巨噬细胞集落刺激因子在卵泡黄素化颗粒细胞中的表达

目的　了解巨噬细胞集落刺激因子 (M CSF)在人卵泡黄素化颗粒细胞中的表达 ,探讨促卵泡激素 (FSH)在体外对人卵泡黄素化颗粒细胞合成分泌M CSF的调节作用。方法　取接受卵母细胞单精子显微注射治疗的 2 0例妇女的卵泡黄素化颗粒细胞 ,采用免疫细胞化学染色法测定黄素化颗粒细胞中M CSF的表达 ,并将黄素化颗粒细胞单独培养及在不同浓度的FSH(2、5、15、2 5IU/ml)作用下培养 72h ,采用酶联免疫吸附法测定黄素化颗粒细胞培养液中的M CSF含量。结果　约 80 %的黄素化颗粒细胞胞浆有M CSF表达 ;黄素化颗粒细胞在培养 72h后 ,基础状态下M CSF分泌量为(5 9± 13)ng/L ,浓度为 2、5、15、2 5IU/ml的FSH作用下M CSF分泌量分别为 (16 5± 32 )、(2 10± 5 8)、(2 99± 6 6 )、(390± 78)ng/L ,在不同浓度的FSH作用下黄素化颗粒细胞培养液中M CSF的含量与基础状态下相比 ,差异均有极显著性 (P <0 0 1)。结论　卵泡黄素化颗粒细胞能合成分泌M CSF ;FSH能促进黄素化颗粒细胞M CSF的分泌 ,FSH对卵泡发育和成熟的调节 ,可能部分通过M CSF及其受体通道完成     

生长激素对卵泡黄素化颗粒细胞分泌雌、孕激素的影响

目的探讨人卵泡黄素化颗粒细胞中生长激素(GH)和胰岛素样生长因子-1(IGF-1)受体的表达,以及GH在体外对人卵泡黄素化颗粒细胞产生雌、孕激素的影响。方法 2010年5月至7月在广州医学院第三附属医院,采用免疫细胞化学染色法,收集24例行体外受精-胚胎移植治疗患者的卵泡液,提取黄素化颗粒细胞,测定其GH和IGF-1受体的表达;并将黄素化颗粒细胞在不同浓度的GH(0、4.7、9.4、18.8nmol/L)作用下单独及与促卵泡素(FSH,75IU/L)共同培养72h,用酶联免疫吸附法测定黄素化颗粒细胞培养液中的IGF-1,用化学发光法测定培养液中雌二醇(E2)和孕酮(P)含量。结果 80%以上黄素化颗粒细胞的GH和IGF-1受体阳性;黄素化颗粒细胞在基础状态下能自分泌一定量的IGF-1(140.00±27.13)μg/L、E2(444.67±67.25)pmol/L和P(655.00±70.07)nmol/L;分别用浓度为4.7、9.4、18.8nmol/L的GH刺激黄素化颗粒细胞合成IGF-1、E2和P,测其含量分别为(140.33±18.60)、(139.08±31.81)、(154.72±32.19)μg/L,(489.00±91.27)、(658.00±219.67)、(660.83±207.95)pmol/L和(821.67±101.27)、(995.00±109.68)、(1193.31±138.80)nmol/L,与基础状态下分泌比较差异无统计学意义(P>0.05);同样浓度GH协同75IU/LFSH刺激黄素化颗粒细胞合成IGF-1、E2和P的含量分别为(149.41±50.30)、155.34±36.34)、(154.33±46.05)μg/L,(627.83±98.44)、(680.17±160.18)、(773.50±80.84)pmol/L和(1785.02±321.61)、(2096.71±344.71)、(3430.02±1538.38)nmol/L,IGF-1与GH剂量相关分析,差异无统计学意义(P>0.05),E2、P水平与GH剂量行相关分析,差异均有统计学意义(P<0.05)。结论卵巢黄素化颗粒细胞存在GH及IGF-1受体;黄素化颗粒细胞能自分泌IGF-1和一定量的E2、P;GH不能直接促进黄素化颗粒细胞分泌E2、P,但能协同FSH促进黄素化颗粒细胞合成E2、P,且呈剂量依赖关系。     

