抗苗勒氏管激素在多囊卵巢综合征患者卵巢功能调节中的作用

抗苗勒氏管激素(AMH)由卵巢颗粒细胞分泌,,在卵泡生长发育中发挥负性调节作用。AMH在多囊卵巢综合征(PCOS)患者中异常升高,可能参与介导了PCOS的发病机制。本文综述了AMH的生物学特征,PCOS患者的AMH分泌水平与AMH基因表达,以及AMH信号转导通路的调节。     

抗苗勒氏管激素(AMH)与多囊卵巢综合征(PCOS)卵泡发育异常的关系

抗苗勒氏管激素(AMH)主要抑制始基卵泡进入生长阶段,在小窦卵泡中表达最高。多囊卵巢综合征(PCOS)主要表现为卵巢持续性无排卵。PCOS患者过高的LH和LH/FSH比值、胰岛素水平促进了雄激素的分泌,高雄激素进一步影响GC产生AMH,导致AMH水平异常增高,高水平的AMH通过降低GC对FSH敏感性,抑制P450芳香化酶表达,雄激素向雌激素转化受阻,E2水平降低,致使体内雄激素堆积,高雄激素又促进AMH生成,形成一个恶性循环,最终导致优势卵泡选择受阻,卵泡发育停滞在小窦状卵泡阶段。     

抗苗勒氏管激素与卵巢储备及反应性相关研究进展

抗苗勒氏管激素(AMH)的水平对卵巢中的卵泡发育与类固醇激素的产生具有重要意义。体循环中AMH水平受性别和年龄等因素影响,在性腺发育和生殖系统疾病的评价中至关重要。AMH可预测卵巢在辅助生殖技术(assisted reproductive technology,ART)中的反应性及女性绝经时间等,并反映卵巢手术或损伤后的卵巢储备能力。本文对近年来关于AMH评价卵巢储备及ART中卵巢反应性的相关研究成果进行综述。     

单侧输卵管切除对血清抗苗勒氏管激素及卵巢功能的影响

目的:探讨单侧输卵管切除术对育龄期妇女血清抗苗勒氏管激素(AMH)及卵巢功能的影响。方法:选择单侧输卵管切除后行体外受精-胚胎移植(IVF-ET)治疗的77例患者为A组,同期行IVF-ET治疗的无输卵管手术史的75例患者为B组。分析患者促排卵启动日血清AMH水平及促排卵治疗结果。结果:患者促排卵启动日的年龄、体质量指数(BMI)、E2、P4、LH、FSH水平组间均无统计学差异(P0.05);A组的窦卵泡数(AFC)(12.2±4.8)较B组(13.6±5.6)少,但差异无统计学意义(P=0.10);A组血清AMH水平(144.57±107.32 pg/ml)低于B组(184.48±112.94 pg/ml)(P0.05);A组的促性腺激素(Gn)用药量较大(24.2±10.2支),hCG注射日血清E2(4 040.6±2 092.9 pg/ml)较低,子宫内膜较薄(9.77±3.32 mm),有效胚胎数(4.2±3.4枚)、优质胚胎数(3.3±3.0枚)较少,但与B组相比无统计学差异(P0.05)。单侧输卵管切除的术后时间长短与AMH水平无显著相关性(r=0.06,sig=0.58)。结论:单侧输卵管切除后,育龄期妇女的血清AMH水平持久降低,预示卵巢贮备功能受损,难以恢复。     

抗苗勒氏管激素评估卵巢储备功能的临床应用现状

卵巢储备功能指卵巢内存留卵泡的数量和质量,其能间接地反映女性的生育能力。抗苗勒氏管激素(anti-Müllerian hormone,AMH)作为卵巢特异性的生长因子,由颗粒细胞分泌,是预测卵巢储备功能的一个有效指标。血清AMH的水平可以预测卵泡池的大小、卵巢的反应性及女性的绝经年龄,同时可以评估癌症患者的卵巢储备功能。但AMH的测定值受到多种因素的影响,存在一定的局限性。     

抗苗勒管激素影响因素的研究进展

抗苗勒氏管激素(anti-Müllerian hormone,AMH)又称为苗勒管抵制物(Müllerian-inhibiting substance,MIS),是转化生长因子β(transforming growth factor,TGF-β)超家族的成员。AMH具有良好的稳定性,一般情况下在整个月经周期中无明显波动,但是仍有一些因素影响AMH的分泌水平,这些变化在临床中有着重要的意义和价值。本文从多囊卵巢综合征、年龄、肥胖、季节、卵巢储备和性分化异常等6个方面总结了可能引起AMH变化的因素,从而深入认识AMH变化的临床意义和价值。     

