罗布麻颗粒对化疗型卵巢早衰大鼠Bax和Bcl-2蛋白表达的影响

目的： 探讨罗布麻颗粒对化疗型卵巢早衰大鼠Bax 和Bcl-2 蛋白表达的影响。方法：性成熟SD雌鼠随机分 为对照组、造模组,腹腔注射（ 顺铂1.5 mg/kg）制备卵巢早衰模型,随机分为卵巢早衰模型组和罗布麻颗粒高、 中、低剂量治疗组。H-E 染色观察卵巢形态;ELISA 检测各组大鼠血清Bax、Bcl-2 和雌二醇、促黄体生成素（LH）、 促卵泡激素（FSH））的含量,免疫组织化学法检测卵巢Bax 与Bcl-2 蛋白表达。结果：卵巢早衰模型组大鼠中初 级卵泡减少,闭锁卵泡增多,罗布麻颗粒高剂量治疗组大鼠可见初级卵泡,闭锁卵泡较卵巢早衰模型组减少;卵 巢早衰模型组大鼠血清中雌二醇及Bcl-2 含量降低,FSH、LH、Bax 的含量升高; 各药物治疗组雌二醇、Bcl-2 含 量升高,FSH、LH、Bax 的含量降低;Bax 蛋白主要表达在颗粒层细胞及卵泡液中,卵巢早衰模型组大鼠较对照 组表达显著升高, 各药物治疗组在不同程度上能够降低其表达;Bcl-2 蛋白在各组主要表达在颗粒层细胞中,卵 巢早衰模型组大鼠较对照组表达显著下降, 各药物治疗组在不同程度上能够升高其表达。结论：顺铂能够导致雌 性大鼠血清中性激素水平的紊乱及卵巢组织形态的改变,可能与细胞凋亡因子Bax 与Bcl-2 在血清及卵巢组织中 表达水平的高低有关;罗布麻颗粒可能通过下调Bax 蛋白、上调Bcl-2 蛋白从而改善顺铂致卵巢早衰大鼠的卵巢 功能。     

中药六味地黄汤对衰老大鼠性激素与其受体表达的影响

目的探讨衰老雌性大鼠性激素及其受体的变化情况和六味地黄汤延缓卵巢组织衰老的作用机制。方法 D-半乳糖连续腹腔注射致亚急性衰老动物模型,造模后灌胃六味地黄汤连续60天后,大鼠断头取垂体、卵巢。采用全自动微粒子化学发光免疫分析方法检测各组大鼠血清LH,E2,FSH的含量;原位杂交方法检测各组大鼠卵巢细胞FSHR和LHR的变化;Western Bloting法检测各组大鼠卵巢ER的变化。结果同正常对照组相比,模型组大鼠垂体指数和卵巢指数均明显降低,血清E2含量明显降低、LH、FSH升高,ER、FSHR、LHR的表达明显降低,差异有统计学意义(P<0.05)。与模型组比较,六味地黄汤组垂体指数和卵巢指数均明显增高,血清E2含量明显升高、LH、FSH降低,ER、FSHR、LHR的表达明显升高,呈现一定的剂量依赖性。结论衰老时大鼠卵巢正常功能被破坏,六味地黄汤通过对性激素和其受体的调节而延缓了卵巢的衰老。     

