多囊卵巢综合征患者卵泡液VEGF和PEDF水平与OHSS的关系

目的:研究多囊卵巢综合征(PCOS)患者卵泡液中血管内皮生长因子(VEGF)和色素上皮衍生因子(PEDF)水平与卵巢过度刺激综合征(OHSS)的关系。方法:行体外受精-胚胎移植(IVF-ET)的54例PCOS患者中,发生中重度OHSS者22例(A组),未发生或发生轻度OHSS者32例(B组)。采用酶联免疫吸附试验(ELISA)测定取卵日卵泡液中VEGF和PEDF水平。结果:A、B组HCG日≥14mm卵泡数、雌二醇(E2)水平、获卵数以及VEGF和VEGF/PEDF比值比较,差异均有统计学意义(P0.05);A组的PEDF水平低于B组,但无统计学意义(P0.05)。卵泡液中VEGF与PEDF呈负相关,与HCG日E2及≥14mm卵泡数呈正相关,VEGF/PEDF比值与HCG日≥14mm卵泡数呈正相关。结论:PCOS患者卵泡液VEGF与PEDF平衡的破坏可能在OHSS中发挥重要作用,VEGF/PEDF比值升高可能成为预测OHSS的新指标。     

多囊卵巢综合征(PCOS)患者在IVF-ET中发生严重卵巢过度刺激综合征(OHSS)的特点分析

目的:通过总结IVF-ET中多囊卵巢综合征(PCOS)患者应用控制性超促排卵(COH)后发生卵巢过度刺激综合征(OHSS)的特点,提出防止中、重度OHSS发生的有效措施。方法:将IVF/ICSI治疗时出现中、重度OHSS的患者根据有无PCOS史分成PCOS组和对照组。比较分析PCOS组和非PCOS组在COH中的雌激素水平、卵泡数、取卵数及发生中、重度OHSS的时间等临床资料;分析妊娠对OHSS的影响。结果:PCOS组的Gn用药总量及hCG注射日的血清E2水平比对照组低,其总卵泡数、中小卵泡数明显高于对照组,发生中、重度OHSS的时间早,妊娠可能加重OHSS病情发展。结论:卵泡总数、中小卵泡数可作为PCOS患者预测中、重度OHSS独立的重要指标,建议即使取卵前E2水平不高、获卵数不多也考虑行全胚冷冻,以阻止严重的OHSS发生。     

血管内皮生长因子在卵巢过度刺激综合征发病机理中作用的初步研究

目的通过对卵巢过度刺激综合征(OHSS)患者血管内皮生长因子(VEGF)水平和表达的测定,初步探讨VEGF在OHSS发病机理中的作用.方法采用酶联免疫吸附试验方法对14例中、重度OHSS患者(OHSS组)和同期13例非OHSS患者(对照组)取卵日卵泡液、人绒毛膜促性腺激素(hCG)注射日、胚胎移植(ET)日血清VEGF水平进行测定;采用免疫组织化学方法和逆转录聚合酶链反应技术检测取卵日卵巢黄素化颗粒细胞VEGF及其mRNA的表达.结果 OHSS组和对照组的卵泡液、hCG注射日血清VEGF水平分别为(1 257.2±648.0)与(1 745.1±802.4) ng/L,(250.1±109.5)与(196.7±81.7) ng/L,两组比较,差异无显著性(P>0.05);OHSS组ET日血清VEGF水平及注射hCG后血清VEGF水平变化程度,显著高于对照组[分别为(342.9±158.5)与(222.2±84.6) ng/L,(92.8±106.7)与(25.9±21.8) ng/L,P<0.05].OHSS组取卵日卵巢黄素化颗粒细胞VEGF mRNA的表达,显著高于对照组,VEGF/β肌动蛋白比值分别为1.50±0.60、0.96±0.56(P<0.05).两组取卵日卵巢黄素化颗粒细胞有较活跃的VEGF表达.结论 VEGF在OHSS的发病机理中可能起一定的作用.     

