来曲唑用于有排卵不孕症妇女的促排卵效果观察——与氯米芬的对照研究

目的 探讨来曲唑用于有排卵不孕症妇女的促排卵效果及其对生殖激素的影响。方法 选择2005-06-01—2005-10-31北京大学第三医院拟行宫腔内人工授精（IUI），或指导同房，或供精人工授精（AID）的111例有排卵的不孕症妇女，于月经周期第3～7天，每日口服来曲唑2．5mg（68例），或于月经周期第5～9天每日口服氯米芬（clomifene）50mg（43例）。超声监测卵泡发育，并于月经周期第8天和HCG日取静脉血测定黄体生成素（LH）、雌二醇（E2）、睾酮（T）和雄烯二酮（A）。当最大卵泡的平均直径／〉20mm时，肌注HCG 10000IU诱发排卵。观察排卵率、妊娠率、子宫内膜厚度及生殖激素的变化。结果 来曲唑组的排卵率和周期妊娠率与氯米芬组相似（P〉0．05），其优势卵泡数以及成熟卵泡数均显著低于氯米芬组（P〈0．01）。来曲唑组在HCG日子宫内膜的厚度显著厚于氯米芬组（P〈0、01）。其在月经周期第8天和HCG日血清E2水平均显著低于氯米芬组（P〈0、01），月经周期第8天血清A显著高于氯米芬组（P〈0．05），这种差异在HCG日消失，但血清T水平在两组之间没有差异来曲唑组在HCG日血清LH水平明显高于氯米芬组。结论 来曲唑用于有排卵的不孕症妇女，具有良好的排卵率，但其排卵率和妊娠率并未优于氯米芬，其能否作为一线的促排卵药物还需要进一步的研究结果来支持。     

定坤丹联合氯米芬治疗多囊卵巢综合征伴不孕疗效观察

目的探讨定坤丹联合氯米芬治疗多囊卵巢综合征伴不孕的临床疗效。方法选择2015年12月至2016年8月河南中医药大学第一附属医院生殖医学科因排卵障碍致不孕的多囊卵巢综合征(PCOS)患者100例,按随机数字表法分为治疗组和对照组,每组各50例。治疗组采用氯米芬联合定坤丹治疗,以氯米芬治疗做对照。比较治疗后两组患者[月经第10天、人绒毛膜促性腺激素(h CG)日]的雌二醇(E2)水平与子宫内膜厚度、h CG日成熟卵泡数、排卵率、生化妊娠率、临床妊娠率。结果治疗后,治疗组月经第10天、h CG日E2水平[(607.92±11.75)pmol/L vs.(461.02±10.19)pmol/L,P=0.039;(1097.78±12.33)pmol/L vs.(899.10±12.80)pmol/L,P=0.000]与子宫内膜厚度[(6.10±0.84)mm vs.(5.28±0.83)mm,P=0.000;(9.28±0.73)mm vs.(5.74±0.72)mm,P=0.000]均大于对照组;两组双卵泡率、多卵泡率(36.0%vs.38.0%;4.0%vs.2.0%),差异均无统计学意义,治疗组单卵泡率、成熟卵泡率及排卵率均较对照组更高(58.0%vs.38.0%,P=0.045;98.0%vs.78.0%,P=0.002;91.5%vs.73.7%,P=0.028);治疗组生化妊娠率、临床妊娠率均优于对照组(8.0%vs.24.0%,P=0.029;42.0%vs.18.0%,P=0.009)。结论定坤丹联合氯米芬能明显改善多囊卵巢综合征伴不孕患者的临床疗效。     