毛蕊花糖苷对顺铂诱导小鼠卵巢损害的保护作用

目的研究毛蕊花糖苷对顺铂所致卵巢损害的保护作用。方法 48只昆明雌性小鼠随机分成4组:对照组、顺铂组、顺铂+毛蕊花糖苷低浓度干预组及顺铂+毛蕊花糖苷高浓度干预组。顺铂组、顺铂+毛蕊花糖苷干预组,分别给予腹腔注射顺铂(2.0 mg/kg·d),同时给予等体积生理盐水及不同浓度毛蕊花糖苷(30、60 mg/kg·d)灌胃处理。干预一周后,停止腹腔注射顺铂,毛蕊花糖苷持续干预一周。对照组小鼠给予同等剂量的生理盐水腹腔注射及灌胃处理。分别通过ELISA方法检测各组小鼠血中雌激素(estradiol,E2)及促卵泡激素(follicle-stimulating hormone,FSH)水平、HE染色观察卵巢形态结构、TUNEL染色检测卵巢细胞凋亡情况、免疫组化法及Western blot方法检测卵巢组织中凋亡相关蛋白(cleaved-caspase 3、cleaved-PARP)的表达水平。结果顺铂组小鼠可见血FSH水平升高,卵巢可见发育中窦状卵泡内的颗粒细胞层明显减少,卵母细胞核碎裂及闭锁卵泡增加;凋亡相关蛋白cleaved-caspase 3、cleaved-PARP的表达水平升高,而毛蕊花糖苷药物干预后在一定程度上能逆转卵巢功能及结构损害,并使卵巢凋亡相关蛋白下调来抑制卵巢组织的凋亡。结论毛蕊花糖苷具有对抗顺铂所致卵巢组织凋亡,保护化疗药物引起的卵巢功能损伤的作用。     

Smad2/3与Smad7在大鼠化疗性卵巢早衰卵泡中的表达和意义

目的 探讨顺铂对大鼠卵巢结构和功能损伤的影响及其可能的分子机制。方法 3月龄SD 雌性大鼠随机分为对照组（C组,5只）和化疗组（H组,5只）。H组给予每只大鼠腹腔注射顺铂2 mg/（kg.d）,C组给予腹腔注射等体积生理盐水,连续注射7 d后检测大鼠卵巢指数（卵巢湿重/体重）;酶联免疫吸附法检测血清雌二醇（E₂）和促卵泡刺激素（FSH）水平;苏木素-伊红染色观察卵泡发育并计数各级卵泡;免疫组织化学和Real-time PCR法检测各组Smad2、磷酸化Smad2（p-Smad2）、Smad3、磷酸化Smad3（p-Smad3）、Smad4和Smad7的蛋白和mRNA表达。结果 与C组相比,H组大鼠卵巢体积减小,生长卵泡数明显减少（P<0.05）,大鼠卵巢指数下降（P<0.05）,血清中E2水平降低和FSH水平上升（P<0.05）。免疫组织化学和Real-time PCR结果显示,Smad2（p-Smad2）、Smad3（p-Smad3）、Smad4和Smad7蛋白在卵巢各级卵泡均有表达,H组Smad2蛋白和mRNA表达增加（P<0.05）,Smad2磷酸化水平（p-Smad2）表达增高（P<0.05）;Smad3、Smad4和Smad7蛋白和mRNA表达减少（P<0.05）,p-Smad3 表达降低（P<0.05）。结论 顺铂诱导大鼠卵泡损伤并促进卵巢早衰,引起卵泡细胞内Smad2表达增加,Smad3、Smad7表达降低,Smad细胞内信号通路参与了化疗性卵巢损伤的过程。     

毓麟珠对卵巢早衰大鼠SIRT1-FoxO1-自噬通路的调控作用

目的：探讨毓麟珠对卵巢早衰（POF）大鼠自噬的影响,并分析其防治POF的作用机制。方法：雌性SD大鼠采用随机数字表法选取16只为正常组,其余大鼠通过腹腔注射环磷酰胺建立POF模型。造模成功大鼠分为POF组、戊酸雌二醇（0.09 mg/kg）组（简称雌二醇组）、低剂量（7.56 g/kg）毓麟珠组、高剂量（15.12 g/kg）毓麟珠组和毓麟珠+沉默信息调节因子1(SIRT1)抑制剂EX527组（简称毓麟珠+EX527组）,每组16只。低、高剂量毓麟珠组大鼠分别灌胃相应剂量的毓麟珠药液,雌二醇组大鼠给予戊酸雌二醇溶液灌胃,毓麟珠+EX527组大鼠在给予15.12 g/kg毓麟珠药液灌胃的同时腹腔注射10 mg/kg EX527,正常组和POF组大鼠给予等体积的生理盐水干预,每天1次,连续给药3周。给药结束后,记录各组大鼠的双侧卵巢重量和体重,计算卵巢指数;ELISA检测各组大鼠血清雌二醇（E2）、促卵泡激素（FSH）和抗缪勒管激素（AMH）水平;检测各组大鼠卵巢组织丙二醛（MDA）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平;苏木精-伊红（HE）染色和TUNEL染色观察各组大鼠卵...     

