本文選題：抑制素B + 體外受精-胚胎移植術(shù)�。� 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:抑制素B(inhibin B,INHB)是由α及β(B型)亞單位構(gòu)成的異源二聚體糖蛋白激素,屬于轉(zhuǎn)化生長(zhǎng)因子β(transforming growth factor-β,TGF-β)超家族的多功能細(xì)胞生長(zhǎng)因子。在卵巢組織,INHB主要由中、小竇卵泡顆粒細(xì)胞分泌,顆粒細(xì)胞分泌的INHB可通過(guò)內(nèi)分泌機(jī)制特異性作用于腦垂體反饋性抑制促性腺激素(follicular stimulation hormone,FSH)分泌,同時(shí)還可通過(guò)自/旁分泌作用增加雌激素(estrogen,E2)底物產(chǎn)生進(jìn)而調(diào)節(jié)E2的生成,INHB的這種經(jīng)典的內(nèi)分泌及自/旁分泌作用,在卵泡發(fā)生、發(fā)育、選擇和成熟等過(guò)程中均起到重要作用。本實(shí)驗(yàn)通過(guò)對(duì)不同控制性超促排卵(controlled ovarian hyperstimu-lation,COH)方案中不同時(shí)間節(jié)點(diǎn)的血清及取卵日不同大小卵泡中抑制素B(inhibin B,INHB)水平進(jìn)行檢測(cè)并與COH結(jié)局進(jìn)行相關(guān)分析,進(jìn)而探討不同COH方案中血清及卵泡液(follicular fluid,FF)中INHB動(dòng)態(tài)變化過(guò)程及其與COH結(jié)局的相關(guān)性。方法:1研究對(duì)象2015.7~2015.12月主因輸卵管因素和/或男方因素在石家莊白求恩國(guó)際和平醫(yī)院生殖中心首次接受IVF/ICSI-ET助孕的76例患者,將其隨機(jī)分為長(zhǎng)方案組(38例)及非降調(diào)方案組(38例)。納入標(biāo)準(zhǔn):年齡35歲;雙側(cè)卵巢AFC共10-20個(gè);體重指數(shù)18-25kg/m2;月經(jīng)周期26-35天;基礎(chǔ)激素水平正常;雙側(cè)卵巢無(wú)手術(shù)史;無(wú)其他內(nèi)分泌疾病,近6個(gè)月內(nèi)未應(yīng)用過(guò)激素類(lèi)藥物。排除標(biāo)準(zhǔn):高泌乳素血癥;PCOS;子宮內(nèi)膜異位癥。所有受試者均經(jīng)醫(yī)院倫理委員會(huì)批準(zhǔn),簽署知情同意書(shū)。2 COH方案2.1短效長(zhǎng)方案治療前一周期的黃體中期皮下注射促性腺激素釋放激素激動(dòng)劑(gonadotropin-releasing hormone agonist,Gn RH-a)達(dá)菲林(注射用醋酸曲普瑞林,0.1mg/支,法國(guó)益普生)0.1mg/d至月經(jīng)第3天起檢測(cè)血清雌二醇(estrogen,E2)、孕酮(progesterone,P)、黃體生成素(luteinzing hormone,LH)、促卵泡生成素(follicular stimulation hormone,FSH)并超聲監(jiān)測(cè)降調(diào)情況,達(dá)降調(diào)標(biāo)準(zhǔn)后(E250pg/ml,P2ng/ml,LH5m IU/ml,FSH5m IU/ml;B超顯示無(wú)直徑大于10mm的卵泡,子宮內(nèi)膜5mm,無(wú)功能性囊腫)改皮下注射達(dá)菲林0.05mg/d,同時(shí)給予促性腺激素(gonadotropins,Gn)75-300IU/d直至扳機(jī)日。當(dāng)B超示雙側(cè)卵巢≥18mm的卵泡個(gè)數(shù)/≥14mm卵泡個(gè)數(shù)≥60%,≥14mm卵泡血清E2平均水平值為200-300pg/ml時(shí),當(dāng)晚皮下注射重組人絨毛膜促性腺激素(Recombinant human chorionic gonadotropin,rh CG,250ugug/支,默克雪蘭諾有限公司)250ug,35-36小時(shí)后經(jīng)陰道超聲引導(dǎo)下穿刺取卵。取卵(ovum pick up,OPU)后3d,當(dāng)子宮內(nèi)膜≥8mm,P1.5ng/ml,且無(wú)卵巢過(guò)度刺激綜合征(OHSS)風(fēng)險(xiǎn)時(shí),行胚胎移植。OPU當(dāng)日起每日肌注射黃體酮(20mg/支,浙江仙琚制藥)60mg,自移植日起添加黃體酮軟膠囊(100mg/膠囊,法國(guó)卡普蘇格爾有限公司)200mg/支陰道給予,行黃體支持。移植14d后檢測(cè)血清h CG水平確定是否妊娠,4周后B超檢查觀(guān)察到妊娠囊確定臨床妊娠。2.2非降調(diào)方案月經(jīng)第3天起口服來(lái)曲唑(LE,2.5mg/片,江蘇恒瑞)2.5mg/d,同時(shí)注射用尿促性素(h MG,75IU/支,中國(guó)麗珠醫(yī)藥集團(tuán)股份有限公司)150-300IU肌注,1次/d,連用5天后停來(lái)曲唑改口服枸櫞酸氯米酚(CC,50mg/片,塞浦路斯高特藥廠(chǎng)),嚴(yán)密超聲監(jiān)測(cè)卵泡直徑,并檢測(cè)血E2、P、FSH、LH。達(dá)扳機(jī)標(biāo)準(zhǔn)后,當(dāng)晚50-100mg/d皮下注射達(dá)菲林0.2mg,吲哚美辛栓(50mg/片,東信藥業(yè)有限公司)50mg,直腸給藥1次/8h。余治療同短效長(zhǎng)方案組。3血清及FF收集收集月經(jīng)第3天、降調(diào)月經(jīng)第3天、Gn啟動(dòng)日、Gn第5天、h CG日、h CG次日、OPU第3天清晨空腹外周靜脈血,并于12小時(shí)內(nèi)2000*rpm離心10min,取上清1ml于1.5ml EP管置于-80℃冰箱,待檢。同時(shí),收集OPU日清亮FF并根據(jù)卵泡大小將其分為大中小三類(lèi)(大卵泡:直徑≥18mm、中卵泡:14mm≤直徑18mm、小卵泡:10mm≤直徑14mm),3000*rpm離心10min,取上液約3ml于5ml EP管置于-80℃冰箱,待檢。4 INHB及血清E2、P、LH、FSH的測(cè)定應(yīng)用酶聯(lián)免疫吸附實(shí)驗(yàn)(enzyme-linked immunosorbent assay,ELISA)試劑盒(美國(guó)Anshlabs公司)檢測(cè)血清和FF中INHB水平。應(yīng)用化學(xué)發(fā)光免疫測(cè)定試劑盒(ELECSYS,羅氏,德國(guó))檢測(cè)血清E2、P、LH、FSH水平。5數(shù)據(jù)統(tǒng)計(jì)分析采用SPSS21.0軟件,計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差表示,組間數(shù)據(jù)比較用兩獨(dú)立樣本t檢驗(yàn)或t’檢驗(yàn)。組內(nèi)數(shù)據(jù)比較采用配對(duì)樣本t檢驗(yàn)或Wilcoxon秩和檢驗(yàn)。相關(guān)性分析采用Pearson相關(guān)系數(shù)進(jìn)行分析。P0.05表示差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1患者一般情況納入76例IVF助孕患者,根據(jù)促排卵方案的不同分為短效長(zhǎng)方案組及非降調(diào)組,每組各38例,共76個(gè)COH周期。