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。     

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。     

非垂体降调节促排卵方案在卵巢储备功能正常患者IVF-ET/ICSI中的应用

目的:探讨非垂体降调节促排卵方案在卵巢储备功能正常的不孕患者IVFET/ICSI中的应用价值。方法:接受IVF-ET/ICSI助孕的卵巢储备功能正常的不孕症患者共200例,根据促排卵方案分为两组:非垂体降调节组(非降调节组)98个周期,GnRH-a长方案组(长方案组)102个周期,比较两组的Gn时间、Gn量、平均获卵数、卵裂率、优胚率、可利用胚胎率、临床妊娠率、种植率、冷冻胚胎周期率等各项指标。结果:非降调节组的获卵数、MⅡ卵数低于长方案组,优胚率及可利用胚率明显高于长方案组,差异均有统计学意义(P<0.05)。非降调节组的鲜胚移植临床妊娠率为51.7%,略低于长方案组的54.5%,但差异无统计学意义。非降调节组在h CG注射日前持续性高LH(LH≥10m IU/ml)者共有9例,其胚胎种植率为30%,临床妊娠率为60%。结论:对于卵巢储备功能正常的不孕症患者,非降调节促排卵方案能明显提高优胚率,且鲜胚移植的临床妊娠率与长方案组无明显差异。非降调节组中持续性高LH不会影响胚胎的种植率及临床妊娠率。     

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。     

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。     

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。     

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。     

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。     

短效达必佳两种降调节方案在控制性超排卵中的效果比较

目的:比较短效达必佳2种降调节方案在控制性超排卵(COH)中的效果。方法:回顾性分析比较本中心接受COH降调节方案的261个周期,根据达必佳用量及用法的不同分成A组:部分半量方案,95个周期;B组:半量方案,166个周期,比较组间的超促排卵情况及妊娠结局。结果:A组Gn用量(75IU/支)、Gn总天数、IVF受精率和优质胚胎率均较B组高(P<0.05);Gn启动日FSH水平和hCG注射日LH水平较B组低(P<0.05);着床率、临床妊娠率、继续妊娠率A组与B组比差异无统计学意义(P<0.05),但有增高趋势。结论:黄体中期短效达必佳0.1mg/d×14d降调节效果比0.05mg/d降调节好。     

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。     

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).

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).     

Extension of the clomiphene citrate stair-step protocol to gonadotropin treatment in women with clomiphene resistant polycystic ovarian syndrome

Our objective was to evaluate the safety and efficacy of direct initiation of gonadotropin ovarian stimulation without prior withdrawal bleeding in anovulatory clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS) patients. Eighteen PCOS patients underwent ovulation induction with CC using a stair-step regimen. Patients who failed to respond to the maximal dose of CC initiated gonadotropin stimulation without inducing withdrawal bleeding, using the chronic low dose regimen. The primary outcome measure was the time to ovulation from the beginning of CC treatment until the day of ovulatory trigger. This was compared with the time to ovulation calculated according to the traditional approach, which includes inducing progesterone withdrawal bleeding between each CC dose increment and before gonadotropin therapy. The time to ovulation in the study group was 67.0?±?6.8 days. The estimated time to ovulation according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence the live birth rate was 38.9% (7/18). Direct initiation of gonadotropin therapy without prior induction of withdrawal bleeding in clomiphene resistant PCOS patients results in considerable reduction of the time to ovulation and is both safe and efficacious.     

克罗米芬兴奋试验预测卵巢储备功能的价值

目的探讨克罗米芬兴奋试验（CCT）在不孕妇女中预测卵巢储备功能的作用。方法对2001年1月至2005年2月就诊于广东省妇幼保健院的666例不孕症患者作为研究对象，分为A组（≥35岁）461例为高龄组，B组（〈35岁）205例为低龄组，另取156例年龄〈35岁、非女方不孕原因者作为对照组，对三组受试者进行CCT。结果CCT异常发生率A组、B组及对照组分别为27．76％、34．14％、2．56％，A组及B组与对照组比较差异均有非常显著性意义（P〈0．01）。基础卵泡刺激素（FSH）〈10IU／L、雌二醇（E2）〈180pmot／L的不孕患者CCT异常发生率分剐为17．46％、24．19％，均明显低于FSH≥10IU／L、E2≥180pmol／L患者的64．19％及39．4％（P〈0．01）。结论CCT预测卵巢储备功能较基础FSH更敏感，CCT可作为常规了解卵巢储备功能的一项检测方法。     

Massive ovarian edema in pregnancy after ovulation induction using clomiphene citrate

Background Massive ovarian edema is a benign enlargement of the ovary caused by accumulation of fluid occurring mainly in young women. Most cases are thought to result from venous and lymphatic obstruction. Case report We treated a 40-year-old multiparous pregnant woman with massive ovarian edema who had been received clomiphene citrate. She was admitted at 13th week of pregnancy for acute pelvic pain. Left oophorectomy was performed, and pathologic examination disclosed massive ovarian edema. Our report is the first case of massive ovarian edema with pregnancy after ovulation induction using clomiphene citrate.     

Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphen citrate gonadotropins in controlled ovarian hyperstimulation: a prospective,simply randomized,clinical trial

OBJECTIVE: To study the efficacy of the aromatase inhibitor letrozole in controlled ovarian hyperstimulation (COH). MATERIAL AND METHODS: In this prospective simply randomized clinical trial, one hundred forty patients with unexplained infertility undergoing intrauterine insemination (IUI) therapy were randomized to receive either letrozole or clomiphene citrate (CC)-gonadotropin. The patients were selected among patients referred to one university hospital and one private infertility clinic. A letrozole dose of 5 mg/day (n = 70) was given on days 3-7 of the menstrual cycles. Clomiphen citrate a dose of 100 mg/day was given like letrozole but combined with human menopausal gonadotropin (hMG) dose of 75 IU/ml administered every day starting on day 6. Ovulation was triggered with urinary hCG (10,000 IU) when the leading follicle(s) reached 18 mm in diameter. A single IUI was performed 36 hours later. The luteal phase was supplemented with micronized progesterone vaginally. Ovarian stimulation response (E2 levels and number of follicles) was primary outcome. RESULTS: There were no differences in demographic characteristics between groups. The number of mature follicles (1.8 +/- 0.7 vs. 2.46 +/- 2.3; P = 0.042) and serum E2 level on the day of hCG (310 +/- 135.4 vs. 1,670.7 +/- 1021.8 pg/ml, respectively; P < 0.0001) were significantly lower in letrozole group. A significantly higher endometrial thickness was observed at the time of hCG administration in patients that received letrozole (9.7 +/- 1.6 mm vs. 7.8 +/- 2 mm; P < 0.001).Clinical pregnancy rates also were significantly higher in letrozole group (32.8% vs. 14.3%, respectively; P < 0.01). CONCLUSION: The aromatase inhibitor letrozole appears to constitute a good alternative to CC-gonadotropin in patients with unexplained infertility undergoing COH cycles combined with IUI therapy.     

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.