中药木尼孜其对慢性应激型卵巢早衰大鼠性腺轴的影响

目的:通过观察慢性应激所致卵巢早衰大鼠垂体、下丘脑及卵巢的组织形态,探讨中药木尼孜其对慢性应激型卵巢早衰的作用。方法:选用90只性成熟Sprague-Dawley雌性大鼠,随机选取10只设为正常组,其余80只为应激模型组,模型建成之后从中筛选出成卵巢早衰者分为卵巢早衰模型组及卵巢早衰药物干预高、中、低剂量组。运用HE染色及Masson染色观察垂体、下丘脑及卵巢组织形态变化并计算卵巢和子宫指数;用ELISA试剂盒检测大鼠血清中雌二醇(E_2)、卵泡刺激素(FSH)及黄体生成素(LH)的水平。结果:中药木尼孜其对慢性应激致卵巢早衰大鼠的垂体、下丘脑及卵巢组织形态以及激素水平有一定的改善作用。与模型组比较,各药物干预组均有不同程度的改变;与正常组比较,模型组的E_2水平明显降低(P0.05),LH和FSH水平显著升高(P0.05)。结论:慢性应激能够导致卵巢早衰的发生;中药木尼孜其有防治卵巢早衰的作用,能有效改变性腺轴的组织形态及激素水平。     

脐带间充质干细胞移植对卵巢早衰模型小鼠卵巢功能的影响

目的探讨人脐带间充质干细胞(hUCMSCs)移植小鼠卵巢修复化学治疗药物诱导的卵巢早衰(POF)。方法选择雌性ICR小鼠40只,鼠龄8周,体质量25～30 g。将ICR小鼠采用SPSS生成随机数字分为空白对照组、POF组、h UCMSCs组。空白对照组不做任何处理,POF组与hUCMSCs组每天腹腔注射环磷酰胺(CTX)70 mg/mL,连续15 d,建立POF模型。建模成功后hUCMSCs组小鼠经尾静脉注射hUCMSCs进行治疗,POF组注射同等剂量的0.9%氯化钠溶液(生理盐水)。观察小鼠一般情况及体质量,并在移植后的7 d、14 d测定血清中雌激素(E2)、卵泡刺激素(FSH)、抗苗勒管激素(AMH)含量及观察卵巢组织形态改变。结果建模完成后,与空白对照组比较,POF组和hUCMSCs组血清E2、AMH均都降低,血清FSH升高,其差异均有统计学意义(P <0.05);hUCMSCs移植后7 d,与POF组比较[(94.39±14.99) mIU/mL、(60.92±14.60) pg/mL、(2 870.00±801.74) pg/mL],hUCMSCs组血清FSH[(80...     