抗苗勒氏管激素(AMH)预测卵巢储备功能及反应性的研究

目的:探讨抗苗勒氏管激素(AMH)对卵巢储备功能及卵巢反应性的预测价值。方法:利用ELISA法对228例不孕症患者基础血清AMH蛋白水平(bAMH)进行检测,其中71例初次接受IVF-ET治疗的患者,分别检测IVF周期中FSH注射后各阶段的血清及卵泡液中AMH蛋白水平,分离并采用RT-PCR检测卵巢颗粒细胞AMH mRNA相对含量。结果:①228例不孕症患者bAMH水平与窦卵泡计数成正相关(r=0.907,P<0.01),与患者年龄、初潮年龄、初潮至就诊的年数成负相关(r=-0.833,P<0.01;r=-0.580,P<0.01;r=-0.783,P<0.01)。②71例接受IVF-ET治疗的患者,bAMH与在FSH注射后各阶段血清AMH水平无明显差异(t=0.042,P>0.05;t=0.278,P>0.05;t=0.255,P>0.05)。③血清、卵泡液AMH蛋白表达及颗粒细胞AMH mRNA相对含量与卵巢反应性有关,卵巢低反应组(获卵数≤5个)与正常组(获卵数>5个)比较,差异有统计学意义(P<0.05)。④获卵数与bAMH水平均呈显著正相关(r=0.527,P<0.01)。颗粒细胞AMH mRNA相对含量与成熟卵数、受精卵数显著相关(r=0.479,P<0.01,r=0.529,P<0.01)。⑤发生卵巢过度刺激综合征患者的bAMH蛋白水平较其他患者显著增高(t=3.173,P<0.01)。结论:AMH的表达不受促性腺激素作用的影响,bAMH水平与患者卵巢的储备功能及卵巢反应性有关,可以作为评价卵巢储备功能及预测促排卵中卵巢反应性的血清学标记物。     

抗苗勒氏管激素在多囊卵巢综合征中的诊断价值初探

目的:研究多囊卵巢综合征(PCOS)患者的血清抗苗勒氏管激素(AMH)水平,并初步探讨其在PCOS中的诊断价值.方法:收集2006年6月至12月在我院妇产科就诊的47例PCOS患者(研究组)和年龄匹配的40例健康女性(对照组),应用酶联免疫吸附(ELISA)法检测血清AMH水平.结果:研究组的血清AMH水平明显高于对照组(9.85±4.93 ng/ml vs 7.13±3.02 ng/ml,P=0.002).血清AMH的曲线下面积在总体人群为0.664(P=0.008),以血清AMH 8 ng/ml为相对最佳的诊断界值,敏感度为61.7%,特异度为70.0%.结论:PCOS患者的血清AMH水平明显增高,血清AMH测定对于PCOS的诊断效能较低.     

抗苗勒氏管激素及其受体Ⅱ的基因多态性与卵巢过度刺激综合征关系初探

目的:初步探讨抗苗勒氏管激素(AMH)及其受体Ⅱ(AMHRⅡ)的基因多态性与卵巢过度刺激综合征(OHSS)的关系。方法:采用聚合酶链反应(PCR)和DNA测序法,分别检测27例OHSS患者和22例促排卵后非OHSS患者(对照组)的AMH及其受体AMHRⅡ的基因外显子DNA序列,行单核苷酸多态性(SNP)分析。结果:OHSS组AMH的第1外显子146位G>T、第2外显子134位G>A基因型分布与对照组比较,有统计学差异(P<0.05)。OHSS组AMH基因的第1外显子303位G>A基因型与对照组比较,无统计学差异(P>0.05)。OHSS组和对照组AMHRⅡ基因的1~11号外显子均未检测出SNP突变。结论:AMH基因多态性可能是导致卵巢对外源性激素敏感性增强、OHSS发病的因素之一。     

