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。     

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。     

二甲双弧治疗多囊卵巢综合征的疗效观察

目的探讨二甲双弧治疗多囊卵巢综合征(PCOS)的疗效。方法选取我院2012年11月~2014年10月收治的PCOS患者50例作为研究对象,将其随机分为观察组和对照组,各25例。观察组给予氯米芬加二甲双弧治疗,对照组给予氯米芬治疗。观察并对比两组患者的疗效。结果观察组患者恢复排卵率明显优于对照组,差异有统计学意义(P0.05)。结论采用二甲双弧治疗PCOS,疗效显著,值得临床推广应用。     

氯米芬用于多囊卵巢综合征不孕妇女促排卵时机的临床观察

目的探讨氯米芬用于多囊卵巢综合征不孕妇女促排卵时机的临床观察。方法选取2010年5月~2015年5月收治的因多囊卵巢综合征无排卵引起的不孕症患者80例,将其随机分为研究组和对照组,各40例。研究组采用口服二甲双胍+达英-35连续治疗3~6个月,查生殖激素+血胰岛素值+葡萄糖耐量试验,基本正常后开始给予氯米芬促排卵;对照组直接给予氯米芬促排卵。比较两组用药后3个月及6个月受孕率、流产率和活产率。结果研究组3个月及6个月受孕率、流产率和活产率均明显高于对照组,差异均有统计学意义(P0.05)。结论多囊卵巢综合征不孕妇女促排卵前降低高血促黄体激素(LH)值,高雄激素血症、高胰岛素血症,明显提高卵巢排卵反应,提高受孕率,改善妊娠结局。     

罗格列酮和二甲双胍治疗多囊卵巢综合征患者的临床疗效比较

目的:比较罗格列酮和二甲双胍治疗多囊卵巢综合征的临床疗效。方法:80例氯米芬抵抗的多囊卵巢综合征患者,随机分为罗格列酮组40例和二甲双胍组40例,疗程为6个月,比较两组用药前、后体重指数、月经周期、生殖激素水平、排卵率、妊娠率、血糖和胰岛素水平的变化。结果:①罗格列酮和二甲双胍均可降低血LH/FSH比值和雄激素水平(P<0.05),恢复卵巢排卵功能;②罗格列酮可降低HomaIR指数和Homaβ指数(P<0.05),二甲双胍降低BMI评分(P<0.05)。结论:罗格列酮和二甲双胍均可改善氯米芬抵抗的多囊卵巢综合征患者生育功能;但罗格列酮改善胰岛素抵抗优于二甲双胍,而降低体重作用二甲双胍优于罗格列酮。     

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。     

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。     

二甲双胍联合氯米芬-促性腺激素治疗多囊卵巢综合征

多囊卵巢综合征（PCOS）是排卵障碍性不孕的重要原因，与患者体内高雄激素、高胰岛素或胰岛素抵抗有关。其中部分患者经氯米芬治疗后能获得妊娠。但仍有相当数量的PCOS患者对氯米芬治疗无效。对此类患者使用氯米芬联合促性腺激素（CC—hMG／hCG）是目前治疗中常用的诱发排卵方法之一，但对PCOS患者使用促性腺激素治疗容易发生卵巢过度刺激综合征（OHSS），严重者可威胁患者生命。我们采用胰岛素增敏剂-二甲双胍联合氯米芬-促性腺激素治疗PCOS，取得肯定疗效，现报道如下。     

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     

二甲双胍治疗高胰岛素血症所致无排卵的临床观察

目的了解高胰岛素对血睾酮水平和排卵功能的影响,二甲双胍治疗高胰岛素血症无排卵的临床效果.方法对29例高胰岛素血症患者,进行12周的二甲双胍治疗,其中19例在二甲双胍治疗前后均接受氯米芬治疗1个周期.观察治疗前后血睾酮水平和排卵功能的变化.结果二甲双胍治疗前血睾酮水平为(2.7±1.6)nmol/L,治疗4周后为(1.9±1.0)nmol/L,两者比较,差异有显著性(P＜0.05).自发排卵,二甲双胍治疗前有3例,治疗后有10例(其中8例为原无排卵者)(P＜0.05);19例在二甲双胍治疗前后均服用过氯米芬,促排卵成功在二甲双胍治疗前有8例、治疗后有15例(P＜0.05).结论高胰岛素血症可引起血睾酮水平升高,排卵功能障碍.应用二甲双胍后胰岛素水平降低,睾酮水平下降,排卵功能有改善.     

