二甲双胍在多囊卵巢综合征促排卵治疗中的作用

目的　评估二甲双胍在多囊卵巢综合征 (PCOS)患者促排卵治疗中的作用。方法　以40例PCOS患者 (PCOS组 )为研究对象 ,其中 2 0例口服二甲双胍治疗 12周 ,治疗后 17例未孕者加用高纯度促卵泡激素 (FSH HP)治疗 1个周期 (A组 ) ,另 2 0例单用FSH HP治疗 1个周期 (B组 ) ;同时 ,以体重和月经周期均正常的 2 0例门诊患者为对照组。观察各组及A组患者口服二甲双胍前后血清FSH、黄体生成激素 (LH)、睾酮、瘦素、空腹血糖及空腹胰岛素水平 ;比较A、B两组促排卵治疗结果。结果　空腹胰岛素和瘦素水平 ,PCOS组显著高于对照组 (P <0 .0 5) ,PCOS肥胖者高于PCOS非肥胖者(P <0 .0 5) ,但PCOS非肥胖者与对照组相比 ,差异无显著性 (P >0 .0 5)。二甲双胍治疗后 ,LH、空腹胰岛素、睾酮及瘦素水平明显下降 (P <0 .0 5～ 0 .0 1)。PCOS组患者中有 3例服二甲双胍治疗期间妊娠 ,另外 3 7例行FSH HP促排卵治疗后有 7例妊娠 (A组 4例 ,B组 3例 ) ,总妊娠率为 19% ( 7 3 7) ;A组的排卵率 ( 88% ,15 17)和妊娠率 ( 2 4% ,4 17)虽高于B组 ( 70 % ,14 2 0 ;15% ,3 2 0 ) ,但差异无显著性 (P >0 .0 5)。结论　二甲双胍能降低胰岛素和瘦素水平 ,逆转PCOS患者性激素异常 ,使部分患者恢复排卵和妊娠 ,可增强PCOS患者对促性腺素的敏感     

二甲双胍、达因-35联合来曲唑治疗多囊卵巢综合征疗效观察

目的：观察二甲双胍、达因-35和来曲唑治疗PCOS的疗效。方法：PCOS患者60例,随机分成3组,A组服用二甲双胍和达因-35治疗3个月后,用来曲唑促排卵;B组服用二甲双胍和达因-35一个月后,用来曲唑促排卵;C组直接用来曲唑促排卵。观察三组优势卵泡数目、子宫内膜厚度、血清雌二醇水平、排卵率、妊娠率。结果：三组有排卵的周期中HCG日子宫内膜的厚度、优势卵泡数目及血雌二醇水平差异无显著性（P〉0．05）,三组排卵率、妊娠率比较,A组和B组差异无显著性（P〉0．05）,c组和A组及B组差异有显著性（P〈0．05）。结论：PCOS患者经二甲双胍和达因-35预处理1到3个月后,可以提高排卵率和妊娠率。     

二甲双胍对多囊卵巢综合征患者胰岛素样生长因子-1的影响

目的探讨二甲双胍对多囊卵巢综合征（PCOS）患者血清胰岛素样生长因子-1（IGF-1）及胰岛素样生长因子结合蛋白-1（IGFBP-1）水平的影响及其作用机制，明确二甲双胍治疗的临床效果。方法2002年1—11月对山西医科大学第二医院24例PCOS患者给予二甲双胍500mg，一日3次，8～24周治疗，比较治疗前后血清IGF-1、IGFBP-1、空腹胰岛素及睾酮水平，并对月经恢复、排卵、妊娠情况进行分析。结果二甲双胍可降低血清空腹胰岛素及睾酮水平，能显著升高IGFBP-1水平，治疗前后血清IGF—1水平差异无显著性。单纯二甲双胍治疗后月经恢复率为41．67％（10／24）；自然排卵率为25．00％（6／24），自然妊娠率为12．50％（3／24）。二甲双胍加促排卵治疗共18个周期，排卵周期率66．67％（12／18），妊娠周期率为11．11％（2／18）。结论二甲双胍可以降低血清空腹胰岛素及睾酮水平，增高IGFBP-1水平，可以改善卵泡微环境，有助于月经恢复，提高促排卵和妊娠率．是治疗PCOS的重要手段。     

