氯米芬在非降调节超促排卵方案中抑制早发LH峰的作用

目的:探讨氯米芬在非降调节超促排卵过程中对早发LH峰的抑制效果。方法:回顾分析2013年4月至2014年10月在我中心应用CC联合Gn超促排卵方案的98例卵巢储备功能正常患者的临床数据,如基础、诱发排卵前2天、诱发排卵前1天、诱发排卵日的LH,平均获卵数、MⅡ卵率、正常受精率、可利用胚胎率、优质胚胎率、基础内膜厚度、诱发排卵日内膜厚度、着床率、临床妊娠率。结果:基础LH水平为(3.19±2.17)m IU/ml,诱发排卵前2天LH水平为(4.25±2.70)m IU/ml,诱发排卵前1天LH水平为(4.70±2.53)m IU/ml,诱发排卵日LH水平为(5.85±3.57)m IU/ml。基础、诱发排卵前2天、诱发排卵前1天、诱发排卵日的LH平均水平均低于10m IU/ml,数据呈递增趋势,但均未发生卵泡早排现象。其中9例出现高LH(LH≥10m IU/ml),未发生卵泡早排,且未影响卵子质量、优胚率及妊娠结局。平均Gn量为(2142.23±712.57)IU,平均Gn天数为(10.4±1.81)天,平均获卵数(12.33±6.29)个,HCG日内膜厚度(9.45±2.20)mm,卵子成熟率86.8%(1071/1235),正常受精率74.1%(794/1071),优质胚胎率52.0%(412/794),可利用胚胎率80.3%(638/794),取卵周期98个,新鲜胚胎移植周期数60个周期,临床妊娠率51.7%(31/60)。结论:CC联合非降调超促排卵方案在卵巢储备功能正常的不孕症患者中能有效抑制早发LH峰,可常规新鲜胚胎移植,且不降低临床妊娠率。     

单次大剂量雌激素在氯米芬促排卵前的应用

目的:观察氯米芬(CC)促排卵时,排卵前单次应用大剂量雌激素的效果。方法:选择排卵障碍的不孕症患者60例,随机分为研究组和对照组,各30例。所有患者均于月经第5天开始服用CC,100mg/d,共5天。研究组患者在最大卵泡的平均直径≥18～20mm时,单次口服戊酸雌二醇12mg;对照组患者于月经第9天起每日加服戊酸雌二醇2mg,直至最大卵泡的平均直径≥18～20cm。阴道超声监测卵泡发育及子宫内膜厚度,比较两组患者妊娠情况。结果:两组HCG日≥18～20cm的优势卵泡个数差异无统计学意义(P>0.05)。研究组HCG日子宫内膜平均厚度显著低于对照组[(8.0±1.3)mm vs(9.8±1.4)mm,P<0.05],但排卵率显著高于对照组(86.7%vs 63.3%,P<0.05),临床妊娠率亦显著高于对照组(60.0%vs 33.3%,P<0.05)。研究组中1例患者出现卵泡未破黄素综合征,对照组中5例出现卵泡黄素化未破裂,两组比较差异无统计学意义(P>0.05)。两组患者均未出现卵巢过度刺激综合征。结论:氯米芬促排卵时,应用雌激素能够改善子宫内膜,排卵前单次大剂量雌激素应用,更利于排卵及妊娠。     

口服妈富隆并延长氯米芬用药时间治疗耐氯米芬的无排卵患者

目的评价常规服用氯米芬促排卵失败的妇女口服避孕药妈富隆配合延长氯米芬服用时间促排卵的治疗效果。方法114例患者在采用传统方法促排卵连续3个周期失败后,改服妈富隆2个周期以上。自停药后月经第5天开始服用氯米芬(50mg/d)促排卵,阴道B超(TVS)监测记录卵泡生长,至出现优势卵泡停服。B超监测排卵经过以及子宫内膜厚度的变化。结果114例患者在服用氯米芬5天后有37例出现优势卵泡,35例成功排卵,2例出现卵泡黄素化未破裂综合征(LUFS);延长服药时间后又有34例成功排卵,17例出现LUFS,13例出现卵泡发育,但未形成优势卵泡即闭锁;13例无卵泡发育。结论对于耐氯米芬的无排卵患者口服妈富隆联合延长氯米芬服药时间,是一种有效的促排卵方案。     