来曲唑用于多囊卵巢综合征患者诱导排卵的系统评价

目的:系统评价来曲唑用于多囊卵巢综合征(polycystic ovary syndrome,P-COS)诱导排卵的疗效和安全性。方法:全面检索相应的中英文数据库,收集来曲唑用于PCOS患者诱导排卵的临床随机对照试验(randomized controlled trials,RCTs)。按Co-chrane系统评价方法,用系统评价专用处理软件RevMan5.0合并分析入选研究。结果:共纳入10个RCT,包括1854例患者。Meta分析显示:(1)来曲唑组周期排卵率高于克罗米芬组,HCG日子宫内膜厚度较薄,每周期成熟卵泡数少于克罗米芬组,差异有统计学意义;妊娠率、流产率两组差异无统计学意义;(2)克罗米芬抵抗的PCOS患者使用来曲唑后,周期排卵率>60%、妊娠率>30%;(3)来曲唑组周期排卵率低于促性腺激素组;妊娠率、HCG日子宫内膜厚度、流产率两组相似;来曲唑组每周期成熟卵泡数、多胎率、OHSS发生率低于促性腺激素组。结论:目前无充分证据证明,来曲唑对PCOS患者的促排卵效果优于克罗米芬,但可用来曲唑促排卵治疗对克罗米芬抵抗或促性腺激素高敏的PCOS患者,并可有效预防卵巢过度刺激综合征和多胎妊娠发生。     

氯米芬合用阿司匹林对子宫内膜发育和子宫血流的影响

目的:观察小剂量阿司匹林是否能改变氯米芬诱导排卵后子宫内膜的厚度、改善子宫血流的灌注。方法:4 5例不明原因不育或男方因素不育的妇女平均分为自然周期组、氯米芬组(CC组)、氯米芬加阿司匹林组(CC加aspirin组) ,观察3组HCG日及HCG加9天的激素水平、子宫内膜厚度、子宫动脉搏动指数(PI) ,HCG日的子宫内膜类型。结果:CC组无论HCG日还是HCG加9天内膜厚度均明显小于自然周期组(P <0 .0 5 ) ,而CC加aspirin组内膜厚度均明显大于CC组(P <0 . 0 5 )。CC组无论HCG日还是HCG加9天的子宫动脉搏动指数(PI)均明显著大于自然周期组(P <0 . 0 5 ) ,而CC加aspirin组子宫动脉搏动指数(PI)均显著小于CC组(P <0 . 0 5 )。结论:小剂量阿司匹林能改善氯米芬诱导排卵中的子宫血流灌注,从而改善子宫内膜发育。     

他莫昔芬用于薄型子宫内膜患者冻融胚胎移植时子宫内膜准备的研究

目的探讨他莫昔芬(tamoxifen)方案应用于以往自然周期和激素替代治疗反复出现子宫内膜薄的患者行冻融胚胎移植(FET)时子宫内膜准备的临床效果。方法 2011年11月至2014年4月南方医科大学南方医院妇产科生殖医学中心,回顾性分析61例既往因自然周期和激素替代治疗准备冷冻周期子宫内膜,显示子宫内膜薄而取消移植或者移植后未妊娠患者使用他莫昔芬治疗,观察子宫内膜厚度、性激素水平以及FET后的妊娠结局。结果他莫昔芬周期和既往激素替代治疗周期相比,前者的子宫内膜厚度[(8.8±1.8)mm、(6.5±0.3)mm]和血清雌二醇(E2)水平[(2091.2±1020.5)pmol/L、(969.6±474.2)pmol/L]明显较高,且差异具有统计学意义(P0.05);子宫内膜准备天数明显减少[(13.2±2.9)d、(23.1±4.9)d],差异有统计学意义(P0.05)。他莫昔芬周期的临床妊娠率、早期流产率、胚胎种植率、畸形率分别为44.3%(27/61)、7.4%(2/27)、24.2%(32/132)、0(0/17)。结论对于子宫内膜薄的患者,在冻融胚胎移植周期使用他莫昔芬准备子宫内膜方法简单可行,而且子宫内膜准备时间较短、子宫内膜厚度显著提高,并可获得较满意的妊娠结局。     