卵泡刺激素对多囊卵巢综合征患者卵巢颗粒细胞分泌抗苗勒管激素的影响

目的 研究卵泡刺激素(FSH)对多囊卵巢综合征(PCOS)患者卵巢颗粒细胞分泌抗苗勒管激素(AMH)的影响.方法 选择2008年8月至2009年12月于中山大学附属第六医院生殖中心就诊的33例PCOS患者,从其直径为8～10 mm的窦卵泡中分离颗粒细胞,并分为以下3组进行培养:未经FSH刺激的颗粒细胞(未刺激组,n=12);外源性FSH刺激的颗粒细胞(体外刺激组,n=12),此组颗粒细胞来源同未刺激组;对患者行FSH促排卵治疗,采集FSH体内刺激的颗粒细胞(体内刺激组,n=21).分别采用ELISA法和实时荧光定量PCR技术检测培养液中颗粒细胞分泌的AMH水平,及AHM mRNA表达水平;构建AMH荧光报告载体,检测卵巢颗粒细胞中AMH启动子的活性.结果 培养液中颗粒细胞分泌的AMH水平,未刺激组为(11.4±4.0)μg/L,体外刺激组为(7.9±1.1)μg/L,体内刺激组为(5.6±1.7)μg/L,体内、体外刺激组分别与未刺激组比较,差异均有统计学意义(P均＜0.05).AMH mRNA表达水平未刺激组为2.5±1.2,体外刺激组为1.5±0.5,体内刺激组为1.1±0.7,未刺激组高于体内、外刺激组,分别比较,差异均有统计学意义(P均＜0.05).未刺激组颗粒细胞中AMH启动子的活性为11.5±2.3,体外刺激组为8.7±2.4,体内刺激组为6.8±2.4,未刺激组高于体内、外刺激组,分别比较,差异均有统计学意义(P均＜0.05).结论 FSH可能通过抑制PCOS患者卵巢颗粒细胞中AMH的启动子活性及其mRNA表达,抑制AHM的过度分泌,促进卵泡的生长发育.     

白介素-6调节颗粒细胞雌孕激素分泌的作用

目的 :探讨白介素 -6 (IL -6 )对颗粒细胞分泌雌孕激素的影响。方法 :收集行 IVF-ET穿卵时的颗粒细胞作体外培养 ,在有或无 FSH条件下 ,以不同浓度的 rh IL-6作用于颗粒细胞 ,2 4、48、72和 96 h后收集培养液作雌二醇、孕酮测定 ,观察基因重组人白介素 -6 (rh IL-6 )对体外培养中的颗粒细胞分泌雌二醇、孕酮的影响 ;通过 m RNA狭缝杂交 (m RNA slotblot)检测颗粒细胞是否存在 IL-6 R m RNA。结果 :在无 FSH条件下 ,rh IL-6对颗粒细胞分泌雌二醇有抑制作用 ,对孕酮分泌的影响不明显 ;而加入 FSH后 ,发现 rh IL-6对 FSH刺激颗粒细胞所分泌的雌二醇、孕酮均有明显抑制作用。这些作用呈现一定的时间和剂量依赖性。结论 :rh IL-6可抑制 FSH刺激颗粒细胞所致的甾体激素分泌 ,从而参与调节卵巢功能。     

