自然及促排卵周期子宫内膜整合素α4β1的表达

目的 了解氯米芬（CC）、绝经期促性腺激素（hMG）对黄体中期子宫内膜整合素α4β1表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术检测48例正常妇女自然周期以及48例正常妇女、30例多囊卵巢综合征患者应用CC／绒毛膜促性腺激素（hCG）及CC／hMG/hCG方案促卵治疗后黄体中期子宫内膜整合素α4β1的表达。结果 子宫内膜整合素α4β1在正常妇女自然周期着床窗口期呈现强阳性表达,而CC、hMG抑制整合率α4β1的表达,两者比较,差异有极显著性（P＜0．01）;妊娠者较妊娠者整合素α4β1表达强度高。结论 促排卵周期黄体中期整合素α4β1表达下降或缺失,子宫内膜容受性下降,妊娠率降低。     

Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial

A total of 202 patients with clomiphene citrate (CC) -resistant polycystic ovary syndrome (PCOS) were randomly allocated into two arms of induction of ovulation; the first group (n?=?102) received CC 100?mg and metformin 500?mg while the second group (n?=?100) received letrozole 2.5?mg with ovulation rate, clinical pregnancy rate, adverse effects, and acceptability were assessed. Patients in the letrozole arm experienced higher rate of ovulation (82% versus 43.1%, p?p?p?p?p?p?p?相似文献   

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.     

促排卵周期PCOS妇女子宫内膜纤维粘连蛋白及层粘连蛋白的表达

目的:了解促排卵药物氯米酚(CC)、hMG及GnRH-a对黄体中期子宫内膜内膜纤维粘连 蛋白(FN)及层粘连蛋白(LN)表达的影响。方法:应用单克隆抗体,采用免疫组织化学技术检测50 例正常妇女自然周期以及50例正常妇女,45例多囊卵巢综合征妇女应用CC／hCG,CC／hMG／hCG 及GnRH-a／hMG／hCG方案促排卵治疗后黄体中期子宫内膜FN和LN的表达。结果:子宫内膜FN 和LN表达在正常妇女自然周期着床窗口时呈现强阳性;而CC、hMG抑制FN和LN的表达,使 其阳性强度减弱,有显著性统计学差异P<0．01;GnRH-a对FN和LN抑制不明显。同时妊娠者较 未妊娠者FN和LN表达强度高。结论:CC／hCG及CC／hMG／hCG方案促排卵后黄体中期子宫内膜 中FN和LN表达下降或缺失,内膜容受性下降,妊娠率降低。     

N-acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome

Aim: The aim of this study was to evaluate the effect of oral N-acetylcysteine (NAC) administration as an adjuvant to clomiphene citrate (CC) on induction of ovulation outcomes in patients with polycystic ovary syndrome (PCOS). Material and Methods: In this placebo-controlled double-blind randomized clinical trial, 180 PCOS infertile patients were randomly divided into two groups for induction of ovulation. Patients in group 1 received CC 100?mg/d plus NAC 1.2?g/d and patients in group 2 received CC plus placebo for 5?days starting at day 3 of the cycle. On the 12th day of the menstrual cycle in the presence of at least one follicle with an 18-20-mm diameter in ultrasound evaluation, 10?000?U hCG was injected intramuscularly and timed intercourse was advised 36?h after hCG injection. Serum β-hCG level was measured on the 16th day after hCG injection. Results: The number of follicles >18?mm and the mean endometrial thickness on the day of hCG administration were significantly higher among the CC+NAC group (P-value?=?0.001). The ovulation and pregnancy rates were also significantly higher in the CC+NAC group (P-value?=?0.02 and 0.04, respectively). No adverse side-effects and no cases of ovarian hyperstimulation syndrome were observed in the group receiving NAC. Conclusion: NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients. It may also have some beneficial impacts on endometrial thickness.     

来曲唑联合克罗米芬治疗多囊卵巢综合征患者的疗效及对排卵、妊娠情况的影响#br#

Objective?To investigate the clinical effect of letrozole (LE) combined with clomiphene (CC) in the treatment of polycystic ovary syndrome (PCOS). Methods?A total of 120 patients with PCOS were selected as the research objects, of which 60 patients who received single CC treatment were the control group, while the combined group (60 patients) was given LE+CC treatment. Menstrual conditions and sex hormone levels [luteinizing hormone (LH), estradiol (E2), and progesterone (P)] were compared between the two groups, and ovulation and pregnancy were recorded in the two groups. Results?The number of mature follicles, endometrial thickness, menstrual cycle, menstrual volume and early abortion rate in the combined group were lower than those in the control group (P<0.05). After treatment, E2, LH, P secretion levels, ovulation rate, pregnancy rate and twin rate in the combined group were higher than those in the control group (P<0.05). Conclusion? LE combined with CC in the treatment of PCOS patients can achieve better efficacy in ovulation induction and pregnancy.     

