【作者】 郜翔；

【导师】 申爱荣；

【作者基本信息】 郑州大学 ， 临床医学， 2012， 硕士

【摘要】 子宫内膜异位症(Endometriosis,EMT)简称内异症,是指具有活力的子宫内膜组织出现在子宫内膜以外的部位,进而引起一系列的临床症状及病理改变的一种疾病,是一种常见的妇科疾病。EMT的主要临床表现包括持续加重的盆腔粘连、疼痛以及不孕等。近年来的研究发现,EMT的发病率呈上升趋势,尤以育龄妇女为高发人群,严重影响着广大妇女的生殖健康。不孕症是指有正常性生活,未经避孕1年未妊娠者。按照既往是否有妊娠史,不孕症分为原发性不孕和继发性不孕两大类。我国的不孕症发病率7%～10%,其中女方因素导致的不孕约40%,约25%～35%的不孕妇女患EMT,可见EMT与不孕的关系之密切。因而有学者提出了EMT相关性不孕的概念。目前,EMT合并不孕的主要治疗手段是手术治疗,主要是通过清除盆腔异位病灶、恢复盆腔解剖、改善盆腔内环境来改善妊娠。美国生育学会修订的EMT分期标准(revised classification of American Fertility Society,r-AFS)在一定程度上反映了EMT病变的严重程度及预后情况,但是对于判断EMT合并不孕的患者的预后,其临床价值仍有待商榷。手术后使用抗EMT药物是目前EMT的金标准治疗,抗EMT药物在抑制内异灶复发及缓解症状方面有积极的作用,但是对于有生育要求的EMT患者是否使用药物治疗仍无统一意见。另外,手术效果与不孕类型、不孕年限、异位囊肿的位置等的关系亦不明确,均有待进一步研究。目的本研究旨在通过对EMT合并不孕患者临床资料的分析及随访,探讨其术后不同治疗方案的疗效,分析术后妊娠与不孕类别、不孕年限、EMT分期、异位囊肿的位置、术后辅助药物治疗等的关系,以求找到影响术后妊娠的因素。材料与方法选取2008年4月至2009年4月郑州大学第三附属医院收治的有生育要求的EMT患者215人,所有患者均接受腹腔镜下保留生育功能的手术治疗,其中180人完成随访,随访率83.72%,随访时时间36个月,患者年龄23岁～40岁,平均年龄(30.13±4.39)岁。完成随访的180例患者,按照不孕类别、不孕年限、r-AFS分期、术后是否使用抗EMT药物等分别分组,卵巢EMT患者按照囊肿侧别,是否合并盆腔粘连、腹膜内异灶、深部内异灶等进行分组,了解术后妊娠与各个因素的关系,并对各因素进行Logistic回归分析,以求找到影响术后妊娠的因素。结果1术后妊娠、症状缓解及复发情况完成随访的180例患者中,术后妊娠共123例,均为自然妊娠,总体妊娠率68.33%；123例妊娠患者中,102例妊娠至足月分娩(其中1例多发畸形),6例自然流产,4例异位妊娠,5例引产,足月分娩率90.24%。术后EMT总体复发率15.00%(27/180)；总体症状缓解率71.43%(75/105),其中疼痛症状彻底缓解率为68.09%(64/94),缓解后复发4例,另有2例术前无明显临床症状,术后出现痛经：月经紊乱症状缓解率为100%(11/11)。对妊娠的患者按照术后不同时间段(每年)分为A、B、C3组,术后妊娠率逐年下降,总体比较差异有统计学意义(χ2=26.410,P<0.05),两两比较差异均有统计学意义(χ2AB=6.254,P=0.012；χ2AC=24.719,P=0.001；χ2Bc=7.915,P=0.005).将术后2年内妊娠的患者按照术术后不同时间段(第6个月)分为a、b、c、d4组,妊娠率逐渐下降,总体比较差异有统计学意义(χ2=8.104,P<0.05),a、b、c3组的妊娠率比较差异无统计学意义(χ2=1.248,P=0.536),d组与a、b两组的妊娠率分别比较,差异均有统计学意义(χ2ad=7.601,P=0.006；χ2bd=5.675,P=0.017),d组与c组妊娠率比较,差异无统计学意义(χ2cd=2.817,P=0.093)。2妊娠相关因素的单因素分析结果2.1妊娠患者与未妊娠患者年龄的比较妊娠患者的平均年龄(29.11±3.71)岁,未妊娠患者平均年龄(32.41±4.84)岁,经t检验差异有统计学意义(t=5.006,P=0.001)。2.2原发不孕组与继发不孕组妊娠率的比较原发不孕组术后妊娠率51.72%(45/87),继发不孕术后妊娠率83.87%(78/93),继发不孕组术后妊娠率明显高于原发不孕组,差异有统计学意义(χ2=22.732,P<0.05)。2.3不孕年限对妊娠的影响比较妊娠患者和未妊娠患者的不孕年限,妊娠患者平均不孕年限(2.41±1.96)年,未妊娠患者平均不孕年限(3.58±3.79)年,经t检验二者无统计学差异(t=1.263,P=0.220)。将不孕在3年以内的患者合并为不孕3年以内组,不孕在3年以上患者合并为不孕3年以上组,比较妊娠率差异无统计学意义(χ2=3.170,P>0.05)。在原发不孕、继发不孕组内按照不孕年限再次分组,分别比较。原发不孕组中,不孕在3年以内的患者术后妊娠率为59.09%(39/66),不孕在3年以上的患者术后妊娠率28.57%(6/21),两者比较差异有统计学意义(χ2=5.943,P<0.05)；继发不孕组中,不孕在3年内的患者术后妊娠率为83.33%(60/72),不孕在3年以上的患者术后妊娠率为85.71%(18/21),两者比较差异无统计学意义(χ2=0.001,P>0.05)。比较不孕在3年以内的原发不孕患者与继发不孕患者的妊娠率,差异有统计学意义(χ2=9.982,P<0.05)。2.4不同分期患者术后妊娠率的比较根据r-AFS分期将患者分成4组,总体比较各组妊娠率差异无统计学意义(χ2=2.250,P>0.05)。2.5不同类型巧囊患者术后妊娠率的比较单纯巧克力囊肿患者妊娠率与巧囊合并盆腔粘连、腹膜EMT或深部EMT的患者妊娠率相比差异无统计学意义(χ2=0.263,P>0.05)。单侧巧囊患者妊娠率与双侧巧囊患者妊娠率相比差异无统计学意义(χ2=3.086,P>0.05)。单侧巧囊患者中,单纯左侧巧囊患者妊娠率与单纯右侧巧囊患者妊娠率比较差异无统计学意义(χ2=1.952,P>0.05)。2.6术后用药组与未用药组妊娠率的比较术后未用药组妊娠率71.23%,用药组妊娠率66.36%,两者比较差异无统计学意义(χ2=0.477,P>0.05)。3影响术后妊娠相关因素的Logistic回归分析将术后3年内是否妊娠作为应变量,对患者年龄、不孕类型、不孕年限、EMT分期、巧囊情况、术后是否用药6个因素进行Logistic回归分析。进入Logistic回归方程的自变量只有年龄、不孕类型,其他因素均被剔除。年龄越大术后妊娠的可能性越小,继发不孕术后妊娠的可能性是原发不孕的14.61倍,不孕年限、EMT分期、巧囊情况和术后用药与否对受孕没有显著影响。结论1手术是治疗子宫内膜异位症合并不孕症的有效手段,手术的彻底性是改善术后妊娠的关键。2术后1年是妊娠的最佳时机,随着术后时间的延迟,妊娠率明显下降。3患者年龄、不孕类别是影响术后妊娠的重要因素,术后辅助药物治疗不提高妊娠率,r-AFS分期、巧囊类型对预妊娠无明显影响。4原发不孕患者不孕年限越长,预后越差,继发不孕患者无论不孕年限长短,均能获得较高的妊娠率。更多还原

【Abstract】 Endometriosis, EMT for short, refers to the presence of functinal endometrial glands and stroma at various extrauterine sites in women. It is a common gynecologic disease which manifests a series of clinical symptoms and pathological changes. The major clinical manifestations include growing pelvic adhesion, pain, infertility, etc. Recent studies show that the incidence of EMT rises, especially for women of childbearing age, which has serious influence on women’s reproductive health. Infertility means that a couple have contraceptive sexual life more than one year but never get pregnant. It can be divided into Primary infertility and Secondary infertility according to the history of pregnancy. The incidence of infertility is7～10%in China, and about40%infertility is attributable to the women factors, in which25～35%suffered from EMT. Thus, they are highly correlated. So the term "Endometriosis-associated infertility" has been proposed by some scholars.Currently, surgery remains the major treatment for Endometriosis-associated infertility, as surgery would clear away endometriotic lesions, restore pelvic anatomy, and improve pelvic environment, and pregnancy rate will be improved as well.Revised classification of American Fertility Society partly reflects the severity of the disease and prognosis of EMT, but remains to be discussed in determination of prognosis. It is the gold standard of medical treatment after surgery, which has a positive effect on reducing the recurrence and relieving symptoms, but no consensus on patients with a fertility requirement has been arrived. Furthermore, there isn’t an explicit relationship between surgical effect and the time with infertility, the site of the cyst, etc., which needs further research.ObjectiveThe present study, through the analysis of clinical data and follow-up of EMT merger infertile patients, aims to discuss the curative effects with different treatments, find the relationship between pregnancy with infertility category, the time of infertility, r-AFS, site of the cyst, medical treatment after surgery, etc, to find the influence factors on pregnancy.Materials and Methods215patients with endometriosis and infertility who were treated by laparoscopic conservative operation in the Third affiliated Hospital of Zhengzhou University from April of2008to April of2009were selected,180of them from23years to40years old, with an average of (30.13±4.39) years, have been completed follow-up, and the follow-up rate is83.72%, follow-up lasted36months. The180patients completed follow-up were grouped by infertility category, time of infertility, r-AFS classification system and medical treatment after surgery. Ovary endometriosis were grouped in terms of site of cyst, weather or not combined with pelvic adhesion, peritoneal endometriosis, deep infiltrating endometriosis. The relationship between fertility with each factors were discussed respectively, and all factors were analyzed by multi-variate logistic regression.Results1General resultsIn all180patients,123got natural pregnancy after surgery, the overall pregnancy rate is68.33%. In the123cases of patients with pregnancy, we got102full term delivery,6spontaneous abortion,4ectopic pregnancy and4induced labour. Full-term delivery rate was90.24%. The postoperative recurrence rate was15%, the symptom remission rate was71.43%.64cases got complete pain relief among the total of94ones,4cases recurred after a remission. Another2cases who had no pain got a pain after surgery. Pain relief rate was68.09%. Paramenia of11cases were completely resolved.Postoperative pregnancy rate declined year by year, there was statistical significance among them (χ2=26.410, P<0.05). Pregnancy rate of the1st year was higher than the2nd year (P<0.05), pregnancy rate of the2nd year was higher than the3rd year (P<0.05). Patients who got pregnancy in two years postoperative were divided into four groups (a, b, c, d) every six months after surgery, there was statistical significance among them (χ2=8.104, P<0.05), but there was no statistical significance among group a, b and c (χ2=1.248, P=0.536). Further comparison shows that there were statistical significance between group a and d (χ2ad=7.601, P=0.006), b and d (χ2bd=5.675, P=0.017), but there was no statistical significance between group c and d (χ2cd=2.817, P=0.093).2Univariate analysis results of pregnancy related factors2.1The comparison of ageThe average age of the patients with pregnancy was (29.11±3.71) years, the average age of the patients without pregnancy was (32.41±4.84) years, there was statistical significance between the two(t=5.006, P=0.001).2.2Pregnancy rate in primary and secondary infertilityPregnancy rate of primary infertility group was51.72%, and83.87%in secondary infertility group, there was statistical significance between the two groups (χ2=22.732, P<0.05).2.3Pregnancy rate and duration of infertilityThe average duration of infertility of patients with pregnancy was (2.41±1.96) years, the average duration of infertility of patients without pregnancy was (3.58±3.79) years, there was no statistical significance between the two groups (t=1.263, P=0.220). All the patients were regrouped, there was no statistical significance between patients with the duration of infertility more than3years and patients with the duration of infertility less than3years (χ2=3.170, P>0.05). Patients in primary and secondary groups were divided by duration of infertility.In primary infertility group, there was statistical significance between patients with the duration of infertility more than3years and patients with the duration of infertility less than3years(χ2=5.943, P<0.05). In secondary infertility group, there was no statistical significance between patients with the duration of infertility more than3years and patients with the duration of infertility less than3years (χ2=0.001, P>0.05). There was statistical significance between primary infertility patients with the duration of infertility less than3years and secondary infertility patients with the duration of infertility less than3years (χ2=5.943, P<0.05).2.4Pregnancy rate at different stagesPregnancy rate were61.54%at stage I,78.57%at stage II,68.97%at stage III and64.10%at stage IV, there was no statistical significance among different stages(χ2=2.250, P>0.05).2.5Pregnancy rate in patients with endometrial cystThere was no statistical significance in pregnancy rate between patients with ovarian endometrial cysts only and patients with ovarian endometrial cysts combined with pelvic adhesion, peritoneal endometriosis or deep infiltrating endometriosis (χ2=0.263, P>0.05). There was no statistical significance in pregnancy rate between patients with endometrial cyst on one ovary only and patients with endometrial cyst on both side (χ2=3.086, P>0.05). There was no statistical significance in pregnancy rate between patients with endometrial cyst on left ovary only and patients with endometrial cyst on right ovary only (χ2-1.952, P>0.05).2.6Pregnancy rate and medical treatment after surgery Pregnancy rate of the medical treatment group was lower than no medical treatment group, but there was no statistical significance between the two groups (χ2=0.477,P>0.05).3Multi-variate logistic regressionPut pregnancy in3years after surgery as dependent variable, age, type of infertility, duration of infertility, stage of EMT, type of endometriosis cyst, medical treatment after sugery were selected factors, and the related factors of successful pregnancy were analyzed by multi-variate logistic regression. Age and type of infertility were the only two factors which were associated with pregnancy rate as shown by the logistic regression analysis. The pregnancy rate declined as the age increased. The possibility of pregnancy of secondary infertility was14.61times of primary infertility, while duration of infertility, stage of EMT, type of endometriosis cyst and medical treatment after sugery had no significant effect on conception.Conclusion1Surgery is an effective treatment for patients with endometriosis-associated infertility. The thoroughness of the surgery is the key to increase pregnancy rate.2The first year is the best time to pregnancy. With the time elapsed after surgery, pregnancy rate decreased significantly.3Age and type of infertility are factors associated with postoperative pregnancy rate. Medical treatment after surgery is of no use in increasing pregnancy rate. R-AFS classification, type of endometriosis cyst is of no significance in estimating prognosis.4The longer the time of patients with endometriosis-associated primary infertility, the worse the prognosis is. But all the patients with endometriosis-associated secondary infertility get good prognosis.更多还原