二甲双胍/CC/HMG序贯用药治疗胰岛素抵抗PCOS患者的临床研究

目的 :探讨二甲双胍对胰岛素抵抗多囊卵巢综合征 (PCOS)患者的治疗效果及作用机理。方法 :随机将 69例胰岛素抵抗PCOS患者分为A、B两组。A组 34例用Diane 35治疗 3个周期后用CC +HMG促排卵 ;B组 35例用二甲双胍治疗 3个月后用CC +HMG促排卵。观察两组患者治疗前后的BMI、T、FINS、TNF α及排卵率。结果 :两组患者治疗后BMI及T差异无显著性(P >0 .0 5) ;FINS、TNF α及排卵率差异有显著性 (P <0 .0 5)。结论 :胰岛素抵抗PCOS患者治疗的关键是应用胰岛素增敏剂降低FINS ,二甲双胍对于PCOS合并不孕的治疗效果优于Diane 35。     

两种剂量来曲唑与克罗米芬对多囊卵巢综合征患者子宫卵巢血流动力学的影响

目的:探讨2种剂量来曲唑(LE)与克罗米芬(CC)对多囊卵巢综合征(PCOS)患者子宫卵巢血流动力学的影响。方法:2种剂量LE与CC治疗90例PCOS不孕症患者,随机分CC组(A组,n=32,50 mg/d)、低剂量LE组(B组,n=30,2.5 mg/d)和高剂量LE组(C组,n=28,5.0 mg/d)。同时以28例正常育龄妇女作为对照组(D组)。经阴道超声监测子宫卵巢血流的参数,比较排卵率、妊娠率。结果:①LE的2个剂量组子宫卵巢血流均出现类似正常育龄妇女的周期性血流变化;②C组方案治疗PCOS有较高的排卵率和妊娠率。结论:来曲唑改善了PCOS患者的子宫卵巢血流供应,5.0 mg可能有更好的促排卵效果。     

不同雄激素水平PCOS患者诱导排卵临床结局分析

目的:探讨多囊卵巢综合征(PCOS)患者在不同雄激素水平下诱导排卵的临床妊娠结局。方法:PCOS合并不孕患者352例,根据诱导排卵前基础睾酮(T)水平分为4组:A组60例,基础T正常,直接诱导排卵;B组64例,基础T正常,但仍给予达英-35治疗3个周期后诱导排卵;C组120例,基础T升高,给予达英-35治疗3个周期,复查T正常后诱导排卵;D组108例,基础T升高,给予达英-35治疗3个周期,复查T仍高于正常水平,经患者知情同意后,诱导排卵。比较4组子宫内膜厚度、尿促性素(HMG)用量、周期排卵率、临床妊娠率、流产率的差异。结果:4组子宫内膜厚度、排卵周期临床妊娠率组间比较差异无统计学意义(P>0.05);A组HMG用量最多,周期排卵率、总临床妊娠率最低,与其它3组的差异均有统计学意义(P<0.01,P<0.01,P<0.05);B、C、D组间周期排卵率、总妊娠率比较差异无统计学意义(P>0.05)。A组早期流产率最高,但4组间比较差异无统计学意义(P>0.05)。结论:基础T水平正常的PCOS患者,诱导排卵前应用口服避孕药治疗可改善临床妊娠结局;口服避孕药治疗后T未降至正常水平,且有生育要求的PCOS患者可试行诱导排卵治疗。     