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。     

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。     

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。     

氯米芬和地塞米松治疗氯米芬抵抗的多囊卵巢综合征：一项前瞻性安慰剂对照研究

对多囊卵巢综合征（PCOS）的持续不排卵，氯米芬（CC）是传统一线疗法。但20%～25% PCOS妇女用大剂量CC也不排卵。1953年首次报道肾上腺皮质类固醇对排卵障碍的治疗作用。1999年、2002年报道地塞米松（DEX）的新作用：即对硫酸脱氢表雄酮（DHEAS）正常、不排卵的PCOS妇女有促排卵作用。据报道卵泡期应用DEX无任何不良反应或后遗症。     

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。     

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。     

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。     

Clomiphene citrate in LH surge suppression for women undergoing ICSI

Objective

To evaluate the effect of adding clomiphene citrate (CC) in the mid-to-late follicular phase as an adjuvant to gonadotropins to suppress luteinizing hormone (LH) surge in women undergoing intracytoplasmic sperm injection (ICSI).

克罗米芬与GnRH拮抗剂在控制性超促排卵中抑制LH峰效果的比较

目的:探讨克罗米芬(CC)与GnRH拮抗剂(GnRH-A)在控制性超促排卵(COH)中对黄体生成素(LH)峰抑制效果的比较。方法:对应用CC后置方案和拮抗剂方案的181个周期的资料进行回顾性分析。其中应用CC抑制LH峰方案65例(CC组),应用GnRH-A(思则凯组)抑制LH峰方案116例。比较2种药物对LH峰的抑制作用、Gn用量、获卵数、可移植胚胎数、优质胚胎数、受精率等。结果:hCG注射日LH值与加用CC或思则凯日LH值的差值[LH(d-)]具有统计学差异(1.30±5.12 IU/L vs-1.37±7.15 IU/L,P=0.004);Gn用量、获卵数、可移植胚胎数、优质胚胎数、受精率等CC组和思则凯组比较差异无统计学意义(P0.05)。结论:CC与思则凯对早发LH峰均有一定抑制效果,但较CC相比其抑制早发LH峰效果可能更明显。     

克罗米芬联合高孕激素促排卵抑制早发LH峰的临床结局研究

目的:探讨在控制性超促排卵中克罗米芬(CC)联合高孕激素促排卵方案抑制早发LH峰的临床效果。方法:回顾性分析126名行体外受精/卵胞质内单精子显微注射(IVF/ICSI)取卵周期的患者,分为CC联合高孕激素促排卵组(试验组,n=63)和短方案治疗组(对照组,n=63)。观察过早LH峰发生率、促排卵中Gn用量和用药天数、获卵数、成熟卵数、内分泌及胚胎试验室结果。结果:试验组获卵数、成熟卵数、有效胚胎数、生化妊娠率、临床妊娠率、胚胎种植率与对照组比较均无统计学差异(P0.05)。所有对象在促排卵过程中未监测到早发LH峰,试验组月经第9~10日和诱发排卵日LH水平与基础值间无统计学差异(P0.05)。试验组Gn用量和用药天数均高于对照组(P0.05)。结论:CC联合高孕激素促排卵方案可以有效抑制早发LH峰,促排卵过程中LH水平平稳,且可以获得有发育潜能的胚胎。     

Progestin-primed ovarian stimulation versus GnRH antagonist protocol in poor responders: Risk of premature LH surge and outcome of oocyte retrieval