卵泡刺激素对上皮性卵巢癌细胞株的增殖及E-钙粘素表达的影响

目的 :研究在上皮性卵巢癌细胞株中卵泡刺激素 (FSH)受体的不同表达并通过不同浓度的FSH作用 ,观察FSH刺激后各卵巢癌细胞株的增殖与上皮钙粘素 (E -cadherin)在各细胞株中的表达情况。方法 :应用逆转录聚合酶链反应(RT -PCR)及免疫细胞化学方法研究体外培养上皮性卵巢癌细胞株HO - 8910、HO - 8910PM及SKOV3中FSH受体表达 ,免疫组化半定量研究各细胞株中E -cadherin表达及其在FSH作用后的表达情况 ,噻唑蓝染色法了解FSH作用后各细胞株的细胞增殖程度。结果 :在卵巢癌细胞株HO - 8910及HO - 8910PM中存在着FSH受体 ,SKOV3细胞株中的FSH受体表达阴性。用不同浓度FSH培养 4 8小时后 ,HO - 8910及HO - 8910PM的细胞增殖指数高于SKOV3。当FSH浓度为 4 0U/L时细胞增殖指数最高 (P <0 .0 5 )。E -cadherin在 3株细胞中的表达随试验中细胞株转移程度的不同而具有差异 ,FSH培养后 ,FSH受体阳性细胞株HO - 8910及HO - 8910PM的E -cadherin表达均减弱。结论 :FSH是FSH受体阳性卵巢癌细胞增长的促进因素并可引起受体阳性肿瘤细胞E -cadherin表达的下调 ,从而增强卵巢癌细胞的转移能力。     

促性腺激素对离体培养金黄色田鼠卵泡生长的影响

本文利用器官培养方法观察了成年金黄色田鼠排卵前Day 4(间情期)和Day 1(动情前期)的卵巢。按培养液中所含激素不同,分四组体外培养三天,观察卵泡生长的变化。结果培养液内未加激素、加促卵泡刺激素(FSH)和加促黄体生成素(LH)组的标本,卵泡生长受抑制,卵母细胞退化。培养液内同时加有促卵泡刺激素(FSH 3.75微克/毫升)和促黄体生成素(LH 8微克/毫升)的标本,在Day 4(间情期)大卵泡直径明显增大至477微米以上、卵泡生长近似动情前期大卵泡大小;Day 1(动情前期)大卵泡生长仍在动情前期阶段,未见有排卵现象。表明成年金黄色田鼠卵巢在体外培养条件下,能反映FSH和LH对卵泡生长的影响。     

血管紧张素(Ang)Ⅱ、Ang-(1-7)对人卵巢黄素化颗粒细胞的增殖及分泌功能的影响

目的:了解血管紧张素(Ang)Ⅱ、Ang-(1-7)对人卵巢黄素化颗粒细胞的增殖及分泌功能的影响。方法:提取行体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)患者卵泡液中的颗粒细胞,经过提纯后随机分为实验组与对照组。实验组根据添加的药物分为AngⅡ组与Ang-(1-7)组。分别向AngⅡ组/Ang-(1-7)组的颗粒细胞培养液中加入10-10~10-5 mmol/L浓度的AngⅡ/Ang-(1-7),对照组的颗粒细胞培养液中不添加药物,各组分别作用24 h、48 h、72 h,用四甲基偶氮唑蓝盐比色法(MTT法)测定颗粒细胞的吸光度(D)值;向AngⅡ组/Ang-(1-7)组的颗粒细胞培养液中分别加入10-6 mmol/L浓度的AngⅡ/Ang-(1-7),对照组的培养液中不添加药物,收集培养0~24 h、24~48 h、48~72 h的上清液,化学发光分析法(CL)测定黄素化颗粒细胞上清液中雌二醇(E2)、孕酮(P)水平。结果:不同浓度的AngⅡ、Ang-(1-7)分别作用颗粒细胞后,其D值均较对照组低,并随着浓度增加D值逐渐降低;随着时间延长,各组D值逐渐升高。10-6 mmol/L浓度的AngⅡ、Ang-(1-7)分别作用于颗粒细胞后,其上清液中E2的浓度均较对照组高,P浓度与对照组无统计学差异,随着时间延长,各组的E2和P含量逐渐增加。结论:AngⅡ及Ang-(1-7)对人卵巢黄素化颗粒细胞生长起抑制作用,其抑制作用随浓度增加逐渐增强。AngⅡ、Ang-(1-7)能够增强人卵巢黄素化颗粒细胞分泌雌激素的作用,但对孕激素的分泌没有影响。提示AngⅡ、Ang-(1-7)在人卵巢黄素化颗粒细胞的增殖及激素分泌中起一定作用,两者可能参与了人类的卵泡闭锁、优势卵泡发育、成熟以及排卵等生理过程。     

