本文選題：抗苗勒管激素　切入點(diǎn)：卵巢儲(chǔ)備　出處：《山東大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：第一章抗苗勒管激素對(duì)卵巢儲(chǔ)備-低-下患者IVF/ICSI妊娠結(jié)局的預(yù)測(cè)價(jià)值背景：在接受體外受精-胚胎移植(in vitro fertilization/ intracytoplasmic sperm injection-embryo transfer, IVF/ICSI-ET)助孕的女性中,大于40歲的高育齡女性以及卵巢儲(chǔ)備低下的年輕女性常因卵巢儲(chǔ)備不良而影響助孕結(jié)局。IVF/ICSI-ET技術(shù)作為一種花費(fèi)高昂、有創(chuàng)的助孕方式,故在助孕前,評(píng)估卵巢儲(chǔ)備功能對(duì)預(yù)測(cè)妊娠結(jié)局具有重要意義。近年來,許多研究表明血清抗苗勒管激素(anti-mil llerian Hormone, AMH)是預(yù)測(cè)卵巢儲(chǔ)備功能的可靠指標(biāo),并已在卵巢儲(chǔ)備正常的女性中初步探究了其與妊娠結(jié)局的關(guān)系,但其相關(guān)性及臨床意義尚存爭(zhēng)議。一些研究認(rèn)為卵泡液中的AMH可能會(huì)更直接地反映卵母細(xì)胞和胚胎的質(zhì)量,進(jìn)而間接反應(yīng)妊娠結(jié)局,但受測(cè)量卵泡液AMH方法以及研究人群的的異質(zhì)性的影響,其相關(guān)性尚未得到證實(shí)。目的：在接受IVF/ICSI-ET治療的患者中,測(cè)定卵巢儲(chǔ)備低下的年輕女性(diminished ovarian reserve, DOR,年齡40歲)、高育齡女性(advanced age, AA,年齡40歲)以及卵巢儲(chǔ)備正常的不孕女性(normal ovarian reserve, NOR,年齡40歲)三組人群中血清AMH及卵泡液AMH(follicular fluids AMH, FFAMH)的水平,并探討其與卵母細(xì)胞質(zhì)量及妊娠結(jié)局是否具有相關(guān)性。方法：通過回顧性的研究方法,選取2013年10月至2014年6月在山東大學(xué)附屬生殖醫(yī)院接受第一周期IVF/ICSI治療的149例女性并根據(jù)卵巢儲(chǔ)備分為3組。組1為年齡小于40歲,基礎(chǔ)促卵泡激素(follicle stimulation hormone, FSH)10IU/L且AMH1.5ng/ml的年輕女性(DOR, 55例),組2為年齡大于40歲的女性(AA,49例),組3為年齡小于40歲的卵巢儲(chǔ)備正常的不孕女性(基礎(chǔ)FSH10IU/L, NOR,45例)記錄年齡、體重指數(shù)(Body Mass Index, BMI);抽取控制性超促排卵(controlled ovarian hyperstimulation, COH)治療前月經(jīng)周期第2-4天外周靜脈血,測(cè)定血清AMH和基礎(chǔ)內(nèi)分泌水平,并應(yīng)用陰道超聲行竇卵泡計(jì)數(shù)(antral follicle count, AFC)。所有DOR及AA患者行常規(guī)短方案促排卵,NOR組行長(zhǎng)方案促排卵。在COH過程中監(jiān)測(cè)卵泡的發(fā)育并測(cè)定血清孕酮(progestone, P)、雌二醇(estrodial, E2)、促黃體生成素(luteinizing Hormon, LH)水平,當(dāng)超聲監(jiān)測(cè)發(fā)現(xiàn)至少有2個(gè)直徑大于等于18mm的優(yōu)勢(shì)卵泡時(shí),給予6000-8000IU人體絨膜促性腺激素(Human Chorionic Gonadotropin, HCG),注射后36小時(shí)行經(jīng)陰B超引導(dǎo)下穿刺取卵并留取卵泡液。計(jì)算促性腺激素(gonadotrophin, Gn)起始量、Gn用藥天數(shù)、Gn總量和獲卵數(shù)、受精率,根據(jù)實(shí)驗(yàn)室記錄登記移植胚胎數(shù)及冷凍胚胎數(shù)并隨訪妊娠結(jié)局。根據(jù)妊娠結(jié)局,分別計(jì)算三組的臨床妊娠率和活產(chǎn)率。通過酶聯(lián)免疫法分別測(cè)定各組女性的卵泡液AMH。結(jié)果：(1)DOR及NOR組病例的年齡匹配,無統(tǒng)計(jì)學(xué)差異(32.36±4.20歲vs.31.02±2.80歲,P0.05),均小于AA組(41.67±1.71歲)。三組的FSH水平：DOR組(13.36±3.75 IU/L)高于AA組(8.45±3.61 IU/L)高于NOR組(6.69±1.34IU/L),AFC:DOR組(7.51±3.5個(gè))少于AA組(7.71±3.18個(gè))少于NOR組(13.53±4.15個(gè)),差異具有統(tǒng)計(jì)學(xué)意義(P0.05),但DOR組與AA組的AFC比較后無統(tǒng)計(jì)學(xué)差異(P0.05)。三組的BMI及基礎(chǔ)水平E2均無統(tǒng)計(jì)學(xué)差異(P0.05)。