妈富隆治疗青春期无排卵性功血的临床应用

<正>功能性子宫出血(功血)可发生于月经初潮至绝经期的任何阶段,其中青春期无排卵型功血(又称青春期功血)占各类功血的20%,在月经初潮1年内,80%的月经是无排卵型月经,初潮后     

二甲双胍治疗高胰岛素血症所致无排卵的临床观察

目的了解高胰岛素对血睾酮水平和排卵功能的影响,二甲双胍治疗高胰岛素血症无排卵的临床效果.方法对29例高胰岛素血症患者,进行12周的二甲双胍治疗,其中19例在二甲双胍治疗前后均接受氯米芬治疗1个周期.观察治疗前后血睾酮水平和排卵功能的变化.结果二甲双胍治疗前血睾酮水平为(2.7±1.6)nmol/L,治疗4周后为(1.9±1.0)nmol/L,两者比较,差异有显著性(P＜0.05).自发排卵,二甲双胍治疗前有3例,治疗后有10例(其中8例为原无排卵者)(P＜0.05);19例在二甲双胍治疗前后均服用过氯米芬,促排卵成功在二甲双胍治疗前有8例、治疗后有15例(P＜0.05).结论高胰岛素血症可引起血睾酮水平升高,排卵功能障碍.应用二甲双胍后胰岛素水平降低,睾酮水平下降,排卵功能有改善.     

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。     

腹腔镜电凝打孔术治疗耐氯米芬多囊卵巢综合征不孕43例疗效分析

目的:探讨腹腔镜下卵巢表面电凝打孔术对耐氯米芬(CC)多囊卵巢综合征(PCOS)所致不孕症患者的疗效。方法:对耐氯米芬的PCOS不孕患者43例,行腹腔镜下卵巢表面电凝打孔术。术后随访3~12个月。观察手术前后血清黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)、雌二醇(E2)、泌乳素(PRL)水平变化,卵巢体积及窦卵泡数的变化,术后月经和排卵情况、妊娠率及流产率。结果:术后LH、T、LH/FSH、PRL水平、卵巢体积、窦卵泡数均较术前明显降低(P<0.01),而FSH、E2术前、术后差异无显著性(P>0.05),月经情况明显改善,术后排卵率为93.0%(40/43),妊娠率为58.1%(25/43),流产率为16.0%(4/25)。结论:腹腔镜下卵巢表面电凝打孔术对于耐CC的PCOS不孕患者具有高排卵率和妊娠率以及低流产率的疗效。同时,具有创伤小、恢复快、并发症少的优点,是治疗耐CC的PCOS不孕患者的有效手段。     

氯米芬-补佳乐-黄体酮胶囊联合治疗排卵障碍性不孕的临床观察

目的:探讨氯米芬联合补佳乐、黄体酮胶囊治疗排卵障碍性不孕症的临床疗效。方法:选择2012年3月—2014年3月天津市北辰区妇女儿童保健中心妇科门诊收治的排卵障碍性不孕症患者60例,随机分为2组(各30例)。对照组单纯给予氯米芬100 mg口服,连续5 d;观察组在给予氯米芬100 mg的基础上,适时补充补佳乐与黄体酮胶囊,同时阴道超声监测排卵;2组均以3个月经周期为1个疗程,观察2组治疗后的总有效率、妊娠率。结果:观察组的总有效率为86.66%,妊娠率为33.33%;对照组的总有效率为43.33%,妊娠率为16.67%。观察组的疗效优于对照组,差异有统计学意义(P<0.05)。观察组双胎妊娠3例,对照组无双胎妊娠。2组均无卵巢过度刺激综合征发生。结论:氯米芬联合补佳乐适时补充黄体酮可以作为一种有效的促排卵方案用于治疗排卵障碍性不孕患者。     

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。     

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。     

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。     

枸橼酸氯米芬与来曲唑治疗多囊卵巢综合征不孕的效果研究

目的 研究在多囊卵巢综合征不孕治疗中应用枸橼酸氯米芬与来曲唑的效果.方法 选取50例多囊卵巢综合征不孕患者,通过抽签法将患者分为对照组与研究组,每组25例.对照组应用枸橼酸氯米芬治疗,研究组应用来曲唑治疗.比较两组患者子宫内膜厚度、卵泡发育状况、内分泌指标以及排卵率、妊娠率、早期流产率.结果 研究组优势卵泡数量、卵泡总...     