年龄与颗粒细胞卵泡刺激素受体表达的关系

目的:探讨卵巢正常反应型妇女中,年龄与颗粒细胞卵泡刺激素受体(follicle-stimulating hormone receptor,FSHR)表达的关系。方法:根据年龄将90例卵巢正常反应型妇女分为A组:>37岁(30例),B组:35～37岁(30例),C组:<35岁(30例)。采用蛋白印迹法测定颗粒细胞FSHR蛋白的水平。电化学发光法测定卵泡液(follicularfluid,FF)中的FSH浓度。比较各组成熟卵泡数、重组FSH(rFSH)使用剂量的差异。结果:3组之间rFSH使用剂量(A组:3494.0±1086.9IU,B组:3000.8±902.9IU,C组:2510.0±726.8IU)、卵泡液FSH浓度(A组:8.6±0.6pmol/L,B组:8.2±0.7pmol/L,C组:7.2±0.6pmol/L)和成熟卵泡数(A组:6.9±1.9,B组:7.9±1.9,C组:9.1±1.6)有显著差异(P均<0.01)。随着年龄增长,FSHR蛋白相对表达量显著降低(A组:20.28±0.08,B组:0.32±0.08,C组:0.36±0.06),P<0.01。结论:年龄与颗粒细胞FSHR蛋白表达有关。临床上对大龄妇女采取增加rFSH剂量的方法并不能增加成熟卵泡数的原因可能与FSHR表达下降有关。     

不同浓度血管活性肠肽(VIP)对新生大鼠原始卵泡体外发育影响的实验研究

目的:观察不同浓度血管活性肠肽(VIP)对新生4 d大鼠卵巢体外培养过程中原始卵泡存活和生长发育的影响。方法:取新生4 d大鼠的卵巢72个,随机分为6组:新鲜组、基础培养组和不同浓度VIP组(10-9~10-6 mol/L)。新鲜组不经培养、其余各组体外培养14 d行组织形态学检查、增殖细胞核抗原(PCNA)免疫组织化学和TUNEL凋亡分析。结果:①各培养组的1级(早期初级)卵泡百分比明显高于新鲜组(P<0.05),且VIP 10-7 mol/L组最高。②各培养组PCNA阳性率与新鲜组比较均有统计学差异(P<0.001);不同浓度VIP组与基础培养组比较有统计学差异(P<0.05);VIP 10-7 mol/L组卵泡PCNA阳性率最高,与其他VIP浓度组比有显著差异(P<0.05),③各培养组卵泡凋亡率均显著高于新鲜组(P<0.001),培养组中以VIP 10-7 mol/L组较低,与VIP 10-8 mol/L组和VIP 10-9 mol/L组间有统计学差异(P<0.05)。结论:在卵巢体外培养过程中,VIP可以促进新生4 d大鼠的原始卵泡向初级卵泡转化;不同浓度的VIP均可降低卵巢组织卵泡细胞的凋亡,提高卵泡体外存活能力,VIP10-7 mol/L较其他浓度更明显地促进卵泡细胞的增殖,降低卵泡细胞的凋亡。     

抑制素-激活素-卵泡抑素系统与PCOS的关系

抑制素(INH)是主要由人体性腺组织分泌的多肽糖蛋白,多囊卵巢综合征(PCOS)患者血清中各型INH浓度的异常,可能和PCOS患者黄体生成素(LH)、卵泡刺激素(FSH)异常及卵泡闭锁有一定关系.激活素(ACT)促进卵泡发育,阻止雄激素(A)的产生,提高FSH和胰岛素的释放.卵泡抑素(FS)是一种ACT/INH结合蛋白,调节卵泡生长发育.卵泡膜细胞及颗粒细胞功能均受抑制素-激活素-卵泡抑素(INH-ACT-FS)系统影响.     