抗苗勒管激素对不同体质量指数多囊卵巢综合征患者卵巢过度刺激综合征的预测作用

目的:探讨抗苗勒管激素(AMH)对不同体质量指数(BMI)多囊卵巢综合征(PCOS)患者控制性超促排卵过程中发生卵巢过度刺激综合征(OHSS)的预测作用。方法:采用回顾性病例分析,将251例行控制性超促排卵的PCOS患者根据BMI分为3组,正常组(18.5 kg/m~2≤BMI24.0 kg/m~2)92例、超重组(24.0 kg/m~2≤BMI28.0 kg/m~2)90例、肥胖组(BMI≥28 kg/m~2)69例,比较3组患者的临床特征、控制性超促排卵和OHSS发生情况,并采用受试者工作曲线(ROC)评估AMH对PCOS患者OHSS发生的预测作用。结果:(1)3组PCOS患者的BMI、AMH、基础黄体生成素(LH)水平、促性腺激素(Gn)使用天数、Gn用量、绒促性素(HCG)扳机日雌二醇(E_2)水平差异均有统计学意义(P0.05),正常组的中重度OHSS发生率(18.48%)明显高于超重组(5.56%)和肥胖组(5.80%),差异有统计学意义(P0.05)。(2)多因素Logistic回归分析示:高BMI是PCOS患者发生OHSS的保护因素(OR 0.58,P0.05),高水平的AMH是OHSS发生的危险因素(OR 1.23,P0.05)。(3)正常组AMH阈值12.06 ng/ml时,预测OHSS发生的灵敏度为70.32%,特异度为88.96%,曲线下面积(AUC)最高为0.81;超重组AMH 10.25 ng/ml时,预测OHSS发生的灵敏度为85.36%,特异度为45.57%,AUC为0.53;肥胖组AMH 10.38 ng/ml时,预测OHSS发生的灵敏度为73.26%,特异度为56.78%,AUC为0.80。结论:可以采用AMH联合BMI评估PCOS患者发生OHSS的风险,其中AMH对正常BMI的PCOS患者发生OHSS的预测效果最佳,阈值为12.06 ng/ml,而对肥胖和超重的PCOS发生OHSS的预测有限。     

血管内皮生长因子在预测卵巢过度刺激综合征中的作用

目的探讨在体外受精-胚胎移植(IVF-ET)周期中血清及卵泡液中血管内皮生长因子(VEGF)水平的变化,及其在预测卵巢过度刺激综合征(OHSS)中的作用.方法收集42例行IVF-ET患者的血清和卵泡液标本,采用定量酶联免疫方法检测血清、卵泡液中VEGF水平,按是否发生OHSS分为OHSS组(10例)及对照组(32例),对两组临床资料、性激素和VEGF水平进行回顾性相关分析.结果 OHSS组血清VEGF水平在月经周期的各个时期均高于对照组,但差异无显著性(P>0.05).OHSS组卵泡液VEGF水平为(1 487.7±365.8) ng/L,较对照组的(1 025.8±474.7) ng/L明显升高;取卵时卵泡数目增多,OHSS组为(10.0±5.9)个,对照组为(6.1±2.3)个;基础黄体生成素(LH),人绒毛膜促性腺激素(hCG)、注射日雌二醇(E2)水平均比对照组高,差异有显著性(P<0.05).结论 OHSS组卵泡液VEGF水平明显高于对照组,提示VEGF可能参与了OHSS的发病;卵泡液VEGF水平可以作为预测OHSS发生的检测指标.     

不同剂量来曲唑预防早发型卵巢过度刺激综合征的临床研究

目的:探讨卵巢过度刺激综合征(OHSS)高危患者在取卵后应用不同剂量来曲唑(LE)预防早发型OHSS发生的效果。方法:88例患者随机分为4组,A~C组为LE组,取卵即日起每日添加LE,LE剂量分别为A组(n=21)2.5 mg/d,B组(n=23)5.0 mg/d,C组(n=20)7.5 mg/d,D组为对照组(n=24)。测患者黄体期内分泌、血管内皮细胞生长因子(VEGF)水平及中重度OHSS发生率。结果:h CG注射后第5日始血清E_2水平随时间变化呈降低趋势,随着LE剂量增加,E_2水平降低速度明显加快,组间差异有统计学意义(P0.05)。血清LH水平在注射h CG后第8日、第10日随着LE剂量的增加而逐渐上升,P水平却逐渐降低,组间差异显著(P0.05)。血清VEGF水平从h CG注射后5日始,D组呈上升趋势,而其它三组呈下降趋势,随着LE剂量的增加,血中VEGF水平越低,各组之间两两比较,差异均具有统计学意义(P0.001)。C组中重度OHSS发生率低于D组。结论:不同剂量的LE均能一定程度降低血清E_2及VEGF水平,当剂量增至7.5 mg/d时,OHSS发生率最低。     