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。     

二甲双胍联合复方醋酸环丙孕酮治疗青春期PCOS疗效分析

目的：探讨二甲双胍联合复方醋酸环丙孕酮（CPA）对青春期多囊卵巢综合征（PCOS）患者的临床疗效。方法：将23例青春期PCOS患者随机分为两组，A组（n=13）给予复方CPA，B组（n=10）联合给予复方CPA和二甲双胍（1500mg／d），用药3个月后，观察洽疗前后临床表现、血浆性激素水平、空腹血糖、空腹胰岛素水平的变化，以及短期对氯米芬（CC）促排卵的反应和黄体生成激素（LH）反跳率。结果：治疗3个月后，两组患者卵泡刺激素（FsH）、LH水平、LH／FSH比值较治疗前明显降低，有显著性差异（P〈O．05），多毛、痤疮症状改善，雄激素水平无明显变化。在A组稳态模型胰岛素抵抗指数（HOMA—IR）较治疗前升高，差异有统计学意义（P〈O．05）。A组8例患者（61．55％）和B组6例患者（60．00％）对CC无反应，在3个周期CC后，A组有8例患者（61．55％）和B组3例患者（30．00％）出现LH反跳，B组的LH反跳比例低于A组。但无统计学差异（P〉O．05）。结论：复方CPA联合二甲双胍治疗青春期PCOS可以改善患者的临床症状，降低LH水平，降低LH反跳率，可作为青春期PCOS治疗的选择。     

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。     

探讨二甲双胍联合炔雌醇环丙孕酮对多囊卵巢综合征PCOS不孕症治疗的效果

目的探讨二甲双胍联合炔雌醇环丙孕酮对多囊卵巢综合征PCOS不孕症治疗的效果。方法选取2016年5月~2018年5月我院收治92例多囊卵巢综合征PCOS不孕症门诊患者为研究对象,将92例患者随机分为治疗组与常规组,每组46例,对常规组使用炔雌醇环丙孕酮进行门诊促排卵治疗,治疗组患者采用二甲双胍联合炔雌醇环丙孕酮进行门诊促排卵治疗,治疗后对两组患者的诱导排卵率、妊娠率与激素水平指标进行观察对比。结果治疗后,治疗组患者的诱导排卵率与妊娠率均高于常规组,P<0.05,与常规组相比,治疗组患者的激素水平指标有明显改善,P<0.05。结论对多囊卵巢综合征PCOS不孕症患者采用二甲双胍联合炔雌醇环丙孕酮进行治疗,可以提高患者的排卵率与妊娠率,调节患者体内的激素水平。     

生活方式调整及药物治疗多囊卵巢综合征的临床研究

目的探讨生活方式调整、二甲双胍及罗格列酮治疗多囊卵巢综合征（PCOS）的临床疗效。方法将106例PCOS患者随机分为单纯生活方式调整（锻炼及饮食控制）、生活方式调整＋二甲双胍与生活方式调整＋罗格列酮治疗3组,分别为43、36、27例,共有60例（分别为22、21、17例）患者完成治疗,观察3组患者治疗前、后排卵情况,比较体重指数（BMI）、腰围、腰围与臀围比值（WHR）、血清睾酮、空腹真胰岛素水平、血脂、稳态模型法测定的胰岛素抵抗指数（HOMA-IR）、空腹血糖与胰岛素比值（GIR）、定量胰岛素敏感检测指数（QUICKI）的变化。结果治疗前3组患者年龄、BMI、腰围、WHR、睾酮水平、空腹真胰岛素水平、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白．胆固醇（HDL-C）、低密度脂蛋白-胆固醇（LDL-C）比较,差异均无统计学意义（P〉0．05）。单纯生活方式调整组的43例患者中22例完成治疗,23％（5／22）恢复排卵;生活方式调整＋二甲双胍组的36例患者中21例完成治疗,43％（9／21）恢复排卵;生活方式调整＋罗格列酮组的27例患者中17例完成治疗,59％（10／17）恢复排卵。3组患者的恢复排卵率比较,差异无统计学意义（P〉0．05）;但生活方式调整＋罗格列酮组较单纯生活方式调整组恢复排卵率高,且差异有统计学意义（P〈0．05）。治疗后3组患者的BMI、腰围、WHR、睾酮、TC、TG、LDL-C、HDL-C比较,差异均无统计学意义（P〉0．05）。结论生活方式调整、二甲双胍、罗格列酮对PCOS患者均有恢复排卵作用。     

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.     

炔雌醇环丙孕酮联合二甲双胍治疗多囊卵巢综合征的临床效果观察

目的 观察炔雌醇环丙孕酮联合二甲双胍治疗多囊卵巢综合征(PCOS)的临床效果.方法 选取90例PCOS患者,按照随机数字表法分为研究组(采用炔雌醇环丙孕酮联合二甲双胍治疗)与对照组(采用炔雌醇环丙孕酮治疗),每组45例.比较两组治疗前后激素水平、排卵率及妊娠率.结果 治疗前,两组卵泡刺激素(FSH)、促黄体生成素(LH...     

Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of ultra-short (12 days) metformin pretreatment in clomiphene-citrate (CC) resistant polycystic ovary syndrome (PCOS). METHOD: Eighty women with CC-resistant PCOS were randomly allocated to metformin pretreatment or usual treatment. Forty women received 1500 mg metformin daily for 12 days, followed by clomiphene 150 mg daily for 5 days along with metformin. Forty women (control group) received the same dose of clomiphene but no metformin pretreatment. RESULTS: In the metformin group, 17 (42.5%) women ovulated, and 6 (15%) conceived. In the control group, 5 (12.5%) women ovulated but none conceived. Compared with the control group, the metformin group had significantly higher ovulation (P = 0.03) and pregnancy rates (P = 0.026). CONCLUSION: Twelve days of metformin pretreatment improves ovulation and pregnancy rates in women with CC-resistant PCOS.     

The role of metformin in ovulation induction: Current status

To define the exact role of metformin in ovulation induction, it is crucial to distinguish three different indications: naïve PCOS, CC-resistant PCOS and ART. In naïve PCOS: metformin as compared to placebo has been shown to improve ovulation rates, but metformin did not exert significant advantage over CC with respect to cumulative ovulation, pregnancy or live-birth rates. The combined approach of metformin plus CC is not better than CC or metformin monotherapy in naïve PCOS. In CC-resistant patients: metformin has no benefit over placebo in ovulation, pregnancy, and live-birth rates as a single agent, but the combination of metformin and CC significantly improved ovulation and pregnancy rates when compared with CC alone. However, combined therapy did not improve the odds of live birth. Metformin pretreatment improves the efficacy of CC in PCOS patients with CC resistance. In PCOS patients scheduled for ART: metformin addition to gonadotropins reduces the duration of gonadotropins administration and the doses of gonadotropins required, and increases the rate of monoovulations, reducing the risk of cancelled cycles. Metformin co-administration to IVF treatment does not improve pregnancy or live-birth rates but reduces the risk of OHSS.     

Risk of multiple gestation after ovulation induction in polycystic ovary syndrome

OBJECTIVE: To compare the incidence of multiple gestation following treatment with clomiphene citrate (CC), metformin (MET) or gonadotropins in polycystic ovary syndrome (PCOS) patients undergoing ovulation induction. STUDY DESIGN: This was a retrospective, cohort study performed in an academic reproductive endocrine practice. PCOS patients presenting for first-trimester ultrasound were identified and assigned to 1 of 3 groups: CC-resistant patients who conceived after use of metformin +/- CC (group A), CC-resistant patients who conceived after gonadotropins (group B) and PCOS patients who conceived with CC only (group C). Multiple pregnancy outcome data were collected by chart review and patient interview. RESULTS: One hundred one pregnancies were identified in PCOS patients who had conceived after ovulation induction (OI). The rate of multiple gestation was higher in group B (36%) than in A (0%) or C (11%). CONCLUSION: The rate of multiple births was significantly lower with MET use during OI. Because multiple gestation is associated with higher complication rates and medical costs, our data offer an additional reason for use of MET for OI in PCOS patients who fail CC.     

Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome

OBJECTIVE: To assess pregnancy outcome in anovulatory infertility patients diagnosed with polycystic ovary syndrome (PCOS) who were treated with metformin. DESIGN: Case series. SETTING: Outpatient. PATIENT(S): Anovulatory patients (n = 48) with a diagnosis of PCOS based on clinical, diagnostic, and laboratory evaluations were enrolled in the study over a 15-month period. INTERVENTION(S): Metformin was started at 500 mg b.i.d. for 6 weeks and then increased to 500 mg t.i.d. if no ovulation occurred. Clomiphene citrate (CC; 50 mg) was added if no ovulatory response occurred after 6 weeks. MAIN OUTCOME MEASURE(S): Resumption of menses, presumptive ovulation, and pregnancy. RESULT(S): Nineteen of 48 (40%) patients resumed spontaneous menses following treatment and showed presumptive evidence of ovulation with metformin alone; 15/48 (31%) required CC (50 mg) in conjunction with metformin therapy, and 10 of these 15 (67%) had evidence of ovulation; 20/48 (42%) conceived with a median time to conception of 3 months, and 7 of these 20 (35%) had spontaneous abortions (SAB); 19/48 (40%) had gastrointestinal-related side effects, and 5 of 48 patients (10%) had to decrease the dosage of metformin. Only 1 patient discontinued therapy. CONCLUSION(S): Metformin alone in patients with PCOS results in a substantial number of pregnancies, with 69% (20/29) of those who ovulated conceiving in less than 6 months.     