PurposeFor poor ovarian responders (PORs), gonadotropin-releasing hormone (GnRH) antagonist was commonly used for prevention of premature LH surge during controlled ovarian stimulation (COS) over the past two decades. The application of progestin-primed ovarian stimulation (PPOS) recently increased, but the role of PPOS for PORs was uncertain. We aimed to analyze the incidence of premature luteinizing hormone (LH) surge and the outcome of oocyte retrieval among PPOS and GnRH antagonist protocol for PORs.MethodsThis was a single-center retrospective study, which enrolled the PORs (defined by the Bologna criteria) undergoing COS with PPOS or flexible GnRH antagonist protocol during January 2018 to December 2021. We compared the incidence of premature LH surge (LH > 10 mIU/mL) and the outcome of oocyte retrieval between the PPOS group and the GnRH antagonist group.ResultsA total of 314 women were recruited, with 54 in the PPOS group and 260 in the GnRH antagonist group. The PPOS group had lower incidence of premature LH surges compared with the GnRH antagonist protocol group (5.6% vs 16.9%, P value 0.035). There was no significant difference between the two groups regarding the number of oocytes retrieved (3.4 vs 3.8, P value 0.066) and oocyte retrieval rates (88.9% vs 88.0%, P value 0.711).ConclusionCompared with PPOS, GnRH antagonist protocol had higher risk of premature LH surges for PORs but may not affect pregnancy rates. PPOS is suitable for oocyte or embryo cryopreservation, but should not totally replace GnRH antagonist protocol for patients undergoing in vitro fertilization (IVF).     

Nitric oxide donors increase the pregnancy rate in patients with unexplained infertility undergoing clomiphene citrate stimulation and intrauterine insemination: a randomized controlled pilot study

This study evaluated the effects of nitric oxide donor’s treatment on the pregnancy rate and uterine blood flow in patients with unexplained infertility undergoing clomiphene citrate stimulation and intrauterine insemination. A total of 120 patients were randomly allocated to a control group who received 100?mg clomiphene citrate daily from day 5 to 9 of cycle plus placebo vaginal tablets, and a study group received clomiphene citrate plus isosorbide mononitrate 10?mg vaginal tablets. Vaginal ultrasound was done before treatment and every other day starting from day 12 of cycle to count mature follicles and ovulation was triggered by IM injection of 10 000?IU hCG when one follicle measured 18?≥?mm followed by intrauterine insemination after 36?h. The endometrial thickness, uterine arteries resistance and pulsation indices, and endometrial vascular flow and vascular flow indices were measured before treatment and at day of hCG injection. Results were analyzed after one cycle treatment using the Mean?±?SD, the Student t test and the Fisher Exact test. Significant result was considered at p values?<0.05. The study group had significant higher pregnancy rate/cycle, higher endometrial and lower uterine artery blood flow indices (p?相似文献   

Effectiveness of GnRH antagonist in intrauterine insemination cycles

Objective

To evaluate the effectiveness of GnRH antagonists in women undergoing controlled ovarian stimulation and intrauterine insemination cycles (COS/IUI).

Study design

Randomized controlled trial. Recruited women were randomized into two groups: GnRH antagonist and control group. The primary outcomes were incidence of premature LH surge and clinical pregnancy rates.

Results

One hundred and forty-one consecutive women were included in the study, with 70 in the antagonist group and 71 in the control arm. The baseline clinical characteristics were similar in both groups. The incidence of premature LH surge and premature luteinization was lower in the antagonist group as compared to the control group (5% vs. 10.3%, P = 0.45 and 5% vs. 13.8, P = 0.31) but not statistically significant. The clinical pregnancy rates were lower in the antagonist group (2.8% vs. 10%, P = 0.12), which was also not statistically significant.

Conclusion

The addition of GnRH antagonist during controlled ovarian stimulation and intrauterine insemination cycles does not lead to improvement in clinical pregnancy rates.     

Clomiphene citrate induced ovulation and intrauterine insemination: effect of timing of human chorionic gonadotropin injection in relation to the spontaneous LH surge on pregnancy rates

Purpose: To determine the optimal time for administration of human chorionic gonadotropin in clomiphene citrate induced intrauterine insemination cycles.Methods: A retrospective analysis of 171 consecutive cycles was performed. An increase in luteinizing hormone level > 100% over the mean of the preceding two days was defined as luteinizing hormone surge. Human chorionic gonadotropin was given in preparation for intrauterine insemination based on the follicle size and estradiol level prior to surge in 85 cycles (Group A), with the spontaneous surge in 64 cycles (Group B) and not given in 22 cycles (Group C) due to high luteinizing hormone levels.Results: The overall pregnancy rate per cycle was 18.1% (31/171), 15.2% (Group A), 20.3% (Group B) and 22.7% (Group C), (p > 0.50).Conclusion: Although there may be physiological reasons to propose that timing the human chorionic gonadotropin to the luteinizing hormone surge will improve the success rate, they were not demonstrated.