Does Metformin combined with Clomiphene Citrate improve fertility related outcomes in Clomiphene resistant women with PCOS: A systematic review

BackgroundPolycystic Ovary Syndrome (PCOS) is clinically associated with infertility. Many women are resistant to Clomiphene Citrate and the addition of insulin sensitisers may help to overcome this challenge.ObjectiveThis review aims to assess if Metformin added to Clomiphene Citrate improves pregnancy outcomes in patients with PCOS and are resistant to Clomiphene Citrate.Search strategyA systematic search was conducted on four electronic databases published until May 2013.Selection criteriaStudies evaluating the use of Metformin in combination with Clomiphene Citrate resistant patients with PCOS compared to placebo. Outcomes assessed were ovulation rate, pregnancy by ultrasound, Sex Hormone Binding Globulin (SHBG), BMI, fasting insulin and testosterone levels.Data collection and analysisThe reviewers carried out data extraction of specific outcomes and evaluated each study according to the sign guidelines.Main resultsIn total 40 citations were identified however only four were eligible for analysis. Two studies were found to have a statistically significant improvement in ovulation and pregnancy rates in the intervention group compared to the control group. These studies used the highest dose of Metformin and Clomiphene Citrate. In two studies we found statistically significant reductions in testosterone concentrations and BMI values.Authors’ conclusionsMetformin and Clomiphene Citrate have been shown to improve ovulation and pregnancy rates in the treatment of infertile patients with PCOS who are Clomiphene resistant. However, the optimal treatment regime remains ambiguous and needs further investigation with larger sample sizes of adequate power.     

Use of micro-dose human chorionic gonadotropin (hCG) after clomiphene citrate (CC) to complete folliculogenesis in previous CC-resistant anovulation

OBJECTIVE: The purpose of this study was to compare the effectiveness of low-dose human chorionic gonadotropin (hCG) in the late follicular phase to induce ovulation and its endocrine response in patients who had previously failed to ovulate on clomiphene citrate (CC) alone. DESIGN: A total of 67 patients from a private tertiary infertility clinic, who had produced a dominant follicle 12 mm or larger but 20 mm or smaller on a prior CC cycle at 100 mg but had failed to ovulate, were prospectively randomly assigned to groups. Group 1 repeated the 100 mg dose of CC but started a 200 IU hCG intramuscular injection daily when the largest follicle was 12 mm or larger mean diameter. Group 2 received a 150 mg dose of CC and both groups were monitored with transvaginal ultrasound and serum levels of E 2 , P 4 , and testosterone. Ultrasound measurements of follicle number and growth, ovulation, pregnancy rates, and serum hormonal levels were recorded and compared between the 2 groups. Analysis of variance and Student t test were used for statistical significance. RESULTS: The low-dose hCG group had significantly higher percentage of ovulatory cycles (57% vs 7% P < .001), peak E 2 levels (378 pg/mL vs 125 pg/mL P < .01), and pregnancy rates (18% vs 0% P < .001). This group showed no evidence of premature leutinization from the hCG with preovulatory P 4 levels less than 1.0 ng/mL and a slight increase in androgen levels. CONCLUSION: The use of micro-dose hCG after CC in the late follicular phase results in continued follicle growth, increased E 2 levels, ovulation, and pregnancies. This treatment offers an efficient and cost-effective alternative before gonadotropin therapy for this type of patient.     

Clomiphene Citrate co-treatment with low dose urinary FSH versus urinary FSH for clomiphene resistant PCOS: randomized controlled trial

Purpose

The aim of this study was to examine the effect of clomiphene citrate [CC] co-administration during the use of exogenous low-dose urinary FSH [uFSH] for induction of ovulation in CC-resistant infertile PCOS women.

