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論文名稱(外文):Comparison of two oral ovulation induction medicines infertile women treatment
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本實驗的目的在用分生及生化的方式去評估和比較不孕症婦女經由anastrozole 和 clomiphene citrate兩種不同排卵藥治療後的差異。在生化檢測方面,比較FSH、LH、T、E2、P4、MIS等荷爾蒙濃度,在分子層級上,我們評估了兩個基因,ㄧ個是會表現在懷孕子宮中的SPP1,一個是參與雌激素合成酵素的CYP19。
本研究共有33位不孕症婦女參與,其年齡範圍是25-41歲。首先我們利用電腦隨機方式將病人分成兩組,並從週期的第三到第七天分別給藥,一組每天給予1 mg 的anastrozole (Arimidex® aromatase inhibitor),另一組則給予100 mg的clomiphene citrate (clomid)。病人在週期的第3、8、10、AIH、21、28天抽血及測量成熟的濾泡 (≧ 18 mm) 數量和子宮內膜厚度。我們將抽出來的血液分成血清和血球,並從血清中測得各種荷爾蒙濃度 (FSH、LH、E2、T、P4、MIS);而血球部分,主要是將白血中的 RNA萃取出來,然後利用real time PCR方法分析CYP19 和 SPP1基因的表現。
我們將測得的數值分析後,兩組的基本生理值 (包含年齡、BMI、不孕期間)和週期第三天的荷爾蒙數值都是相似的( p>0.05),除了FSH之外( AI組4.3 mIU/mL,CC 組6.3 mIU/mL ; p<0.05 )。而排卵濾泡數目則是AI組較CC組少 (AI組1.2,CC組1.8 ; p<0.05),但AI組有較厚的子宮內膜 (AI組10.6 mm,CC組7.8 mm ; p< 0.05)。其中P4和T的濃度在兩組間很相似並沒有顯著差異。另外,AI組的LH和MIS都是顯著高於CC組,但E2則是顯著低於CC組。從分子分析的結果看,我們發現CYP19表現量在AI這組也顯著低於CC組,因為AI會抑制CYP19的表現,而SPP1基因有表現在正常人,但是不孕症婦女卻沒有表現,此結果顯示,SPP1也許是ㄧ個在子宮中跟αvb3 integrin或是其他細胞外蛋白質交互作用的重要的因子。
In this study, we evaluated and compared the ovulation stimulation by anastrozole and clomiphene citrate in women with infertility. A total of 33 infertile patients were enrolled, ages 25-41 years. Patients received either anastrozole 1 mg daily or clomiphene citrate 100 mg daily from cycle day 3 to day 7. Number of mature follicles (≧ 18 mm), endometrial thickness, and pregnancy rate were measured. Blood samples were taken on cycle day 3, day 8, day 10, AIH day, post-AIH day 7 (day 21), and post-AIH day 14 (day 28) for serial hormonal profiles (FSH, LH, E2, T, and P4) and gene expression analyses of CYP19 and SPP1 using real-time PCR.
The basic parameters were similar in two groups, including age, BMI, infertility duration and day 3 serum hormones expect FSH. The mean FSH value on day 3 was significantly different (4.3 mIU/mL in the AI group to 6.3 mIU/mL in the CC group; p<0.05 ). The anastrozole group had a fewer number of ovulatory follicles (1.2 in the AI group to 1.8 in the CC group; p<0.05) with a thicker endometrium (10.6 in the AI group to 7.8 mm in the CC group; p< 0.05 ). The level of progesterone and testosterone were similar during ovulation stimulation cycle in both groups. On the other hand, the anastrozole group has a significantly higher LH level, but a significantly lower estradiol level in the stimulation cycle. The result of molecular level showed that CYP19 expression were significantly 11 folds lower in AI group than CC group. In addition, SPP1 did not express in infertile women, but in normal control. It indicates that SPP1 may be an important factor contributing to uterine receptivity possibly by interaction with αvb3 integrin and/or other extracellular matrix proteins.
Anastrozole has high pregnant rate, though it induces less ovulatory follicles when comparing with clomiphene citrate. The effects of both drugs gave different response of FSH, LH and estradiol during stimulation.
摘要 Ⅰ
Abstract Ⅲ
誌謝 Ⅴ
前言 01
實驗目的 12
材料方法 13
結果 22
討論 27
參考文獻 34
附圖 39
附表 61
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