二甲双胍对体外受精/卵胞质内单精子显微注射中多囊卵巢综合征患者妊娠结局有效性的系统评价

目的:系统性评价二甲双胍对常规体外受精/卵胞质内单精子显微注射(IVF/ICSI)中多囊卵巢综合征(PCOS)患者妊娠结局的有效性,旨在为助孕前的干预措施提供理论依据。方法:计算机检索中国学术期刊全文数据库(CNKI)、万方数据库、维普数据库、Pub Med、Medline、Embase有关二甲双胍对IVF/ICSI中PCOS患者妊娠结局的临床随机对照试验(RCT)。按Cochrane系统评价方法,首先对纳入的文献进行质量评价和资料提取后,采用Rev Man5.2软件进行Meta分析。结果:纳入11个RCT研究,共1 310例患者,其中二甲双胍组713例,对照组597例。Meta分析结果显示:与对照组相比较,二甲双胍组的临床妊娠率(OR=1.60,95%CI:1.26~2.04,P=0.000 2)较高,卵巢过度刺激综合征(OHSS)发生率较低(OR=0.45,95%CI:0.31~0.64,P=0.000 1)。而活产率(OR=1.38,95%CI:0.98~1.94,P=0.06)和流产率(OR=0.72,95%CI:0.51~1.02,P=0.07)组间无统计学差异。结论:二甲双胍可提高IVF/ICSI中PCOS患者的妊娠率、降低OHSS发生率,但不能提高活产率及降低流产率。     

复方醋酸环丙孕酮联合二甲双胍对多囊卵巢综合征患者内分泌及代谢影响的Meta分析

目的:系统评价二甲双胍与复方醋酸环丙孕酮(CPA)联合应用对多囊卵巢综合征(PCOS)患者内分泌及代谢的影响。方法:计算机检索Cochrane Library、Pub Med、EMbase、中国生物医学文献数据库、维普数据库、中国知网数据库,纳入关于二甲双胍与复方CPA联合应用治疗PCOS的对照研究,检索时限均截止至2015年1月。由2位研究者独立按照纳入与排除标准筛选文献、提取资料和评价纳入研究的方法学质量后,采用Rev Man 5.2软件进行Meta分析。结果:共纳入9个对照研究,合计641例患者。Meta分析结果显示:二甲双胍联合复方CPA组LH/FSH(MD=-0.42,95%CI=-0.55~-0.28,P0.000 01)、睾酮(SMD=-0.42,95%CI=-0.78~-0.07,P=0.02)、空腹血糖(MD=-0.91,95%CI=-1.28~0.54,P0.000 01)和空腹胰岛素(MD=-0.63,95%CI=1.07~0.43,P=0.005)等方面均优于单纯复方CPA组。结论:当前证据表明,二甲双胍联合复方CPA对PCOS患者内分泌激素及代谢的改善效果优于单纯复方CPA。     

醋酸环丙孕酮联合二甲双胍对多囊卵巢综合征患者内分泌及代谢影响的Meta分析

目的:系统评价二甲双胍与复方醋酸环丙孕酮(CPA)联合应用对多囊卵巢综合征(PCOS)患者内分泌及代谢的影响.方法:计算机检索Cochrane Library、PubMed、EMbase、中国生物医学文献数据库、维普数据库、中国知网数据库,纳入关于二甲双胍与复方CPA联合应用治疗PCOS的对照研究,检索时限均截止至2015年1月.由2位研究者独立按照纳入与排除标准筛选文献、提取资料和评价纳入研究的方法学质量后,采用RevMan5.2软件进行Meta分析.结果:共纳入9个对照研究,合计641例患者.Meta分析结果显示:二甲双胍联合复方CPA组LH/FSH(MD=-0.42,95％CI=-0.55～-0.28,P＜0.000 01)、睾酮(SMD=-0.42,95％CI=-0.78～-0.07,P=0.02)、空腹血糖(MD=-0.91,95％CI=-1.28～0.54,P＜0.000 01)和空腹胰岛素(MD=-0.63,95％CI=1.07～0.43,P=0.005)等方面均优于单纯复方CPA组.结论:当前证据表明,二甲双胍联合复方CPA对PCOS患者内分泌激素及代谢的改善效果优于单纯复方CPA.     

