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。     

二甲双胍联合氯米芬-促性腺激素治疗多囊卵巢综合征

多囊卵巢综合征（PCOS）是排卵障碍性不孕的重要原因，与患者体内高雄激素、高胰岛素或胰岛素抵抗有关。其中部分患者经氯米芬治疗后能获得妊娠。但仍有相当数量的PCOS患者对氯米芬治疗无效。对此类患者使用氯米芬联合促性腺激素（CC—hMG／hCG）是目前治疗中常用的诱发排卵方法之一，但对PCOS患者使用促性腺激素治疗容易发生卵巢过度刺激综合征（OHSS），严重者可威胁患者生命。我们采用胰岛素增敏剂-二甲双胍联合氯米芬-促性腺激素治疗PCOS，取得肯定疗效，现报道如下。     

多囊卵巢综合征不育的腹腔镜治疗──30例临床分析

多囊卵巢综合征（ＰＣＯＳ）是妇女内分泌紊乱的一种常见疾病,其发病原因至今未明。ＰＣＯＳ患者的病理生理变化以雄激素过多和排卵功能障碍的内分泌紊乱为特征［１］,同时有高胰岛素血症及胰岛素抵抗代谢的特征［２］。表现为;１．慢性无排卵或排卵稀发与闭经;２．雄激素分泌过盛以致多毛;３．组织活动代谢增高而出现体重增加,肥胖。ＰＣＯＳ患者求治的目的主要为需求生育或治疗月经不调。我院经用腹腔镜内凝法治疗ＰＣＯＳ患者,取得了较好的效果。现收集３０例不育病例报告如下。 资料与方法 一、资料来源 １９９２年元月至１９９…     

难治性多囊卵巢综合征的治疗策略及结局

目的 探讨对持续无排卵的多囊卵巢综合征（ＰＣＯＳ）患者使用诱发排卵的治疗方案及其治疗效果。方法 收集氯米芬抵抗的ＰＣＯＳ患者５９例,共８１个治疗周期,分为３组：（１）促卵泡激素（ＦＳＨ）组,４９个治疗周期;（２）ＦＳＨ＋促性腺激素释放激素（ＧｎＲＨ）泵组,１３个周期;（３）常规体外受精（ＩＶＦ）组,１９个周期。前两组给予前期降黄体生成素（ＬＨ）及睾酮（Ｔ）治疗。观察用促排或超排治疗后雌二醇（Ｅ２）     

应用复方醋酸环丙孕酮治疗多囊卵巢综合征及合并耐氯Di酚不育的 …

目的 评估复方醋酸环丙孕酮（复方ＣＰＡ）治疗多囊卵巢综合征（ＰＣＯＳ）的疗效及安全性,探索葶药后改善促排卵效果的可行性。方法 ２９例ＰＣＯＳ患者「１６例为耐氯Ｄｉ酚（ＣＣ）或绝经期促性腺激素（ｈＭＧ）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ＣＰＡ,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ＣＣ的１２例再行ＣＣ促排卵２２个     

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、他莫昔芬和氯米芬治疗多囊卵巢综合征不孕疗效比较

目的比较多囊卵巢综合征(PCOS)不孕患者经纠正内分泌代谢紊乱后应用3种不同促排卵药物的效果及对子宫内膜的影响。方法选择2009年3月至2010年1月中山大学孙逸仙纪念医院妇产科生殖中心128例PCOS不孕患者,于本院行第1次促排卵,有高雄激素或胰岛素抵抗者经预处理至少3个月。随机分为3组,来曲唑44个周期、他莫昔芬40个周期和氯米芬44个周期。结果月经第10天的子宫内膜厚度,他莫昔芬组[(6.4±1.2)mm]高于来曲唑组[(5.4±1.7)mm]和氯米芬组[(5.4±1.3)mm](P=0.01);HCG日血雌二醇(E2)水平,来曲唑组[(838.6±678.2)pmol/L]低于他莫昔芬组[(2629.2±1931.5)pmol/L]和氯米芬组[(1971.2±1222.8)pmol/L](P<0.001);3组间加用尿促性腺激素(HMG)周期数,HCG日子宫内膜厚度、血黄体生成素及孕酮、直径≥18mm成熟卵泡数,妊娠率和早期流产率,差异无统计学意义(P>0.05);HCG日子宫内膜的厚度与注射HCG的月经周期日及月经第10天的子宫内膜厚度呈正相关(P<0.05),与药物的种类及HCG日血E2水平等无显...     

