連部位再次粘連。在促進(jìn)創(chuàng)傷部位子宮內(nèi)膜生長(zhǎng)方面,主要是利用大劑量外源性雌激素,另外還有報(bào)道應(yīng)用小劑量阿司匹林、一氧化氮等,但是目前公認(rèn)的促進(jìn)子宮內(nèi)膜生長(zhǎng)的有效方法僅為應(yīng)用大劑量外源性雌激素療法。雖然大劑量雌激素對(duì)促進(jìn)子宮內(nèi)膜生長(zhǎng)的有效性是公認(rèn)的,但是有關(guān)應(yīng)用外源性雌激素的諸多問(wèn)題尚無(wú)統(tǒng)一的答案。比如應(yīng)用雌激素的具體劑量、用法和療程,是否聯(lián)合應(yīng)用孕激素以及如何聯(lián)合應(yīng)用等問(wèn)題,是臨床實(shí)踐中至關(guān)重要的問(wèn)題,亟待解決。 有人認(rèn)為連續(xù)性大劑量外源性雌激素的治療相比周期性的應(yīng)用大劑量雌激素更能有效促進(jìn)子宮內(nèi)膜的生長(zhǎng),在目前的臨床工作中,很多婦科醫(yī)生往往采用連續(xù)大劑量外源性雌激素治療的方法治療那些子宮內(nèi)膜較薄的宮腔粘連患者,但這僅是一種臨床的經(jīng)驗(yàn)性用藥,目前尚無(wú)隨機(jī)對(duì)照研究(Randomized controlled trial,RCT)來(lái)驗(yàn)證這一結(jié)論。本研究的目的是希望通過(guò)前瞻性隨機(jī)對(duì)照的研究,比較兩種雌激素治療方案對(duì)宮腔粘連治療效果的影響,重點(diǎn)探討術(shù)后使用連續(xù)性或周期性雌激素的方法對(duì)宮腔粘連復(fù)發(fā)率、月經(jīng)改善率及妊娠率的影響,為臨床治療提供參考依據(jù)。 資料與方法：2012年12月至2014年3月在中南大學(xué)湘雅三醫(yī)院婦科因經(jīng)量減少、不孕或反復(fù)自然流產(chǎn)而行宮腔鏡檢查確診為中度宮腔粘連的81例患者被納入本研究。所有病例均根據(jù)美國(guó)生育協(xié)會(huì)(American Fertility Society)1988年宮腔粘連分度標(biāo)準(zhǔn)進(jìn)行分度。 病例分組及治療方案：81例中度宮腔粘連患者隨機(jī)分為2組。研究組：40例,采用治療方案A：首先行宮腔鏡下宮腔粘連分離術(shù)使子宮恢復(fù)正常解剖,術(shù)后留置Foley導(dǎo)尿管于宮腔內(nèi),球囊內(nèi)注入生理鹽水3m],經(jīng)導(dǎo)尿管注入2ml透明質(zhì)酸鈉至宮腔內(nèi)防粘連。術(shù)后第3天再次注射同劑量透明質(zhì)酸鈉。術(shù)后第4天拔出Foley導(dǎo)尿管,同時(shí)置入合適大小的宮形環(huán)。雌孕激素治療方案：術(shù)后即開(kāi)始連續(xù)服用戊酸雌二醇(3mg,bid)56天,最后6天同時(shí)加用黃體酮膠丸(200mg,QN×6天)治療,本周期治療完畢后,繼續(xù)予以2個(gè)人工周期治療(戊酸雌二醇3mg,bid×21天,最后6天同時(shí)加用黃體酮膠丸200mg,QNX6天)。對(duì)照組：41例,采用治療方案B：除雌激素治療方案外,其他處理均同研究組。雌孕激素治療方案：術(shù)后給予4個(gè)周期的人工周期治療(戊酸雌二醇3mg,bid×21天,最后6天同時(shí)加用黃體酮膠丸200mg,QN×6天)。 所有患者在術(shù)后完成所有雌孕激素療程后,于月經(jīng)干凈2-7天內(nèi)進(jìn)行宮腔鏡復(fù)查并了解月經(jīng)情況,觀察和記錄粘連復(fù)發(fā)情況及子宮內(nèi)膜生長(zhǎng)情況,若本次復(fù)查情況好,則可取出宮形環(huán),嘗試受孕。若發(fā)現(xiàn)再次粘連則同時(shí)行第二次宮腔粘連分離術(shù),重新進(jìn)行術(shù)后輔助治療并定期復(fù)查,直至宮腔情況良好,可取出宮形環(huán),嘗試受孕；或因?qū)m腔粘連療效太差而放棄治療。 