(2) DOR、AA、NOR三組的血清AMH分別為0.33 ng/ml (0.13～0.49),0.51 ng/ml (0.23～0.93),2.35 ng/ml (1.65～2.90),卵泡液AMH依次為2.32 ng/ml (1.14～4.44),2.66 ng/ml (1.48-4.72),6.77 ng/ml (4.56～13.21),差異均具有統(tǒng)計(jì)學(xué)意義(P0.05),但AA組與DOR組的卵泡液AMH水平無差異性。HCG日E2水平,NOR組高于AA組及DOR組(2550.29±608.97 pg/ml1890.42±1049.27 pg/ml1493.45±667.59 pg/ml),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。HCG日1.4cm以上的卵泡數(shù)及獲卵數(shù),AA組多于DOR組(4.41±2.54個(gè)vs.3.53±1.76個(gè)；3.76±1.99枚vs.5.47±3.55枚),少于NOR組(大卵泡數(shù)：9.13±2.64個(gè)；獲卵數(shù)：11.22±3.97枚),差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。(3) DOR、AA、NOR三組間的受精率(64%±33% vs.55%±32% vs.65%±19%)及D2天優(yōu)質(zhì)胚胎率(51%±34% vs.42%±31%vs.52%±21%),均無統(tǒng)計(jì)學(xué)差異(P0.05)。AA組的臨床妊娠率(7/40,17.50%)及活產(chǎn)率(2/40,5.00%)遠(yuǎn)低于DOR組(18/47,38.30%；15/47,31.91%)及NOR組(27/43,62.79%；26/43,60.47%),差異具有統(tǒng)計(jì)學(xué)意義(P0.01)。(4)在DOR及AA組,血清AMH與AFC及獲卵數(shù)呈正相關(guān)性(AFC：相關(guān)系數(shù)r=0.46,P0.01；相關(guān)系數(shù)r=0.51,P0.01；獲卵數(shù)：相關(guān)系數(shù)r=0.38,P0.01；相關(guān)系數(shù)r=0.30,P0.05)。在AA組,卵泡液AMH與獲卵數(shù)成正相關(guān)關(guān)系(相關(guān)系數(shù)m=0.42,P0.01),但在DOR及NOR組中未發(fā)現(xiàn)此相關(guān)性。血清及卵泡液AMH與D2天優(yōu)質(zhì)胚胎率、臨床妊娠率及活產(chǎn)率的相關(guān)性在三組中均未發(fā)現(xiàn)結(jié)論：1.血清及卵泡液AMH與卵母細(xì)胞的質(zhì)量及妊娠結(jié)局均無明顯相關(guān)性。2.卵巢儲(chǔ)備低下的年輕女性,其妊娠結(jié)局優(yōu)于40歲以上的高齡女性。3.血清AMH對(duì)卵巢儲(chǔ)備具有良好的評(píng)估價(jià)值,但對(duì)妊娠結(jié)局的預(yù)測(cè)價(jià)值仍有待于進(jìn)一步評(píng)估。第二章卵巢良性囊腫手術(shù)對(duì)IVF/ICSI妊娠結(jié)局的影響背景：卵巢良性囊腫好發(fā)于育齡期女性,如成熟畸胎瘤、囊腺瘤、子宮內(nèi)膜異位囊腫(卵巢巧克力囊腫)等,這些囊腫的發(fā)生不僅會(huì)造成慢性盆腔痛,還會(huì)引起月經(jīng)周期不規(guī)律,嚴(yán)重者導(dǎo)致不孕。手術(shù)治療可以明確診斷,緩解盆腔疼痛,改善生活質(zhì)量,但切除囊腫的同時(shí)也會(huì)損傷部分卵巢皮質(zhì),影響卵巢儲(chǔ)備。既往研究發(fā)現(xiàn),剝除卵巢巧克力囊腫或單純卵巢良性囊腫剝除的女性,術(shù)后1周AFC降低,且手術(shù)側(cè)卵巢AFC較健側(cè)AFC明顯減少。同時(shí),作為評(píng)價(jià)卵巢儲(chǔ)備敏感指標(biāo)的AMH水平也在術(shù)后明顯下降,雖然在6個(gè)月內(nèi)AMH水平可逐漸升高,但無法恢復(fù)到術(shù)前水平。在IVF/ICSI-ET助孕過程中,卵巢良性囊腫剝除術(shù)后患者的卵巢反應(yīng)性下降,獲卵數(shù)降低、優(yōu)質(zhì)胚胎及冷凍胚胎數(shù)量減少。但手術(shù)是否對(duì)妊娠結(jié)局有不良影響仍存有爭(zhēng)議。目的：探討卵巢囊腫剝除術(shù)對(duì)體外受精-胚胎移植妊娠結(jié)局的影響方法：回顧性分析2013年1月至2014年6月于山東大學(xué)附屬生殖醫(yī)院行IVF/ICSI-ET 的 622例不孕癥女性患者。病例組為卵巢良性囊腫術(shù)后患者153例,包括44例卵巢巧克力囊腫,35例成熟性畸胎瘤,67例單純性卵巢囊腫及7例黏液性囊腺瘤；以年齡匹配、同期469例因輸卵管因素或男方因素行IVF/ICSI-ET助孕、無卵巢手術(shù)史的患者為對(duì)照組,比較兩組卵巢儲(chǔ)備的基本指標(biāo)及IVF/ICSI妊娠結(jié)局。并進(jìn)一步分析不同卵巢囊腫類型對(duì)卵巢儲(chǔ)備及IVF/ICSI-ET助孕結(jié)局的影響。結(jié)果：(1)和對(duì)照組相比,手術(shù)組患者血清AMH[1.92(1.22～3.34) ng/ml vs.2.90(1.90-4.20)ng/ml]、AFC[12.00(9.00-16.00)個(gè) vs.13.00(11.00-17.00)個(gè)]、獲卵數(shù)[(11.87±5.01)枚vs.