甲磺酸溴隐亭辅助克罗米芬诱导多囊卵巢综合征不孕患者排卵的随机、开放、对照临床研究

目的研究多巴胺激动剂溴隐亭(BCT)联合克罗米芬(CC)对多囊卵巢综合征(PCOS)合并不孕患者促排卵助孕的疗效。方法本研究为随机、开放、对照试验,在上海2家医院共收集PCOS合并不孕患者100例,随机分为对照组和试验组,对照组在月经周期3~7 d给予CC 50 mg/d,试验组在此基础上同时全周期给予BCT 2.5 mg/d,两组均治疗1个周期。在月经第3日、hCG注射日、hCG注射第7日抽血化验激素水平,包括促卵泡激素(FSH)、促黄体生成素(LH)、催乳素(PRL)、雌二醇(E_2)、总睾酮(T)、孕激素(P),并行阴道超声测定子宫内膜厚度、卵泡大小、数量。结果两组的基础激素水平无统计学差异。对照组和试验组的促排卵成功率分别为72.0%和75.4%(P0.05),试验组的持续妊娠率(18.4%)明显高于对照组(8.0%)。hCG注射日的FSH、E_2、P水平无统计学差异,LH水平有所降低,PRL和T显著降低(分别为P=0.00,P=0.00);hCG注射第7日的E_2、P水平无统计学差异,PRL显著下降,试验组的子宫内膜厚度[(10.20±1.92)mm]明显高于对照组[(9.22±1.88)mm](P=0.01)。结论 BCT联合CC可以提高PCOS患者促排卵的助孕成功率,降低PRL、LH、T水平并增加着床窗口期的子宫内膜厚度。提示多巴胺激动剂BCT可能通过降低垂体激素及雄激素水平、降低子宫内膜血管阻力并增加内膜血供改善PCOS不孕患者的助孕结局。     

来曲唑序贯氯米芬在多囊卵巢综合征患者中的应用

目的:探讨来曲唑(LE)序贯氯米芬(CC)对多囊卵巢综合征(PCOS)患者的促排卵效果。方法:分析PCOS患者共62例,72个促排周期。按促排卵方案分为LE序贯尿促性素(HMG)组和LE序贯CC组,比较两组单卵泡率、HCG日子宫内膜厚度、未成熟卵泡率、排卵率、卵泡过度刺激综合征(OHSS)发生率、临床妊娠率、多胎妊娠率及用药时间、费用的差异。结果:LE序贯HMG组和LE序贯CC组的单卵泡率分别为78.95%、88.24%,未成熟卵泡率为7.89%、2.94%,排卵率分别为89.47%、97.06%,OHSS发生率分别为5.26%、0,临床妊娠率分别为13.16%、11.76%,多胎妊娠率分别为5.26%、2.94%,差异均无统计学意义(P0.05),LE序贯HMG组HGC日子宫内膜厚度(10.27±1.92 mm)明显厚于LE序贯CC组(9.13±2.32 mm)(P0.05)。LE序贯CC组用药时间(10.00±0.00天)明显少于LE序贯HMG组(12.16±1.98天)(P0.05)。LE序贯HMG组的费用明显高于LE序贯CC组。结论:LE序贯CC与LE序贯HMG的排卵效果及妊娠率近似,OHSS发生率无明显差别,LE序贯CC用药时间更短,费用更低,但HCG日子宫内膜更薄,应用中应适当补充雌激素促进内膜生长。     

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。     

氯米芬和来曲唑在多囊卵巢综合征不孕患者微刺激促排卵中的应用比较

目的:探讨氯米芬(CC)和来曲唑(LE)在多囊卵巢综合征(PCOS)不孕患者微刺激促排卵中的作用。方法:选择2011年10月至2014年2月在北京大学深圳医院治疗的230例PCOS不育患者,于月经第3~5天应用CC(CC组82例)或LE(LE组148例)。CC组每日50mg,连服5日;LE组随机分两组,一组(85例)每日2.5 mg,连服7日,另一组(63例)每日5.0mg,连服5日。月经第10日开始定期经阴道超声监测各组子宫内膜和卵泡。对各组获得平均直径≥18 mm卵泡数、诱发排卵日子宫内膜厚度和每个平均直径≥18 mm卵泡产生的E2量、周期妊娠率等进行统计比较。结果:1230例PCOS患者促排卵230个周期,CC组促排卵82个周期;LE 2.5 mg组促排卵85个周期;LE 5.0 mg组促排卵63个周期。CC组、LE 2.5 mg组及LE5.0 mg组周期妊娠率分别为7.3%、20.0%、31.7%,3组周期妊娠率比较,CC组与LE 2.5 mg组及LE 5.0 mg组差异均有统计学意义(P0.05)。2CC组、LE 2.5 mg组及LE 5.0 mg组促排卵应用HMG率分别为26.8%、43.5%、44.4%。CC组与LE 2.5 mg组及LE 5.0 mg组比较,差异均有统计学意义(P0.05);CC组、LE 2.5 mg组及LE 5.0 mg组促排卵应用戊酸雌二醇率分别为72.0%、44.7%、33.3%。CC组与LE 2.5 mg组及LE 5.0 mg组比较,差异均有统计学意义(P0.01)。3诱发排卵日子宫内膜厚度CC组较LE 2.5 mg组及LE 5.0 mg组薄,差异有统计学意义(P0.01)。诱发排卵日E2量CC组大于LE 2.5 mg组及LE 5.0 mg组,差异有统计学意义(P0.01)。结论:PCOS微刺激促排卵应用LE较CC对子宫内膜影响小、周期妊娠率高。     