地塞米松对伴有肾上腺雄激素分泌过多的PCOS患者的疗效观察

目的:探讨地塞米松对伴肾上腺雄激素分泌过多PCOS患者的疗效。方法:采用前瞻、随机、对照的研究方法,将60例经达英-35治疗后高雄激素和临床表现仍然未能明显改善且伴有肾上腺雄激素分泌过多的PCOS不孕患者作为研究对象,将患者随机分成对照组(达英-35+安慰剂)和实验组(达英-35+地塞米松),所有患者治疗3个月,比较2组患者性激素水平、临床表现。随后给予氯米芬(CC)及人绝经期促性腺激素(hMG)促排卵治疗,比较分析临床结局。结果:所有患者治疗后雄烯二酮(A2)均降低,下降率组间无差异(P>0.05),实验组硫酸脱氢表雄酮(DHEAS)降低率、性结合球蛋白(SHBG)提高率明显好于对照组(P<0.05);实验组较对照组的痤疮及多毛症状改善明显(P<0.05),而体质量指数(BMI)及腰臀比(WHR)的改变不明显(P>0.05)。实验组比对照组的成熟卵泡率、排卵率及妊娠率效果更好(P<0.05)。结论:经用达英-35治疗后高雄激素血症和临床表现仍然未能明显改善,并伴肾上腺雄激素分泌过多的PCOS不孕患者,加用地塞米松,较单纯应用达英-35更能有效抑制高雄激素血症,提高SHBG,改善临床表现,提高成熟卵泡率、排卵率及妊娠率。     

中药联合西药治疗排卵障碍性不孕症及对妊娠结局的影响

目的:探讨温肾活血法结合克罗米芬(CC)联合补佳乐在治疗排卵障碍性不孕症中的疗效。方法:将排卵障碍性不孕症患者89例随机分为A组(CC+补佳乐)、B组(温肾活血汤+CC+补佳乐)和C组(阿司匹林+CC+补佳乐)3种方案治疗。比较3组的排卵率、未破裂卵泡黄素化综合征(LUFS)发生率、妊娠率、流产率,以经阴道彩色多普勒B超测量3组治疗前、后的排卵期子宫内膜厚度、子宫动脉阻力指数(RI),观察内膜容受性。结果:A组周期排卵率为79.0%,妊娠率为23.3%,流产率为28.6%,LUFS发生率为14.8%。B组周期排卵率达87.6%,妊娠率为56.7%,流产率为0.0%,LUFS发生率为4.1%,C组周期排卵率为86.9%,妊娠率为44.8%,流产率为15.4%,LUFS发生率为8.7%,3组排卵率无统计学差异(P0.05),3组妊娠率、流产率比较差异有统计学意义(P0.05),其中,B组妊娠率最高,流产率最低,显著高于A组、C组(P0.05),C组妊娠率高于A组,流产率低于A组,但差异均无统计学意义(P0.05)。B组及C组h CG注射日子宫内膜厚度及A型子宫内膜比例明显高于A组(P0.05),子宫动脉RI明显低于A组(P0.05);LUFS发生率B组明显低于A组(P0.05),C组略低于A组,但差异无统计学意义(P0.05)。结论:温肾活血法能显著提高CC联合补佳乐治疗排卵障碍性不孕症的临床妊娠率,降低流产率,其效果好于阿司匹林。其机制主要与中药降低LUFS发生率、促进卵泡排出及改善CC对子宫内膜容受性的抑制作用有关,其改善内膜容受性的效果好于阿司匹林。     

腹腔镜卵巢打孔术结合药物促排卵治疗难治性多囊卵巢综合征的临床研究

目的　探讨腹腔镜卵巢打孔术 (LOD)后结合克罗米芬 (CC)和中药排卵汤对难治性多囊卵巢综合征(PCOS)不孕的治疗效果。方法　 1998年 2月至 2 0 0 3年 4月将 5 8例患者随机分成A组 (LOD) 18例 ,B组(LOD CC) 2 1例及C组 (LOD CC 排卵汤 ) 19例 ,所有患者进行LOD。手术前后分别测血黄体生成激素、卵泡刺激素、雄激素及雌二醇水平 ,术后第 9天起监测患者卵泡发育和排卵共 3个周期 ,并记录妊娠数和流产数。结果　三组患者术后LH和T水平与术前相比均有显著性下降 (P <0 0 1)。 3个治疗周期内共有 4 5例排卵 ,其中A组 9例 (5 0 0 % ) ,B组 19例 (90 5 % ) ,C组 17例 (89 5 % ) ,三组间排卵率差异有显著性意义 (P <0 0 0 5 )。1年内累计妊娠 2 6例 ,其中A组 3例 ,B组 10例 ,C组 13例。自然流产A组有 1例 ,B组 2例 ,C组无发生。结论　LOD后结合CC和中药排卵汤能明显改善难治性PCOS患者的排卵和受孕机会。     