促性腺激素释放激素激动剂在多囊卵巢综合征促排卵高危周期中的 …

OBJECTIVE: To evaluate the efficacy and safety of gonadotropin-releasing hormone agonist (GnRH-a) instead of hCG for triggering ovulation in high risk gonadotropin stimulating cycles of infertile polycystic ovary syndrome (PCOS) patients. METHODS: GnRH-a was given for triggering follicular final maturation and ovulation in 18 gonadotropin stimulating cycles of 14 PCOS patients with mean serum estradiol (E2) level of 8,379 +/- 2,958 pmol/L. Their outcomes and complications were analysed. RESULTS: Ovulation achieved in 15 (83.3%) treated cycles, 4 (22.2%) became pregnant. Only 1 developed moderate ovarian hyperstimulation syndrome (OHSS) and another 1 had multiple pregnancy. CONCLUSIONS: The use of GnRH-a instead of hCG in high risk gonadotropin stimulating cycles is able to successfully induce ovulation and pregnancy and decrease the incidence of severe OHSS and multiple gestation.     

超声下未成熟卵泡抽吸术治疗多囊卵巢综合征不孕的临床研究

目的　探讨超声下未成熟卵泡抽吸术(IMFA)对多囊卵巢综合征(PCOS)不孕患者卵巢窦卵泡计数及其内分泌功能的影响;观察IMFA后,应用人绝经期促性腺激素(hMG)促排卵治疗的效果、妊娠及并发症情况。方法　将71例PCOS不孕患者随机分为两组。组Ⅰ: 37例,穿刺前用少量hMG促排卵; 组Ⅱ: 34例,不用任何促排卵药物。在阴道超声引导下进行IMFA,检查穿刺后第2个周期患者的内分泌功能和卵巢基础窦卵泡计数,可连续2~3个周期进行穿刺。随后2组均用hMG常规促排卵治疗,随访其排卵及妊娠情况。结果　组Ⅰ进行了88个周期的穿刺治疗,经过2~3次穿刺后,睾酮水平、黄体生成素(LH )与卵泡刺激素(FSH)的比值均明显降低,与治疗前比较,差异有统计学意义(P<0. 01), 33例(89%, 33 /38)患者基础窦卵泡计数降至10个/卵巢以下。组Ⅱ进行了87个周期治疗,所有患者睾酮水平均显著降低,与治疗前比较,差异有统计学意义(P<0 01 ); 30例LH/FSH<2, 28例(82%, 28 /34)患者基础窦卵泡计数降到10个/卵巢以下。在IMFA之后, 诱发排卵时hMG用量组Ⅰ为(21±6)支,组Ⅱ(23±10)支,两组比较,差异无统计学意义(P>0 .05),在注射人绒毛膜促性腺激素(hCG)后均出现排卵, 组Ⅱ有2例发生轻度卵巢过度刺激综合征(OHSS)。连续促排卵治疗1 ~3个月后, 共36例(51% )     

Consensus on infertility treatment related to polycystic ovary syndrome

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. On the basis of the currently available evidence, a group of experts reached a consensus regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counseling should be provided emphasizing the importance of lifestyle, especially weight reduction and exercise in overweight women, smoking, and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotropins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotropins is associated with increased chances for multiple pregnancy, and, therefore, intense monitoring of ovarian response is required. Laparoscopic ovarian surgery alone is usually effective in less than 50% of women, and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC-gonadotropin paradigm) is reported to be highly effective with a cumulative singleton live-birth rate of 72%. Recommended third-line treatment is in vitro fertilization (IVF). More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-line, second-line, or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.     