氯米芬联合HMG在促排卵人工授精周期中防止过早内源性黄体生成素峰的有效性研究

目的:探讨氯米芬(CC)联合人绝经尿促性腺激素(HMG)在原因不明性不孕患者促排卵人工授精(COS/IUI)周期中防止过早内源性黄体生成素(LH)峰的有效性,为提高IUI妊娠率提供临床依据。方法:将2012年1月至2015年1月在我院生殖中心因原因不明性不孕行COS/IUI的144例患者随机分为观察组和对照组,每组72例。观察组给予CC+HMG方案促排卵,对照组单用HMG促排卵。观察两组的过早LH峰发生率、临床妊娠率、未破裂黄素化卵泡(LUF)发生率、周期取消率、卵巢过度刺激综合征(OHSS)发生率、多胎妊娠率,以及HCG注射日子宫内膜厚度、E2水平、成熟卵泡数。结果:观察组的过早LH峰发生率(5.8%)及LUF发生率(8.7%)显著低于对照组(17.9%、20.9%,P0.05),E2水平[(379.4±127.8)pg/ml]、成熟卵泡数(2.43±0.75)、临床妊娠率(21.7%)均高于对照组[(288.8±97.3)pg/ml,1.71±0.78,9.0%](P0.05);两组的周期取消率、子宫内膜厚度、OHSS发生率及多胎妊娠率比较,差异均无统计学意义。结论:原因不明性不孕患者COS/IUI过程中,CC+HMG促排卵方案可以有效防止过早内源性LH峰的发生,并提高IUI的临床妊娠率。     

两种剂量来曲唑与克罗米芬对多囊卵巢综合征患者子宫卵巢血流动力学的影响

目的:探讨2种剂量来曲唑(LE)与克罗米芬(CC)对多囊卵巢综合征(PCOS)患者子宫卵巢血流动力学的影响。方法:2种剂量LE与CC治疗90例PCOS不孕症患者,随机分CC组(A组,n=32,50 mg/d)、低剂量LE组(B组,n=30,2.5 mg/d)和高剂量LE组(C组,n=28,5.0 mg/d)。同时以28例正常育龄妇女作为对照组(D组)。经阴道超声监测子宫卵巢血流的参数,比较排卵率、妊娠率。结果:①LE的2个剂量组子宫卵巢血流均出现类似正常育龄妇女的周期性血流变化;②C组方案治疗PCOS有较高的排卵率和妊娠率。结论:来曲唑改善了PCOS患者的子宫卵巢血流供应,5.0 mg可能有更好的促排卵效果。     

Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome

Objective

To compare the clinical outcomes of letrozole and laparoscopic ovarian drilling (LOD) in patients with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS).

Methods

In the present prospective randomized trial, 140 women with clomiphene-citrate-resistant PCOS were randomly allocated to receive 5 mg letrozole from day 3 to day 7 of menses for 6 consecutive cycles, or to undergo LOD. When a leading follicle of at least 18 mm was present, ovulation was triggered with human chorionic gonadotropin (hCG). The 6-month rates of ovulation, pregnancy, abortion, and live births were evaluated.