达英-35与胰岛素增敏剂治疗多囊卵巢综合征后促排卵药物的效果观察

目的:探讨比较单独应用达英-35以及达英-35分别与二甲双胍、罗格列酮联合治疗多囊卵巢综合征(PCOS)伴有胰岛素抵抗(IR)不孕患者效果及促排卵结局的差异.方法:97例PCOS伴有IR不孕患者随机分成3组.A组(单独应用达英-35)35例,B组(达英-35和二甲双胍)32例,C组(达英-35和罗格列酮)30例,3组患者治疗3个周期后均促排卵.比较用药后对体重、WHR、BMI、糖代谢、性激素及促排卵结局的影响.结果:3组患者治疗后血清睾酮较治疗前明显降低,B组、c组患者空腹胰岛素,胰岛素抵抗指数等显著下降;治疗后B组、C组妊娠率较A组增高,周期取消率、OHSS发生率较A组降低,差异均有统计学意义.结论:PCOS伴有IR不孕患者应用达英-35联合胰岛素增敏剂(二甲双胍及罗格列酮),可以明显改善内分泌、代谢紊乱,在此基础上促排卵,可以明显提高妊娠率.但因罗格列酮的用药安全性问题及价格较贵,所以此类患者应首选二甲双胍治疗.     

来曲唑联合氯米芬对PCOS患者子宫卵巢血流动力学影响

目的:经阴道超声观察来曲唑联合氯米芬(CC)治疗多囊卵巢综合征(PCOS)的血流动力学变化,探讨来曲唑联合CC治疗PCOS的临床价值。方法:来曲唑联合CC治疗49例PCOS患者,经阴道超声观察子宫内膜厚度,优势卵泡个数,子宫动脉和优势侧卵巢基质收缩期血流峰值(PSV)、舒张末期血流速(EDV)、搏动指数(PI)、阻力指数(RI)及卵巢基质血流信号数。结果:来曲唑联合CC治疗PCOS有较高排卵率和妊娠率,使PCOS患者形成了子宫卵巢血流的周期性变化。结论:来曲唑联合CC用药能改善PCOS的子宫卵巢血流,促进PCOS患者排卵,利于妊娠并能减少流产的发生。     

溴隐亭对氯米芬拮抗、泌乳素水平正常的多囊卵巢综合征患者一项前瞻性随机双盲安慰剂对照的临床试验

对多囊卵巢综合征 (PCOS)相关的无排卵不育妇女的首选治疗是氯米芬 (CC) ,使用CC排卵率可超过 80 %。然而 ,尚有 15 %～2 0 %的妇女尽管增加了CC治疗剂量仍然无排卵。本研究的目的是评估泌乳素水平正常、对CC拮抗的PCOS患者联合使用CC与溴隐亭的效果。选择 10 0例泌乳素水平正常、对CC拮抗的PCOS患者进行前瞻性随机双盲对照研究。试验组自月经周期第 5～ 9天接受 15 0mgCC ,并连续服用溴隐亭 7.5mg/d。对照组则接受同样剂量的CC与安慰剂治疗 ,治疗前所有患者的血浆泌乳素水平均在正常范围。观察两组的激素水平、排卵率 ,并监测…     