二甲双胍联合辛伐他汀治疗多囊卵巢综合征疗效的Meta分析

目的:评价二甲双胍联合辛伐他汀治疗多囊卵巢综合征(PCOS)的疗效,进而指导临床治疗。方法:计算机检索Pub Med、EMbase、Cochrane Library、中国知网、万方、维普及中国生物医学文献数据库,纳入关于二甲双胍联合辛伐他汀治疗PCOS的随机对照试验(RCT)。用Rev Man 5. 1软件进行Meta分析,发表偏倚采用Stata 12. 1软件进行分析。结果:共纳入9篇RCT文献。Meta分析结果显示:二甲双胍联合辛伐他汀可明显提高患者的临床总有效率(OR=6. 56,95%CI 2. 95～14. 60,P 0. 00001);显著降低患者血浆总胆固醇(TC)(SMD=-2. 66,95%CI-3. 65～-1. 66,P 0. 00001),甘油三酯(TG)(SMD=-1. 25,95%CI-2. 02～-0. 49,P=0. 001),低密度脂蛋白(LDL)(SMD=-2. 91,95%CI-3. 98～-1. 84,P 0. 00001),睾酮(T)(SMD=-0. 64,95%CI-1. 13～-0. 15,P=0. 01),空腹胰岛素(FIN)(SMD=-1. 17,95%CI-2. 09～-0. 26,P=0. 01)。但是对血浆高密度脂蛋白(HDL)(P=0. 84)、黄体生成素(LH)(P=0. 29)、卵泡刺激素(FSH)(P=0. 50)、催乳素(PRL)(P=0. 08)、空腹血糖(FBS)(P=0. 55)、C反应蛋白(CRP)(P=0. 44),体质量指数(BMI)(P=0. 91)以及胰岛素敏感指数(ISI)(P=0. 30)和多毛症得分(P=0. 87)差异无统计学意义。结论:二甲双胍联合辛伐他汀治疗PCOS患者的疗效优于二甲双胍单用,对改善患者性激素、血脂、血糖水平更具优势,提高临床总有效率,疗效显著,值得临床推广使用。     

IVF/ICSI术后孕激素黄体支持最佳终止时间的Meta分析

目的:系统评价体外受精/单精子卵泡浆内显微注射(IVF/ICSI)术后孕激素黄体支持的不同终止时间对妊娠结局的影响。方法:检索MEDLINE、EMBASE、CENTRAL、中国生物医学数据库和万方数据库,检索时间截止2012年7月。纳入关于IVF/ICSI术后早期停用孕激素和持续使用孕激素的所有随机对照试验,质量评价后采用RevMan 5.1软件进行Meta分析。结果:共纳入6个随机对照试验,1201例患者,IVF/ICSI术后妊娠的妇女接受早期停用孕激素组和持续孕激素治疗组在活产率(RR=0.95,95%CI 0.86~1.05)、流产率(RR=1.01,95%CI 0.74~1.38)和持续妊娠率(RR=0.97,95%CI 0.90~1.05)上差异均无统计学意义(P0.1);敏感性分析前后结果保持稳定。结论:目前最佳证据表明IVF/ICSI治疗后妊娠的妇女在尿妊娠实验阳性后常规使用孕激素支持黄体可能是没有必要的,但上述结论尚需大样本的随机对照试验来进一步验证。     

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。     

药物预处理对降低多囊卵巢综合征卵巢刺激高反应的效果评价

多囊卵巢综合征(PCOS)患者在行促排卵时常出现卵巢刺激的高反应性,表现为多卵泡发育、血雌二醇(E2)升高和卵泡过度刺激综合征(OHSS)的增加等,而影响临床妊娠结局。如何在PCOS患者卵巢刺激前或卵巢刺激中使用药物改善妊娠结局,尽量降低OHSS发生率,成为人们关注的问题。结合目前现有研究数据,尚不能推荐何种预处理方式应该作为PCOS患者的常规,鉴于PCOS患者卵巢刺激的异质性、复杂性,某些患者可能得益于其中一种或几种治疗:如胰岛素抵抗PCOS患者推荐体外受精(IVF)前使用二甲双胍;卵巢刺激前使用口服避孕药(OC),使促性腺激素释放激素激动剂(GnRH-a)降调节更完全;卵巢刺激中使用多巴胺受体激动剂,降低OHSS风险;PCOS患者因OHSS高风险取消移植时使用来曲唑明显降低血E2水平。另外,还没有足够证据支持糖皮质激素在卵巢刺激前的预处理应用。     