The effectiveness of metformin ovulation induction treatment in patients with PCOS: a systematic review and meta-analysis

Objective: To evaluate of metformin effectiveness of ovulation induction treatment in polycystic ovary syndrome (PCOS) women. Methods: Eight databases and nine related journals were searched for randomized controlled trails (RCTs) on the comparison between metformin and clomiphene citrate used for PCOS women. Meta analysis was performed after quality assessment. Results: Ovulation rate in metformin group compared with clomiphene citrate group was lower with a significant difference [OR = 0.48 (0.26–0.87), p = 0.01]; no significant difference was found for pregnancy rate [OR = 0.94 (0.26–3.43)], miscarriage rate [OR = 0.63 (0.06–6.47)] between two groups. Compared with the combination of metformin and clomiphene citrate group, pregnancy rate in metformin group was significantly lower [Peto OR = 1.56 (1.16–2.08), p = 0.003], but there was no significant difference in the two groups about ovulation rate [OR = 1.52 (0.95–2.45)], miscarriage rate [Peto OR = 1.40 (0.79–2.48)]. Conclusions: Compared with clomiphene citrate, metformin used for ovulation induction treatment in PCOS women, can promote ovulation induction and pregnancy rate, the effect of the combination treatment is better than that of a single drug use.     

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC?+?MET, or LE and LE?+?MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.     

Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of metformin therapy on hyperandrogenism, insulin resistance, cervical scores, ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Infertility clinic of a tertiary referral center. PATIENT(S): Fifty-six women with clomiphene citrate-resistant PCOS. INTERVENTION(S): Two cycles of oral metformin therapy (850 mg, twice daily) in group I and placebo therapy (twice daily) in group II. Clomiphene citrate (100 mg/day) on cycle days 3-7 of the second cycle in both groups. MAIN OUTCOME MEASURE(S): Insulin, T, DHEAS, FSH, LH, body mass index (BMI), waist-to-hip ratio, endometrial thickness, cervical score, ovulation, and pregnancy rates in clomiphene-induced cycles after metformin therapy. Result(s): Metformin therapy resulted in a significant decrease in total T, LH level, LH/FSH ratio, insulin resistance, and mean BMI. No difference in waist-to-hip ratio, DHEAS level, and fasting insulin level was observed. Clomiphene citrate induction resulted in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group. There was higher cumulative pregnancy rate in the metformin group; however, there was no significant difference in the pregnancy rate between the two groups. CONCLUSION(S): Metformin therapy not only decreases hyperandrogenism and insulin resistance but also improves ovulation rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with PCOS.     

Review of nonsurgical and surgical treatment and the role of insulin-sensitizing agents in the management of infertile women with polycystic ovary syndrome

OBJECTIVES: To review the nonsurgical and surgical treatment and the role of insulin-sensitizing agents in the management of anovulatory infertile women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The search term of subfertile women with anovulation and PCOS was used for identification of randomized controlled trials. Nonrandomized controlled studies were identified through computer MEDLINE and EMBASE searches for the years 1980-2002. RESULTS: For obese PCOS women weight loss of > 5% of pretreatment weight restores menstrual regularity in 89%, of whom 30% achieved spontaneous pregnancy. It was estimated that 75-80% of anovulatory PCOS women will respond to clomiphene citrate (CC) and 35-50% will achieve pregnancy. For CC-resistant PCOS women (20-25%), CC + metformin (1.5 g/day) for 3-6 months has a 70% chance of restoration of regular menses and ovulation, and a 23% chance of pregnancy. Laparoscopic ovarian drilling (LOD) can be offered to CC-resistant PCOS women. There was no statistically significant difference in the ovulation rate following LOD with electrocoagulation and laser [83% vs. 77.5%; odds ratio (OR) 1.4; 95% CI 0.9-2.1], while there was a significantly higher cumulative pregnancy rate at 12 months after surgery (65% vs. 54.5%; OR 1.5; 95% CI 1.1-2.1). CONCLUSION: Diet and exercise followed by CC should be used for nonsurgical ovulation induction. For CC-resistant PCOS women, metformin may be included in a stepwise approach before a surgical approach. LOD with electrocautery is superior to laser drilling and gonadotropin therapy.     

Effects of metformin on body mass index,menstrual cyclicity,and ovulation induction in women with polycystic ovary syndrome

OBJECTIVE: Metformin has been used as a treatment in many studies of the infertility associated with polycystic ovary syndrome (PCOS). We will review the literature on this topic as it specifically relates to changes in body mass index (BMI), improvement in menstrual cyclicity, and effects on ovulation and pregnancy rates. DESIGN: Review of studies addressing biochemical and clinical changes in women with PCOS on metformin. MAIN OUTCOME MEASURE(S): Changes in BMI, menstrual cyclicity, ovulation rate, and pregnancy rate. RESULT(S): Metformin has been shown to produce small but significant reductions in BMI. Multiple observational studies have confirmed an improvement in menstrual cyclicity with metformin therapy. The studies addressing the concomitant use of metformin with clomiphene citrate initially predicted great success, but these have been followed by more modest results. There is little data in the literature concerning the use of metformin and hMGs. CONCLUSION(S): Some (but not all) women with PCOS have improvements in their menstrual cycles while on metformin. The data supporting the use of metformin in ovulation induction with clomiphene citrate and hMG remain to be confirmed by large, randomized, prospective studies.     