腹腔镜治疗多囊卵巢综合征所致不孕症31例分析

目的：探讨腹腔镜下卵巢表面电凝术对多囊卵巢综合征（PCOS）所致不孕症患者的疗效。方法：对31例PCOS不孕症患者观察术前术后血黄体生成素（LH）、卵泡刺激素（FSH）、睾酮（T）水平,术后排卵情况、妊娠率及妊娠结果。结果：31例患者中失访3例,除1例术后3个月应用克罗米芬（CC）一个疗程后恢复月经外,月经情况均明显改善。术后LH、LH/FSH和T均较术前明显降低,而FSH明显升高,差异具有显著性（P＜0.01)。术后排卵率为89.3%(25/28),排除干扰因素后妊娠率为70.6%（12/17）,早期流产率为15.4%(2/13),术后附件区粘连的发生率为14.3%(3/21)。结论：腹腔镜下卵巢表面电凝术治疗PCOS相对于促性激素治疗和卵巢楔切术具有术后排卵率高、妊娠率高、流产率低、并发症少的优点,是CC治疗失败后的一个有效治疗手段。     

Letrozole combined with low dose highly purified HMG for ovulation induction in clomiphene citrate-resistant infertile Chinese women with polycystic ovary syndrome: a prospective study

Background and aim: There are still open questions about ovulation induction in clomiphene citrate-(CC)-resistant infertile women. Especially little is known about efficacy and safety of letrozole (LTZ) combined with low-dose highly purified human menopausal gonadotropin (Hp-HMG) in women with polycystic ovary syndrome (PCOS).

Methods: Prospective, single-arm single-center trial in 200 infertile PCOS patients refractory for at least three CC-treatment cycles. Women with hyperandrogenism took Diane-35 for at least 3?months. All patients got LTZ on day 3 for 5?d in combination with Hp-HMG, starting with 75?IU from cycle day 7 and maintained for up to 3?d. The maximum dose was 150?IU. Primary end-points were ongoing and clinical pregnancy rate, secondary end-points mono-follicular development, ovulation rate, OHSS, multiple pregnancy and early pregnancy loss. Major safety end-point was the incidence of adverse events.

Results: Within 395 cycles the ongoing pregnancy rate was 28.24%, for cycles 35.23%, for patients 68%. The rate of ovulation per cycle was 97.7%, percentage of mono-follicular development 70.9%. No severe OHSS, multiple pregnancy, local or systemic side effects were seen.

Conclusions: LTZ combined with low-dose Hp-HMG is an effective and safe choice for reducing hyperstimulation and increasing pregnancy rate in CC-resistant women with PCOS.     

二甲双胍治疗耐克罗米酚多囊卵巢综合征23例临床分析

目的探讨二甲双胍在多囊卵巢综合征(PCOS)治疗中的作用.方法对23例耐克罗米酚PCOS患者的临床资料进行回顾性分析,比较二甲双胍治疗前后各项内分泌代谢指标的变化及其对恢复月经、促排结局及妊娠的影响.结果二甲双胍治疗前后比较,血清睾酮、空腹胰岛素水平下降,胰岛素敏感性指数上升(P<0.01).6例(26.09%)的患者恢复月经,4例(17.39%)恢复自然排卵,2例妊娠. 二甲双胍加促排治疗共26个周期,排卵周期率为61.54%(16/26),妊娠周期率为23.08%(6/26). 结论二甲双胍可以降低雄激素水平及胰岛素水平,改善PCOS妇女对克罗米酚促排的反应.     

多囊卵巢综合征氯米芬抵抗的预测及促排卵治疗

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是无排卵性不孕症最常见的原因,对于有生育要求的PCOS患者,促排卵是其首选治疗方案。枸橼酸氯米芬（clomiphene citrate,CC）是目前国内外指南推荐治疗PCOS不孕症的传统一线促排卵药物,但CC的治疗反应性个体差异显著,其中约40%的患者对CC不反应,即CC抵抗。综述近年来CC抵抗的PCOS患者预测指标及替代的促排卵策略的研究进展,主要从表型、生化特征和基因组学角度阐述PCOS不孕症患者CC抵抗预测指标,从来曲唑（Letrozole,LE）、促性腺激素（gonadotropin,Gn）、腹腔镜卵巢打孔术（laparoscopic ovarian drilling,LOD）、体外受精（in vitro fertilization,IVF）及中医辅助治疗等治疗方式中选用单一或联合的方案阐述其替代促排卵策略,并比较各种方案或方案组合的优势与潜在不足,以期为临床PCOS不孕症患者提供更加精准、个体化的促排卵方案。     

Clomiphene citrate plus cabergoline versus clomiphene citrate for induction of ovulation in infertile euprolactinemic patients with polycystic ovary syndrome: A randomized clinical trial

Objective

To compare the effect of adjunctive use of cabergoline with clomiphene citrate (CC) in infertile polycystic ovarian syndrome (PCOS) patients with normal prolactin level.