抗苗勒管激素(AMH)在多囊卵巢综合征患者促性腺激素促排卵治疗中的预测意义

目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者高抗苗勒管激素(anti-Müllerian hormone,AMH)水平对人绝经期促性腺激素(h MG)促排卵结局的影响。方法:采用前瞻性研究,分析63例接受h MG促排卵的PCOS患者。比较对h MG有反应与无反应组间的AMH浓度。采用受试者工作特征(receiver operating characteristic,ROC)曲线评估AMH预测卵巢反应性价值。结果:有反应组AMH水平明显低于无反应组(8.43±2.18μg/L vs 11.05±2.85μg/L,P0.001)。多因素逐步回归分析提示AMH是预测卵巢反应性的唯一指标。ROC曲线分析显示AMH是一项潜在有效的预测卵巢反应性的指标。将血AMH界值10.12μg/L作为判断标准,其预测卵巢对h MG反应的敏感性达91.7%,特异性达66.7%。结论:血清AMH可作为有效的预测PCOS患者对h MG反应性的指标。     

PCOS患者血清抗苗勒管激素(AMH)水平与胰岛素抵抗及雄激素的关系

目的:研究多囊卵巢综合征(PCOS)患者血清抗苗勒管激素(AMH)水平的变化及其与胰岛素抵抗(IR)和雄激素的关系。方法:回顾性分析85例PCOS患者及79例正常女性的体质量指数(BMI)、血清AMH、血糖、胰岛素、雄激素、稳态模型胰岛素抵抗指数(HOMA-IR)间的相互关系。血清AMH采用ELISA法测定,空腹血浆葡萄糖(FPG)采用葡萄糖氧化酶法测定,空腹胰岛素(FIns)采用化学发光法测定,睾酮(T)采用酶联免疫法测定。结果:PCOS组血清AMH水平明显高于对照组;Person相关分析表明,PCOS组血清AMH水平与HOMA-IR及BMI不相关,与雄激素、年龄相关。多元线性回归分析显示,PCOS组中血清雄激素水平是血清AMH的影响因素。结论:PCOS人群中血清AMH较正常女性升高,但其升高与IR无关,而与雄激素水平密切相关。     

Anti-Mullerian hormone and insulin resistance in polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent disease affecting women of reproductive age. It may be associated with metabolic disorders such as insulin resistance (IR) and obesity. The anti-Mullerian hormone (AMH) levels seem to be higher in patients with PCOS.

Objective: The present study was designed to evaluate the association between AMH and insulin in women with PCOS with and without IR.

Methods: Cross-sectional study, including 86 patients, selected and divided into three groups: Group A: 26 women with PCOS and IR; Group B: 30 women with PCOS and without IR; and Group C: 30 controls without PCOS.

Results: We found significant difference between serum AMH levels in the group of women with PCOS and without IR when compared to the control group, thus showing that PCOS and IR play an important role in elevating the levels of this hormone. When the groups were compared with each other following adjustment for BMI, serum AMH levels were significantly higher in the group of women with PCOS and IR.

Conclusion: AMH levels are significantly higher in patients with PCOS, particularly in those women with PCOS and IR. Nevertheless, larger samples are required to confirm these findings.     

二甲双胍在多囊卵巢综合征患者IVF-ET治疗中疗效分析

目的:探讨应用二甲双胍(Met)对多囊卵巢综合征(PCOS)患者行IVF-ET治疗结局的影响。方法:回顾性分析120例行IVF-ET长方案治疗的PCOS患者,按是否预先服用Met分为Met组(M组)66个周期和对照组(NM组)58个周期。结果:①M组与NM组间获卵数(19.9±10.7vs17.8±10.1)、卵裂率(93.43±16.48%vs92.18±15.73%)、移植胚胎数(2.1±0.9vs2.3±0.6)均无统计学差异(P>0.05);②组间hCG注射日E2值(9358.65±1551.10nmol/Lvs14777.44±1799.63nmol/L)、优质胚胎率(40.07%vs30.61%)、临床妊娠率(39.40%vs20.69%)、卵巢过度刺激综合征(OHSS)发生率(9.09%vs22.41%)间有显著差异(P<0.05)。结论:Met在PCOS患者IVF-ET治疗中,可改善患者的临床妊娠结局,降低OHSS发生率。     

Association between anti-Mullerian hormone and insulin resistance in non-obese adolescent females with polycystic ovary syndrome

Objective: The present study was designed to evaluate the association between anti-Mullerian hormone (AMH) and insulin resistance (IR) in non-obese adolescent females with polycystic ovary syndrome (PCOS) with and without IR.

