月经期取卵在卵巢低储备患者IVF-ET中的应用

目的:探讨月经期取卵在卵巢低储备(diminished ovarian reserve,DOR)患者体外受精-胚胎移植(IVF-ET)中应用的可行性。方法:回顾性分析70例DOR行IVF/卵胞质单精子注射(ICSI)-ET治疗的不孕症患者的临床资料,比较其73个月经期取卵和270个非月经期取卵的结局。若月经2~4 d阴道超声提示优势卵泡直径≥14 mm且E2水平200 ng/L则行月经期取卵,若无优势卵泡按常规促排卵方案行IVF/ICSI,观察其临床结局。结果:月经期组获卵数、成熟卵数和可用胚胎数分别为1.0±0.4个、0.8±0.4个、0(0,1)个,非月经期组分为1.6±1.2个、1.4±1.1个、1(0,1)个,组间有统计学差异(P0.05)。月经期组周期取消率为72.6%,显著高于非月经期组43.0%(P0.05)。月经期组获卵率、卵裂率、卵子利用率分别为83.1%、94.7%和34.5%,非月经期组分别为70.6%、96.7%和51.7%,组间无统计学差异(P0.05)。结论:尽管月经期取卵的获卵数、成熟卵数、可用胚胎数小于非月经期取卵,但获卵率、卵裂率和卵子利用率组间无统计学差异,为反复周期取消、高基础雌激素的DOR不孕症患者节约了治疗时间,提供了新的方法。     

Genetic associations with diminished ovarian reserve: a systematic review of the literature

Purpose

Diminished ovarian reserve (DOR) affects 10 % of women seeking fertility treatment. Although it is much more prevalent than premature ovarian failure, less is known about its etiology. The purpose of this article is to review the possible genetic causes of, and associations with, pathologic DOR.

Methods

A systematic review was conducted using PubMed from 1966 through November 2013.

Results

Twenty-one articles identified genes associated with DOR: one gene mutation (FMR1), three polymorphisms (GDF9, FSHR, and ESR1), and seven genes differentially expressed between women with DOR and controls (AMH, LHCGR, IGF1, IGF2, IGF1R, IGF2R and GREM1). Six candidate genes were discovered in mice, including Foxl2, Gdf9, Bmp15, Aire, Wnt4, and Gpr3. Two case reports of chromosomal translocations were also identified.

Conclusions

While the etiology of pathologic DOR is likely multifactorial, it is possible that many cases attributed to an idiopathic cause may have a genetic component. Larger studies are needed to expose the impact gene mutations, polymorphisms, and epigenetics have on pathologic DOR.     

脱氢表雄酮对卵巢储备功能低下患者的胚胎质量及卵泡液中标志物的作用

目的探讨脱氢表雄酮(DHEA)对于卵巢储备功能低下(DOR)患者胚胎质量及卵泡液标志物的影响。方法采用前瞻性随机对照研究将116名DOR患者按照1︰1随机分为DHEA组与对照组。DHEA组58名患者,给予DHEA 25 mg/次,tid,连用12周。对照组58名患者直接进入体外受精(IVF)周期。比较两组的IVF参数(获卵数、M_Ⅱ卵数、卵裂数、有效胚胎数、优质胚胎数和临床妊娠率)并利用酶联免疫吸附法(ELISA)检测两组卵泡液中的抗苗勒管激素(AMH),胰岛素样生长因子(IGF)-1的含量及蛋白免疫印迹法(Western blotting assay)检测骨形态发生蛋白(BMP)-15及生长分化因子(GDF)-9在卵泡液中的表达。结果 DHEA组的有效胚胎数(2.0±1.3)及优质胚胎数(1.4±1.1)明显多于对照组(1.5±1.2,P=0.018;1.0±1.0,P=0.033),卵泡液样本中的AMH[(2.83±1.14)μg/L]及IGF-1[(94.02±38.28)μg/L]的含量明显高于对照组[(1.37±0.55)μg/L,P=0.000;(74.03±25.46)μg/L,P=0.004]。Western blotting显示,DHEA组的BMP-15蛋白的相对表达量明显增高(P0.000 1),但是GDF-9的相对表达量在两组中无统计学差异(P=0.987)。临床妊娠率在两组中也未见统计学差异(P=0.223)。结论 DOR患者在IVF周期前进行DHEA预处理可以提高优质胚胎率,这可能与卵泡微环境中的相关标志物(AMH,IGF-1和BMP-15)含量的增加有关。     

高淑红脑肾同治法治疗卵巢储备功能低下

神志失调、肾气亏虚、气机不调可致卵巢储备功能低下。临床上,应尤其重视脑肾同治,即调神和补益肾气共同发挥作用。高淑红主任结合多年临床经验,总结出"调""补""通"治疗卵巢储备功能低下的方法。"调"即调神,"补"即补益肾气,"通"即疏通气机。临证重用百会以解郁安神,鸠尾、中脘以疏通气机,关元、神阙以补益肾气、温通经络;善用局部腧穴以直接作用于子宫及卵巢,注重针灸结合,重用灸法以化瘀通络、调理气机。     

The Diagnostic Accuracy of Fractional Exhaled Nitric Oxide Testing in Asthma: A Systematic Review and Meta-analyses

Objective

To evaluate the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) measurement in individuals with suspected asthma.

