二甲双胍治疗耐克罗米芬的多囊卵巢综合征40例分析

目的：观察二甲双胍单用或联合高纯度卵泡刺激素（metrodin-HP即FSH－HP）治疗耐克罗米芬（CC)多囊卵巢综合征（PCOS）患者的疗效。方法：选择耐CC的PCOS患者40例，随机分成A组和B组。A组：20例患者从卵泡早期开始服二甲双胍，每天1500mg共12周，若未孕则加FSH－HP促排卵1个周期，B组；20例患者单独用FSH－HP促排卵1个周期。测定所有患者的性激素、空腹血糖（FG）及空腹胰岛素（FINS）。结果：服二甲双胍后，LH、T及FINS的水平明显下降（P＜0．05），A组有7例患者排卵且3例妊娠，妊娠率为15．0％，17例未孕者继续服二甲双胍联合FSH－HP促排卵，15例排卵和4例妊娠，妊娠率23．5％，B组单用FSH－HP促排卵，有14例排卵且3例妊娠，妊娠率15．0％，两者的妊娠率差异无显著性意义（P＞0．05）。A组的FSH－HP用量少于B组，差异有显著性意义（P＜0．05），中度以上OHSS发生率分别为0和10％，前者的发生率低于后者（P＜0．05）。结论：单用二甲双胍能使部分患者恢复排卵和妊娠。FSH－HP联合二甲双胍能减少FSH－HP的用量和OHSS的发生。二甲双胍单用或联合FSH－HP促排卵为耐CC的PCOS患者找到一种有效的治疗方法。     

二甲双胍治疗多囊卵巢综合征新进展

多囊卵巢综合征（PCOS）是生育年龄妇女常见的生殖内分泌疾病。由于胰岛索抵抗在其发病中起重要作用．胰岛素增敏剂二甲双胍被用于PCOS的治疗。随着临床的广泛应用，对其作用机理和临床效果有了更深入的认识。兰甲双胍可以恢复规律月经，改善多毛，降低体质量，促进排卵，改善妊娠结局，改善子宫内膜的胰岛素抵抗，避免远期并发症．特别是对青春期PCOS患者有较好的疗效。不同剂量的二甲双胍具有不同的治疗作用。对二甲双胍在治疗PCOS中的新进展做综述。     

二甲双胍治疗多囊卵巢综合征

二甲双胍通过降血胰岛素的作用,纠正了PCOS患者的高雄激素血症,改善了卵巢排卵功能,提高了促排卵治疗疗效,是PCOS治疗的新选择。     

二甲双胍治疗多囊卵巢综合征的研究进展

多囊卵巢综合征 (ＰＣＯＳ)以慢性无排卵、高雄激素血症为特征 ,是育龄妇女常见的内分泌紊乱。因涉及下丘脑 垂体 卵巢轴、肾上腺、胰腺及遗传等因素 ,生化及临床表现有高度的异质性 ,病因尚不明了。有关ＰＣＯＳ的发病原因、病理生理及治疗等方面尚存在争议。现就二甲双胍治疗ＰＣＯＳ的机制及效果作一综述。一、胰岛素抵抗及高胰岛素血症在ＰＣＯＳ中的作用胰岛素抵抗是指机体外周组织对胰岛素敏感性降低 ,使胰岛素生物学作用减弱 ,通常是指对糖代谢的效应下降 ,即在生理水平胰岛素情况下 ,器官、组织、细胞吸收、利用葡萄糖的效能低于正…     

二甲双胍治疗多囊卵巢综合征新进展

多囊卵巢综合征(PCOS)是生育年龄妇女常见的生殖内分泌疾病.由于胰岛素抵抗在其发病中起重要作用,胰岛素增敏剂二甲双胍被用于PCOS的治疗.随着临床的广泛应用,对其作用机理和临床效果有了更深入的认识.二甲双胍可以恢复规律月经,改善多毛,降低体质量,促进排卵,改善妊娠结局,改善子宫内膜的胰岛素抵抗,避免远期并发症,特别是对青春期PCOS患者有较好的疗效.不同剂量的二甲双胍具有不同的治疗作用.对二甲双胍在治疗PCOS中的新进展做.     