Methods: Seventy-seven consecutive non-obese patients were recruited and distributed into three groups according to diagnoses of PCOS and IR. Group I included 27 females diagnosed with PCOS and IR, group II included 18 females diagnosed with PCOS but without IR, and group III included 32 controls without PCOS.

Results: Group I had significantly higher AMH levels compared to group II and group III (p?p?p?=?0.004). There was a significant positive correlation between serum AMH and HOMA-IR levels in adolescent females with PCOS (p?=?0.003).

Conclusion: We found that serum AMH levels were higher in non-obese adolescent females with PCOS and IR than in PCOS patients without IR and the healthy controls. There was a significant positive correlation between AMH levels and IR in non-obese adolescent females with PCOS.     

抗苗勒管激素与非肥胖型多囊卵巢综合征合并胰岛素抵抗的关系

目的:探究抗苗勒管激素(AMH)与非肥胖型多囊卵巢综合征(PCOS)合并胰岛素抵抗(IR)的关系。方法:研究纳入102例非肥胖型PCOS患者为PCOS组,其中PCOS合并IR组(n=48),单纯PCOS组(n=54),50名非肥胖型健康人作为对照组。比较3组血清AMH水平以及AMH水平与PCOS合并IR的关系。结果:PCOS合并IR组血清AMH水平和HOMA-IR高于单纯PCOS组和对照组,差异有统计学意义(均P0.001)。PCOS组AMH水平与HOMAIR呈正相关(r=0.704,P0.001)。结论:非肥胖型PCOS患者合并IR血清AMH水平升高,AMH水平与PCOS合并IR相关。     

The value of anti-Mullerian hormone in the management of polycystic ovary syndrome in adolescents

Abstract

A prospective study was carried out in 110 adolescents (13–19 years), 90 patients with polycystic ovary syndrome (PCOS) (study group) and 20 healthy adolescents (control group). The study group was divided into two: Group I – patients without insulin resistance (n?=?30) and Group II – patients with insulin resistance (n?=?60). Group I was treated with oral contraceptives (OCs), while Group II was divided into treatment subgroups of 20 patients each: Subgroup A received OCs; Subgroup B ? myo-inositol; subgroup C – OCs + myo-inositol. Data were analyzed at baseline, 3 and 6 months of treatment. Results showed average anti-Mullerian hormone (AMH) levels were significantly higher in PCOS patients (11.8?±?5.3?ng/ml) than in controls (2.98?±?4.5?ng/ml). After treatment, in Group I and Group II Subgroup A: AMH, luteinizing hormone (LH), free testosterone (FT), total testosterone (T), Ov/v, antral follicle count (AFC), and Ferriman–Gallwey modified scale (mFG) significantly decreased, homeostatic model assessment-insulin resistance (HOMA-IR), body mass index (BMI) did not change significantly. In Group II Subgroup B only HOMA-IR and BMI significantly decreased; in Subgroup C all the parameters decreased significantly. The correlation between AMH and hormonal, morphological characteristics of ovaries were established. The results indicate that AMH could possibly be a valuable marker for the diagnosis of PCOS in adolescents, and for the assessment of treatment efficacy as well.     

肥胖与非肥胖多囊卵巢综合征患者血清肿瘤坏死因子-α(TNF-α)水平的比较

目的:比较肥胖与非肥胖多囊卵巢综合征(PCOS)患者血清肿瘤坏死因子-α(TNF-α)水平的差异。方法:55例PCOS患者,根据体质量指数(BMI)分为肥胖组(BMI>25,n=31)和非肥胖组(BMI≤25,n=24);同期选择50例非PCOS育龄妇女,分为肥胖对照组(BMI>25,n=25)和非肥胖对照组(BMI≤25,n=25)。应用酶联免疫吸附法(ELISA)测定血清TNF-α的含量,分析TNF-α与胰岛素抵抗指数(HOMA-IR)的相关性。结果:PCOS肥胖组与PCOS非肥胖组的TNF-α水平分别显著高于其相应的对照组(P<0.01),PCOS非肥胖组的TNF-α水平也显著高于肥胖对照组(P<0.05)。PCOS肥胖组与PCOS非肥胖组之间的TNF-α水平无显著差异(P>0.05)。PCOS组TNF-α与HOMA-IR呈显著正相关(P<0.05)。结论:肥胖与非肥胖PCOS患者的血清TNF-α水平均升高,可能存在肥胖以外升高TNF-α的途径;TNF-α与PCOS的IR发生有密切联系。