补肾活血方对小鼠卵泡刺激素及其受体mRNA表达的影响

目的:探讨补肾活血复方中药对免疫性卵巢早衰小鼠卵泡刺激素(Follicle stimulating hormone,FSH)及其受体(Follicle stimulating hormone receptor,FSHR)mRNA表达水平的影响。方法:以小鼠透明带3(Zona pellucida3)为抗原,皮下多点注射免疫雌性小鼠建立免疫性卵巢早衰模型,以生理盐水注射免疫的小鼠作为空白对照组。设补肾活血中药低、中、高不同剂量的3组治疗组,以泼尼松、倍美力为西药治疗对照组,用酶联免疫竞争法检测小鼠治疗后血清中抗透明带抗体(ZPAb)、FSH和雌二醇(E2)浓度,用实时荧光定量逆转录-多聚酶链反应(RT-PCR)检测小鼠卵巢组织FSHR mRNA表达水平。结果:模型组小鼠血清ZPAb的含量明显比空白对照组高,但血清E2的含量比空白对照组低,差异都有显著性意义(P0.01);补肾活血中药治疗的3组小鼠血清E2的含量都比模型组有显著性升高,差异有非常显著性意义(P0.001)。模型组小鼠血清FSH的含量与空白对照组比较,差异没有统计学意义(P0.05),补肾活血中药治疗的3组小鼠血清FSH的含量与模型组比较,含量都有显著性升高,差异有显著性意义(P0.05)。模型组小鼠卵巢组织FSHR表达的mRNA量比空白对照组低,但差异没有统计学意义(P0.05);补肾活血中药治疗的3组小鼠卵巢组织FSHR表达的mRNA量比模型组高,差异有显著性意义(P0.05)。小鼠血清E2的含量与卵巢组织FSHR mRNA表达量呈线性正相关关系(R2=0.359,F=64.888,P0.001)。结论:补肾活血复方中药通过促进垂体分泌FSH的增加和卵巢颗粒细胞表面FSHR表达量的增加,提高卵巢组织对FSH的反应性,促使卵巢颗粒细胞分泌雌激素量增加,并且卵巢颗粒细胞分泌E2的量与卵巢颗粒细胞表面FSHR表达量呈正相关关系。     

白藜芦醇治疗POI大鼠药物浓度筛选

目的　通过观察不同浓度白藜芦醇治疗早发性卵巢功能不全（POI）成模大鼠的疗效，确定其治疗早发性卵巢功能不全大鼠的最佳药物浓度。 方法　将90只5周龄SPF级SD健康雌性大鼠按随机数字表分为低剂量白藜芦醇灌胃治疗组(a组18只)、中剂量白藜芦醇灌胃治疗组(b组18只)、高剂量白藜芦醇灌胃治疗组(c组18只)、模型对照组(d组18只)、空白对照组(e组18只)。e组从造模前的动物中随机抽取；a、b、c、d组从成功造模（72只给予雷公藤多苷片50 mg·kg-1·d-1 灌胃14 d，根据观测指标确定早发性卵巢功能不全成模）的动物中随机分组获得。a、b、c组分别采用每日20、50、80 mg/kg 灌胃剂量，模型对照组采用0.5％羧甲基纤维素钠溶液灌胃。42 d后采用ELISA法检测大鼠血清性激素：抗苗勒管激素（AMH）、黄体生成素（LH）、卵泡刺激素（FSH）、雌二醇（E2）水平，HE染色镜检大鼠单位卵巢面积内成熟卵泡、闭锁卵泡和黄体数，评价其疗效。 结果　不同浓度白藜芦醇灌胃治疗组POI大鼠较0.5％羧甲基纤维素溶液灌胃组POI大鼠血清中AMH、E2水平高（P<0.05），LH、FSH水平低（P<0.05）。不同浓度白藜芦醇灌胃治疗组POI大鼠较空白对照组大鼠血清中AMH、E2水平低（P<0.05），LH、FSH水平高（P<0.05）。与a、b、c、e组比较，d组卵巢内颗粒细胞层数，成熟卵泡数以及黄体数量少（P<0.05），闭锁卵泡数明显增加（P<0.05）。 结论　不同浓度白藜芦醇灌胃治疗POI大鼠均有一定的疗效，50 mg/kg浓度效果最好，是最佳药物浓度。     

