来曲唑与克罗米芬对多囊卵巢综合征患者促排卵治疗结局的前瞻性随机对照研究

目的:比较来曲唑和克罗米芬在多囊卵巢综合征(PCOS)患者促排卵治疗中的效果和妊娠结局。方法:选取拟行促排卵治疗的PCOS患者136例,随机分为来曲唑组(LE)68例和克罗米芬组(CC)68例。HCG注射日观察平均直径14～18mm的卵泡数、平均直径≥18mm的卵泡数、子宫内膜厚度和血清E2水平;比较两组HMG用量、排卵率、临床妊娠率、流产率、畸形率及卵巢过度刺激综合征(OHSS)的发生率。结果:LE组HCG注射日平均直径14～18mm卵泡数、E2水平显著低于CC组(P<0.05),子宫内膜厚度及单卵泡排卵率显著高于CC组(P<0.05);LE组HCG日注射日平均直径≥18mm卵泡数略低于CC组,但差异不显著(P>0.05);CC组OHSS发生率为7.4%,LE组无OHSS发生,两组相比差异有统计学意义(P<0.05);LE组临床妊娠率略高于CC组,但差异无统计学意义(P>0.05)。结论:来曲唑用于治疗多囊卵巢综合征引起的无排卵性不孕,单卵泡排卵率和临床妊娠率良好,临床应用前景较好,有可能成为新一代一线促排卵药物。     

来曲唑联合人绝经期促性腺激素治疗克罗米酚抵抗的多囊卵巢综合症研究

目的探讨来曲唑联合人绝经期促性腺激素治疗克罗米酚抵抗的多囊卵巢综合症的疗效。方法选择2014年4月~2015年10月我院使用克罗米酚治疗6个周期仍无效的多囊卵巢综合症患者112例,将其随机分为对照组46例和实验组66例。对照组从自然月经周期、黄体撤退性出血或者人工月经周期第2~4天给予来曲唑口服,5 mg/d,共5天;实验组在同样时间给予来曲唑口服,5 mg/d,服用5天后,给予人绝经期促性腺激素肌肉注射,75 IU/支,1支/d,共注射2天。所有患者当超声监测到卵巢内至少1个≥18 mm卵泡且卵泡直径≥16 mm超过3个时,或者至少1个≥18 mm卵泡且有较多直径为10~12 mm的卵泡时,注射曲普瑞林0.1 mg。阴道B超监测卵泡发育和子宫内膜厚度。结果两组患者注射曲普瑞林子宫内膜厚度对比,差异无统计学意义(P0.05)。结论来曲唑联合人绝经期促性腺激素和单用来曲唑促排卵能获得相似的妊娠率和流产率,但来曲唑联合人绝经期促性腺激素促排卵更有利于优势卵泡的成熟,并可以降低多胎妊娠和卵巢过度刺激综合征的风险。     

促性腺激素释放激素激动剂触发排卵的临床观察

目的:探讨促性腺激素释放激素激动剂(GnRH-a)触发排卵的疗效。方法:对应用氯米芬(CC)、来曲唑(LE)和/或人绝经期促性腺激素(hMG)促排卵治疗的不孕患者,卵泡成熟时给与GnRH-a(A组)或人绒毛膜促性腺激素(hCG)(B组)触发排卵,卵巢过度刺激综合征(OHSS)高危周期则给予GnRH-a,观察比较其临床结局。结果:共分析了81例患者132个促排卵周期,A、B组周期数分别为75和57,组间周期排卵率、多胎率、流产率相似(P>0.05)。周期临床妊娠率、OHSS发生率A组高于B组(P<0.05),无重度OHSS发生。结论:GnRH-a触发排卵临床妊娠率高,可有效预防重度OHSS的发生。     

来曲唑、他莫昔芬和氯米芬治疗多囊卵巢综合征不孕疗效比较

目的比较多囊卵巢综合征(PCOS)不孕患者经纠正内分泌代谢紊乱后应用3种不同促排卵药物的效果及对子宫内膜的影响。方法选择2009年3月至2010年1月中山大学孙逸仙纪念医院妇产科生殖中心128例PCOS不孕患者,于本院行第1次促排卵,有高雄激素或胰岛素抵抗者经预处理至少3个月。随机分为3组,来曲唑44个周期、他莫昔芬40个周期和氯米芬44个周期。结果月经第10天的子宫内膜厚度,他莫昔芬组[(6.4±1.2)mm]高于来曲唑组[(5.4±1.7)mm]和氯米芬组[(5.4±1.3)mm](P=0.01);HCG日血雌二醇(E2)水平,来曲唑组[(838.6±678.2)pmol/L]低于他莫昔芬组[(2629.2±1931.5)pmol/L]和氯米芬组[(1971.2±1222.8)pmol/L](P<0.001);3组间加用尿促性腺激素(HMG)周期数,HCG日子宫内膜厚度、血黄体生成素及孕酮、直径≥18mm成熟卵泡数,妊娠率和早期流产率,差异无统计学意义(P>0.05);HCG日子宫内膜的厚度与注射HCG的月经周期日及月经第10天的子宫内膜厚度呈正相关(P<0.05),与药物的种类及HCG日血E2水平等无显...     