来曲唑预防取卵术后卵巢过度刺激综合征的临床效果研究

目的:探讨卵巢过度刺激综合征(OHSS)高危人群在取卵术后,口服来曲唑预防OHSS发生的临床效果。方法:回顾性分析厦门市妇幼保健院2011年11月至2016年5月行体外受精-胚胎移植(IVF-ET)助孕,使用(GnRH-a)长方案或超长方案超促排卵,因预防OHSS取消移植,行全胚冷冻患者621例,按照是否于取卵术后口服来曲唑分为两组。一组于取卵术后未口服来曲唑(对照组),共298例;另一组于取卵术后口服来曲唑(研究组),共323例。对比两种方案患者助孕情况和OHSS的发生率、中重度OHSS的发生率。结果:研究组323例患者中OHSS的发生率为15.17%,显著低于对照组(P0.05)。研究组中重度OHSS的发生率为4.64%,也显著低于对照组(P0.05)。研究组促性腺激素(Gn)总量、Gn总天数、HCG日的雌二醇(E2)、黄体生成激素(LH)、孕酮(P)和获卵数与对照组比较差异无统计学意义(P0.05)。结论:来曲唑可以更好地降低高危人群在取卵术后OHSS的发生率及中重度OHSS的发生率。临床上可以考虑将来曲唑作为预防OHSS的药物使用。     

多囊卵巢综合征患者体外受精中促性腺激素释放激素拮抗剂方案安全性分析

目的探讨多囊卵巢综合征(PCOS)患者应用促性腺激素释放激素拮抗剂(GnRH-A)方案的可行性、安全性及预防中重度卵巢过度刺激综合征(OHSS)的方法。方法回顾性病例对照研究使用GnRH-A方案PCOS患者的304个取卵周期的临床资料。取卵后评估有无OHSS高风险,无OHSS风险者纳入A组,有OHSS高风险者纳入B组。比较患者的基本特征、促性腺激素(Gn)启动剂量及使用总量、Gn使用时间、获卵数、优质胚胎率、妊娠率、OHSS发生率等。结果 PCOS患者的年龄、体质量指数(BMI)、平均不孕年限组间比较差异均无统计学意义(P0.05)的情况下,OHSS高风险与基础高黄体生成素(LH)、高LH/卵泡刺激素(FSH)、高睾酮(T)水平有关,组间比较差异均有统计学意义(P均=0.000)。A组进行新鲜移植共197个周期,临床妊娠率为58.89%(106/197)。B组行全部胚胎冷冻93个周期,首次冻融胚胎移植的临床妊娠率为81.81%(72/88)。分析可见,卵巢的反应性与启动日血清LH/FSH比值有相关性,LH/FSH比值越高,其促排卵的反应性就越好。总体中重度OHSS发生率为6.91%(21/304),A组的中重度OHSS发生主要是迟发型,与妊娠及多胎妊娠相关,B组的中重度OHSS发生主要是早发型。结论 GnRH-A方案应用于PCOS患者,可以通过减少启动剂量,新鲜周期移植前评估OHSS风险;如有OHSS风险者全部胚胎冷冻,期待冻融周期移植,可获得安全有效的结局。     

重度卵巢过度刺激综合征发病风险因素的预测研究

目的:研究窦卵泡数、h CG注射日血清E_2水平、获卵数对于预测重度卵巢过度刺激综合征(OHSS)的作用,特别是晚发型重度OHSS的可能危险作用。方法:回顾性分析IVF周期早发型和晚发型重度OHSS患者的临床资料并与对照组相比。结果:早发型重度OHSS(n=184)与对照组(n=5 044)相比,当获卵数0~9个/周期时,患者年龄、获卵数、窦卵泡数的妊娠结局组间无统计学差异;随着获卵数的增多,总窦卵泡数、h CG注射日E_2水平、Gn用量等组间有显著性差异;晚发型重度OHSS(n=279)与对照组(n=13 074)相比,当获卵数0~9个/周期,总窦卵泡数、h CG注射日E_2水平、Gn用量组间有统计学差异;随着获卵数的增多,年龄、BMI、基础雄激素(A)、总窦卵泡数、h CG注射日E_2水平、Gn用量、内膜厚度有差异;随着获卵数增多(20个/周期),患者BMI、基础FSH、总窦卵泡数、h CG注射日E_2水平、Gn用量组间有差异。当获卵数15个/周期时,h CG注射日血清E_212 000 pmol/L,卵巢窦卵泡数12个/周期时,重度OHSS的发病率明显上升。多因素Logistic回归分析筛选出:获卵数、可移植胚胎数、h CG注射日E_2水平及总窦卵泡数为晚发型OHSS的危险因素。结论:早发型重度OHSS与晚发型重度OHSS发生机制不同,早发型和晚发型重度OHSS的发生与获卵数(12个/周期)、h CG注射日E_2水平(12 000 pmol/L)、Gn用量相关;可移植胚胎多者建议全部胚胎冷冻,减少晚发型OHSS发生。     