二甲双胍治疗多囊卵巢综合征的研究进展

胰岛素抵抗是多囊卵巢综合征 (PCOS)的主要发病机制之一。用胰岛素增敏剂二甲双胍可治疗与PCOS有关的月经失调、雄激素过多症状、不排卵及不育。而且 ,二甲双胍可用于治疗各年龄段多囊卵巢综合征 ,能有效降低PCOS中的早期自然流产 ,并有保护心血管、降低II型糖尿病危险的作用。     

二甲双胍在多囊卵巢综合征中的作用

多囊卵巢综合征(PCOS)的基本病理生理特征为胰岛素抵抗和高胰岛素血症,二甲双胍为胰岛素增敏剂,可调整PCOS患者月经周期,促进排卵,提高妊娠率,减少流产,并改善脂质代谢,降低患者超促排卵后过度刺激及妊娠期糖尿病的发生.但其长期疗效、个体剂量和可能的不良影响尚待研究.     

二甲双胍治疗多囊卵巢综合征的临床应用

多囊卵巢综合征(PCOS)是妇科最常见的内分泌紊乱性疾病,胰岛素抵抗是PCOS发病机制的重要因素和显著临床特征.近年研究发现胰岛素增敏剂二甲双胍单独或与克罗米芬合用有助于诱导卵巢排卵、恢复规则月经周期,对克罗米芬抵抗者亦有效,并可改善其他症状,妊娠期应用亦可能减少早期流产及妊娠糖尿病的危险,副作用相对较少,可作为PCOS临床治疗的一个可行选择.     

二甲双胍治疗多囊卵巢综合征28例疗效分析

近年研究表明 :胰岛素抵抗 (ＩＲ)及由此而引起的高胰岛素血症 (ＨＩ)是ＰＣＯＳ的发病环节之一。从理论上讲 ,使用胰岛素 (Ｉｎｓ)增敏剂二甲双胍将改善ＰＣＯＳ的ＩＲ状态 ,有助于恢复卵巢功能 ,但目前的研究结果不尽相同。本研究探讨了二甲双胍治疗ＰＣＯＳ的效果。1　资料与方法1 1　研究对象　 1999年 10月至 2 0 0 0年 10月在本院生殖内分泌门诊就诊的ＰＣＯＳ患者 2 8例 ,诊断标准见参考文献[1] 。年龄 18～ 33岁 ,ＢＭＩ为 2 1 6～ 2 7 3,ＢＢＴ均为单相 ,未婚 9例 ,19例已婚者均不孕 ,不孕年限 2～ 6年。月经稀发 2 0例 ,闭经 6例 …     

口服避孕药联合二甲双胍治疗多囊卵巢综合征疗效观察

目的观察口服避孕药联合二甲双胍治疗多囊卵巢综合征(PCOS)的疗效。方法选择2001年11月至2004年6月在昆明医学院第一附属医院就诊的PCOS患者90例,随机分为A、B、C3组。A组32例,口服妈富隆联合二甲双胍治疗;B组40例,口服达因-35联合二甲双胍治疗;C组18例,单用妈富隆治疗。3组用药时间均为3个月。测定患者血清卵泡刺激素(FSH)、黄体生成素(LH)和睾酮(T),测量腰/臀比值(WHR)及体质指数(BMI)并进行治疗前后的比较。结果A、B两组治疗后LH、LH/FSH、T及WHR均较治疗前明显降低(P<0.05或P<0.01)且两组间差异无显著性(P>0.05);C组治疗后LH、LH/FSH、T较治疗前明显降低(P<0.01),但WHR明显升高(P<0.05)。A、B、C3组治疗后各项指标比较LH、LH/FSH及T差异无显著性(P>0.05),而C组WHR明显高于A、B两组(P<0.01)。结论口服避孕药联合二甲双胍治疗PCOS疗效优于单用口服避孕药。妈富隆与达因-35疗效比较,差异无显著性。     

Evaluating the equivalence of clomiphene citrate with and without metformin in ovulation induction in PCOS patients