Results

The groups were similar with regard to baseline clinical characteristics and hormonal profiles. The ovulation rate was significantly higher in the letrozole group than in the LOD group (59.0% versus 47.5%). On the days of the hCG injection, women in the letrozole group had a significantly thicker endometrium than those in the LOD group (P < 0.0001). Women receiving letrozole had a higher pregnancy rate (35.7% versus 28.6%) and a lower rate of spontaneous abortion (8.0% versus 20.0%, respectively), but these differences were not statistically significant.

Conclusion

Letrozole seems to be a suitable second-line ovulation-inducing alternative to LOD in women with PCOS who do not conceive with clomiphene citrate.     

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a,and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100?mg CC or 5?mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.     

Cyclic changes in serum levels of insulin-like growth factor binding protein-1 in women treated with clomiphene citrate and tamoxifen.

In order to investigate the cyclic changes of serum insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 levels in menstrual cycles treated with or without antiestrogens (clomiphene citrate and tamoxifen), we treated 24 young women having irregular menstrual cycles with either clomiphene citrate (100 mg/day) (n = 12) or tamoxifen (60 mg/day) (n = 12) from the 5th to the 9th day of the menstrual cycle. Without antiestrogens, 12 women with regular menstrual cycles were recruited as controls. There was a preovulatory (day 13) peak of circulating IGFBP-1 in women treated with or without antiestrogens. A significant concomitant increase in serum estradiol was also observed on day 13 of the menstrual cycle in subjects treated with clomiphene citrate and in controls. However, no significant elevation in preovulatory estradiol was detected in women treated with tamoxifen. In clomiphene citrate and control groups, a significant positive correlation was found between circulating IGFBP-1 and estradiol, and between serum levels of IGFBP-1 and inhibin A at the preovulatory stage (on day 13). In contrast, no such association was observed in the tamoxifen group. Unlike cyclic changes in circulating IGFBP-1, serum concentrations of IGF-I and IGFBP-3 remained unchanged throughout the menstrual cycle in all groups. In conclusion, the preovulatory peak of circulating IGFBP-1 can be induced in cycles treated with both clomiphene citrate and tamoxifen. In addition, a significant positive correlation between estradiol, inhibin A and IGFBP-1 at the preovulatory stage indicates that IGFBP-1 may also reflect follicular development and may further be used as an additional indicator to monitor folliculogenesis under clomiphene citrate treatment.     

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.     

Cyclic changes in serum levels of insulin-like growth factor binding protein-1 in women treated with clomiphene citrate and tamoxifen

In order to investigate the cyclic changes of serum insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 levels in menstrual cycles treated with or without antiestrogens (clomiphene citrate and tamoxifen), we treated 24 young women having irregular menstrual cycles with either clomiphene citrate (100 mg/day) (n = 12) or tamoxifen (60 mg/day) (n = 12) from the 5th to the 9th day of the menstrual cycle. Without antiestrogens, 12 women with regular menstrual cycles were recruited as controls. There was a preovulatory (day 13) peak of circulating IGFBP-1 in women treated with or without antiestrogens. A significant concomitant increase in serum estradiol was also observed on day 13 of the menstrual cycle in subjects treated with clomiphene citrate and in controls. However, no significant elevation in preovulatory estradiol was detected in women treated with tamoxifen. In clomiphene citrate and control groups, a significant positive correlation was found between circulating IGFBP-1 and estradiol, and between serum levels of IGFBP-1 and inhibin A at the preovulatory stage (on day 13). In contrast, no such association was observed in the tamoxifen group. Unlike cyclic changes in circulating IGFBP-1, serum concentrations of IGF-I and IGFBP-3 remained unchanged throughout the menstrual cycle in all groups. In conclusion, the preovulatory peak of circulating IGFBP-1 can be induced in cycles treated with both clomiphene citrate and tamoxifen. In addition, a significant positive correlation between estradiol, inhibin A and IGFBP-1 at the preovulatory stage indicates that IGFBP-1 may also reflect follicular development and may further be used as an additional indicator to monitor folliculogenesis under clomiphene citrate treatment.     