二甲双胍治疗2型糖尿病患者罹患妇科恶性肿瘤风险Meta分析

目的评估二甲双胍治疗2型糖尿病患者罹患妇科恶性肿瘤的风险。方法从Pubmed、CNKI、万方数据库获得2型糖尿病女性患者使用二甲双胍与妇科恶性肿瘤发生风险的文献,评估二甲双胍治疗2型糖尿病患者中发生宫颈癌、子宫内膜癌、卵巢癌的风险。结果共纳入8篇文献9项研究,其中治疗组876 809例,对照组704 965例。Meta分析结果,二甲双胍组与未使用二甲双胍组相比,发生妇科恶性肿瘤的风险差异无统计学意义[OR=0.74,95%CI 0.52~1.05,P=0.09]。对宫颈癌、子宫内膜癌、卵巢癌3种妇科恶性肿瘤进行亚组分型,Meta分析结果发现:二甲双胍组与未使用二甲双胍组发生宫颈癌的风险差异无统计学意义[OR=0.59,95%CI 0.25~1.37,P=0.22];两组患者发生子宫内膜癌的风险差异无统计学意义[OR=0.97,95%CI 0.60~1.55,P=0.88];但二甲双胍组发生卵巢癌的风险低于未使用二甲双胍组[OR=0.71,95%CI 0.55~0.92,P=0.01]。结论在2型糖尿病患者中,使用二甲双胍作为降糖药物,不能减少宫颈癌和子宫内膜癌发生风险,但可降低患者发生卵巢癌的风险。     

基因重组促卵泡激素(FSH)与尿源性FSH用于体外受精-胚胎移植的Meta分析

目的:比较体外受精(IVF)或卵胞质内单精子注射(ICSI)治疗周期基因重组促卵泡激素(rFSH)与尿源性促卵泡激素(uFSH)在控制性促排卵(COS)中的有效性。方法:检索Pub Med、EMBASE、Cochrane,CNKI及万方数据库中自rFSH上市至2013.09前发表的文章,收集rFSH与uFSH在IVF或ICSI中应用的随机对照研究,对纳入的研究进行质量评价,提取数据,采用Rev Man5.2软件对IVF或ICSI治疗周期的获卵数、FSH总用量、周期出生率、临床妊娠率、持续妊娠率、卵巢过度刺激综合征(OHSS)的相对有效性进行Meta分析。结果:共纳入21篇研究,6 496个周期。总体上,rFSH较uFSH获卵数更多,FSH总用药量更少,差异有显著统计学意义;周期出生率和临床妊娠率r FSH和u FSH之间无显著性差异。结论:rFSH较uFSH在辅助生殖中具有更好的COS有效性。     

肌醇与二甲双胍对多囊卵巢综合征患者疗效对比的meta分析

目的:系统评价肌醇与二甲双胍治疗多囊卵巢综合征(PCOS)的疗效。方法:通过检索Pubmed、The Cochrane Library、Embase、Web of Science、CNKI、Wanfang、CBM数据库,搜集肌醇与二甲双胍治疗PCOS的随机对照试验(RCT),检索时限均从建库至2019年10月。严格筛选文献、提取资料后,采用RevMan 5.3软件对文献进行质量评价和meta分析。结果:共纳入8个RCT,包括PCOS患者523例,其中肌醇组262例,二甲双胍组261例。meta分析显示,肌醇组和二甲双胍组治疗后的FBG水平、INS水平及HOMA-IR差异无统计学意义(P0.05),FSH、LH及T水平差异无统计学意义(P0.05),TC、HDL、LDL、BMI及妊娠率亦无统计学意义(P0.05);治疗后,肌醇组患者的TG改善程度、月经正常率明显高于二甲双胍组,差异有统计学意义(P0.05)。肌醇组在治疗过程中的副反应发生率显著低于二甲双胍组,差异有统计学意义(P0.05)。结论:肌醇与二甲双胍在治疗PCOS患者中,其糖代谢水平及性激素水平改善情况无明显差异,但对于脂代谢紊乱的患者及不能耐受二甲双胍治疗的患者,肌醇可以起到更好的疗效。相对于二甲双胍治疗PCOS患者,肌醇具有更高的临床应用价值。     

Metformin treatment in patients with polycystic ovary syndrome undergoing in vitro fertilization: a prospective randomized trial

In the present study, we investigated the impact of metformin therapy on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in patients with polycystic ovary syndrome (PCOS). Metformin does not lead to any improvement in IVF/ICSI outcomes among patients with PCOS.     

Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization

This study was designed to determine if metformin therapy improves ovarian stimulation and IVF outcomes in coasted patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). A retrospective data analysis was performed on women with clomiphene citrate-resistant PCOS treated with or without metformin, who underwent 72 cycles of IVF-embryo transfer with intracytoplasmic sperm injection (ICSI). In 59 cycles, patients were coasted to allow oestradiol concentrations to drop before human chorionic gonadotrophin administration. In patients undergoing coasting, the outcome of IVF with ICSI was compared in those who were treated and untreated. In patients treated with metformin, follicular fluid concentrations of testosterone and insulin were significantly lower (60.5 +/- 5 versus 79.1 +/- 6 ng/dl; P < 0.05 and 18 +/- 2.5 versus 22 +/- 2.4 micro IU/ml; P < 0.05 respectively), and the mean number of oocytes retrieved (22.3 +/- 2.4 versus 19.7 +/- 1.6) did not differ. The metformin-treated group showed an increase in the mean number of mature oocytes, oocytes fertilized and cleaving embryos (4-cell or greater by 72 h). However, in the group of patients undergoing coasting, maximum oestradiol concentrations and number of days of coasting were all lower in the metformin-treated group with increased clinical pregnancy rates (71 versus 30%, P < 0.05). Therefore, metformin use appears beneficial in improving IVF outcomes in clomiphene citrate-resistant PCOS patients.     

Effect of metformin taken in the ‘fresh’ in vitro fertilization/intracytoplasmic sperm injection cycle upon subsequent frozen embryo replacement in women with polycystic ovary syndrome

Objective.?We aimed to determine whether metformin when taken during a fresh in?vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle affects live birth rate (LBR) in subsequent frozen embryo replacement cycles (FERC).

Design. A retrospective database analysis of women with polycystic ovary syndrome (PCOS) undergoing FERC at a university teaching hospital between 2002 and 2007 (n?=?142). The outcome of FERC in women who had taken metformin in the ‘fresh’ IVF/ICSI cycle (group A, n?=?28) and those who had not (group B, n?=?114) were compared.

Results.?In the first FERC there was a significantly higher LBR (A?=?28.6%, B?=?12.3%, OR 2.86 95% CI 1.06–7.71). Women who had elective cryopreservation due to ovarian hyperstimulation syndrome risk were found to have significantly higher LBRs if metformin was taken in the fresh IVF/ICSI cycle (A?=?44.4%, B?=?7.9%, OR 9.33 95% CI 1.60–54.58).

Conclusions.?Women with PCOS who take metformin during IVF/ICSI may have a higher LBR in subsequent FERC, especially in those who have elective cryopreservation for OHSS risk. The findings of this study are limited by its retrospective design and small sample size and require confirmation in an adequately powered prospective randomized controlled trial.     

多囊卵巢综合征(PCOS)患者在IVF-ET中发生严重卵巢过度刺激综合征(OHSS)的特点分析

目的:通过总结IVF-ET中多囊卵巢综合征(PCOS)患者应用控制性超促排卵(COH)后发生卵巢过度刺激综合征(OHSS)的特点,提出防止中、重度OHSS发生的有效措施。方法:将IVF/ICSI治疗时出现中、重度OHSS的患者根据有无PCOS史分成PCOS组和对照组。比较分析PCOS组和非PCOS组在COH中的雌激素水平、卵泡数、取卵数及发生中、重度OHSS的时间等临床资料;分析妊娠对OHSS的影响。结果:PCOS组的Gn用药总量及hCG注射日的血清E2水平比对照组低,其总卵泡数、中小卵泡数明显高于对照组,发生中、重度OHSS的时间早,妊娠可能加重OHSS病情发展。结论:卵泡总数、中小卵泡数可作为PCOS患者预测中、重度OHSS独立的重要指标,建议即使取卵前E2水平不高、获卵数不多也考虑行全胚冷冻,以阻止严重的OHSS发生。     

Pituitary suppression regimens in poor responders undergoing IVF treatment: a systematic review and meta-analysis

Many randomized trials have evaluated the use of various pituitary suppression regimens to improve outcome of poor responders undergoing IVF treatment. A systematic review was conducted of the trials of gonadotrophin-releasing hormone (GnRH) agonist long regimen, GnRH agonist short regimen, GnRH antagonist regimen, as well as other pituitary suppression regimens in poor responders undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. The search included MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI proceedings, and all randomized controlled trials comparing the various pituitary suppression regimens in poor responders were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measures were number of oocytes retrieved, cycles cancelled before oocyte retrieval and pregnancy rates. A total of 680 women considered as poor responders undergoing IVF/ICSI treatment were included in nine randomized controlled trials. The quality of these studies was variable: for example, only three of the studies had clear evidence of allocation concealment. Meta-analyses of the results of the studies did not show a consistent benefit for any one pituitary suppression regimen over the other regimens in improving outcome measures. Currently available evidence does not favour any one pituitary suppression regimen for women with poor ovarian response undergoing IVF/ICSI treatment.     

Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro fertilization/intracytoplasmic sperm injection cycles

To determine the impact of maternal metabolic state on oocyte development in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), we retrospectively analyzed a cohort of women with PCOS undergoing IVF/ICSI from 2008-2009 in a university-based fertility center. We determined that women with PCOS and obesity have smaller oocytes than control subjects, and that when further subdivided by body mass index, both PCOS and obesity independently influence oocyte size.     

Outlook: metformin use in infertile patients with polycystic ovary syndrome: an evidence-based overview

Metformin is an insulin sensitizer currently used for treating type-2 diabetes mellitus and recently administered for inducing ovulatory menstrual cycles in oligo-amenorrhoeic patients with polycystic ovary syndrome (PCOS). The aim of the present review is to describe the efficacy of metformin as an ovulation inducer on the basis of the most important evidence-based medicine supported data, including meta-analyses and randomized controlled trials. Specifically, we reviewed the uses of metformin as first- and second-step treatment for PCOS related anovulatory infertility and as co-treatment in infertile PCOS patients who receive gonadotrophins. To date, there is evidence that metformin is effective for restoring normal menstrual cycles in anovulatory PCOS patients, and that it is more effective and cheaper than laparoscopic ovarian drilling as the second therapeutic step in PCOS patients previously defined as resistant to clomiphene citrate. Co-administration of metformin in PCOS patients treated with gonadotrophin improves the mono-ovulation rate and can prevent ovarian hyperstimulation syndrome in patients treated with gonadotrophins for IVF cycles.     

Intracytoplasmic sperm injection versus in vitro fertilization: a randomized controlled trial and a meta-analysis of the literature

OBJECTIVE: To compare ICSI with IVF using two insemination concentrations in moderate male infertility and to compare these data with other randomized controlled trials (RCTs). DESIGN: Prospective, randomized, controlled trial and meta-analysis. SETTING: University-based tertiary referral center. PATIENT(S): Seventy-three couples undergoing ART. INTERVENTION(S): In one IVF group a standard insemination concentration of 0.2 x 10(6)/mL was used, whereas in the other group a high insemination concentration (HIC) of 0.8 x 10(6)/mL was used. Each protocol was compared with ICSI on sibling oocytes. MAIN OUTCOME MEASURE(S): Fertilization, fertilization failure, and embryonic development. RESULT(S): The overall fertilization rate was significantly lower after standard IVF than after ICSI: 37.4% vs. 64.3%. Where HIC IVF was used, the overall fertilization rate was not significantly different from that after ICSI: 59.6% vs. 67.6%. Eight randomized controlled trials were selected and reviewed together with the present randomized controlled trial by meta-analysis. The risk ratio for an oocyte to become fertilized was 1.9 (95% confidence interval of 1.4 to 2.5) in favor of ICSI, and 3.1 ICSI cycles may be needed to avoid one complete fertilization failure after conventional IVF (95% CI of 1.7 to 12.4). CONCLUSION(S): The data from this study and the meta-analysis show that ICSI is a more efficient technique in terms of fertilization, but not in comparison with HIC IVF.     

Effect of androgen supplementation or modulation on ovarian stimulation outcome in poor responders: a meta-analysis

Many trials have evaluated the use of androgen supplements and androgen-modulating agents to improve outcome of poor responders undergoing IVF treatment. This study conducted a systematic review and meta-analysis of controlled trials of androgen adjuvants (testosterone, dehydroepiandrostereone) and the androgen-modulating agent (letrozole) in poor responders undergoing IVF treatment. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, ISRCTN Register and ISI proceedings. All randomized and non-randomized controlled trials were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measure was clinical pregnancy rate. The secondary outcome measures were dose and duration of gonadotrophin use, cycles cancelled before oocyte retrieval, oocytes retrieved and ongoing pregnancy rates. A total of 2481 cycles in women considered as poor responders undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included in nine controlled trials. Meta-analyses of these studies did not show any significant difference in the number of oocytes retrieved and ongoing pregnancy/live-birth rates with androgen supplementation or modulation compared with the control groups. There is currently insufficient evidence from the few randomized controlled trials to support the use of androgen supplementation or modulation to improve live birth outcome in poor responders undergoing IVF/ICSI treatment.