来曲唑对多囊卵巢综合征患者子宫内膜厚度、分型及性激素水平影响

发布时间：2018-07-06 07:08

本文选题：来曲唑 + 多囊卵巢综合征　；参考：《河北医科大学》2017年硕士论文

【摘要】：多囊卵巢综合征(polycystic ovarian syndrome,PCOS)作为常见的妇科内分泌疾病,其多发年龄为17-46岁,流行病学调查显示其发病率为6-10%,是育龄妇女月经失调、闭经及不孕最常见的原因,占排卵障碍不孕患者中的50-70%,促排卵治疗是治疗PCOS患者不孕的重要方法,目前临床上常用的促排卵药物有克罗米芬(Clomiphene Citrate,CC)、促性腺激素(gonadotropins,Gn)药物及来曲唑(letrozole,LE),因CC及促性腺激素应用时存在妊娠率低、卵巢过度刺激综合征等明显缺陷,LE逐渐成为一线药物,本研究旨在证实LE促排卵效果,并探讨LE的最佳用法,为更好的使用LE提供依据。目的:使用不同剂量LE对PCOS患者进行促排卵治疗,观察其在卵泡发育不同阶段对雌激素水平、子宫内膜厚度及分型、卵泡发育个数、排卵率及妊娠率的影响,分析各变量之间的相关性;通过与正常人群比较,明确两者之间有无差异并分析原因,以探讨LE在PCOS患者促排卵治疗的最佳剂量。方法:选取2016年1月至2016年10月于承德市中心医院生殖医学中心就诊的PCOS并应用LE促排卵治疗的患者80例,随机分为2.5mg及5mg两个实验组。同时选取排卵功能正常妇女40例为对照组。所有研究对象均于月经的第3天经阴道B超观察子宫内膜厚度,测定雌二醇水平。实验组给予LE2.5及5mg/d,均连用5天,对照组不予干预。连续监测卵泡发育情况及子宫内膜厚度、分型并观察卵泡发育个数,分别于优势卵泡10-12mm,14-16mm,18-20mm时测定雌二醇(Estradiol,E2)水平,待B超监测到1个成熟卵泡(卵泡直径≥20mm)时诱发排卵,当日及次日同房。排卵后14天如血清人绒毛膜促性腺激素水平阳性,1周后行阴道超声检查,阴道超声提示宫内孕囊或宫外孕囊,诊断临床妊娠。如血清人绒毛膜促性腺激素水平逐渐转阴,诊断生化妊娠。研究数据应用SPSS19.0统计软件进行分析。计量数据用χ±s表示,采用方差分析进行比较。计数资料采用百分比表示,应用卡方检验分别进行比较。当P0.05时认为有统计学差异。结果:1雌激素水平及子宫内膜厚度、分型比较:在课题设定的三个观察时间窗内,LE2.5mg组及5mg组在雌激素水平及子宫内膜厚度上均低于对照组,有统计学差异(P0.01)。在两个实验组间比较中显示:在优势卵泡10-12mm时,5.0mg组雌激素水平低于2.5mg组,有统计学差异,P0.05;LE5.0mg组子宫内膜厚度与2.5mg组比较无统计学差异。在优势卵泡14-16mm时,5.0mg组雌激素水平及子宫内膜厚度均低于2.5mg组,有统计学差异,P0.05。在优势卵泡18-20mm时,5.0mg组在雌激素水平及子宫内膜厚度较2.5mg组无统计学差异。HCG日内膜分型:三组均未见C型子宫内膜,A、B型子宫内膜三组之间比较无统计学差异。2卵泡发育个数、卵泡成熟时间、排卵率及妊娠率比较:卵泡发育个数:对照组、2.5mg组均为单卵泡发育,5.0mg组单卵泡发育90%,2个卵泡发育7.5%,≥3个卵泡发育2.5%,与对照组及2.5mg组比较有统计学差异,P0.05;卵泡发育时间:对照组与2.5mg组及5mg组比较均存在统计学差异,P0.01;2.5mg组与5mg组比较存在统计学差异,P0.05。排卵率:对照组排卵率较LE2.5mg组高,有统计学差异,P0.05。对照组排卵率较LE5mg组高,LE5mg组较LE2.5mg组排卵率高,但均无统计学差异。妊娠率:对照组、LE2.5mg及5mg组之间比较均无统计学差异。结论:在促排卵治疗过程中,LE对体内雌激素水平的下降作用是十分明显的,早期过低的雌激素导致子宫内膜增生达不到正常水平,LE5mg组影响更大,停药后由于优势卵泡大量分泌内源性雌激素,导致体内雌激素水平快速回升,排卵前LE2.5mg组及5mg组在雌激素水平及子宫内膜厚度已无统计学差异,但仍低于对照组。LE2.5mg组及5mg组在HCG日均为A、B型子宫内膜,与对照组无差异,说明LE对子宫内膜形态无明显影响。LE2.5mg组及5.0mg组卵泡发育时间均短于对照组,5.0mg组更短,说明LE抑制雌激素,继发FSH升高,有促进卵泡成熟作用。对照组及LE2.5mg组均为单卵泡发育,5.0mg组多卵泡发育比例升高,说明过高的FSH会导致多个卵泡同时发育。LE5mg组的排卵效果优于2.5mg组,已达到对照组水平,应用LE的妊娠率比正常人群已无统计学差异。所以LE促排卵治疗的效果是确切的,虽然应用LE对雌激素水平及子宫内膜均有抑制作用,但是已经达到胚胎着床的要求,所以妊娠率较对照组已无统计学差异,因为LE5mg组有着更高的排卵率,所以应为临床首选剂量,但需注意可能多妊娠发生率升高。
[Abstract]:Polycystic ovarian syndrome (PCOS), as a common gynecologic endocrine disease, has a multiple age of 17-46 years. Epidemiological investigation shows that its incidence is 6-10%. It is the most common cause of menstrual disorder, amenorrhea and infertility in women of childbearing age, accounting for 50-70% in patients with ovulatory hindrance. The treatment of ovulation promoting is the treatment of PCOS patients. The important methods of infertility are Clomiphene Citrate (CC), gonadotropins (Gn) and letrozole (LE). There are obvious defects in the application of CC and gonadotropin, such as low pregnancy rate, ovarian hyperstimulation syndrome and so on. LE is gradually becoming a first-line drug. The purpose of this study was to confirm the effect of LE ovulation, and to explore the best use of LE to provide the basis for better use of LE. Objective: to use different doses of LE to promote ovulation in PCOS patients, and to observe the effects on the level of estrogen, the thickness and type of endometrium, the number of follicle development, the rate of ovulation and pregnancy rate in different stages of follicle development. The correlation between the quantity and the normal population was compared to determine the difference between the two and analyze the reasons for the best dosage of LE in the treatment of ovulation for PCOS patients. Methods: 80 cases of PCOS in the center for reproductive medicine in the Center Hospital of Yu Chengde from January 2016 to October 2016 were selected and the patients were treated with LE to promote ovulation, and were randomly divided into 2 .5mg and 5mg two experimental groups. At the same time, 40 patients with normal ovulation were selected as the control group. All the subjects were observed the endometrium thickness and the estradiol level by vaginal ultrasound on third days of menstruation. The experimental group was given LE2.5 and 5mg/d for 5 days, and the control group did not intervene. The number of follicular development was observed and the levels of estradiol (Estradiol, E2) were measured at 10-12mm, 14-16mm and 18-20mm of the dominant follicles. 1 mature follicles (follicle diameter > 20mm) were monitored to induce ovulation at the same day and the next day. After 14 days of ovulation, the level of human chorionic gonadotropin was positive after 14 days of ovulation, and the transvaginal ultrasound examination was performed after 1 weeks. Intrauterine gestation sac or extrauterine gestation sac was diagnosed by vaginal ultrasound to diagnose clinical pregnancy. Such as serum human chorionic gonadotropin (hCG) level gradually turned negative to diagnosis of biochemical pregnancy. The data were analyzed by SPSS19.0 software. The measurement data were expressed by chi square s and the ratio of variance analysis was compared. The results were compared. Results: there were statistical differences when P0.05. Results: 1 estrogen level and endometrium thickness were compared. In the three observation time windows, the estrogen level and the thickness of endometrium in group LE2.5mg and 5mg were lower than those in the control group (P0.01). The comparison between the two experimental groups was significant. In the dominant follicle 10-12mm, the estrogen level in group 5.0mg was lower than that in group 2.5mg, with statistical difference, P0.05. The endometrial thickness of group LE5.0mg was not significantly different from that of the 2.5mg group. In the dominant follicle 14-16mm, the estrogen level and the thickness of the endometrium in the 5.0mg group were lower than those in the 2.5mg group, with a statistically significant difference, P0.05. in the dominant follicle 18-20mm, 5 The estrogen level and endometrial thickness in group mg were not statistically different from group 2.5mg in group.HCG: no C endometrium was found in three groups. There was no statistical difference in the number of.2 follicles between groups of A, B type endometrium, follicle maturation time, ovulation rate and pregnancy rate: the number of follicle development: the control group and 2.5mg group were single follicles. Development, 5.0mg group single follicle developed 90%, 2 follicles developed 7.5%, more than 3 follicles developed 2.5%, compared with the control group and the 2.5mg group, there were statistical differences, P0.05, follicle development time: the control group and 2.5mg group and 5mg group were statistically different, P0.01; 2.5mg group and 5mg group had statistical difference, P0.05. ovulation rate: control group ovulation rate Compared with the LE2.5mg group, there were statistical differences. The ovulation rate in the P0.05. control group was higher than that in the LE5mg group, and the ovulation rate in the LE5mg group was higher than that in the LE2.5mg group, but there was no statistical difference. The pregnancy rate was not statistically different between the control group and the LE2.5mg and 5mg groups. Conclusion: in the process of ovulation promoting, LE has a very obvious effect on the decrease of estrogen level in the body. The early low estrogen causes the endometrial hyperplasia to not reach the normal level, the LE5mg group has greater influence. The estrogen level in the body increases rapidly after the withdrawal of the dominant follicle, which leads to the rapid recovery of the estrogen level in the body. There is no statistical difference between the LE2.5mg group and the 5mg group before ovulation in the estrogen level and the internal membrane thickness of the uterus, but it is still lower than the control group. Group.LE2.5mg and group 5mg had A, B type endometrium, and no difference from the control group at HCG, indicating that LE had no obvious influence on the morphology of endometrium in the.LE2.5mg group and 5.0mg group, and the 5.0mg group was shorter than the control group, and the 5.0mg group was shorter, indicating that LE inhibited estrogen, the secondary FSH increased, and the follicle ripening was promoted. Both the control group and the LE2.5mg group were single follicles. Development, the proportion of multiple follicles in the 5.0mg group increased, indicating that excessive FSH could lead to multiple follicles in the.LE5mg group and the ovulation effect was superior to that of the 2.5mg group, which had reached the level of the control group. The pregnancy rate of LE was no statistically different than that of the normal group. Therefore, the effect of LE for ovulation promotion was accurate, although LE was applied to estrogen levels and children. The endometrium has a inhibitory effect, but it has reached the requirements of the implantation of the embryo, so the pregnancy rate has no statistical difference compared with the control group, because the LE5mg group has a higher rate of ovulation, so it should be the first choice of clinical dose, but it is necessary to pay more attention to the possibility of increasing the incidence of multiple pregnancies.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.75

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