Methods

In a randomised controlled setting, 174 CC-resistant infertile PCOS women were randomized into two parallel groups; Group I received CC 100 mg/day for 5 days plus uFSH 37.5 IU/day while group II received only uFSH 37.5 IU /day. Subsequent increments of uFSH by 37.5 IU/day were made according to response. Primary outcome was ovulation rate. Secondary outcomes were clinical pregnancy rates, number of follicles, endometrial thickness, and gonadotropins consumption.

Results

Our results have demonstrated that group I compared to group II had significantly higher ovulation rate per intention to treat [ITT] [72.4 % vs. 34.2 %, p < 0.001]. Clinical pregnancy and live birth rates were comparable between the two groups. Group I consumed significantly lower total FSH dose and needed significantly shorter stimulation duration compared to group II.

Conclusion

CC co-administered during low dose HP uFSH versus uFSH for CC-resistant PCOS yields significantly higher ovulation rate and less consumption of FSH.     

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。     

腹腔镜卵巢打孔对PCOS耐氯米芬患者的疗效研究

目的:观察腹腔镜手术治疗耐氯米芬(CC)多囊卵巢综合征(PCOS)不孕患者疗效的影响因素。方法:对46例耐氯米芬的PCOS患者行腹腔镜卵巢打孔术,按术后6周内是否恢复排卵分有效组(排卵)和无效组(无排卵)。分析两组间患者的年龄、不孕年限、体重指数(BMI)、性激素水平对临床疗效的影响。结果:术后有38例患者发生排卵,26例成功妊娠;8例即使在加用CC后仍无排卵与妊娠。有效组术前患者血清LH、LH/FSH的水平明显比无效组高,而不孕年限、BMI明显比无效组低;术后血清LH、LH/FSH及T水平明显下降,FSH及PRL水平无明显变化。无效组手术前后患者血清LH、LH/FSH水平无明显变化,术后血清FSH及PRL水平有上升的趋势。结论:对耐氯米芬PCOS患者行腹腔镜治疗时,术前患者不孕年限、BMI、LH、LH/FSH水平及术后LH、LH/FSH及T水平的下降幅度是预测术后排卵有效的指标,同时应该全面考虑患者的FSH、PRL水平的变化。     

应用复方醋酸环丙孕酮治疗多囊卵巢综合征及合并耐氯菧酚不育的探讨

目的　评估复方醋酸环丙孕酮（ 复方 Ｃ Ｐ Ａ） 治疗多囊卵巢综合征（ Ｐ Ｃ Ｏ Ｓ） 的疗效及安全性,探索停药后改善促排卵效果的可行性。方法　２９ 例 Ｐ Ｃ Ｏ Ｓ患者［１６ 例为耐氯菧酚（ Ｃ Ｃ） 或绝经期促性腺激素（ｈ Ｍ Ｇ） 促排卵失败的无排卵性不育］ ,于自然月经或撤退性出血第５ 天服复方 Ｃ Ｐ Ａ,共４ ～６ 个周期。服药前后观察临床表现、盆腔超声相、血清生殖激素、血脂水平的变化及副反应。停药后,耐 Ｃ Ｃ的１２ 例再行 Ｃ Ｃ 促排卵２２ 个周期,５ 例（１ 例耐ｈ Ｍ Ｇ,４ 例耐 Ｃ Ｃ） 行ｈ Ｍ Ｇ 促排卵６ 个周期,监测卵泡发育及效果。结果　服药后,８ 例有痤疮者中５ 例消失,３ 例缓解;多毛评分无显著下降。皆有规则的月经样出血。与服药前比较,服药２ ～３ 个周期起,血清各项生殖激素水平均显著降低（ Ｐ＜ ０ ．０５ ～０ ．０１） ,血清黄体生成素、促卵泡激素及雌二醇均值下降幅度各为７７ ．２ ％ 、２９ ．１ ％ 及７２ ．８ ％ 。雄烯二酮、睾酮及去氢表雄酮硫酸盐减少幅度各为３７ ．０ ％ 、５８ ．９ ％ 及２１ ．８ ％ 。但血性激素结合球蛋白（ Ｓ Ｈ Ｂ Ｇ） 升高５ ．１ 倍,胰岛素无显著变化。双侧卵巢体积、卵泡数目及卵泡直径均显著减少。高     