促排卵治疗对多囊卵巢综合征患者子宫内膜整合素αv,β3表？…

目的 了解促排卵药物对多囊卵巢综合征（ＰＣＯＳ）患者黄体中期子宫内膜整合素αｖ、β３表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术对２２例正常妇女、４０例无排卵ＰＣＯＳ患者促排卵治疗后黄体中期的子宫内膜整合素αｖ、β３进行测定。结果正常妇女子宫内膜整合素αｖ、β３表达在“着床窗口期”呈现强阳性;而氯米芬（ＣＣ）及绝经期促性腺激素（ｈＭＧ）抑制αｖ、βｂ的表达,使其表达呈弱阳性;而促性腺素释     

Letrozole versus clomiphene citrate for superovulation in Egyptian women with unexplained infertility: a randomized controlled trial

Objectives

To compare the efficacy of letrozole with clomiphene citrate (CC) in Egyptian women with unexplained infertility.

Study design

This randomized controlled trial was conducted at Ain Shams University Hospital and Dar Al Hekma hospital between February 2010 and May 2011.

Patients and methods

Two hundreds and seventy women with unexplained infertility were randomized into two groups using computer-generated randomization plan, and were given letrozole 2.5?mg/day from cycle day 3 to 7 (Letrozole group, n?=?136) or CC 100?mg/day from cycle day 3 to 7 (CC group, n?=?134). On day 9, the participants underwent a transvaginal sonography (TVS) every other day to monitor their ovulation and measure both endometrial thickness and Doppler flow indices of uterine and subendometrial vessels. Single injection of 10,000?IU of human chorionic gonadotropin (hCG) was given when the mean diameter of at least one ovarian follicle was ≥18?mm, quantitative βhCG was done 2?weeks after hCG injection to diagnose chemical pregnancy. Clinical pregnancy was confirmed by observing a gestational sac with fetal echoes and pulsation 4?weeks after positive pregnancy test by TVS.

Results

Both groups were comparable with regard to the day of hCG administration (letrozole 13.4?±?5 vs CC 12.1?±?4.9, respectively, p?=?0.06). The mean number of mature follicles was significantly higher in CC group (2?±?0.9 vs 1?±?0.0, P?=?0.02). Serum estradiol was significantly greater in CC group (817?±?299 vs 364?±?149?pg/ml, P?<?0.001). The clinical pregnancy rate was significantly higher in letrozole group (23.07 vs 10.68?%, P?<?0.001). There was statistically significant increase in endometrial receptivity in letrozole group as assessed by endometrial thickness and Doppler flow indices of uterine and subendometrial vessels. No serious side effects were reported in either group.

Conclusion

Letrozole has beneficial effect on endometrium, an action that may improve the implantation and pregnancy rates in women with unexplained infertility.     

Luteal support with vaginal dydrogesterone increases pregnancy rate in patients with clomifene resistant polycystic ovary syndrome receiving letrozole for ovulation induction

A prospective observational study was conducted on 186 patients with clomifene citrate (CC)-resistant polycytic ovary syndrome (PCOS) who were allocated into two treatment arms for three months; letrozole alone (n?=?92) and letrozole with luteal support using vaginal dydrogestrone (n?=?94). Patients received luteal support experienced significantly higher clinical pregnancy rate than those who received letrozole alone (48.9% vs. 23.9%, respectively). Luteal support in letrozole treated CC-resistant PCOS significantly improves pregnancy rate and should be implemented in ovulation induction regimens.     

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.     

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.     

Assessment of endometrial receptivity during implantation window in women with unexplained infertility

Abstract

This study aimed to assess the endometrial receptivity during implantation window in women with unexplained infertility. A prospective study recruited 168 women with unexplained infertility and 169 fertile women. Ultrasonic parameters and biomarkers in the uterine fluid were detected. The endometrial vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were significantly higher in fertile women as compared with unexplained infertile women, and the integrin αvβ3, vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), and leukemia inhibitory factor (LIF) levels in uterine fluid were significantly higher in fertile women. The biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate in fertile women were 20.12%, 18.34%, and 17.75%, respectively, which were significantly higher compared with unexplained infertile women (7.14%, 5.36%, and 4.17%, respectively). Endometrial thickness (ET), endometrial volume (EV), VI, FI, and VFI measured by ultrasound, and the integrin αvβ3, VEGF, TNF-α, and LIF levels in uterine fluid were all significantly higher in pregnant women as compared with nonpregnant women. The best parameters of ultrasonic indicators for predicting endometrial receptivity in women with unexplained infertility were FI(AUC = 0.894, sensitivity 93.8%, and specificity 83.1%). Integrin αvβ3 had the best predictive value for endometrial receptivity among biomarkers in the uterine fluid (AUC = 0.921, sensitivity 96.7%, and specificity 89.5%). Women with unexplained infertility present declined endometrial receptivity. Endometrial ultrasonic parameters detected by three-dimensional power Doppler and biomarkers in the uterine fluid may be effective indicators to predict endometrial receptivity.     