Time of initiation of clomiphene citrate and pregnancy rate in polycystic ovarian syndrome.

OBJECTIVE: To investigate whether the timing of clomiphene citrate (CC) administration affects hormonal levels, follicular growth, endometrial thickness, and ovulation and pregnancy rates in women with polycystic ovarian syndrome (PCOS). METHODS: Of the 78 infertile women with PCOS who participated in this prospective, double-blind, randomized clinical trial, 37 collectively underwent 71 cycles of CC (100 mg/day) on days 1 through 5 of the menstrual cycle (group 1) and 41 collectively underwent 73 cycles of CC at the same concentration on days 5 through 9 (group 2). Hormonal levels, follicular growth, endometrial thickness, and ovulation and pregnancy rates were compared. RESULTS: The mean number of follicles and the maximum follicular size were greater in group 2. However, ovulation rates were 72.8% in group 1 and 70.8% in group 2 (P=.78), and pregnancy rates were 40.5% in group 1 and 19.5% in group 2 (P=.04). CONCLUSION: Treatment with CC is associated with higher rates of pregnancy if started early (days 1-5) in the menstrual cycle.     

Metformin improves ovulation and pregnancy rates in patients with polycystic ovary syndrome

We evaluated the fertility promoting effect of metformin in infertile patients with polycystic ovary syndrome. Twenty-nine infertile patients with polycystic ovary syndrome (PCOS) are included in our prospectively designed study and 15 normal menstruating women served as controls for reproductive hormones and ovarian volumes. All PCOS patients received a total of 78 cycles of clomiphene citrate (CC) in the beginning, then patients who could not get pregnant were switched to metformin plus clomiphene citrate. PCOS patients served as their own controls for the ovulation and pregnancy rates. At the end of the CC cycles 4.2% of patients got pregnant and 65.2% of the remaining group got pregnant with metformin plus CC cycles (p=0.0001). We have not observed any serious side effects of metformin. The high pregnancy rate of our study population is consistent with the hypothesis that insulin resistance plays an important role in the pathogenesis of anovulation in patients with PCOS.     

多囊卵巢综合征患者达英-35治疗后不同问隔启动促排卵的妊娠结局

目的探讨多囊卵巢综合征（polycysticovarysyndrome,PCOS）高雄激素血症不孕患者应用达英-35（炔雌醇醋酸环丙孕酮）降低雄激素后,不同间隔启动HMG促排卵对妊娠结局以及子宫内膜血管体积百分比的影响。方法33名高雄激素PCOS不孕患者,在给予达英-35治疗至血睾酮正常后,启动HMG促排卵。根据促排卵前停用达英-35的时间不同分为短间隔组和长间隔组。统计组间HCG日子宫内膜厚度、妊娠率等差异。再选择实验组5名高雄激素PCOS患者,停用达英-35月经来潮第3天开始应用人工周期诱导胚胎种植窗子宫内膜;对照组为5名因男性不孕就诊,月经周期正常的女性患者,尿LH峰值后7～9d取子宫内膜。病理证实为分泌中期子宫内膜后,CD34免疫组织化学染色内膜组织,计数血管内皮细胞体积百分比。结果人选病例的一般情况、HCG日内膜厚度等组间差异无统计学意义。短间隔组（20．83％）的临床妊娠率较长间隔组（54．2％）显著降低（P〈0.05）。达英-35后月经来潮当月胚胎种植窗的子宫内膜血管内皮细胞体积百分比中位数（4．82％）较对照组（6．35％）显著降低（P〈0．05）。结论PCOS不孕患者停用达英-35后月经来潮当月启动促排卵的临床妊娠率较停用至少一个月经周期的患者显著降低。达英-35治疗后月经来潮当月的胚胎种植窗子宫内膜血管较正常月经周期患者明显稀疏。     