人工授精周期中诱发排卵方法选择

在人工授精周期促排卵治疗时,为了减少卵巢的过度刺激,降低多胎妊娠发生率,必须进行卵巢微刺激的控制性促排卵方案,主要通过控制早卵泡期的启动数及优势卵泡的排卵数来完成。氯米芬、来曲唑是一线方案,人绝经期促性腺激素（HMG）或卵泡刺激素（FSH）低剂量渐增方案是比较容易达到控制目的的方案。在促排卵周期中,监测自发性黄体生成激素（LH）峰形成后产生的级联效应,可以获得最佳妊娠率。注射人绒毛膜促性腺激素（HCG）扳机后36h完成人工授精手术可能是最佳时机。     

多囊卵巢综合征不孕患者未成熟卵泡抽吸术的疗效分析

目的:探讨对克罗米芬抵抗的多囊卵巢综合征(PCOS)不孕患者在超声引导下行小卵泡抽吸术(IMFA)的治疗效果。方法:将42例PCOS合并克罗米芬(CC)抵抗的不孕患者,随机分为A组:19例,穿刺前用CC或来曲唑(LE)联合少量hMG促排卵;B组:23例,穿刺前用少量hMG促排卵。在阴道B超引导下进行未成熟卵泡抽吸术(IMFA),观察穿刺前及穿刺后第2周期患者的卵巢基础窦卵泡数(AFC)、抗苗勒氏管激素(AMH)、血中游离睾酮指数(FAI)、黄体生成素与卵泡刺激素的比值(LH/FSH),以及术后并发症、3个月促排卵情况和妊娠率。结果:42例患者治疗时均没有发生卵巢过度刺激综合征(OHSS)。与治疗前比较,穿刺术后A、B组AFC显著减少,AMH、FAI和LH/FSH显著降低(P<0.01)。A、B组间比较,FAI、LH/FSH、排卵率和妊娠率无统计学差异(P>0.05)。A、B组共21例妊娠,妊娠率为50%。42例患者均没有发生出血、感染、OHSS。结论:IMFA治疗克罗米芬抵抗的PCOS不孕患者有较好的疗效,本方法安全、有效。     

安宫黄体酮和来曲唑联合Gn超促排卵在卵巢储备减退患者IVF/ICSI-FET中应用效果的比较

目的:比较安宫黄体酮(MPA)联合促性腺激素(Gn)超促排卵与来曲唑微刺激促排卵在卵巢储备功能减退(DOR)患者体外受精及冻融胚胎移植(FET)中的应用效果。方法:回顾分析730周期拟行体外受精助孕的DOR的不孕症患者的临床资料,380周期行MPA联合Gn促排卵(MPA组),350周期行来曲唑联合Gn促排卵(来曲唑组)。观察两组的周期取消率、Gn天数、Gn剂量、性激素水平、获卵数、可利用胚胎数、优胚率和FET妊娠率、种植率、流产率和活产率。结果:MPA组患者的Gn使用时间、Gn使用总量、优胚率均显著高于来曲唑组(P0.05),而HCG日LH水平、HCG日P水平、可用胚胎数显著低于来曲唑组(P0.05)。两组的获卵数、成熟卵数、受精卵数、卵裂数比较,差异均无统计学意义(P0.05)。MPA组患者的FET种植率和临床妊娠率均显著高于来曲唑组(P0.05)。两组患者的流产率、异位妊娠率和活产率比较,差异均无统计学意义(P0.05)。结论:与来曲唑联合Gn促排卵比较,MPA联合Gn促排卵对于DOR患者可有效抑制早发LH峰,减少提前排卵发生,能获得可观的临床妊娠率,值得临床应用推广。     

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。     

中西医结合治疗无排卵性不孕症的临床研究

目的探讨中西医结合治疗无排卵性不孕症的临床疗效。方法将85例无排卵性不孕症患者分为三组。组1采取克罗米芬治疗;组2除克罗米芬外,再加上戊酸雌二醇促内膜生长、黄体酮胶丸黄体支持;组3除克罗米芬外,再加上中药周期治疗。观察三组临床疗效。结果克罗米芬促排卵加上中药周期治疗无排卵性不孕症,排卵率为72.29%,妊娠率为51.43%,排卵日子宫内膜厚度优于单用克罗米芬周期,黄体功能优于单用克罗米芬周期、而与克罗米芬加雌激素和孕激素周期相当,中医症候评分改善情况明显优于单用克罗米芬周期、克罗米芬加雌激素和孕激素周期,不良反应发生率低。结论在无排卵性不孕症诊治过程中,利用西药的高效促排,并积极应用中药周期疗法进行辨证论治,可以提高临床疗效、而副作用少。     