Objective  To evaluate the benefit of Metfomin added to Clomiphene Citrate in a primary ovulation induction protocol in PCOS patients Design  Prospective randomised controlled study Setting  Tygerberg Academic Hospital, Stellenbosch University and the Institute of Reproductive Medicine at Vincent Pallotti Hospital, Cape Town Patients  107 patients presenting with PCOS Study  Group A was pre-treated with metformin 850 mg twice a day for at least 6 weeks before clomiphene was added and the metformin was used throughout the study period. Group B received clomiphene without pre-treatment with metformin. In both groups clomiphene was given at a starting dose of 50 mg day 4–8 and increase with increments of 50 mg to a maximum of 150 mg if no response was achieved. Results  The ovulation rate achieved in women in the M+C/C arm was 34/52 (65.4%) compared to 36/55 (65.5%) in the C/C arm. The treatment effect ((M+C/C) – C/C) is 0% with 95% confidence interval of −18.1% to 18%. The per protocol ovulation results were 34/42 (81%) in the M+C/C arm compared to 36/48 (75%) in the C/C arm. The ovulation rate difference was 6% with 95% confidence interval −11% to 22%. In a comparison of successful ovulating versus non-ovulating women from the trial the following were significant baseline determinants: lower median weight in the ovulating group (77 kg versus 86 kg, p = .021), lower median bmi (29.0 versus 32.9, p = .009), lower median DHEAS at baseline (4.6 compared to 7.0, p = .049), lower median 17OH-progesterone (2.2 versus 4.6, p = .027) and higher baseline median SHBG ( 37.8 compared to 28.5, p = .036). Conclusion  Although identical ovulation rates were observed in both arms equivalence could not be concluded with respect to the specified criteria. Capsule   Clomiphene with Metformin achieved the same ovulation rate (65%) compared to Clomiphene alone. However the 2-sided 95% confidence interval for ovulation rate difference was −18.1% to 18%.     

克罗米芬联合促卵泡素治疗多囊卵巢综合征的疗效观察

目的:比较单用克罗米芬(CC)及其联合不同促卵泡素(FSH)治疗多囊卵巢综合征(PCOS)患者的效果,以指导PCOS患者选择合适的促排卵方案.方法:选取2009年1月至2012年7月就诊于我院生殖门诊的81例PCOS患者(共92周期),患者均以CC促排卵,根据月经第8天的卵泡生长情况,决定是否联合应用基因重组促卵泡素(rFSH)或尿促卵泡素(uFSH).按促排卵方案不同将患者分为3组:CC+ HCG组(A组,26例,32周期);CC+rFSH+HMG+HCG组(B组,23例,26周期);CC+uFSH+HMG+HCG组(C组,32例,34周期).患者排卵后均用黄体酮胶丸或地屈孕酮黄体支持12 ～ 14天.比较3组患者促排卵治疗的效果.结果:A组中2例患者发生黄素化综合征(LUFS);B组中4例发生轻度卵巢过度刺激综合征(OHSS);C组中1例发生重度OHSS,1例LUFS.3组患者的HCG日最大卵泡直径、内膜厚度、排卵率及妊娠率均无显著差异(P＞0.05).A组D8优势卵泡直径大于B、C组(P＜0.05);至HCG日平均时间少于B、C组(P＜0.05);B组直径≥1.5cm卵泡数和排卵数均显著高于A、C组(P＜0.05).B组与C组的至HCG注射日时间和FSH用量均无显著差异(P＞0.05).结论:CC促排周期D8优势卵泡直径大小对决定联合FSH治疗PCOS患者有一定的参考意义.单用CC促排卵可能抵抗周期,联合uFSH是经济有效的促排卵方案.     

Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome

Objective

To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Methods

Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate.

Results

After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group.

Conclusion

The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.     