Effect of metformin on ovulation and reproductive outcomes in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials

Purpose

To evaluate the effect of MET on ovulation and reproductive outcomes in patients with polycystic ovary syndrome.

Methods

Meta-analysis of available data from randomized controlled trials that examined the ovulation, pregnancy and live birth rate after the administration of clomiphene citrate (CC) or MET alone or combined.

Results

The ovulation rate was found to be higher in the group treated with MET combined with clomiphene citrate (CC) than only with CC, odds ratio (OR): 1.27, 95 % confidence interval (95 % CI) (1.03–1.56), while the pregnancy and live birth rate showed no significant difference between the two groups, OR: 1.19, 95 % CI (0.99–1.42) and OR: 0.99, 95 % CI (0.84–1.17), respectively. The MET + CC group produced a higher ovulation and pregnancy rate than MET group, OR: 2.10, 95 % CI (1.89–2.34) and OR: 2.08, 95 % CI (1.55–2.80), respectively, while between two groups the live birth rate showed no significant difference, OR: 1.50, 95 % CI (0.75–3.00). The ovulation rate was lower in MET than in CC group, OR: 0.65, 95 % CI (0.43–0.995), while between the two groups the pregnancy and live birth rate showed no significant difference, OR: 0.86, 95 % CI (0.42–1.74) and OR: 0.89, 95 % CI (0.71–1.13).

Conclusion

The current study indicated that combination of MET and CC could gain advantage over a single administration in the ovulation induction and pregnancy rate.     

Ovulation induction--optimizing results and minimizing risks

The aim of ovulation induction therapy should be, wherever possible, to correct the underlying disturbance and achieve safe, repeated unifollicular ovulation to achieve the live birth of singleton babies. This article outlines the main causes of anovulatory infertility but deals mostly with the management of anovulatory polycystic ovary syndrome (PCOS), which is the most common problem to confront specialists in reproductive medicine. PCOS is associated with insulin resistance, particularly in those who are overweight. Thus, strategies to achieve weight loss and improve insulin sensitivity, including the use of drugs such as metformin, enhance reproductive function. Therapies to induce ovulation involve first the use of the anti-oestrogen clomiphene citrate. For those who fail to ovulate in response to clomiphene citrate, the principal options include parenteral gonadotrophin therapy or laparoscopic ovarian diathermy.     

Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome

The aim of this study was to systematically compare the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). The Cochrane Central Register of Controlled Trials, PubMed, EMbase, CBMdisc and CNKI were searched for eligible randomized controlled trials (RCT) comparing letrozole with clomiphene citrate in PCOS patients. Two reviewers independently extracted information and evaluated methodological quality according to the Cochrane Handbook 5.0. Meta-analysis was performed with the fixed-effects model or random-effects model according to the heterogeneity. Six eligible RCT involving 841 patients were included. Letrozole was associated with a number of lower mature follicles per cycle (standardized mean difference (SMD) -1.41; 95% confidence intervales (CI) -1.54 to -1.28; P<0.00001) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk (RR) 0.97; 95% CI 0.79 to 1.18), abortion rate (RR 1.38; 95% CI 0.48 to -3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to -1.72) between the two groups. The evidence from ovulation rates was not enough to support either letrozole or clomiphene citrate. In conclusion, letrozole is as effective as clomiphene citrate for ovulation induction in patients with PCOS.     

The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with Polycystic Ovary Syndrome

Abstract

Objectives: To assess the adjuvant effect of metformin and N-acetylcysteine (NAC) to clomiphene citrate (CC) in induction of ovulation in Polycystic Ovary Syndrome (PCOS) patients.

Study design: 120 women with PCOS were randomly divided into three equal groups: group I received CC only, group II received CC plus NAC and group III received CC plus metformin.

Results: There was a significant difference between group II and other two groups regarding average number of ovulatory follicles >18?mm (2.25 versus 1.75 and 1.89, respectively), but no significant difference between the three study groups regarding number of intermediate follicles 14–18?mm (4, 10 and 4, respectively). There was no significant difference between the three study groups regarding occurrence and laterality of ovulation, pregnancy rate per cycle but a significant difference between group II and other two groups regarding pregnancy rate per patient (20% versus 10% and 10%, respectively, p value 0.05). There was a highly statistically significant difference between group II and other two groups regarding peak endometrial thickness (7.3?±?1.1 versus 5.4?±?0.6 and 5.3?±?0.6, respectively).

Conclusions: NAC as an adjuvant to CC for induction of ovulation improves ovulation and pregnancy rates in PCOS patients with beneficial impacts on endometrial thickness.     

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.