抗苗勒管激素及卵巢囊肿手术与卵巢储备低下女性助孕结局的相关研究

发布时间：2018-03-06 23:17

  本文选题：抗苗勒管激素　切入点：卵巢储备　出处：《山东大学》2016年硕士论文　论文类型：学位论文

【摘要】：第一章抗苗勒管激素对卵巢储备-低-下患者IVF/ICSI妊娠结局的预测价值背景：在接受体外受精-胚胎移植(in vitro fertilization/ intracytoplasmic sperm injection-embryo transfer, IVF/ICSI-ET)助孕的女性中,大于40岁的高育龄女性以及卵巢储备低下的年轻女性常因卵巢储备不良而影响助孕结局。IVF/ICSI-ET技术作为一种花费高昂、有创的助孕方式,故在助孕前,评估卵巢储备功能对预测妊娠结局具有重要意义。近年来,许多研究表明血清抗苗勒管激素(anti-mil llerian Hormone, AMH)是预测卵巢储备功能的可靠指标,并已在卵巢储备正常的女性中初步探究了其与妊娠结局的关系,但其相关性及临床意义尚存争议。一些研究认为卵泡液中的AMH可能会更直接地反映卵母细胞和胚胎的质量,进而间接反应妊娠结局,但受测量卵泡液AMH方法以及研究人群的的异质性的影响,其相关性尚未得到证实。目的：在接受IVF/ICSI-ET治疗的患者中,测定卵巢储备低下的年轻女性(diminished ovarian reserve, DOR,年龄40岁)、高育龄女性(advanced age, AA,年龄40岁)以及卵巢储备正常的不孕女性(normal ovarian reserve, NOR,年龄40岁)三组人群中血清AMH及卵泡液AMH(follicular fluids AMH, FFAMH)的水平,并探讨其与卵母细胞质量及妊娠结局是否具有相关性。方法：通过回顾性的研究方法,选取2013年10月至2014年6月在山东大学附属生殖医院接受第一周期IVF/ICSI治疗的149例女性并根据卵巢储备分为3组。组1为年龄小于40岁,基础促卵泡激素(follicle stimulation hormone, FSH)10IU/L且AMH1.5ng/ml的年轻女性(DOR, 55例),组2为年龄大于40岁的女性(AA,49例),组3为年龄小于40岁的卵巢储备正常的不孕女性(基础FSH10IU/L, NOR,45例)记录年龄、体重指数(Body Mass Index, BMI);抽取控制性超促排卵(controlled ovarian hyperstimulation, COH)治疗前月经周期第2-4天外周静脉血,测定血清AMH和基础内分泌水平,并应用阴道超声行窦卵泡计数(antral follicle count, AFC)。所有DOR及AA患者行常规短方案促排卵,NOR组行长方案促排卵。在COH过程中监测卵泡的发育并测定血清孕酮(progestone, P)、雌二醇(estrodial, E2)、促黄体生成素(luteinizing Hormon, LH)水平,当超声监测发现至少有2个直径大于等于18mm的优势卵泡时,给予6000-8000IU人体绒膜促性腺激素(Human Chorionic Gonadotropin, HCG),注射后36小时行经阴B超引导下穿刺取卵并留取卵泡液。计算促性腺激素(gonadotrophin, Gn)起始量、Gn用药天数、Gn总量和获卵数、受精率,根据实验室记录登记移植胚胎数及冷冻胚胎数并随访妊娠结局。根据妊娠结局,分别计算三组的临床妊娠率和活产率。通过酶联免疫法分别测定各组女性的卵泡液AMH。结果：(1)DOR及NOR组病例的年龄匹配,无统计学差异(32.36±4.20岁vs.31.02±2.80岁,P0.05),均小于AA组(41.67±1.71岁)。三组的FSH水平：DOR组(13.36±3.75 IU/L)高于AA组(8.45±3.61 IU/L)高于NOR组(6.69±1.34IU/L),AFC:DOR组(7.51±3.5个)少于AA组(7.71±3.18个)少于NOR组(13.53±4.15个),差异具有统计学意义(P0.05),但DOR组与AA组的AFC比较后无统计学差异(P0.05)。三组的BMI及基础水平E2均无统计学差异(P0.05)。(2) DOR、AA、NOR三组的血清AMH分别为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依次为2.32 ng/ml (1.14～4.44),2.66 ng/ml (1.48-4.72),6.77 ng/ml (4.56～13.21),差异均具有统计学意义(P0.05),但AA组与DOR组的卵泡液AMH水平无差异性。HCG日E2水平,NOR组高于AA组及DOR组(2550.29±608.97 pg/ml1890.42±1049.27 pg/ml1493.45±667.59 pg/ml),差异有统计学意义(P0.05)。