二甲双胍对多囊卵巢综合征患者纤溶系统、内分泌、代谢的影响及对耐氯米芬的作用

目的：评估二甲双胍对多囊卵巢综合征（PCOS）与耐氯米芬患者的治疗作用。方法：31例PCOS患者（8例为耐氯米芬者）,用二甲双胍375mg/次、3次／d,治疗12－16周,观察服药前后血纤溶酶原激活物抑制物－1（PAI－1）及组织型纤溶酶原激活物（tPA）水平,月经、生殖内分泌激素,糖、脂代谢,卵巢体积的变化及副反应。服用二甲双胍未恢复正常月经、耐氯米芬的患者,再加用氯米芬促排卵,观察排卵情况。非耐氯米芬未恢复正常月经的患者,二甲双胍加量至500mg／次、3次／d,至少8周,观察月经情况。结果：二甲双胍治疗后,PAI－1、黄体生成素／促卵泡激素（LH／FSH）、睾酮、雄烯二酮、低密度脂蛋白胆固醇、总胆固醇、胰岛素、胰岛素曲线下面积、舒张压明显下降,下降幅度分别为3％、41％、25％、34％、28％、14％、27％、23％、7％;左侧卵巢体积缩小59％,右侧卵巢体积缩小41％;雌二醇和FSH水平分别上或42％、58％（P＜0．05－0．01）。二甲双胍375mg/次、3次／d治疗后,61％（19／31）的患者恢复正常月经,2例妊娠;12例恢复正常月经周期,其中6例伴耐氯米芬者再用氯米芬,5例（12／18周期）排卵,2例妊娠,余6例二甲双胍加量至500mg／次、3次／d,1例恢复月经并妊娠。结论：二甲双胍可改善PCOS患者的纤溶系统,生殖内分泌激素,糖、脂代谢,月经失调等,增强耐氯米芬患者对氯米芬的敏感性。     

Comparison between two clomiphene citrate protocols for induction of ovulation in clomiphene resistant polycystic ovary syndrome

ObjectiveTo compare two protocols of CC therapy for induction of ovulation in a group CC resistant PCOS women.Study designDouble blind randomized controlled trial.Subjects and methods260 nulliparous CC resistant PCOS women randomized between two groups; In the first group each patient received 200 mg/day for 5 days while the second group received 100 mg/day for 10 days, both starting on day 3 of progestin induced withdrawal bleeding.Main outcome measuresOvulation defined as at least one follicle reaching ⩾14 mm diameter, and confirmed by timed serum progesterone. Secondary outcome measures included; number of dominant follicles, endometrial thickness, clinical pregnancy rate, and live birth rate.ResultsThe extended protocol resulted in significantly higher ovulation, pregnancy, and live-birth rates than the high dose protocol (p 0.001). Serum FSH levels on day 6 of treatment were comparable between the two groups while the level on day 11 was significantly higher in the second group (p 0.02). Serum LH levels were comparable both on days 6 and 11. Patients on longer protocol (group II) required a longer time to ovulate (18 ± 4.4 versus 14 ± 3.6 days) but had a significantly higher endometrial thickness at the time of ovulation. (p 0.02) FSH and LH levels were comparable between responders and non-responders in both groups.ConclusionsThe current study reports significantly higher ovulation and pregnancy rates with the longer lower dose protocol probably because of prolonged FSH rise. Study web address: ACTRN12611000639921.     

Metformin versus laparoscopic unilateral ovarian drilling in clomiphene resistant women with polycystic ovary syndrome

ObjectivesTo compare the hormonal-metabolic profiles and reproductive outcomes between women receiving metformin and women undergoing unilateral ovarian drilling in clomiphene citrate(CC) resistant patients with polycystic ovary syndrome (PCOS)DesignNon randomized controlled trial.SettingObstetrics and Gynecology department, Faculty of medicine, Zagazig University, Egypt.MethodsA total of 120 patients were divided into group 1(n=58) who received metformin therapy and group 2 (n=62) who underwent unilateral ovarian drilling. Hormonal-metabolic profiles changes after treatment were reported and reproductive outcomes were compared between both groups.Main outcomeFSH and LH were reduced significantly in unilateral drilling group (P=<0.001and 0.001), while there was significant improvement in testosterone level , fasting insulin, fasting glucose to insulin ratio and homeostasis model assessment index in metformin therapy group. Pregnancy and ovulation rates were higher after unilateral drilling with significant difference (P=0.048 and 0.004). No significant difference in early miscarriage rate between both groups (P=0.51).ConclusionUnilateral LOD was associated with greater ovulation and pregnancy rates than metformin in women with PCOS who did not conceive with CC.     