術(shù)后監(jiān)測(cè)指標(biāo)包括：月經(jīng)情況、粘連復(fù)發(fā)情況、宮深、子宮內(nèi)膜厚度及腺體密度改善的情況、術(shù)后到妊娠的時(shí)間間隔、妊娠結(jié)局(包括流產(chǎn)、早產(chǎn)、異位妊娠)。隨訪(fǎng)時(shí)間持續(xù)至2014年3月,隨訪(fǎng)期間所有的妊娠情況均通過(guò)電話(huà)隨訪(fǎng)的方式予以記錄。 結(jié)果： 1.由于患者未遵醫(yī)囑規(guī)律服藥和按時(shí)復(fù)查、環(huán)位置下移、失訪(fǎng)等原因?qū)е虏糠植±型就顺霰狙芯?最后隨訪(fǎng)人數(shù)為研究組31例,對(duì)照組38例。 2.宮腔鏡復(fù)查情況： (1)術(shù)后第一次宮腔鏡復(fù)查時(shí),研究組患者月經(jīng)量恢復(fù)正常率顯著高于對(duì)照組(P=0.04)。對(duì)照組發(fā)現(xiàn)6/29例月經(jīng)量未得到改善(含1例減少),研究組有4/28例(P0.05)。 (2)兩組患者術(shù)后第一次宮腔鏡復(fù)查時(shí)的經(jīng)期比較,研究組患者的經(jīng)期明顯長(zhǎng)于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(研究組：4.94±1.16天,對(duì)照組：4.20±1.19天,P=0.03)。 (3)術(shù)后第一次宮腔鏡復(fù)查時(shí)研究組患者的宮腔粘連平均AFS評(píng)分比對(duì)照組低,差異無(wú)統(tǒng)計(jì)學(xué)意義(研究組：1.23±1.99,對(duì)照組：0.87±1.66,P0.05)。 (4)術(shù)后第一次宮腔鏡復(fù)查中有61例患者宮腔恢復(fù)了滿(mǎn)意的解剖形態(tài)(宮腔鏡檢查示宮腔粘連完全消失并未見(jiàn)再粘連現(xiàn)象)。其中研究組有28/31例(90.3%),對(duì)照組有33/38例(89.5%),差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。術(shù)后研究組中有3例需要進(jìn)行多次宮腔粘連分離術(shù),對(duì)照組有5例。兩組差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。術(shù)后子宮內(nèi)膜腺體密度及子宮內(nèi)膜厚度改善情況兩組無(wú)明顯差異(P0.05)。 3.術(shù)后妊娠及妊娠結(jié)局： (1)69例患者中有64例(研究組29例,對(duì)照組35例)嘗試受孕,另外5位病人暫無(wú)受孕計(jì)劃。平均隨訪(fǎng)7.18±2.23月,妊娠率分別為研究組27.6%(8/29)、對(duì)照組34.3%(12/35)。兩組差異無(wú)統(tǒng)計(jì)意義(P0.05)。 (2)研究組的受孕時(shí)間距最后一次行宮腔粘連分離術(shù)的平均時(shí)間為8.37±2.44月,對(duì)照組為8.25±2.01月,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 (3)對(duì)照組術(shù)后的產(chǎn)科并發(fā)癥(如自然流產(chǎn)、稽留流產(chǎn)、異位妊娠)發(fā)生率略高于研究組。研究組為25%(2/8),對(duì)照組為50%(6/12),但差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論：初步研究提示中度宮腔粘連分離術(shù)后采用連續(xù)性雌激素治療效果并不優(yōu)于周期性雌激素治療。
[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.
Result錛，

本文編號(hào)：1772962