妈富隆与雌激素治疗青春期功血临床疗效探讨

目的：探讨妈富隆与雌激素治疗青春期功血的临床疗效。方法：以54例青春期功血患者为研究对象,随机均分为观察组和对照组。观察组采取妈富隆治疗,对照组采取雌激素治疗。比较两组患者治疗效果。结果：两组出血完全停止时间比较,观察组（54.04±10.71）h比对照组（75.24±11.85）h时间短,差异具有统计学意义（P＜0.05）。两组总有效率比较,观察组（100%）高于对照组（85.19%）,差异具有统计学意义（P＜0.05）。两组患者均无严重不良反应。结论：妈富隆治疗青春期功血能够有效降低完全停止出血时间,提高治疗总有效率,值得临床推广。     

Use of Clomiphene Citrate in the Treatment of Men with High Sperm Chromatin Stability

Objective: To determine whether improvements of the seminal vesicle function after a 5-day course with clomiphene citrate (CC) may reduce the prevalence of men with high sperm chromatin stability under conditions of sodium dodecyl sulfate (SDS)-ethylenediaminetetraacetic acid (EDTA).

Design: A prospective study.

Setting: Andrology laboratory at the Instituto de Investigaciones de la Altura, Universidad Peruana Cayetano Heredia, Lima, Peru.

Patient(s): Forty-one male partners of infertile couples attending the andrology laboratory.

Intervention(s): Clomiphene citrate was administered orally twice a day. Men were treated with CC at 100 mg daily for 5 days. Blood and semen samples were collected before treatment and 24 hours after the last administration.

Main Outcome Measure(s): Serum testosterone, seminal fructose, sperm motility, sperm chromatin stability after SDS and EDTA, and prevalence of high sperm chromatin stability.

Result(s): The percentage of stable sperm after SDS-EDTA correlated inversely with the basal corrected concentration of seminal fructose (−1.77 ± 0.89, β ± SE). High sperm chromatin stability was observed in 53.8% of the study population and in 66.7% of patients with hypofunction of the seminal vesicles. In those men whose seminal vesicle function improved after treatment with CC, the prevalence of high sperm chromatin stability was reduced from 67% to 25% (χ² = 5.34). Logistic regression analysis showed that the higher the basal corrected seminal fructose levels and the higher the basal serum testosterone levels, the lower the probability of nonresponse of the sperm chromatin stability to treatment with CC (0.54 ± 0.15, odds ratio ± SE for corrected fructose; and 0.50 ± 0.15, odds ratio ± SE for serum testosterone).

Conclusion(s): Hypofunction of the seminal vesicles was associated with high sperm chromatin stability, and this high sperm chromatin stability under SDS-EDTA conditions may be reduced by treatment with CC.     

达英-35联合克罗米芬治疗顽固性PCOS所致不孕症的临床观察

目的　观察达英 - 35 (Diane - 35 )联合克罗米芬 (CC)治疗顽固性多囊卵巢综合征 (polycysticovarysyndrome ,PCOS)所致不孕症的疗效。方法　排卵障碍所致不孕的 6 0例顽固性PCOS患者随机分为Diane CC组 (n =30 )和CC组 (n =30 ) ,Diane CC组采用达英 - 35联合CC治疗 ,CC组采用剂量与治疗组相同的CC治疗。结果　治疗组睾酮 (T) ,黄体生成素 (LH)水平较前明显下降 (P <0 0 5 )。治疗组排卵率达 6 1 1 % ,妊娠率达 5 3 3% ,而对照组周期排卵率 9 0 % ,妊娠率 6 7% ,两组疗效比较 ,差异有显著性 (P <0 0 1 )。结论　达英 - 35联合CC治疗顽固性PCOS所致不孕症能获得较高的排卵率及受孕率