(13.32±5.54)枚]、冷凍胚胎數(shù)[1.00(0.00～4.00)個(gè)vs.3.00(1.00～5.00)個(gè)]減少,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。兩組的FSH、Gn用藥天數(shù)及Gn用藥總量無差異(P0.05)。手術(shù)組臨床妊娠率(61.36%,81/132)低于無手術(shù)對(duì)照組(61.64%,241/391),但無統(tǒng)計(jì)學(xué)意義(P0.05)。(2)將巧囊術(shù)后患者作為病例A組,畸胎瘤、卵巢囊腫及黏液性囊腺瘤術(shù)后患者為病例B組。A組的AMH、AMH、獲卵數(shù)及冷凍胚胎數(shù)減少明顯低于B組[(10.57±4.36)個(gè) vs.(13.45±4.97)個(gè)；1.65(1.04～2.31)ng/ml vs. 2.15(1.32～4.10)ng/ml;(9.39±3.90)枚vs.(12.87±5.08)枚]；0.00(0.00-2.00)個(gè)vs.2.00(0.00～4.00)個(gè)],差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。和B組相比,A組的臨床妊娠率降低(50.00% vs.65.96%)、流產(chǎn)率增高(15.79% vs.9.68%),但差異不顯著(P0.05)。結(jié)論：1.卵巢囊腫剝除術(shù)后卵巢儲(chǔ)備下降,獲卵數(shù)、冷凍胚胎數(shù)減少,但臨床妊娠率無明顯變化。2.相對(duì)于其他卵巢囊腫,卵巢巧克力囊腫手術(shù)對(duì)卵巢儲(chǔ)備的損傷更為嚴(yán)重。
[Abstract]:The first chapter of anti Mullerian hormone in predicting ovarian reserve low background value under the IVF/ICSI pregnancy outcome in patients undergoing in vitro fertilization and embryo transfer (in vitro fertilization/ intracytoplasmic sperm injection-embryo transfer, IVF/ICSI-ET) to help pregnant women, women of childbearing age higher than 40 year old and young women often because of ovarian poor ovarian reserve adverse pregnancy outcomes and effects of reserve.IVF/ICSI-ET technology as an expensive, there is a way to help pregnant, so help in pregnancy, assessment of ovarian reserve function in predicting pregnancy outcome has important significance. In recent years, many studies have shown that serum anti Mullerian hormone (anti-mil llerian, Hormone, AMH) is a reliable predictor of ovarian the reserve function, and has been in the female normal ovarian reserve in the initial exploration of the relationship between them and the outcome of pregnancy, but the correlation and clinical significance remains controversial. Some researchers believe that the follicular fluid AMH may directly reflect the quality of oocytes and embryos, and indirect response to pregnancy outcome, but by the measurement of follicular fluid AMH method and the influence of heterogeneity of the study population, the relationship has not yet been confirmed. Objective: in patients receiving IVF/ICSI-ET, determination of ovarian reserve poor young women (diminished DOR, ovarian reserve, age 40, women of childbearing age (Advanced) high age, AA, age 40) and infertile women with normal ovarian reserve (normal NOR, ovarian reserve, age 