兩組患者年齡、月經(jīng)周期、不孕年限、基礎(chǔ)內(nèi)分泌情況及AFC差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),兩組資料具有可比性。2 COH相關(guān)參數(shù)比較長(zhǎng)方案組Gn用量為1998.68±154.76IU較非降調(diào)組的2110.20±150.00IU明顯降低(P=0.002);長(zhǎng)方案組Emh CG日厚度及E2h CG日分別為10.83±1.51mm和4160.40±1073.67pg/ml較非降調(diào)組的9.12±0.98mm及3737.51±643.28pg/ml明顯升高(P=0.000;P=0.041)。與非降調(diào)組比,長(zhǎng)方案組獲卵數(shù)稍高,而Gn天數(shù)、MⅡ卵數(shù)、2PN受精數(shù)、優(yōu)質(zhì)胚數(shù)及可利用胚數(shù)稍低(P0.05)。3 COH中血清及FF中INHB水平變化降調(diào)過(guò)程中,降調(diào)月經(jīng)第3天和降調(diào)18天即Gn啟動(dòng)日血清INHB水平分別為:50.63±23.80pg/ml、28.99±8.83pg/ml,兩者較基礎(chǔ)的89.07±26.07pg/ml明顯下降,差異有顯著統(tǒng)計(jì)學(xué)意義(P=0.000)。Gn啟動(dòng)日長(zhǎng)方案組血清INHB水平為28.99±8.83pg/ml,明顯低于非降調(diào)組的79.08±21.98pg/ml,有顯著統(tǒng)計(jì)學(xué)差異(P=0.000)。Gn啟動(dòng)后兩組血清INHB水平呈上升趨勢(shì)至h CG日達(dá)高峰后下降,OPU第3天顯著下降。且兩組基礎(chǔ)及Gn啟動(dòng)后的血清INHB水平無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。兩組FF中INHB水平隨卵泡直徑增大而升高。大卵泡INHB水平差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);但長(zhǎng)方案組中小卵泡INHB水平明顯高于非降調(diào)組,差異有顯著統(tǒng)計(jì)學(xué)意義(P=0.000)。4 INHB與COH結(jié)局的相關(guān)性分析兩方案中與COH結(jié)局相關(guān)性由強(qiáng)到弱的血清INHB檢測(cè)時(shí)間分別是:Gn第5天、h CG日、h CG次日、基礎(chǔ)月經(jīng)第3天及OPU第3天。且長(zhǎng)方案降調(diào)月經(jīng)第3天及Gn啟動(dòng)日INHB水平與COH結(jié)局也有較好的相關(guān)性,其中Gn啟動(dòng)日血清INHB水平與Gn用量顯著負(fù)相關(guān)(r=-0.716,P0.01)與E2h CG日顯著正相關(guān)(r=0.600,P0.01)。兩方案中,大卵泡INHB水平與COH結(jié)局相關(guān)性最強(qiáng);中卵泡INHB水平與COH結(jié)局也存在較好的相關(guān)性;而小卵泡INHB水平與COH結(jié)局相關(guān)性不明確。結(jié)論:1長(zhǎng)方案降調(diào)過(guò)程中血清INHB水平顯著下降,且降調(diào)后的血清INHB水平預(yù)示著降調(diào)節(jié)對(duì)卵泡同步化作用較好。2 COH過(guò)程中的血清及大中卵泡INHB水平能夠很好的預(yù)測(cè)卵巢反應(yīng)性及COH結(jié)局。
[Abstract]:Objective: inhibin B (inhibin B, INHB) is a heterogenous two polymer glycoprotein composed of alpha and beta (B) subunits. It belongs to the multifunction cell growth factor of the superfamily of transforming growth factor beta (transforming growth factor- beta, TGF- beta). In ovarian tissue, INHB is mainly secreted by small sinus granulosa cells, and INHB can be secreted by granular cells in ovarian tissue. The endocrine mechanism specifically acts on follicular stimulation hormone (FSH) secreted by the feedback inhibition of the pituitary gland, and can also increase the production of E2 by increasing the substrate of the estrogen (estrogen, E2) through the self / paracrine effect. This classic endocrine and paracrine role of INHB in the follicle and the development of the follicle. In the process of selection and maturation, this experiment was carried out by detecting and analyzing the levels of inhibin B (inhibin B, INHB) in different sizes of serum and ovum follicles in different controls of controlled ovarian hyperstimu-lation (COH). The dynamic changes of INHB in the serum and follicular fluid (FF) in the same COH scheme and their correlation with the COH outcome. Methods: 1 the 1 subjects were randomly divided into 76 patients who were first received IVF/ICSI-ET assisted pregnancy for the main factors of the fallopian tube factors and / or male factors at the Bethune International Heping Hospital reproductive center in Shijiazhuang. For the long square case group (38 cases) and the non downfall program group (38 cases), the age 35 years old; bilateral ovarian AFC 10-20; body mass index (BMI) 18-25kg/m2; menstrual cycle 26-35 days; normal basal hormone level; bilateral ovarian no surgery history; no other