AMH、E2、FSH/LH联合检测评估不孕症女性卵巢状态的效果

目的:分析AMH、E2、FSH/LH联合检测评估不孕症女性卵巢状态的效果.方法:将本院2019年1月至2021年5月间收诊的103例不孕症患者作为研究对象.根据患者促排卵期间的卵子数目进行分组,分为正常组、高反应组、低反应组.分析比较三组患者经期第2-3d血清中抗苗勒管激素(Anti-mullerian Hormone,AMH)、雌二醇(Estradiol,E2)、促卵泡激素(Follicle Stimulating Hormone,FSH)/促黄体生成素(Luteinizing Hormone,LH)水平,并对患者卵巢储备和反应程度进行对比研究,从而分析AMH、E2、FSH/LH联合检测评估不孕症女性卵巢状态的效果.结果:三组比较,基础E2、FSH/LH水平呈现高反应组<正常组<低反应组,而AMH水平表达呈现高反应组>正常组>低反应组(P<0.05);单项AMH检测、E2检测、FSH/LH检测卵巢高反应性患者的灵敏度、特异度分别为77.54％、82.69％、65.71％、81.32％、73.95％、76.43％,AMH+E2+FSH/LH联合检测卵巢高反应性患者的灵敏度、特异度为87.44％、89.54％均高于单项检测(P<0.05);单项AMH检测、E2检测、FSH/LH检测卵巢低反应性患者的灵敏度、特异度分别为74.66％、80.41％、63.54％、82.73％、72.19％、79.62％,AMH+E2+FSH/LH联合检测卵巢低反应性患者的灵敏度、特异度为86.93％、85.60％均高于单项检测(P<0.05).结论:AMH、E2、FSH/LH联合检测对不孕症女性卵巢储备功能及卵巢反应程度有较高评估价值,应推广应用.     

Anti‐Müllerian hormone levels in patients with turner syndrome: Relation to karyotype,spontaneous puberty,and replacement therapy

Most girls with Turner syndrome (TS) suffer from incomplete sexual development, premature ovarian failure, and infertility due to abnormal ovarian folliculogenesis. Serum anti‐Müllerian hormone (AMH) levels reflect the ovarian reserve in females, even in childhood. Thus, we aimed to assess serum AMH levels in girls with TS and its relation to karyotype, spontaneous puberty, and growth hormone (GH) therapy. Fifty TS were compared to 50 age‐ and sex‐matched controls. All subjects were subjected to history, anthropometric assessment, Tanner pubertal staging and measurement of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and AMH. Karyotype results were obtained from patients’ records. Serum AMH was measurable in 12 TS patients (24%). The lowest frequency of measurable AMH was in patients with a karyotype of 45,X. The measurable AMH was associated with spontaneous breast development (p = .003) and spontaneous menarche (p = .001). AMH correlated negatively with FSH (r = ?.846, p = .000) and LH (r = ?.83, p = .034). GH therapy increased the odds of having measurable AMH in TS girls (p = .002). In conclusion, AMH was associated with karyotype, spontaneous pubertal development, LH, and FSH in TS girls and may serve as a useful marker of ovarian function and ongoing follicular development in prepuberty.     

Fresh human orthotopic ovarian cortex transplantation: long-term results

BACKGROUND: Ovarian orthotopic transplantation in patients with premature ovarian failure is reported to result in full-term pregnancies. Ischaemia and freezing/thawing are potentially injurious for tissues. This study was designed to analyse the effect of ischaemia on long-term ovarian function in humans. METHODS: Prospective case-control study. Subjects were 12 premenopausal women undergoing hysterectomy and fresh orthotopic transplantation of the entire ovarian cortex plus a control group of five patients undergoing hysterectomy only. Follow-up lasted 2 years. Serum FSH and anti-Müllerian hormone (AMH) were recorded, and ovulatory cycles were determined by vaginal ultrasound and serum progesterone levels. RESULTS: Follow-up showed that ovulation was restored in 11 of the 12 patients who received grafts over the duration of the study (9.3 +/- 1.73 ovulations versus 12.0 +/- 0.86 in controls, NS), and 9 of 12 patients remained ovulatory after 2 years. We identified four patterns of FSH secretion during the study, 5 of 12 (41.7%) women having the same pattern as controls. There was a trend for serum AMH levels 7 days after surgery (0.16 +/- 0.02 microg/l) to be lower than pre-surgery levels (0.38 +/- 0.09 microg/l, P = 0.07) and higher in women whose FSH patterns suggested normal ovarian function, but the results did not reach significance. After transplantation, FSH correlated more closely (r = -0.639, P = 0.02) with normal ovarian function than AMH (r = 0.465, P = 0.12). CONCLUSIONS: Fresh orthotopic ovarian cortex transplantation is a viable procedure. It maintains normal ovarian function after 2 years in 75% of cases and preserves ovarian function against ischaemia in 41.7% of patients.     