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     

超声引导下经阴道卵巢内激光治疗多囊卵巢综合征的剂量研究

目的 评价不同激光剂量对超声引导下经阴道卵巢内激光治疗多囊卵巢综合征(PCOS)排卵障碍患者的临床及内分泌效果的影响.方法 选择2005年1月至2007年7月就诊于深圳市妇幼保健院的对枸橼酸氯米芬治疗无反应的PCOS不孕患者56例,随机分为A、B、C、D共4组,行超声引导下经阴道卵巢内激光治疗,激光治疗的剂量以卵巢内凝固点数表示,每个凝固点采用功率为3～5 W的激光持续作用1～3 min,直径约为10 mm.其中A组为1个点,B组为2个点,C组为3个点,D组为4～5个点.比较治疗后6个月内各组患者自发排卵率、妊娠率及月经周期情况,并比较治疗前后各组患者血清性激素水平的变化.结果 (1)C组和D组治疗后自发排卵率分别为71%(10/14)和79%(11/14),均高于A组(0)和B组(21%,3/14),差异均有统计学意义(P<0.05).C组和D组治疗后6个月累积临床妊娠率分别为43%(6/14)和36%(5/14),均高于A组(0),差异均有统计学意义(P<0.01、P<0.05);与B组(14%,2/14)比较,差异无统计学意义(P>0.05).C组与D组的自发排卵率及累积临床妊娠率分别比较,差异均无统计学意义(P>0.05).(2)治疗前的各项性激素水平,各组患者之间分别比较,差异均无统计学意义(P>0.05);治疗后的黄体生成素(LH)、睾酮水平及LH/卵泡刺激素(FSH)比值,A组[分别为(11.9±3.1)U/L、(3.9±1.6)nmol/L和2.1±0.5]、B组[分别为(10.4±3.9)U/L、(3.3±1.1)nmol/L和2.0±0.6]分别与C组[分别为(6.3±2.6)U/L、(2.2±0.7)nmol/L和1.1±0.3]、D组[分别为(5.8±2.5)U/L、(2.1±0.4)nmol/L和1.0±0.4]比较,差异均有统计学意义(P<0.05);C组与D组分别比较,差异均无统计学意义(P>0.05).C、D组治疗后的平均LH、睾酮水平及LH/FSH比值分别较治疗前下降了42%、39%、42%和53%、40%、58%,均高于A组(分别下降了4%、9%和16%)和B组(分别下降了11%、6%和5%),差异均有统计学意义(P<0.05);C组与D组之间比较,差异均无统计学意义(P>0.05).结论 每侧卵巢内选择1～2个激光凝固点的临床效果较差,3个激光凝固点是卵巢内激光治疗PCOS排卵障碍的有效剂量,在此基础上增加凝固点数不能提高治疗效果.     

Leutinizing hormone/choriogonadotropin receptor and follicle stimulating hormone receptor gene variants in polycystic ovary syndrome

Purpose

Previous studies identified follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) genes as polycystic ovary syndrome (PCOS) susceptibility loci, which was dependent on the racial/ethnic background of studied population. We investigated the association of genetic variants in FSHR and LHCGR with PCOS in Bahraini Arab women.

Methods

A retrospective case–control study, involving 203 women with PCOS, and 211 age- and ethnically-matched control women. FSHR and LHCGR genotyping was done by allelic exclusion method (real-time PCR).