endocrine diseases, no hormone drugs in the last 6 months. Exclusion criteria: hyperprolactinemia; PCOS Endometriosis. All subjects were approved by the hospital ethics committee to sign the.2 COH scheme 2.1 short effect long prescription for the prior period of the treatment of the.2 COH agonist, Gn RH-a (Gn RH-a) Dafilin (Triptorelin acetate for injection, 0.1mg/ branch). From 0.1mg/d to third days of menstruation, serum estradiol (estrogen, E2), progesterone (progesterone, P), luteinizing hormone (Luteinzing hormone, LH), follicle stimulating hormone (follicular stimulation hormone, FSH) and ultrasonic monitoring were monitored. The follicles with a diameter larger than 10mm, endometrium 5mm, non functional cyst) were subcutaneously injected with Da field 0.05mg/d, and were given gonadotropin (gonadotropins, Gn) 75-300IU/d until the trigger day. When B ultrasound showed that the number of follicles in the follicle of the bilateral ovaries more than 18mm was more than 60%, and the average level of the serum E2 average of more than 14mm follicular serum was 200-300pg/ml, the evening skin. The recombinant human chorionic gonadotropin (Recombinant human chorionic gonadotropin, Rh CG, 250ugug/ branch, Merck snow lano Limited) 250ug, after 35-36 hours of transvaginal ultrasound guided puncture, was taken from the eggs. The ovum (ovum pick up, OPU) was taken after the endometrium was above the endometrium, and there was no ovarian hyperstimulation syndrome. On the day of embryo transfer,.OPU was injected daily with progesterone (20mg/ branch, Zhejiang immortal pharmaceuticals) 60mg. From the day of transplantation, Progesterone Soft Capsules (100mg/ capsule, French Karp sugel Co., Ltd.) was given 200mg/ vagina, and luteal support was given. The serum h CG level was detected after 14d transplantation, and pregnancy was determined by the serum h CG level. After 4 weeks, B ultrasound examination observed the pregnancy sac. To determine the.2.2 non - descending scheme of clinical pregnancy, third days after menstruation, oral letrozole (LE, 2.5mg/ tablet, Jiangsu Heng Rui) 2.5mg/d, and Menotropins for Injection (H MG, 75IU/ branch, Chinese Li Zhu Pharmaceutical Group Limited by Share Ltd) 150-300IU muscle injection, 1 /d, and 5 days later, to stop letrozole to oral chloramol citrate (CC, 50mg/ tablet, Cyprus high special medicine). After strict ultrasonic monitoring of follicle diameter and detecting blood E2, P, FSH and LH., 50-100mg/d subcutaneous injection of Da phifo 0.2mg, Indomethacin Suppositories (50mg/ tablet, Dongxin Pharmaceutical Co., Ltd.) 50mg, rectal administration 1 times /8h. residual therapy and.3 sera and FF collection for third days, third days of menstruation and Gn start day. N fifth days, H CG day, H CG on the next day, OPU third days early morning venous blood, and 2000*rpm centrifuge 10min within 12 hours, take the supernatant 1ml at 1.5ml EP tube in -80 C fridge, to be examined. < < diameter 14mm), 3000*rpm centrifuge 10min, take the upper liquid about 3ml to 5ml EP tube at -80 centigrade refrigerator, wait for.4 INHB and serum E2, P, LH. CSYS, Roche, Germany) detected the serum E2, P, LH, FSH level of.5 data statistical analysis using SPSS21.0 software, the measurement data were expressed with mean standard deviation, and the inter group data were compared with two independent samples t test or T 'test. The intra