Systematic review and meta-analysis of letrozole and clomiphene citrate in polycystic ovary syndrome

This study aims to systematically evaluate the clinical efficacy and safety of both clomiphene citrate (CC) and letrozole, and to examine if the efficacy of letrozole is superior to CC in women with polycystic ovary syndrome (PCOS).Major databases were searched for eligible randomised controlled trials (RCTs). The methodological quality of the included studies was assessed by two independent reviewers. Meta-analysis was performed using random-effect model to account for the high levels of heterogeneity. Overall, ten eligible RCTs involving 1905 women were included. Letrozole was associated with significantly higher ovulation rate (relative risk (RR) 1.20; 95% CI 1.03–1.40; P?=?0.02); clinical pregnancy rate (RR 1.48; 95% Cl 1.12–1.94; P?=?0.005) and endometrial thickness (standardized mean difference (SMD) 2.31; 95% Cl 0.85–3.76; P?=?0.002). There was no evidence of a difference between the treatment groups in the rate of miscarriage, number of mature follicles and multiple pregnancy rates. The result suggests that letrozole is a superior ovulation induction agent for women with PCOS as it is associated with higher ovulation and clinical pregnancy rates with no obvious increased side effects. However, this conclusion should be considered with a slight caution in that the quality of the evidence could have improved if more recent studies on the subject were available to be included in the review.     

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.     

卵泡期地塞米松应用对克罗米芬抵抗的多囊卵巢综合征促排卵作用研究

目的:探讨克罗米芬(CC)联合地塞米松(DEX)对CC抵抗的多囊卵巢综合征(PCOS)患者的促排卵效果。方法:将50名CC抵抗患者随机分为治疗组(A组)和对照组(B组)。A组患者在月经第3￣7日口服CC100mg/d,同时在月经周期的第3￣12日口服DEX1.0mg/d;B组CC的应用同A组,同时在月经周期的第3￣12日口服叶酸片0.5mg/d。月经第8日开始监测卵泡发育情况。当有1个卵泡直径≥18mm或2个卵泡直径≥17mm时,肌注hCG10000IU,36h后性生活。观察2组注射hCG日成熟卵泡数和子宫内膜厚度、促排卵天数、月经周期第22日孕酮水平、排卵率和妊娠率。结果:A组注射hCG日的成熟卵泡数、子宫内膜厚度、月经第22日血清中孕酮水平以及排卵率和妊娠率与B组相比差异均有显著性(P<0.05￣P<0.01);促排卵天数组间无统计学差异(P>0.05)。结论:对CC抵抗的PCOS患者,DEX可以促进排卵,改善CC对子宫内膜的抗雌激素效应,增加子宫内膜厚度,提高排卵率和妊娠率。     

来曲唑和克罗米酚对小鼠着床期子宫内膜容受性的影响

目的:探讨来曲唑和克罗米酚对小鼠着床期胞饮泡和白血病抑制因子(LIF)表达的影响。方法:将30只小鼠随机分为3组:来曲唑(LE)组(n=10)、克罗米酚(CC)组(n=10)及对照组(n=10)。促排卵后妊娠d4．5取小鼠子宫,采用扫描电镜观察3组子宫内膜胞饮突的变化以及免疫组化技术检测子宫内膜LIF的表达强弱。结果:在3组妊娠天数一致的情况下,LE组中无论是子宫内膜胞饮突,还是LIF的表达,均与对照组相似。而CC组的表达显著弱于前二组。结论:与CC促排卵相比,LE不影响小鼠着床期子宫内膜超微结构和相关基因LIF的表达,然而CC组子宫的容受性呈现一定的抑制性。     

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.     

Effect of estradiol valerate on the pregnancy rate in patients receiving letrozole for induction of ovulation

Background

Letrozole is as effective as clomiphene citrate for induction of ovulation in patients with PCOS. Adequate endometrial development is required for pregnancy to occur, and pregnancy rates were found to be higher when the endometrium reached at least 10 mm thickness.

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome

Background.?The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity.

Methods.?Retrospective case–control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase.

Results.?Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%).

Conclusions.?CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

来曲唑联合促性腺激素用于行宫腔内人工授精的排卵障碍者的促排卵研究

目的:探讨来曲唑在促排卵过程中的功效。方法:100例不孕症常规检查确诊为女性排卵障碍并接受超促排卵及IUI的不孕患者,随机分为A组(50例):口服来曲唑(LE)+hMG,B组(50例):口服氯米芬(CC)+hMG,分别监测hCG注射日子宫内膜的厚度、形态、血E2、P水平,分别统计排卵率及妊娠率。结果:A组血清中雌激素水平明显较低,hCG注射日子宫内膜较厚。直径>17mm卵泡数组间无明显差异,临床妊娠率也无明显差异。结论:对因女性排卵障碍引起的不孕,用LE或CC促排卵,其获卵数和临床妊娠率无差异,但用LE促排卵,可以减少CC抗雌激素样作用对子宫内膜的不良影响,使子宫内膜有较好的容受性,有利于妊娠。