Anti-Müllerian hormone concentrations in maternal serum during pregnancy

BACKGROUND: In females, anti-Müllerian hormone (AMH) is expressed only by the ovary. AMH is secreted by the granulosa cells of ovarian follicles and appears to regulate early follicle development. AMH is detected in serum from women of reproductive age and its levels vary slightly with the menstrual cycle, reaching the peak value in the late follicular phase. This study investigated serum AMH levels throughout gestation and after delivery in healthy pregnant women. METHODS: This cross-sectional study recruited pregnant women and healthy non-pregnant women, 84 in total. AMH, FSH and E2 were measured in the follicular phase, in the three trimesters of pregnancy and in early puerperium. RESULTS: Estradiol and FSH levels followed the expected patterns during gestation. During the follicular phase of the menstrual cycle AMH levels were 1.9 +/- 0.5 ng/ml. In the three trimesters of pregnancy and in early puerperium AMH levels were: 2.1 +/- 0.56, 2.4 +/- 0.64, 1.95 +/- 0.6 and 2.05 +/- 0.55 ng/ml respectively. No significant modifications were found in AMH levels during pregnancy and in the early puerperium. CONCLUSIONS: This study has obtained information on AMH and on the possible relationship with FSH. We hypothesize that the profile of the new marker of ovarian activity AMH may indicate that initial non-cyclic ovarian follicular activity during pregnancy is not abolished. Moreover FSH, does not seem to play a direct role on AMH synthesis and secretion.     

Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B,estradiol, FSH and LH on day 3

BACKGROUND: The study aim was to compare the relationship between serum anti-Müllerian hormone (AMH) levels and other markers of ovarian function with early antral follicle count on day 3. METHODS: A total of 75 infertile women was studied prospectively. On cycle day 3, serum levels of AMH, inhibin B, estradiol (E(2)), FSH and LH levels were measured, and the number of early antral follicles (2-10 mm in diameter) estimated at ultrasound scanning to compare the strengths of hormonal-follicular correlations. RESULTS: Median (range) serum levels of AMH, inhibin B, E(2), FSH and LH were 1.39 ng/ml (0.24-6.40), 90 (16-182) pg/ml, 31 (15-111) pg/ml, 7.0 (2.9-19.3) mIU/ml and 4.7 (1.2-11.7) mIU/ml respectively, and follicular count was 12 (1-35). Serum AMH levels were more strongly correlated (P < 0.001) with follicular count (r = 0.74, P < 0.0001) than were serum levels of inhibin B (r = 0.29, P < 0.001), E(2) (r = -0.08, P = NS), FSH (r = -0.29, P < 0.001) and LH (r = 0.05, P = NS). CONCLUSIONS: Serum AMH levels were more robustly correlated with the number of early antral follicles than inhibin B, E(2), FSH and LH on cycle day 3. This suggests that AMH may reflect ovarian follicular status better than the usual hormone markers.     

Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies

BACKGROUND: In female cancer survivors, the accelerated loss of primordial follicles as a result of gonadal damage may lead to premature ovarian failure (POF). However, the extent of the damage is unpredictable. Anti-Müllerian hormone (AMH) constitutes a sensitive marker of ovarian reserve. Serum AMH levels were measured to assess sub-clinical ovarian damage in patients treated with gonadotoxic therapy. METHODS: In 25 patients with haematological malignancies, serum AMH concentrations were measured prior to and after cancer therapy and were compared with normo-ovulatory controls. RESULTS: In all patients, AMH concentrations were lower than controls prior to treatment. Thirteen patients were treated with multi-drug chemotherapy. Although in most patients treated with chemotherapy menstrual cyclicity was restored, median serum AMH levels were lower than in controls. Twelve patients had stem cell transplantation (SCT) after total body irradiation. They all developed POF and their serum AMH concentrations were undetectable. CONCLUSIONS: Female cancer survivors treated with SCT all developed POF. Hence, in these patients fertility preservation should be considered. In patients treated with chemotherapy, ovarian reserve seems to be compromised as well.     