Extension of the clomiphene citrate stair-step protocol to gonadotropin treatment in women with clomiphene resistant polycystic ovarian syndrome

Our objective was to evaluate the safety and efficacy of direct initiation of gonadotropin ovarian stimulation without prior withdrawal bleeding in anovulatory clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS) patients. Eighteen PCOS patients underwent ovulation induction with CC using a stair-step regimen. Patients who failed to respond to the maximal dose of CC initiated gonadotropin stimulation without inducing withdrawal bleeding, using the chronic low dose regimen. The primary outcome measure was the time to ovulation from the beginning of CC treatment until the day of ovulatory trigger. This was compared with the time to ovulation calculated according to the traditional approach, which includes inducing progesterone withdrawal bleeding between each CC dose increment and before gonadotropin therapy. The time to ovulation in the study group was 67.0?±?6.8 days. The estimated time to ovulation according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence the live birth rate was 38.9% (7/18). Direct initiation of gonadotropin therapy without prior induction of withdrawal bleeding in clomiphene resistant PCOS patients results in considerable reduction of the time to ovulation and is both safe and efficacious.     

Evaluation of unilateral versus bilateral ovarian drilling in clomiphene citrate resistant cases of polycystic ovarian syndrome

Objectives  Laparoscopic ovarian drilling (LOD) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS), with tubo-ovarian adhesion formation as the major disadvantage. Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling. Methods  This prospective randomized study included 44 patients with anovulatory infertility due to PCOS. Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007. The number of drilling site in each ovary was limited to five. The clinical and biochemical response, ovulation and pregnancy rates over a follow-up period of 1 year were compared. Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy. Results  There was no statistical difference between the two groups in terms of clinical and biochemical response, ovulation rate and pregnancy rate. Postoperatively, tubo-ovarian adhesions could be assessed in 36.3% of the patients and no adhesions were found in a single case in either group. Conclusion  Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy. Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation.     

多囊卵巢综合征患者用克罗米酚促排卵结局与相关因素的探讨

目的　探讨在多囊卵巢综合征 (PCOS)患者中影响克罗米酚 (CC)促排卵因素。方法　对 94例因多囊卵巢综合征不孕患者 ,用CC促排卵治疗。采用放射免疫方法测定卵泡刺激素 (FSH)、黄体生成素 (LH)、雌二醇 (E2 )、睾酮 (T)、雄烯二酮 (A)、泌乳素 (PRL)水平及胰岛素释放反应。分析了排卵结局与年龄、基础激素水平、胰岛素抵抗 (IR)、胰岛素反应曲线下面积 (AUCI)及体重指数 (BMI)之间的关系。结果　用克罗米酚促排卵 94个周期中排卵率为 5 5 2 % (5 2 / 94) ,未排卵组的基础血雄激素、LH、AUCI 和BMI均较排卵组高。结论　PCOS患者的高雄激素、高LH血症、IR、高BMI对促排卵的结局产生负影响。     

二甲双胍用于多囊卵巢综合征患者促排卵治疗有效性的系统性评价

目的:系统性评价二甲双胍对多囊卵巢综合征(PCOS)促排卵治疗的有效性。方法:计算机检索CBMDISC(中国生物医学文献数据库,1979～2011年)、万方(1994～2011年)、CNKI(中国学术期刊网专题全文数据库,1994～2011年)、维普(中国生物医学期刊数据库,1989～2011年),PubMed(1997～2011年)、ProQust Medical Libraray(PML,1997～2011年)、外文生物医学期刊文献数据库(FMJS,2000～2011年),读秀学术搜索(www.duxiu.com),并手检9种相关杂志。纳入二甲双胍与氯米芬用于PCOS促排卵治疗的随机对照试验,质量评价后进行Meta分析。结果:共纳入8篇RCT,合计1168例。Meta分析结果显示:与氯米芬组比较,二甲双胍组排卵率低于氯米芬组[OR 0.48(0.26～0.87)],两组差异有统计学意义;妊娠率[OR 0.94(0.26～3.43)],流产率[OR 0.63(0.06～6.47)],活产率[OR 0.90(0.11～7.32)],两组差异无统计学意义。氯米芬联合二甲双胍组妊娠率较高,与氯米芬组的差异有统计学意义[Peto OR 1.56(1.16～2.08)];排卵率[OR 1.54(0.96～2.49)],流产率[Peto OR 1.40(0.79～2.48)],活产率[Peto OR1.26(0.83～1.91)],两组差异无统计学意义。结论:较之氯米芬用于PCOS患者促排卵治疗,二甲双胍可能促进排卵、有利于妊娠,二甲双胍与氯米芬联合用药的治疗效果要好于单一用药。