腹腔镜下采用绝缘针烧灼治疗多囊卵巢的评估

对患多囊卵巢综合征 (Polycystic ovary syndrome,PCOS)无排卵不孕的妇女 ,第一线治疗是克罗米芬 (柠檬酸盐 )。该药促排卵率 >80 %。然而 ,15 %～ 2 0 %妇女增加克罗米芬量仍然无排卵。此外 ,排卵率与妊娠率 40 %～ 5 0 %不相符合 ,流产率高 (30 %～40 % )。克罗米芬耐药的妇女可采用促性腺激素或脉冲式 L H释放激素 (L H- RH)治疗。但是 ,二者成功率均不高。替代药物治疗的方法是手术治疗。目前 ,最普遍的手术治疗是腹腔镜下卵巢打洞。1990年 6月至 1998年 12月 ,112例 PCOS无排卵不孕妇女 ,采用规范腹腔镜卵巢电凝打洞 ,所有妇女均…     

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.     

Ovulation induction using sequential letrozole/gonadotrophin in infertile women with PCOS: a randomized controlled trial

Research questionIs sequential letrozole/human menopausal gonadotrophin (HMG) superior to letrozole alone in ovulation induction and pregnancy promotion among infertile women with polycystic ovary syndrome (PCOS)?DesignThis open-label randomized controlled trial comparing sequential letrozole/HMG and letrozole alone included 174 participants enrolled from August 2019 to January 2020 at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. Infertile women aged between 18 and 40 years who met Rotterdam criteria for PCOS and without other known causes of infertility were selected for this study. Patients were randomly assigned at a 1:1 ratio to receive 2.5 mg letrozole on cycle days 3–7 (n = 87) or 2.5 mg letrozole on cycle days 3–7 with a sequential injection of 75 IU HMG on cycle days 8–10 for one treatment cycle (n = 87). The pregnancy outcome was recorded after one treatment cycle.ResultsWomen receiving sequential treatment achieved a significantly higher ovulation rate than those in the letrozole group (90.8% versus 70.1%, P = 0.001) and the live birth rate of the sequential group was significantly higher than that of the letrozole protocol (23.0% versus 10.3%, P = 0.025); there was no statistical variation with respect to adverse events.ConclusionsThe data suggest that the sequential letrozole/HMG protocol may be superior to the letrozole alone protocol in terms of ovulation induction and pregnancy promotion among infertile women with PCOS.     

Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate

OBJECTIVE: To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. DESIGN: Prospective trial in infertility patients treated with CC. SETTING: Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates. RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.     

Polycystic Ovary Syndrome: Fertility Management

Polycystic ovary syndrome (PCOS) is characterized by a series of symptoms, including oligomenorrhea or amenorrhea anovulation or infertility; it is associated with insulin resistance and compensatory hyperinsulinemia. Several treatment options are available for women with anovulatory infertility related to PCOS. Clomiphene citrate (CC) is the first-choice for induction of ovulation in PCOS patients. Laparoscopic ovarian drilling (LOD) or gonadotropin ovarian stimulation can be offered after failure of CC to achieve pregnancy. Hyperinsulinemia related to PCOS can be corrected by weight loss or insulin-sensitizing agents, such as metformin, which alone or in combination with other agents are capable of restoring ovulation. Only very limited clinical data are available on the use of letrozole at present, so letrozole cannot be recommended for routine use in ovulation induction. When all treatments fail, in vitro fertilization and embryo transfer (IVF/ET) can be tried and can have excellent results. Many treatment options available today ensure that the majority of women who are subfertile due to PCOS can be treated successfully.     

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。     

Comparison of endometrial receptivity of clomiphene citrate versus letrozole in women with polycystic ovary syndrome: a randomized controlled study

Abstract

The aim of the study was to compare the effect of clomiphene citrate (CC) and letrozole on endometrial receptivity for ovulation induction in women with polycystic ovary syndrome (PCOS). A randomized controlled study included 160 patients diagnosed with PCOS, out of which 80 patients received 50?mg of CC and 80 patients received 2.5?mg of letrozole for successful ovulation induction. Endometrial thickness and pattern, the blood flow of uterine artery and subendometrial region, endometrial volume and vascularization index were measured. The ratio of multilayered endometrial pattern in letrozole group was significantly increased on the day of human chorionic gonadotropin (hCG) administration compared with CC group (77.5% vs. 55.0%). The volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) of endometrium on the day of hCG administration and 7–9?days after ovulation in letrozole group were significantly increased. The biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate in letrozole group were significantly increased compared with CC group (36.3%, 30.0%, 22.5% vs. 21.3%, 13.8%, 10.0%, respectively). Letrozole increased pregnancy rates by improving endometrial receptivity compared with CC in patients with PCOS.     

Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial

Purpose  

To compare the effect of letrozole with laparoscopic ovarian diathermy (LOD) for ovulation induction in clomiphene citrate (CC) resistant women with polycystic ovary syndrome (PCOS).     

Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis

Abstract

The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR)?=?1.55 (95% confidence interval (CI): 1.26–1.90; I^2?=?0%) and RR?=?1.38 (95% CI: 1.05–1.83; I^2?=?61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.