巨噬细胞集落刺激因子对卵泡颗粒黄体细胞性激素分泌的影响及其受体的测定

目的　了解人卵泡颗粒黄体细胞中巨噬细胞集落刺激因子 (M CSF)受体的表达 ,M CSF在体外对人卵泡颗粒黄体细胞产生雌、孕激素的影响。方法　采用免疫细胞化学染色法 ,测定 2 0例行卵母细胞浆内单精子注射治疗患者的卵泡颗粒黄体细胞的M CSF受体 ;采用酶免疫分析法 ,测定卵泡颗粒黄体细胞在M CSF(浓度分别为 0、10、2 5、5 0、10 0、2 5 0ng/ml)单独及与促卵泡激素 (FSH ,浓度75IU/ml)联合作用 72h后的上清液中雌二醇 (E2 )和孕酮 (P)的浓度。结果　约 80 %的颗粒黄体细胞膜上M CSF受体阳性。在无FSH存在时 ,M CSF空白对照颗粒黄体细胞培养上清液中E2 浓度为(2 185± 189)pmol/L ,P浓度为 (315 7± 4 0 1)nmol/L ;M CSF为 10～ 10 0ng/ml时 ,E2 浓度在 (2 789± 36 5 )～ (42 82± 318)pmol/L之间 ,P浓度在 (42 5 6± 5 95 )～ (7789± 82 8)nmol/L之间。在有FSH作用时 ,M CSF空白对照的E2 和P浓度分别为 (5 0 4 5± 4 86 )pmol/L和 (86 6 7± 92 3)nmol/L ;M CSF为 10～ 10 0ng/ml时 ,E2 浓度在 (6 5 6 7± 6 73)～ (8373± 935 )pmol/L之间 ,P浓度在 (10 999± 985 )～ (14 990±115 8)nmol/L之间。M CSF促颗粒黄体细胞E2 和P分泌的作用随浓度增加而增强 (P均 <0 0 5 ) ;M CSF与FSH共同作用下颗粒黄体     

Ovarian follicular maturation in women. II. Reversal of estrogen inhibited ovarian folliculogenesis by human gonadotropin

The current study was undertaken to investigate the role of follicle-stimulating hormone (FSH) in reversing estrogen-induced follicular atresia. Normal menstruating women received ethinyl estradiol (EE2) 50 micrograms/day orally from days 2 to 7 after the onset of menses. Concomitant intramuscular injections of 1.0 ml of saline were administered to group 1, 75 IU of FSH and luteinizing hormone (LH) to group 2, and 150 IU units of FSH and LH to group 3. Daily blood samples were obtained throughout the investigative cycle for FSH, LH, 17 beta-E2, and progesterone. The women in group 1 had evidence of follicular atresia and a significant reduction in serum FSH and LH when compared to group 3 (P less than 0.002 and less than 0.001 respectively). Ovarian follicular development was maintained in groups 2 and 3, based on ultrasound evidence and the interval from menses to midcycle LH surge. These data indicate that the exogenous administration of FSH and LH results in maintenance of ovarian follicular development in women treated with exogenous estrogen.     

Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization

OBJECTIVE: To investigate whether IVF outcome of patients older than 40 years of age with basal FSH levels less than 15 IU/L differs from that in patients 40 years of age or younger with basal FSH levels of 15 IU/L or greater. DESIGN: Prospective observational study. SETTING: Tertiary academic fertility center. PATIENT(S): Women 41 years of age or older with basal FSH levels less than 15 IU/L (n = 50), and women 40 years of age or younger with elevated basal FSH levels (n = 36) undergoing their first IVF cycle. INTERVENTION(S): IVF treatment using a long suppression protocol with recombinant FSH at a fixed starting dose of 150 IU/L. MAIN OUTCOME MEASURE(S): Ovarian response, ongoing pregnancy rates, and implantation rates. RESULT(S): The high FSH group experienced more cycle cancellations due to absent follicular growth than did the high age group (31% vs. 8%). However, the high FSH group had better implantation rates per embryo (34% vs. 11%), higher ongoing rates per ET (40% vs.13%), and higher ongoing pregnancy rates per cycle (25% vs. 10%). In both groups, poor responders had lower pregnancy rates. CONCLUSION(S): The outcome of IVF differs between patients older than 40 years of age with normal FSH levels and relatively young patients with elevated FSH levels. This finding may have implications for the management of these patients.     