Extending clomiphene treatment in clomiphene-resistant women with PCOS: a randomized controlled trial

The purpose of this study was to test the effect of extended clomiphene citrate treatment compared with gonadotrophin therapy for the management of clomiphene-resistant women with polycystic ovary syndrome (PCOS). The study comprised 318 women (802 cycles) with clomiphene-resistant PCOS randomized to two treatment groups. Patients in the clomiphene citrate group were given 100 mg of clomiphene citrate daily starting on day 2 of menses for 9 days (160 patients, 405 cycles) while patients in the gonadotrophin group were given human menopausal gonadotrophin 75 IU intramuscularly daily for 5 days starting on day 3 of menses (158 patients, 397 cycles). The number of ovulating patients was significantly higher (P = 0.001) in the gonadotrophin group (57.6 versus 28.1%). The total number of follicles during stimulation was significantly greater (P = 0.01) in the gonadotrophin group (6.7 +/- 0.3 versus 4.1 +/- 0.4). Pregnancy occurred in 46/405 cycles in the clomiphene citrate group (11.4%) and in 80/397 cycles (20.2%) in the gonadotrophin group; the difference was statistically significant (P = 0.03). The extended clomiphene citrate regimen resulted in modest ovulation and pregnancy rates with no side effects. This therapy seems to offer economic, efficacy and safety advantages and it is worth undergoing before starting more expensive or sophisticated alternatives.     

A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women

OBJECTIVE: To evaluate the ovarian follicular dynamics of cycle modification with the aromatase inhibitor letrozole compared with clomiphene citrate in normal ovulatory women. DESIGN: Randomized double-blind controlled trial. SETTING: Tertiary care hospital. PATIENT(S): Nineteen ovulatory female volunteers, ages 18-35 years. INTERVENTION(S): Subjects were monitored in one control cycle. Subjects then received either letrozole 2.5 mg daily or clomiphene citrate 50 mg daily on days 5-9 after menses. MAIN OUTCOME MEASURE(S): Number of mature follicles, endometrial thickness and endometrial pattern at ovulation, and follicular profiles of LH, FSH, and E(2). RESULT(S): The number of mature follicles at the LH surge in natural cycles was 1.0 with an exaggerated response seen for treatment both with clomiphene and letrozole. There was no difference in the endometrial thickness at midcycle during either the natural cycles or the medicated cycles. LH surges and spontaneous ovulation were documented in all natural and medicated cycles. When measured daily, follicular profiles of LH and FSH are similar between the groups in both the natural and medicated cycles. In the medicated cycles, clomiphene results in a significant increase in E(2) levels, while E(2) levels in letrozole-stimulated cycles appeared lower than in natural cycles. CONCLUSION(S): Transient inhibition of aromatase activity in the early follicular phase with the aromatase inhibitor letrozole results in stimulation of ovarian folliculogenesis similar to that seen with clomiphene citrate with no apparent adverse effect on endometrial thickness or pattern at midcycle.     

Clomiphene citrate versus letrozole for ovarian stimulation: a pilot study

The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle.     

Fertility after ovarian drilling by transvaginal fertiloscopy for treatment of polycystic ovary syndrome

STUDY OBJECTIVE: To evaluate fertiloscopy ovarian drilling with bipolar energy in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). DESIGN: Prospective study (Canadian Task Force classification II). SETTING: University teaching hospital and private clinic. PATIENTS: Eighty women with clomiphene citrate-resistant PCOS. INTERVENTION: Operative transvaginal fertiloscopy with a coaxial bipolar electrode. MEASUREMENTS AND MAIN RESULTS: During a mean follow-up of 18.1 months (+/- 6.4), 73 women (91%) recovered regular and ovulatory cycles. The cumulative pregnancy rate was 60% (44/73) for spontaneous and stimulated cycles, with 39.7% (29/73) imputed to drilling alone. The mean time to conceive was 3.9 months (range 1-11.8). There were eight miscarriages (18%), and no ectopic pregnancies or multiple pregnancy. No complications occurred. CONCLUSION: Ovarian drilling by transvaginal fertiloscopy with bipolar electrosurgery appears to be an effective minimally invasive procedure in patients with PCOS resistant to clomiphene citrate.