Results

Significantly lower frequencies of heterozygous LHCGR rs7371084 and FSHR rs11692782 genotype carriers were seen between women with PCOS vs. controls, and increased frequency of heterozygous homozygous LHCGR rs4953616 genotype carriers were detected between women with PCOS compared to control women. Limited linkage disequilibrium was noted among LHCGR and FSHR SNPs, and 2 blocks were constructed: the first (Block 1) spanning 61 kb contained the six tested LHCGR SNPs, and the second (Block 2) spanning 298 kb contained four of the five tested FSHR SNPs. Higher frequency of LHCGR GTCAAG haplotype was seen in women with PCOS compared to controls; the frequencies of the remaining LHCGR haplotypes, and all FSHR haplotypes were similar between cases and controls.

Conclusion

This is the first study to confirm the association of novel LHCGR (rs7371084, rs4953616) and FSHR (rs11692782) SNPs with PCOS. The differential association of LHCGR and FSHR variants with PCOS confirms the racial/ethnic contribution to their association with PCOS.

     

无刺激周期未成熟卵母细胞体外培养用于多囊卵巢综合征不孕患者治疗的临床观察

目的探讨无刺激周期未成熟卵母细胞体外培养在治疗多囊卵巢综合征(PCOS)不孕患者的应用价值。方法对70例PCOS患者,在人工周期或自然周期第10～12天行阴道B超监测,如双侧卵巢中无直径>8mm的卵泡,即肌内注射人绒毛膜促性腺激素10000IU,36h后经阴道穿刺取卵,将取出的未成熟卵母细胞进行体外成熟及体外受精胚胎移植。结果共进行体外成熟周期94个,移植周期75个。共获得卵母细胞1283个,获得成熟838个(65.3%,838/1283),其中受精553个(66.0%,553/838),获得胚胎402个(48.0%,402/838),获得优质胚胎199个(23.7%,199/838)。生发泡期卵母细胞的成熟率、受精率、获得胚胎率及优质胚胎率,分别为67.7%、66.4%、47.6%及24.1%;第1次减数分裂中期的卵母细胞,分别为69.7%、71.7%、52.2%及26.1%,生发泡期与第1次减数分裂中期比较,差异均无统计学意义(P>0.05)。无法评价的卵母细胞的成熟率、受精率、获得胚胎率及优质胚胎率,分别为44.8%、53.8%、46.2%及16.9%,与生发泡期及第1次减数分裂中期比较,差异均有统计学意义(P<0.05)。75个移植周期中,18例获得临床妊娠,妊娠率为24%(18/75)。结论无刺激周期未成熟卵母细胞体外成熟及体外受精胚胎移植可用于PCOS不孕患者的治疗,并能取得一定的妊娠成功率。     

An algorithm for treatment of infertile women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common condition with both a reproductive and metabolic phenotype. Women with PCOS often seek care because of infertility or menstrual cycle irregularities that result from chronic anovulation interspersed with occasional ovulatory cycles. Initially, it is important to delineate a differential diagnosis for oligo- or amenorrhea and to evaluate for disorders that may “masquerade” as PCOS. If fertility is a desired goal, then it is critical to optimize health conditions that impact fertility and gestation. Lifestyle modifications, including nutritional counseling and weight loss, should be a part of all treatment plans. Even minimal (5%) weight loss in obese women with PCOS improves both ovulation and pregnancy rates. The first line of treatment for ovulation induction remains the selective estrogen receptor modulator (SERM) clomiphene citrate. The role of insulin sensitizers, particularly metformin, remains unclear. A recent consensus panel recommended against its routine use in the absence of an elevated glucose or hemoglobin A1c. If a woman fails to achieve pregnancy after a trial of weight loss and six ovulatory cycles induced by clomiphene citrate, then ovulation induction with exogenous gonadotropin, with or without timed intrauterine insemination, or in vitro fertilitization, is a reasonable next step. Women with PCOS are particularly prone to excessive follicle development and are at increased risk for ovarian hyperstimulation syndrome (OHSS). Although limited data exist comparing approaches to ovulation induction or controlled ovarian stimulation in women with PCOS, the American Society for Reproductive Medicine recommends the use of “step-up” or “step-down” protocols in which a low dose of exogenous FSH or combined gonadotropins are employed in an attempt to constrain ovarian responsiveness. In vitro fertilization allows for the transfer of only one embryo or for cryopreservation of all embryos with subsequent transfer of a single embryo in a subsequent cycle without ovarian stimulation. Countless questions regarding pathogenesis and treatment of PCOS create opportunity for basic and clinical research and for refinement of existing therapeutic approaches.     

多囊卵巢综合征不孕患者辅助生殖治疗临床效果分析

目的 探讨多囊卵巢综合征(PCOS)不孕患者辅助生殖治疗的临床效果及方案选择.方法 回顾性分析2003年1月至2007年11月间,在山东大学附属省立医院生殖医学中心就诊的PCOS不孕患者的临床资料,根据治疗方案不同,分为药物治疗[分别用来曲唑(LE组,58个周期)或枸橼酸氯米芬(CC组,45个周期)]、体外受精-胚胎移植(IVF-ET)治疗、经阴道B超未成熟卵泡穿刺治疗、未成熟卵体外成熟(IVM)治疗等方案,分析其临床效果.结果 (1)药物治疗者中,LE组排卵率为66%(38/58),Cc组为47%(21/45);人绒毛膜促性腺激素(hCG)注射日平均子宫内膜厚度,LE组为(0.89±0.13)cm,CC组为(0.78±0.08)cm;hCG注射日宫颈黏液评分,LE组为(11.9±1.8)分,CC组为(9.9±1.8)分;平均成熟卵泡数,LE组为(1.08±0.28)个,CC组为(1.73±0.59)个;hCG注射日平均雌二醇水平,LE组为(983±138)pmol/L,CC组为(1676±372)pmol/L,两组各项指标比较,差异均有统计学意义(P<0.05);LE组周期妊娠率为14%(8/58),CC组为13%(6/45),两组比较,差异无统计学意义(P>0.05).(2)IVF-ET治疗者中,1584例PCOS不孕患者(PCOS组)促性腺激素(Gn)总用量[(980±1192)IU]低于对照组[(1194±1389)IU,同期因输卵管因素行IVF-ET治疗者1615例],但两组使用Gn平均天数[分别为(9.6±1.8)、(9.5±1.8)d]、hCG注射日平均雌二醇水平[分别为(15 752±6206)、(9675±4818)pmol/L]、平均获卵数[分别为(21±6)、(9±3)个]、平均受精数[分别为(15±6)、(7±3)个]、平均卵裂数[分别为(12.9±5.7)、(5.7±2.8)个]和重度卵巢过度刺激综合征(OHSS)发生率(分别为4.86%、1.67%)比较,PCOS组均明显高于对照组,差异均有统计学意义(P<0.05).但两组临床妊娠率(分别为44.7%、45.0%)比较,差异无统计学意义(P>0.05).(3)109例经阴道B超未成熟卵泡穿刺治疗患者的睾酮和黄体生成素水平均较治疗前明显下降,卵巢基础窦卵泡计数随穿刺次数增加而减少.穿刺治疗后应用尿促性腺激素促排卵治疗时,OHSS发生率很低,穿刺治疗后妊娠率达50%以上.(4)IVM治疗的286例PCOS不孕患者,取卵周期304个,平均每周期取卵12.3个,有76例患者获得临床妊娠.结论 PCOS不孕患者治疗的选择方案较多,上述4种治疗方案均有效,应结合患者具体情况给予个体化处理.     

增生期血清泌乳素水平与多囊卵巢综合征不孕的关系探讨

研究多囊卵巢综合征不孕与增生期血清泌素的关系。方法采用放射免疫测定法测定血清泌乳素质量浓度。结果ＰＣＯＳ不孕组和非ＰＣＯＳ不孕组的增生期血清泌乳素水平无明显差异,但两组与生育组比较,血清乳素水平明显增高。