HCG日1.4cm以上的卵泡数及获卵数,AA组多于DOR组(4.41±2.54个vs.3.53±1.76个；3.76±1.99枚vs.5.47±3.55枚),少于NOR组(大卵泡数：9.13±2.64个；获卵数：11.22±3.97枚),差异具有统计学意义(P0.05)。(3) DOR、AA、NOR三组间的受精率(64%±33% vs.55%±32% vs.65%±19%)及D2天优质胚胎率(51%±34% vs.42%±31%vs.52%±21%),均无统计学差异(P0.05)。AA组的临床妊娠率(7/40,17.50%)及活产率(2/40,5.00%)远低于DOR组(18/47,38.30%；15/47,31.91%)及NOR组(27/43,62.79%；26/43,60.47%),差异具有统计学意义(P0.01)。(4)在DOR及AA组,血清AMH与AFC及获卵数呈正相关性(AFC：相关系数r=0.46,P0.01；相关系数r=0.51,P0.01；获卵数：相关系数r=0.38,P0.01；相关系数r=0.30,P0.05)。在AA组,卵泡液AMH与获卵数成正相关关系(相关系数m=0.42,P0.01),但在DOR及NOR组中未发现此相关性。血清及卵泡液AMH与D2天优质胚胎率、临床妊娠率及活产率的相关性在三组中均未发现结论：1.血清及卵泡液AMH与卵母细胞的质量及妊娠结局均无明显相关性。2.卵巢储备低下的年轻女性,其妊娠结局优于40岁以上的高龄女性。3.血清AMH对卵巢储备具有良好的评估价值,但对妊娠结局的预测价值仍有待于进一步评估。第二章卵巢良性囊肿手术对IVF/ICSI妊娠结局的影响背景：卵巢良性囊肿好发于育龄期女性,如成熟畸胎瘤、囊腺瘤、子宫内膜异位囊肿(卵巢巧克力囊肿)等,这些囊肿的发生不仅会造成慢性盆腔痛,还会引起月经周期不规律,严重者导致不孕。手术治疗可以明确诊断,缓解盆腔疼痛,改善生活质量,但切除囊肿的同时也会损伤部分卵巢皮质,影响卵巢储备。既往研究发现,剥除卵巢巧克力囊肿或单纯卵巢良性囊肿剥除的女性,术后1周AFC降低,且手术侧卵巢AFC较健侧AFC明显减少。同时,作为评价卵巢储备敏感指标的AMH水平也在术后明显下降,虽然在6个月内AMH水平可逐渐升高,但无法恢复到术前水平。在IVF/ICSI-ET助孕过程中,卵巢良性囊肿剥除术后患者的卵巢反应性下降,获卵数降低、优质胚胎及冷冻胚胎数量减少。但手术是否对妊娠结局有不良影响仍存有争议。目的：探讨卵巢囊肿剥除术对体外受精-胚胎移植妊娠结局的影响方法：回顾性分析2013年1月至2014年6月于山东大学附属生殖医院行IVF/ICSI-ET 的 622例不孕症女性患者。病例组为卵巢良性囊肿术后患者153例,包括44例卵巢巧克力囊肿,35例成熟性畸胎瘤,67例单纯性卵巢囊肿及7例黏液性囊腺瘤；以年龄匹配、同期469例因输卵管因素或男方因素行IVF/ICSI-ET助孕、无卵巢手术史的患者为对照组,比较两组卵巢储备的基本指标及IVF/ICSI妊娠结局。并进一步分析不同卵巢囊肿类型对卵巢储备及IVF/ICSI-ET助孕结局的影响。结果：(1)和对照组相比,手术组患者血清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)个 vs.13.00(11.00-17.00)个]、获卵数[(11.87±5.01)枚vs.(13.32±5.54)枚]、冷冻胚胎数[1.00(0.00～4.00)个vs.3.00(1.00～5.00)个]减少,差异有统计学意义(P0.05)。两组的FSH、Gn用药天数及Gn用药总量无差异(P0.05)。手术组临床妊娠率(61.36%,81/132)低于无手术对照组(61.64%,241/391),但无统计学意义(P0.05)。(2)将巧囊术后患者作为病例A组,畸胎瘤、卵巢囊肿及黏液性囊腺瘤术后患者为病例B组。A组的AMH、AMH、获卵数及冷冻胚胎数减少明显低于B组[(10.57±4.36)个 vs.(13.45±4.97)个；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)个vs.2.00(0.00～4.00)个],差异具有统计学意义(P0.05)。和B组相比,A组的临床妊娠率降低(50.00% vs.65.96%)、流产率增高(15.79% vs.9.68%),但差异不显著(P0.05)。结论：1.卵巢囊肿剥除术后卵巢储备下降,获卵数、冷冻胚胎数减少,但临床妊娠率无明显变化。2.相对于其他卵巢囊肿,卵巢巧克力囊肿手术对卵巢储备的损伤更为严重。
[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. 缁勭殑FSH姘村钩锛欴OR缁，

本文编号：1576932