40) serum AMH and follicular fluid AMH in the three groups (follicular fluids, AMH, FFAMH) the level, and to investigate the quality of oocytes and the outcome of pregnancy is highly related. Methods: through retrospective method, from October 2013 to June 2014 in the reproductive Hospital Affiliated to Shandong University 149 cases of female IVF/ICSI in the first cycle of treatment and the ovarian reserve were divided into 3 groups. Group 1 was less than 40 years of age, basal follicle stimulating hormone (follicle stimulation hormone, FSH 10IU/L) and AMH1.5ng/ml of young women (DOR, 55 cases), group 2 for women older than 40 years (AA, 49) in group 3, age less than normal female infertility ovarian reserve at the age of 40 (FSH10IU/L, NOR, 45 cases). The age, body mass index (Body Mass, Index, BMI); extraction of COH (controlled ovarian, hyperstimulation, COH) before the treatment of menstrual cycle 2-4 days of peripheral venous blood serum AMH and the basic endocrine level, and the application of transvaginal ultrasound for antral follicle count (antral follicle count, AFC DOR and AA). All patients underwent routine short protocol ovulation, ovulation. NOR group president scheme and determination of serum progesterone in monitoring follicular development during COH (progestone P, (Estrodial), estradiol, luteinizing hormone (E2), luteinizing Hormon, LH) level, when the ultrasonic monitoring found at least 2 diameter greater than or equal to 18mm of the dominant follicle, 6000-8000IU human chorionic gonadotropin (Human Chorionic, Gonadotropin, HCG), 36 hours after injection for transvaginal ultrasound guided oocyte and specimens from follicular fluid. Calculation of gonadotropin (gonadotrophin, Gn) Gn initial dose, duration of medication, Gn and the total number of oocytes, fertilization rate, according to the laboratory records the number of embryos and frozen embryo registration number and pregnancy outcomes were followed up. According to the outcome of pregnancy, clinical pregnancy rate and the three group the live birth rate were calculated. The results of AMH. follicular fluid were measured by enzyme linked immunosorbent assay for women: (1) the DOR and NOR groups were matched in age, no significant difference (32.36 + 4.20 vs.31.02 + 2.80, P0.05), were less than group AA (41.67 + 1.71) three. 緇勭殑FSH姘村鉤錛欴OR緇，

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