Opioid μ-receptors as new target for insulin resistance

Type-2 diabetes is one of the fastest growing public health problems worldwide resulting from both environmental and genetic factors. Activation of μ-opioid receptor (MOR) could result in reversal of the impairment of insulin-stimulated glucose disposal in genetically obese Zucker rats via exercise training. This improvement of insulin resistance was associated with an elevation of circulating β-endorphin to ameliorate the post-receptor insulin signaling cascade, including downstream effectors of the phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway. In insulin resistant rats, Loperamide treatment effected on the insulin receptor substrate (IRS)-1/PI3-kinase/Akt signaling cascade and subsequent insulin-stimulated glucose transport trafficking on skeletal muscle, which were all suppressed by MOR antagonism. In addition, induction of insulin resistance by the intake of high fructose is more rapid in MOR knockout mice than in wild-type mice. Improvements in insulin sensitivity through the peripheral MOR activation overcoming defects related to the post-receptor in IRS-1-associated PI3-kinase step have been defined. Opioid receptor activation, especially of the μ-subtype, may provide merits in the amelioration of defective insulin action. Atypical zeta (ζ) isoform of protein kinase C serves as a factor that integrates with peripheral MOR pathway and insulin signals for glucose utilization. The developments call new insights into the chemical compounds and/or herbal products that might enhance opioid peptide secretion and/or stimulate MOR in peripheral insulin-sensitive tissues to serve as potential agents or adjuvants for helping the glucose metabolism. In the present review, we update these topics and discuss the concept of targeting peripheral MOR pathway for the treatment of insulin resistance.     

艾灸对卵巢储备功能减退大鼠Nrf2/HO-1信号通路的影响

目的:观察艾灸对卵巢储备功能减退(DOR)大鼠核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的影响,探讨艾灸对卵巢储备功能的保护效应机制。方法:将40只SD大鼠随机分为空白组、模型组、艾灸组、激素组,每组10只。模型组、艾灸组、激素组均采用雷公藤多苷片混悬液灌胃制备DOR大鼠模型,空白组灌胃等体积的0.9%氯化钠溶液,每日1次,连续灌胃14 d。激素组在造模即日起采用激素序贯疗法连续干预14 d;艾灸组在造模即日起每日给予双侧"肾俞"或"关元""中脘"艾灸治疗,两组穴隔日交替,每次10 min,连续14 d。每日采用阴道脱落细胞涂片观察大鼠的动情周期,统计各组大鼠动情周期紊乱率。干预结束后,采用HE染色观察各组大鼠卵巢组织学形态;ELISA法检测各组大鼠血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、抗苗勒管激素(AMH)和超氧化物歧化酶(SOD)、丙二醛(MDA)含量;免疫组化法检测各组大鼠卵巢组织Nrf2和HO-1蛋白水平;实时PCR(TaqMan探针法)检测各组大鼠卵巢组织Nrf2和HO-1 mRNA的表达。结果:与空白组比较,模型组大鼠动情周期紊乱率升高(P<0.01);与模型组比较,艾灸组和激素组大鼠动情周期紊乱率降低(P<0.01)。与空白组比较,模型组大鼠血清FSH、LH、MDA含量增多(P<0.01),血清E2、AMH、SOD含量减少(P<0.01);与模型组比较,艾灸组和激素组大鼠血清FSH、LH、MDA含量减少(P<0.01,P<0.05),血清E2、AMH、SOD含量增多(P<0.01)。与空白组比较,模型组大鼠卵巢组织Nrf2和HO-1蛋白及mRNA表达减少(P<0.01);与模型组比较,艾灸组和激素组大鼠卵巢组织Nrf2和HO-1蛋白及mRNA表达增多(P<0.01)。结论:艾灸可以降低DOR大鼠的动情周期紊乱率,改善血清性激素水平和抗氧化应激能力,其机制可能与调控Nrf2/HO-1信号通路有关。     

补肾益冲抗衰汤对卵巢储备功能下降大鼠卵巢颗粒细胞凋亡因子Bcl-2、Bax、Caspase-3的影响

[目的]观察补肾益冲抗衰汤对卵巢储备功能下降模型大鼠卵巢颗粒细胞凋亡因子Bcl-2、Bax、Caspase-3蛋白表达的影响。[方法]以70只8周龄雌性SD大鼠为研究对象,采用雷公藤多苷片制作卵巢储备功能下降大鼠模型。观察大鼠一般情况、卵巢指数、卵巢组织病理形态、血清E2、FSH、FSH/LH水平及卵巢颗粒细胞凋亡因子Bcl-2、Bax、Caspase-3蛋白表达。[结果]补肾益冲抗衰汤能使卵巢储备功能下降大鼠动情周期缩短、子宫、卵巢重量增加,大鼠血清FSH水平、FSH/LH降低,血清E2水平增高（P〈0.05或P〈0.01）,使卵巢颗粒细胞抑制细胞凋亡因子Bcl-2蛋白表达增加,促进细胞凋亡因子Bax、Caspase-3蛋白表达减少（P〈0.05或P〈0.01）。[结论]雷公藤多甙片致DOR大鼠模型与人类卵巢储备功能下降的临床表现基本一致。细胞凋亡调节因子Bcl-2、Bax、Caspase-3蛋白与卵巢储备功能密切相关,补肾益冲抗衰汤有抑制卵巢颗粒细胞凋亡、减少卵泡闭锁从而改善卵巢储备功能的作用。