瘦素对人卵巢黄素化颗粒细胞雌、孕激素分泌的体外实验研究

目的探讨瘦素在体外对人卵巢颗粒细胞雌激素和孕激素生成的影响。方法将来自体外受精-胚胎移植（IVF-ET）的卵巢黄素化颗粒细胞纯化后，在不同浓度瘦素(0、10、30、100、300ng/ml)和人绝经期促性腺激素（hMG，0、0.1、0.2、0.5、1、2、5、10IU/ml）单独或联合作用下进行体外培养，收集培养液，采用放射免疫方法测定颗粒细胞产生雌二醇及孕酮的量。结果不同浓度的瘦素对雌二醇、孕酮的生成无影响；hMG为5IU/ml时，雌二醇水平平均为2.36×10-11mol/L，加入不同浓度瘦素（10、30、100、300ng/ml），雌二醇的生成均受到明显的抑制，随瘦素浓度增加，雌二醇水平逐渐降低（P<0.05），孕酮水平无明显变化；hMG浓度小于0.5IU/ml时，瘦素对雌二醇生成无影响；hMG浓度大于0.5IU/ml、瘦素为100ng/ml时，雌二醇水平低于不加瘦素的对照（P<0.05）。结论瘦素参与卵巢颗粒细胞激素生成的调节，在卵泡发育和黄体形成中有一定的作用。     

Luteinizing hormone concentrations after gonadotropin-releasing hormone antagonist administration do not influence pregnancy rates in in vitro fertilization-embryo transfer

OBJECTIVE: To determine the impact of circulating LH concentrations during controlled ovarian hyperstimulation on the outcome of IVF. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): Two-hundred seventy women who had a short stimulation protocol with GnRH antagonist and ovarian stimulation with recombinant FSH (rFSH). INTERVENTION(S): GnRH antagonist and rFSH were administered SC; blood samples were collected on the day of GnRH antagonist administration, 1 day after, and on the day of hCG administration. MAIN OUTCOME MEASURE(S): A threshold of 0.5 IU/L on the day of hCG was chosen to discriminate between women with LH concentrations 0.5 IU/L (group B, n = 151). RESULT(S): The two groups were comparable with regard to the clinical parameters. In group A, significantly lower LH concentrations were observed on day 9 of the cycle and on the day of hCG administration. The numbers of oocytes retrieved, embryos obtained, and embryos cryopreserved were significantly higher in group A compared with group B. The proportion of clinical pregnancies was similar in the two groups (21.1% vs. 22.7 % per ET). CONCLUSION(S): In GnRH antagonist and rFSH protocols, suppressed serum LH concentrations do not have any influence on the final stages of follicular maturation, pregnancy rates, or outcomes.     

Elevated peritoneal fluid luteinizing hormone and prolactin concentrations in infertile women with endometriosis