Serum anti-Müllerian hormone dynamics during controlled ovarian hyperstimulation

BACKGROUND: The study aim was to investigate possible changes in serum anti-Müllerian hormone (AMH) levels during controlled ovarian hyperstimulation (COH), and their possible relationship with follicular development and other ovarian hormones. METHODS: A total of 93 women undergoing COH with GnRH agonist and FSH was studied prospectively. Serum levels of AMH, inhibin B, estradiol (E(2)), progesterone, testosterone and Delta(4)-androstenedione were measured when pituitary suppression was achieved (baseline), on days 6 and 8 of FSH treatment, and on the day of hCG. The number of small (<12 mm) and large (>/=12 mm) antral follicles were estimated using ultrasound. RESULTS: Serum AMH levels declined progressively (baseline, 1.21 +/- 0.11 ng/ml; day 6, 0.91 +/- 0.09 ng/ml; day 8, 0.77 +/- 0.08 ng/ml; and day of hCG, 0.53 +/- 0.06 ng/ml), whereas-as expected-the other hormone levels increased during FSH treatment. Throughout COH, serum AMH levels correlated positively with the number of small but not large antral follicles, and with inhibin B serum levels. No correlation between AMH and the other hormones was observed. CONCLUSIONS: Serum AMH levels decline gradually during multiple follicular maturation, probably reflecting the dramatic reduction in the number of small antral follicles due to COH, and confirming the scarce AMH expression by larger follicles.     

Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women

BACKGROUND: In mice, anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment and decreases FSH sensitivity. Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach. METHODS: The association of the AMH Ile(49)Ser and the AMH type II receptor (AMHR2) -482 A > G polymorphisms with menstrual cycle characteristics was studied in a Dutch (n = 32) and a German (n = 21) cohort of normo-ovulatory women. RESULTS: Carriers of the AMH Ser(49) allele had higher serum estradiol (E(2)) levels on menstrual cycle day 3 when compared with non-carriers in the Dutch cohort (P = 0.012) and in the combined Dutch and German cohort (P = 0.03). Carriers of the AMHR2 -482G allele also had higher follicular phase E(2) levels when compared with non-carriers in the Dutch cohort (P = 0.028), the German cohort (P = 0.048) and hence also the combined cohort (P = 0.012). Women carrying both AMH Ser(49) and AMHR2 -482G alleles had highest E(2) levels (P = 0.001). For both polymorphisms no association with serum AMH or FSH levels was observed. CONCLUSIONS: Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E(2) levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary.     

The ovarian markers of the FSH insufficiency in functional hypothalamic amenorrhoea

BACKGROUND: The purpose of this work was to revisit the gonadotrophin insufficiency of functional hypothalamic amenorrhoea (FHA) with the use of relevant ovarian markers. METHODS: Serum anti-Mullerian hormone (AMH), estradiol (E2), inhibin B, LH and FSH were immunoassayed in 31 women with FHA and in 30 healthy women in early follicular phase. The ovarian antral follicle number (FN) was determined within two distinct diameter ranges (2-5 and 6-9 mm) by ultrasound in real time, the same day as the blood sampling. RESULTS: The 2-5 mm FN was similar between the two groups, while the 6-9 mm FN was significantly less in FHA than in controls, in relation with lower serum FSH levels (r=0.428; P<0.024). Nine (29%) FHA patients had a low serum basal FSH level (i.e. <4.5 IU/l, 5th percentile of control values). In the 22 (71%) patients with apparently normal FSH, the mean 6-9 mm FN was similar to controls. However, in this sub-group, the mean AMH serum level and the AMH:2-5 mm FN ratio were significantly higher and the mean inhibin B serum level was significantly lower than in controls. No significant relationship was found between the serum LH levels and the FN, AMH or inhibin B values. CONCLUSION: Only a minority of patients with FHA have a low serum basal FSH level, and we show that this is associated with fewer 6-9 mm follicles at the ovarian level. Despite a normal serum FSH level and 6-9 mm FN in the majority of patients with FHA, the functional follicle markers are abnormal. This suggests that the FSH action on the ovary is incomplete and is not properly reflected by its serum level nor by FN at ultrasound.