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.     

Effects of low-dose metformin in Japanese women with clomiphene-resistant polycystic ovary syndrome

Background and Aims  The aim of the present prospective observational study was to evaluate the effects of low-dose, short-term metformin, in combination with domiphene (CC), in CC-resistant infertile Japanese women with polycystic ovary syndrome (PCOS). Methods  Metformin therapy was administered orally (one 250 mg tablet, twice daily) to 15 CC-resistant infertile patients with PCOS, beginning on the third day of progestin-induced withdrawal bleeding, and was continued for 14 days in the first cycle. In the event of anovulation, 100 mg/day of CC was given during subsequent cycles on days 5–9, in addition to the aforementioned dose of metformin. Hormonal and metabolic parameters were measured on the second or third days of the first cycle and also the fourth cycle, following an overnight fast. Results  None of the 15 women successfully ovulated during the first cycle with metformin treatment alone. After two subsequent cycles with the combination of CC and metformin, ovulation was confirmed in 17 of 29 cycles (61%) and in 13 of 15 patients (87%). Two women became pregnant within 2 months of therapy (13%). There were no cases of ovarian hyperstimulation syndrome. Following three cycles of metformin therapy, a slight reduction in serum levels of luteinizing hormone (LH), free testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin Alc and total cholesterol was seen, while serum LH/follide-stimulating hormone ratio and serum level of low-density lipoprotein cholesterol were significantly decreased. Although there were no significant differences between the responder (n = 11) and non-responder (n = 2) groups at baseline, the levels of plasma fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the non-responder group compared with the responder group after three cycles. Conclusion  Low-dose, short-term metformin, combined with CC, can improve ovulation rates in CC-resistant infertile Japanese women with PCOS.     

Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial

Aim.?To compare the effect of combined metformin–clomiphene citrate (CC) with highly purified urinary FSH (HP-uFSH) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).

Methods.?One-hundred fifty-three anovulatory women with CC-resistant PCOS were selected in this randomised controlled trial. Patients received combined metformin–CC (n?=?75, 205 cycles) or HP-uFSH (n?=?78, 186 cycles) for three cycles. Outcome measures were; Ovulation rate, number of growing and mature follicles, serum E2, serum P, endometrial thickness, pregnancy and miscarriage rates.

Results.?The ovulation rate per cycle was significantly higher in the HP-uFSH group (83.8% vs. 62%, p?=?0.01). The number of follicles ≥12?mm ≥14?mm and ≥18?mm on the hCG day was significantly greater in the HP-uFSH group (p?=?0.01, p?=?0.02 and p?=?0.03, respectively). Pregnancy occurred in 23/205 cycles (11.2%) in combined metformin–CC group and 40/186 cycles (21.5%) in the HP-uFSH group; the difference was statistically significant (p?=?0.02). Two patients in the HP-uFSH group suffered mild OHSS.

Conclusions.?Combined metformin–CC resulted in modest ovulation and pregnancy rates without side effects. It is logical to offer this first for CC-resistant PCOS women before resorting to more expensive alternatives especially in developing communities where economic aspects of therapy are important.     

Metformin monotherapy in lean women with polycystic ovary syndrome

This study was carried out to compare ovulation and pregnancy rates in response to metformin therapy in lean and obese women with polycystic ovary syndrome (PCOS). A total of 34 (17 lean and 17 obese) women with PCOS were treated with 500 mg metformin 3 times daily for 12 weeks. In the lean and obese groups, the mean body mass index was 24 and 36, and the mean fasting insulin concentrations were 12 and 21 mIU/l respectively. There was no difference between the two groups as regarding age, DHEA-S, androstenedione, 17-OH progesterone and LH concentrations. In the lean and obese groups 15/17 women (88%) and 5/17 women (29%) ovulated while 11/17 women (65%) and 3/17 women (18%) conceived respectively. Comparison between the groups was found to be statistically significant. Metformin monotherapy is very effective in improving ovulation and pregnancy rates in lean women with PCOS as compared with obese women.     

Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone

OBJECTIVE: To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Multicenter environment. PATIENT(S): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC. INTERVENTION(S): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy rates. RESULT(S): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant. CONCLUSION(S): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.