In this study, we compared (Mann-Whitney U-test) the peritoneal fluid FSH, LH and PRL levels, measured by RIA, at the follicular and luteal phases of the menstrual cycle in women with (n = 43; age 25-44 years) and with no evidence of endometriosis (n = 35; age 25-39 years) who were considered as controls. Both follicular and luteal phase FSH concentrations of women with endometriosis were not statistically different (n = 22 vs 18; 0.32-5.8 vs 0.50-8.2 IU/l, P = 0.247; n = 13 vs 14; 0.6-6.5 vs 0.66-6.7 IU/l, P = 0.604) compared to their respective controls. In contrast to FSH, the concentrations of LH at follicular (n = 19 vs 17; 3.1-34.2 vs 2.3-12.2 IU/l, P = 0.01) and luteal (n = 17 vs 15; 2.1-95.4 vs 1.3-17.9 IU/l, P = 0.02) phases of the test group was significantly elevated at both phases of the cycle. With respect to differences in PRL concentrations at follicular phase no significant change (n = 21 vs 16; 1030-5800 vs 1305-4650 mIU/l; P = 0.255) was observed. The greatest difference in luteal PRL concentrations (P = 0.007) was obtained between the women with endometriosis and controls (n = 17 vs 17; 1895-8600 vs 1041-5000 mIU/l). The results suggest that disordered synchronization of neuroendocrine mechanisms controlling LH and PRL may be the underlying abnormality causing infertility in our group of patients with endometriosis.     

Recombinant Human Follicle-Stimulating Hormone for Ovulation Induction in Polycystic Ovary Syndrome: A Prospective, Randomized Trial Of Two Starting Doses in a Chronic Low-Dose Step-up Protocol

Purpose: The aim was to compare the follicular response to 37.5 and 50 IU of recombinant follicle-stimulating hormone (FSH) as starting doses for ovulation induction in patients with polycystic ovary syndrome (PCOS). Methods: Prospective, randomized, crossover study including 15 women with clomiphene citrate-resistant chronic anovulatory infertility. Patients were treated with subcutaneous recombinant FSH at starting doses of 37.5 IU and 50 IU, respectively, according to a low-dose step-up protocol. Each woman received both treatments, in a randomized order, with an interval of 1 month between treatments. Results: All treatment cycles were ovulatory after an appropriate follicular response and hormone levels were similar with both treatments, although the total quantity of FSH required and the mean daily dose required to induce identical follicular development were significantly lower with a starting dose of 37.5 IU FSH. The mean duration of treatment to achieve ovulation was approximately 13 days with both treatments but treatment periods 20 days were required in some patients. Conclusions: In women with PCOS, a starting dose of 37.5 IU recombinant FSH may be adequate to induce follicular growth. However, the use of low starting doses may result in some cases in increased treatment periods and need for monitoring.     

Production of pregnancy-associated plasma protein-A (PAPP-A) by cultured tumour granulosa cells

Ten ovarian and 2 cervical tumour cell lines were analysed for the production of pregnancy-associated proteins. Pregnancy-associated plasma protein-A (PAPP-A) was detected by radioimmunoassay in culture media of 2 out of 4 (50%) tumour granulosa cell lines (mean = 104 microIU/10(5) cells/24 h) but not in any ovarian (n = 6) or cervical (n = 2) tumour cell lines. By contrast, human chorionic gonadotrophin (hCG), pregnancy specific beta 1-glycoprotein and alpha-fetoprotein (AFP) were not detected in any of the PAPP-A positive media. Only two cell lines produced hCG (58.5 and 25.5 mIU/10(5) cells/24 h). No AFP was produced by any of these 12 cell lines, whereas placental protein 5 was positive in 7. None of these proteins were detected in the culture media of 4 cell lines. In vitro derived PAPP-A was immunologically indistinguishable from either pregnancy or ovarian follicular PAPP-A. All PAPP-A species interacted reversibly with immobilised heparin and were determined by molecular sieve chromatography to have an apparent molecular weight of 820,000 daltons. Cultured tumour granulosa cells specifically synthesised and secreted a large protein which was immunologically and physicochemically indistinguishable from in vivo (pregnancy and ovarian follicular) derived PAPP-A.     

Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone

OBJECTIVE: To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG. DESIGN: Controlled, prospective, randomized comparison of fixed gonadotropin regimens. SETTING: Academic research institution. PATIENT(S): Fifty infertile patients who were candidates for IUI. INTERVENTION(S): Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen). MAIN OUTCOME MEASURES: Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications.Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ. CONCLUSION: The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha.