本文選題：來曲唑 + 多囊卵巢綜合征�。� 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：多囊卵巢綜合征(polycystic ovarian syndrome,PCOS)作為常見的婦科內(nèi)分泌疾病,其多發(fā)年齡為17-46歲,流行病學(xué)調(diào)查顯示其發(fā)病率為6-10%,是育齡婦女月經(jīng)失調(diào)、閉經(jīng)及不孕最常見的原因,占排卵障礙不孕患者中的50-70%,促排卵治療是治療PCOS患者不孕的重要方法,目前臨床上常用的促排卵藥物有克羅米芬(Clomiphene Citrate,CC)、促性腺激素(gonadotropins,Gn)藥物及來曲唑(letrozole,LE),因CC及促性腺激素應(yīng)用時存在妊娠率低、卵巢過度刺激綜合征等明顯缺陷,LE逐漸成為一線藥物,本研究旨在證實LE促排卵效果,并探討LE的最佳用法,為更好的使用LE提供依據(jù)。目的:使用不同劑量LE對PCOS患者進(jìn)行促排卵治療,觀察其在卵泡發(fā)育不同階段對雌激素水平、子宮內(nèi)膜厚度及分型、卵泡發(fā)育個數(shù)、排卵率及妊娠率的影響,分析各變量之間的相關(guān)性;通過與正常人群比較,明確兩者之間有無差異并分析原因,以探討LE在PCOS患者促排卵治療的最佳劑量。方法:選取2016年1月至2016年10月于承德市中心醫(yī)院生殖醫(yī)學(xué)中心就診的PCOS并應(yīng)用LE促排卵治療的患者80例,隨機(jī)分為2.5mg及5mg兩個實驗組。同時選取排卵功能正常婦女40例為對照組。所有研究對象均于月經(jīng)的第3天經(jīng)陰道B超觀察子宮內(nèi)膜厚度,測定雌二醇水平。實驗組給予LE2.5及5mg/d,均連用5天,對照組不予干預(yù)。連續(xù)監(jiān)測卵泡發(fā)育情況及子宮內(nèi)膜厚度、分型并觀察卵泡發(fā)育個數(shù),分別于優(yōu)勢卵泡10-12mm,14-16mm,18-20mm時測定雌二醇(Estradiol,E2)水平,待B超監(jiān)測到1個成熟卵泡(卵泡直徑≥20mm)時誘發(fā)排卵,當(dāng)日及次日同房。排卵后14天如血清人絨毛膜促性腺激素水平陽性,1周后行陰道超聲檢查,陰道超聲提示宮內(nèi)孕囊或?qū)m外孕囊,診斷臨床妊娠。如血清人絨毛膜促性腺激素水平逐漸轉(zhuǎn)陰,診斷生化妊娠。研究數(shù)據(jù)應(yīng)用SPSS19.0統(tǒng)計軟件進(jìn)行分析。計量數(shù)據(jù)用χ±s表示,采用方差分析進(jìn)行比較。計數(shù)資料采用百分比表示,應(yīng)用卡方檢驗分別進(jìn)行比較。當(dāng)P0.05時認(rèn)為有統(tǒng)計學(xué)差異。結(jié)果:1雌激素水平及子宮內(nèi)膜厚度、分型比較:在課題設(shè)定的三個觀察時間窗內(nèi),LE2.5mg組及5mg組在雌激素水平及子宮內(nèi)膜厚度上均低于對照組,有統(tǒng)計學(xué)差異(P0.01)。在兩個實驗組間比較中顯示:在優(yōu)勢卵泡10-12mm時,5.0mg組雌激素水平低于2.5mg組,有統(tǒng)計學(xué)差異,P0.05;LE5.0mg組子宮內(nèi)膜厚度與2.5mg組比較無統(tǒng)計學(xué)差異。在優(yōu)勢卵泡14-16mm時,5.0mg組雌激素水平及子宮內(nèi)膜厚度均低于2.5mg組,有統(tǒng)計學(xué)差異,P0.05。在優(yōu)勢卵泡18-20mm時,5.0mg組在雌激素水平及子宮內(nèi)膜厚度較2.5mg組無統(tǒng)計學(xué)差異。HCG日內(nèi)膜分型:三組均未見C型子宮內(nèi)膜,A、B型子宮內(nèi)膜三組之間比較無統(tǒng)計學(xué)差異。2卵泡發(fā)育個數(shù)、卵泡成熟時間、排卵率及妊娠率比較:卵泡發(fā)育個數(shù):對照組、2.5mg組均為單卵泡發(fā)育,5.0mg組單卵泡發(fā)育90%,2個卵泡發(fā)育7.5%,≥3個卵泡發(fā)育2.5%,與對照組及2.5mg組比較有統(tǒng)計學(xué)差異,P0.05;卵泡發(fā)育時間:對照組與2.5mg組及5mg組比較均存在統(tǒng)計學(xué)差異,P0.01;2.5mg組與5mg組比較存在統(tǒng)計學(xué)差異,P0.05。排卵率:對照組排卵率較LE2.5mg組高,有統(tǒng)計學(xué)差異,P0.05。對照組排卵率較LE5mg組高,LE5mg組較LE2.5mg組排卵率高,但均無統(tǒng)計學(xué)差異。妊娠率:對照組、LE2.5mg及5mg組之間比較均無統(tǒng)計學(xué)差異。結(jié)論:在促排卵治療過程中,LE對體內(nèi)雌激素水平的下降作用是十分明顯的,早期過低的雌激素導(dǎo)致子宮內(nèi)膜增生達(dá)不到正常水平,LE5mg組影響更大,停藥后由于優(yōu)勢卵泡大量分泌內(nèi)源性雌激素,導(dǎo)致體內(nèi)雌激素水平快速回升,排卵前LE2.5mg組及5mg組在雌激素水平及子宮內(nèi)膜厚度已無統(tǒng)計學(xué)差異,但仍低于對照組。LE2.5mg組及5mg組在HCG日均為A、B型子宮內(nèi)膜,與對照組無差異,說明LE對子宮內(nèi)膜形態(tài)無明顯影響。LE2.5mg組及5.0mg組卵泡發(fā)育時間均短于對照組,5.0mg組更短,說明LE抑制雌激素,繼發(fā)FSH升高,有促進(jìn)卵泡成熟作用。對照組及LE2.5mg組均為單卵泡發(fā)育,5.0mg組多卵泡發(fā)育比例升高,說明過高的FSH會導(dǎo)致多個卵泡同時發(fā)育。LE5mg組的排卵效果優(yōu)于2.5mg組,已達(dá)到對照組水平,應(yīng)用LE的妊娠率比正常人群已無統(tǒng)計學(xué)差異。所以LE促排卵治療的效果是確切的,雖然應(yīng)用LE對雌激素水平及子宮內(nèi)膜均有抑制作用,但是已經(jīng)達(dá)到胚胎著床的要求,所以妊娠率較對照組已無統(tǒng)計學(xué)差異,因為LE5mg組有著更高的排卵率,所以應(yīng)為臨床首選劑量,但需注意可能多妊娠發(fā)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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R711.75

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相關(guān)期刊論文 前6條

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