group data were compared with the paired sample t test or Wilcoxon rank sum test. Correlation analysis adopted Pearson correlation coefficient. .P0.05 showed that the difference was statistically significant. Results: 1 patients were generally included in 76 cases of IVF pregnancy. According to the difference of ovulation promotion, there were 38 cases in each group and 76 COH cycles. The age of the two groups, the period of menstruation, the limit of infertile years, and the difference of basal endocrine and AFC were not statistically significant. P0.05), the data of the two groups were comparable to the.2 COH related parameters. The dosage of Gn was 1998.68 + 154.76IU compared with 2110.20 + 150.00IU in the non lowering group (P=0.002). The Emh CG day thickness and E2h CG were 10.83 + 1.51mm and 4160.40 + 4160.40 +, respectively, 9.12 + and 3737.51 +. Higher (P=0.000; P=0.041). Compared with the non lowering group, the number of ovum was slightly higher in the long Fang case group, while the number of Gn days, the number of M II eggs, the number of 2PN fertilization, the number of high quality embryos and the decrease of INHB levels in the serum and FF in P0.05.3 COH, the third days of the menstruation and the 18 days of the Gn startup day were 50.63 +, 28., respectively. 99 + 8.83pg/ml, compared with the base 89.07 + 26.07pg/ml, the difference was significantly decreased. The difference was significant (P=0.000), the serum INHB level was 28.99 + 8.83pg/ml in the.Gn start day long program group, obviously lower than the 79.08 + 21.98pg/ml in the non descending group. There were significant statistical differences (P=0.000) after.Gn startup, the level of serum INHB increased to h CG day. There was a significant decrease in the OPU third days after the peak, and there was no significant difference in the level of serum INHB between the two groups and the Gn. The level of INHB in the two groups increased with the increase of follicle diameter. The difference in INHB level between the large follicles was not statistically significant (P0.05), but the level of INHB in the medium and small groups was significantly higher than that in the non lowering group, and the difference was significant. The correlation analysis between the P=0.000.4 INHB and the COH outcome in the two scheme, the correlation between the strong to weak serum INHB detection time and the COH outcome was: Gn fifth days, H CG days, H CG, third days of basal menstruation and third days of OPU. There was a significant negative correlation between the serum INHB level of N on the start day and the dosage of Gn (r=-0.716, P0.01) and E2h CG day (r=0.600, P0.01). In the two scheme, the correlation between the INHB level of the large follicle and the COH outcome was the strongest; the median follicle INHB level had a good correlation with the outcome, but the correlation between the level of the follicle and the outcome was not clear. Conclusion: the conclusion: 1 long prescription The serum level of INHB decreased significantly during the downfall of the case, and the serum INHB level after the downfall indicates that the serum and the large and medium follicle INHB levels in the.2 COH process can predict the ovarian responsiveness and the outcome of COH well.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R714.8

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