Clomiphene Citrate co-treatment with low dose urinary FSH versus urinary FSH for clomiphene resistant PCOS: randomized controlled trial

Purpose

The aim of this study was to examine the effect of clomiphene citrate [CC] co-administration during the use of exogenous low-dose urinary FSH [uFSH] for induction of ovulation in CC-resistant infertile PCOS women.

Methods

In a randomised controlled setting, 174 CC-resistant infertile PCOS women were randomized into two parallel groups; Group I received CC 100 mg/day for 5 days plus uFSH 37.5 IU/day while group II received only uFSH 37.5 IU /day. Subsequent increments of uFSH by 37.5 IU/day were made according to response. Primary outcome was ovulation rate. Secondary outcomes were clinical pregnancy rates, number of follicles, endometrial thickness, and gonadotropins consumption.

Results

Our results have demonstrated that group I compared to group II had significantly higher ovulation rate per intention to treat [ITT] [72.4 % vs. 34.2 %, p < 0.001]. Clinical pregnancy and live birth rates were comparable between the two groups. Group I consumed significantly lower total FSH dose and needed significantly shorter stimulation duration compared to group II.

Conclusion

CC co-administered during low dose HP uFSH versus uFSH for CC-resistant PCOS yields significantly higher ovulation rate and less consumption of FSH.     

二甲双胍和噻唑烷二酮类分别与达因-35联用治疗多囊卵巢综合征的疗效比较

目的:比较二甲双胍和噻唑烷二酮类(TZDs)分别与达因-35联用治疗多囊卵巢综合征(PCOS)的临床疗效。方法:随机将53例患者分成两组,A组予以二甲双胍治疗3个月后与达因-35共用3个月,B组予以TZDs治疗3个月后和达因-35共用3个月,总治疗期6个月,比较治疗前后内分泌激素、体重指数、血糖、排卵率等的改变。结果:两组治疗后胰岛素(INS)、胰岛素抵抗指数(HOMA-IR)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、睾酮(T)及黄体生成素(LH)均明显降低(P<0.05,P<0.01)。A组降低体重优于B组,B组改善胰岛素抵抗优于A组。两组在排卵率和妊娠率方面无显著差异(P>0.05),双胍组4例自发性妊娠,TZDs组也有4例自发性妊娠。随访1年,8例婴儿发育均无异常。结论:二甲双胍和TZDs分别与达因-35联用,均能改善PCOS患者的胰岛素抵抗及内分泌紊乱,肥胖的PCOS患者推荐首选二甲双胍+达因-35,体重正常者或胰岛素抵抗严重者选用TZDs+达因-35。     

Results of clomiphene citrate ovarian stimulation vs laparoscopic electrocoagulation of the ovaries in infertile women with PCOS

OBJECTIVE: To assess the results of clomiphene citrate ovarian stimulation vs laparoscopic electrocoagulation of the ovaries in infertile women with PCOS. DESIGN: 47 women with PCOS were included into the study. 25 of them had ovarian stimulation using clomiphene citrate (100 mg for 5 consecutive days, during 6 cycle) and 22 underwent laparoscopic electrocoagulation of the ovary (6 cycle follow-up) No significant differences were detected between age and body mass index. RESULTS: In the first group ovulatory cycles were confirmed in 68% of women, pregnancy rate was 28%. In the second group ovulations were observed in 90.9% of women and pregnancy rate was 63.6%. There were statistically significant differences. CONCLUSION: In summarising, the results showed lower, statistically significant differences in pregnancy rate in the treatment of infertility associated with PCOS. It seems that the much more successful result of the PCOS therapy may be achieved after laparoscopic ovarian diathermy in comparison with stimulation of the ovaries with CC.