子宫内膜异位症不孕患者行IVF-ET的疗效分析及维生素E对该类患者的临床改善作用初探

发布时间：2018-03-01 18:22

本文关键词： 子宫内膜异位症体外受精-胚胎移植临床结局子宫内膜异位症氧化应激不孕维生素E 体外受精-胚胎移植　出处：《广州医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：研究背景子宫内膜异位症，简称为内异症，是指子宫内膜组织（腺体和间质）出现在子宫体以外的部位。内异症是一种激素依赖性疾病，可人为地应用药物和手术来减缓和暂停其发展。其在组织学上是良性的，但是在临床行为学上具有种植、侵袭及远处转移等类似恶性肿瘤的特点。主要临床表现是持续性加重的盆腔粘连、疼痛以及不孕。在育龄期妇女中患病率约为25%，其中21%~44%合并有不孕。子宫内膜异位症及其不孕症的相关发病机制尚未完全阐明，导致了对其治疗效果的不理想。一直以来，子宫内膜异位症及其所导致的不孕患者都是以手术及药物治疗为主，，随着辅助技术的发展与成熟，为该类患者带来了新的希望。但是在临床工作中发现，子宫内膜异位症不孕患者行辅助生殖技术的成功率仍不理想，这可能与子宫内膜异位症对盆腔结构、卵巢功能、排卵功能、卵子质量、精卵结合能力、胚胎质量以及子宫内膜和相关环境的影响均具有一定的关系。为了进一步阐明子宫内膜异位症不孕患者的发病机制，了解该类患者行辅助生殖技术的成功率偏低的原因，氧化应激在子宫内膜异位症中的作用受到了越来越多的关注。氧化应激与多种机体疾病的发生发展密不可分，其在不孕患者行辅助生殖中所起的作用与子宫内膜异位症在不孕患者所起作用有相似之处。近年来，对于氧化应激在内异症患者中所起的作用也得到了多方面研究的证实。维生素E作为一种众所周知的抗氧化物质，被广泛应用到农业与生活中，但是其在辅助生殖技术领域的应用仍未得到广泛认可。对于维生素E的剂量及用药时间仍然存在争议。本课题将探讨子宫内膜异位症的严重程度对IVF-ET的影响，了解内异症可能从哪些方面影响不孕患者行IVF-ET的成功率；另外，利用维生素E的抗氧化作用降低内异症不孕患者体内的氧化应激水平，探讨其在临床应用的前景。研究内容第一部分子宫内膜异位症不孕患者行IVF-ET结局分析研究目的探讨子宫内膜异位症对IVF-ET的影响，初步分析内异症的严重程度从哪些方面影响该类患者行IVF-ET结局。研究方法收集2012年1月至2013年12月期间在广东省妇幼保健院生殖健康与不孕症科接受IVF-ET治疗的子宫内膜异位症不孕患者92例。IVF治疗前均进行腹腔镜或开腹手术确定子宫内膜异位症的分期。按内异症的不同分期把研究对象分为两组，A组（65例）为子宫内膜异位症Ⅰ、Ⅱ期患者，B组（27例）为Ⅲ、Ⅳ期患者。研究对象均为首次接受IVF-ET治疗，术前B超未提示内异症复发并排除多囊卵巢综合征等其他全身内分泌疾病。C组（154例）为随机选取的同时期因双侧输卵管阻塞行IVF-ET的患者，排除多囊卵巢综合征等其他全身内分泌疾病。所有研究对象均进行IVF-ET的控制性超排卵长方案治疗，比较各组间的基本背景、超促排卵情况和临床结局指标。研究结果应用SPSS19.0统计学软件包进行统计学分析。各组均数之间采用t检验，各组率的比较采用卡方检验。P值0.05为差异有统计学意义。研究结果 1.各组不孕患者的年龄、不孕年限、基础FSH、LH和E2水平均无统计学意义（P0.05）。 2.各组在超促排卵过程中，HCG日E2水平及移植日内膜厚度均无明显差异；而随着内异症病情的加重，Gn用量和Gn时间呈现增加趋势、获卵数则逐渐减少，其中B组的Gn用量及获卵数较C组有明显改变，有统计学意义（P0.05）。 3.A组及B组分别与对照组比较，两组患者行IVF-ET的受精率、优质胚胎率、种植率及临床妊娠率都有减少，但是差异无统计学差异（P0.05）。研究结论 1.子宫内膜异位症患者不孕的原因可能主要是异位病灶影响了患者的机体内环境； 2.IVF-ET是有效的提高该类患者的妊娠机会的技术，但其行IVF-ET的成功率较输卵管因素的偏低。第二部分维生素E对内异症不孕患者行IVF-ET的效果探讨研究目的探讨维生素E对子宫内膜异位症不孕患者行IVF-ET的治疗效果，为其临床应用提供理论依据。研究方法选取于2013年8月至2014年2月在广东省妇幼保健院生殖健康与不孕症科行IVF-ET的子宫内膜异位症患者作为研究对象进行前瞻性病例对照研究。研究对象均为经开腹手术或者腹腔镜手术证实为Ⅰ、Ⅱ期子宫内膜异位症患者，IVF-ET术前检查未发现内异症复发及排除子宫腺肌症患者。其中给予维生素E的子宫内膜异位症患者作为研究组，没有给予维生素E的子宫内膜异位症患者作为对照组。所有研究对象均采用黄体中期降调节长方案，于取卵日收集两组患者外周静脉血及卵泡液，采用比色法、黄嘌呤氧化酶法(羟胺法)及化学荧光法分别测定两组患者血清及卵泡液中的维生素E（VE）、超氧化物歧化酶（SOD）及活性氧簇（ROS）的水平。比较两组间的临床结局以及上述氧化应激指标与临床结局的相关性。研究结果应用SPSS19.0统计学软件包对实验数据进行统计学分析。计数资料采用卡方检验，计量资料采用独立样本t检验，实验数据与临床评价指标间行相关性分析，用Spearman相关系数表示。P0.05为差异有统计学意义。结果 1.研究组血清及卵泡液中的VE含量较对照组血清及卵泡液中的VE含量显著增高，有统计学意义（P0.05），研究组中SOD以及ROS水平较对照组水平无明显改变，无统计学意义（P0.05）。 2.研究组与对照组中，VE的水平在血清中较卵泡液中明显增高，SOD的水平在卵泡液中较血清中明显增高，有统计学差异（P0.05）。 3.研究组与对照组之间的平均获卵数以及临床妊娠率均无统计学意义（P0.05）。对照组的受精率及优质胚胎率较研究组高，研究组的种植率较对照组高，但是均无统计学意义（P0.05）。 4.对照组中将血清和卵泡液中的VE、SOD和ROS水平与IVF-ET结局评价指标进行相关性分析发现血清和卵泡液中ROS水平与IVF-ET结局评价指标呈负相关趋势，其中在卵泡液中ROS的水平与种植率呈负相关，有统计学意义（P0.05）。但是发现SOD与结局评价指标呈负相关趋势。研究组中，ROS在血清中与IVF-ET结局评价指标基本上呈现负相关趋势，但均无统计学差异（P0.05）。总体来说，对照组与研究组VE、SOD及ROS与IVF-ET结局评价指标的相关性不大。结论子宫内膜异位症不孕患者体内存在氧化应激，通过损害全身或者卵泡局部环境，继而影响行IVF-ET的结局；添加维生素E对于子宫内膜异位症不孕患者行IVF-ET的疗效不明确，可能与维生素E的原氧化性质有关，添加维生素E的剂量与用药时间仍需进一步完善。
[Abstract]:Research background
Endometriosis, referred to as endometriosis, refers to endometrial tissue (glands and stroma) in uterine tissue outside. Endometriosis is a hormone dependent disease, can be used for medicine and surgery to slow down and suspend its development. It is benign in histology, but in the clinical behavior of planting, similar to the characteristics of malignant invasion and distant metastasis of tumor. The main clinical manifestations of pelvic adhesions is durative accentuation, pain and infertility. The prevalence rate is about 25% in women of childbearing age, including 21%~44% infertility. The pathogenesis of endometriosis and infertility have not been fully elucidated and the cause of its treatment effect is not ideal. All the time, endometriosis and infertility are caused by surgery and drug therapy, with the development of assistive technology and mature, for this kind of patients Bring new hope. But in clinical work, is still not ideal of infertile patients with endometriosis for assisted reproductive technology success rate, which may be related to endometriosis of pelvic structure, ovarian function, ovulation, egg quality, sperm egg binding capacity, effect of embryo quality and endometrial and related environment have certain relationship. In order to further elucidate the pathogenesis of endometriosis infertility patients, the patients understand the reasons for the low success rate of assisted reproductive technology, role of oxidative stress in endometriosis has attracted more and more attention. Oxidative stress and various body disease development are inseparable, the in the patients with infertility for assisted reproduction and the role of endometriosis in the patients with infertility effects are similar. In recent years, the oxidative stress, The different patients function also obtained the various research confirmed. Vitamin E as an antioxidant as everyone knows, is widely used in agriculture and life, but its application in the field of assisted reproductive technology has not been widely recognized. Controversy still exists for the dosage and medication time of vitamin E.
This paper will discuss the influence of the severity of endometriosis on IVF-ET, endometriosis may understand from what influence the success rate of IVF-ET for patients with infertility; in addition, reduce the level of oxidative stress in patients with infertility of endometriosis using vitamin E antioxidant effect and explore its clinical application in the future.
research contents
Analysis of IVF-ET outcome in the first part of endometriosis infertile patients
research objective
To investigate the effect of endometriosis on IVF-ET, and to analyze the effect of the severity of endometriosis on the IVF-ET outcome in this type of patients.
research method
During the period from January 2012 to December 2013 in IVF-ET treated in Guangdong Provincial Maternity and Child Care Center of reproductive health and infertility of endometriosis and 92 cases of.IVF patients before treatment were performed laparotomy or laparoscopic staging of endometriosis endometriosis. According to the different stages of the study subjects were divided into two groups, A group (65 cases) for endometrial endometriosis I and II patients, B group (27 cases) for III and IV patients. The subjects were first treated with IVF-ET, preoperative ultrasonography showed no recurrence of endometriosis and exclusion of polycystic ovary syndrome and other body endocrine disorders in.C group (154 cases) were randomly selected at the same period due to bilateral fallopian tube obstruction in IVF-ET patients, exclusion of polycystic ovary syndrome and other endocrine diseases. All subjects were controlled IVF-ET superovulation long treatment, basic back between groups were compared The ovulation and clinical outcome were investigated. The results of the study were statistically analyzed by SPSS19.0 statistical software package. The t test was used to calculate the mean between the 0.05 groups. The chi square test and the.P value of each group were compared with each other. The difference was statistically significant.
Research results
1. the age, infertile years, basic FSH, LH and E2 levels were not statistically significant (P0.05) in all groups of infertile patients.
In the 2. groups during COH, there were no significant difference between the HCG and E2 levels on endometrial thickness and transplantation; with the aggravation of endometriosis disease, dosage of Gn and Gn increased, the number of oocytes is gradually reduced, the amount of Gn in the B group and the number of oocytes than in the C group have obvious change there was statistical significance (P0.05).
3.A group and B group were compared with the control group, the two groups of patients IVF-ET fertilization rate, quality embryo rate, implantation rate and clinical pregnancy rate all decreased, but the difference was not statistically significant (P0.05).
research conclusion
1. the causes of infertility in patients with endometriosis may be mainly due to the effect of ectopic focus on the patient's internal environment.
2.IVF-ET is an effective technique to improve the chances of pregnancy in this type of patient, but the success rate of IVF-ET is lower than that of the fallopian tube factor.
The effect of the second part of vitamin E on IVF-ET in infertile patients with endometriosis
research objective
To investigate the effect of vitamin E on the treatment of endometriosis infertile patients with IVF-ET, and provide a theoretical basis for its clinical application.
research method
From August 2013 to February 2014 in Guangdong Provincial Maternity and Child Care Center Department of reproductive health and infertility in IVF-ET patients with endometriosis as the research object for prospective case-control study. The subjects were underwent open surgery or laparoscopic surgery confirmed I, II patients with endometriosis, IVF-ET preoperative examination showed no recurrence of endometriosis and uterus exclusion the patients with adenomyosis. The vitamin E given endometriosis patients as the study group, not given vitamin E in endometriosis patients as the control group. All subjects were using the mid luteal phase falling day long program, the two groups were collected peripheral venous blood and follicular fluid on the day of oocyte retrieval by colorimetric by the method of xanthine oxidase (hydroxylamine) two groups of serum and follicular fluid of patients with vitamin E in the determination of fluorescence and chemical method respectively (VE), superoxide dismutase Enzyme (SOD) and reactive oxygen species (ROS) level. The clinical outcomes were compared between the two groups and the correlation between oxidative stress indexes and clinical outcomes. Results using SPSS19.0 statistical software package was used for statistical analysis of experimental data. Count data using chi square test, measurement data using independent samples t test, correlation analysis of the experimental data and clinical evaluation index, using Spearman correlation coefficient.P0.05 difference was statistically significant.
Result
1. the content of VE in serum and follicular fluid of the study group was significantly higher than that of the control group in serum and follicular fluid VE (P0.05). The level of SOD and ROS in the study group did not change significantly compared with that in the control group, with no statistical significance (P0.05).
2. in the study group and the control group, the level of VE increased significantly in serum than follicular fluid, and the level of SOD in follicular fluid was significantly higher than that in serum (P0.05).
3., the average number of eggs and clinical pregnancy rate between the study group and the control group were not statistically significant (P0.05). The fertilization rate and quality embryo rate in the control group were higher than those in the study group, and the implantation rate in the study group was higher than that in the control group, but there was no statistical significance (P0.05).
4. in the control group, serum and follicular fluid in VE, SOD and ROS levels and IVF-ET outcome evaluation index correlation analysis found that ROS levels and outcome of IVF-ET in serum and follicular fluid index was negatively correlated with the level of trend, planted in the follicular fluid of ROS was negatively correlated, with statistical significance (P0.05). But SOD and outcome evaluation index was negatively correlated. In the study group, the serum ROS in IVF-ET evaluation and outcome basically shows a negative trend, but there were no significant differences (P0.05). In general, the control group and study group VE, SOD and ROS have little relevance to the outcome of IVF-ET and the evaluation index.
conclusion
Oxidative stress of infertile patients with endometriosis in vivo, by systemic or local environmental damage follicle IVF-ET, thereby affecting the outcome; effect of adding vitamin E for endometriosis infertility patients with IVF-ET is not clear, may be related to the original oxidation properties and vitamin E, dosage and medication time of adding vitamin E still need further perfect.

【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.71

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