超排卵治疗中VEGF和E2对OHSS的预测作用

目的检测超排卵治疗的不孕症患者血清血管内皮生长因子(VEGF)和雌二醇(E2)水平,探讨VEGF和E2对卵巢过度刺激综合征 (OHSS)的预测作用.方法采集41例高危患者注射HCG前和注射后34～36h血清标本,测定VEGF和E2水平,并与同期30例非高危病人进行对照.结果高危各组在注射HCG前,血清 VEGF水平与对照组无显著性差别(P>0.05 ),注射后 OHSS组VEGF水平明显升高 (P< 0.01),显著高于对照组和非OHSS组(P< 0.01);高危各组 E2水平在注射HCG日显著高于对照组,注射后OHSS组E2水平与注射前比明显升高(P<0.01),显著高于对照组(P<0.01),但非OHSS组变化不明显(P>0.05).结论 VEGF在HCG注射后可作为预测OHSS的标志物,结合连续测定E2水平,有助于预测和治疗卵巢过度刺激综合征.     

吲哚美辛治疗卵巢过度刺激综合征的实验研究

目的　探讨吲哚美辛 (INDO)治疗卵巢过度刺激综合征 (OHSS)的疗效。方法　未成年Wis tar雌鼠分为对照组、PMSG +hCG组和拮抗剂组 3组。其中PMSG +hCG组和拮抗剂组皮下注射PMSG和hCG ,建立鼠OHSS模型。拮抗剂组围绕注射hCG前后 ,依皮下注射INDO 0 3mg或 3mg。 4 8h后从鼠尾静脉注入亚甲蓝取灌洗腹腔液 ,用分光光度计测定腹腔灌洗液中亚甲蓝含量 ,以了解卵巢和腹膜的通透性 ,称双侧卵巢重量后将卵巢匀浆 ,通过Bligh -Dyer法提取脂质、薄层色层法 (TLC)纯化PAF ,计算卵巢PAF ,并进一步测定血小板的聚集功能。结果　PMSG +hCG组卵巢的总重量、腹腔灌洗液中亚甲蓝的含量和卵巢PAF含量显著高于对照组 ,两组比较 ,差异均有显著性 (P <0 0 5 )。INDO组卵巢重量与PMSG +hCG组比较 ,差异无显著性 (P >0 0 5 )。但0 3mgINDO组卵巢重量与PMSG +hCG组比较降低了 1 2 798%。INDO腹腔灌洗液中亚甲蓝的含量与PMSG +hCG组比较 ,差异无显著性 (P >0 0 5 )。但 0 3mgINDO组腹腔灌洗液中亚甲蓝的含量与PMSG +hCG组比较降低了1 5 72 6 %。 0 3mgINDO组卵巢PAF含量显著低于PMSG +hCG组 ,两组比较差异有显著性 (P <0 0 5 )。结论　在注射hCG后围绕注射hCG前后给予 0 3mgINDO可以在一定程度上降低OHSS鼠卵巢的重量、     

Polycystic ovarian syndrome in adolescence

Background.?Polycystic ovarian syndrome (PCOS), which is a common endocrinopathy seen not only in adult women but also in female adolescents nowadays, is associated with reproductive, metabolic and cardiovascular problems.

Objective.?This article aims to review the current evidence on managing PCOS in adolescence. In addition, the pathophysiology, risk factors, clinical presentations and existing diagnostic criteria of PCOS will also be discussed.

Discussion.?Certain risk factors are available to assist the clinicians to identify adolescents at risk of PCOS as the signs can be masked by the normal physiological changes during puberty. It is important to screen and diagnose adolescent PCOS in order to prevent the development of future infertility, type II diabetes mellitus, cardiovascular disease, and even endometrial cancer. Lifestyle modification is of the greatest benefit for adolescents in terms of management, with the condition that full support is available from both the clinicians and their families. The psychological impact of PCOS also constitutes a major concern in adolescent PCOS.     

Thrombosis following ovarian hyperstimulation syndrome

The aim of this review is to analyse the pathophysiology and complications of thrombosis in conjuction with ovarian hyperstimulation syndrome (OHSS) following ovulation induction and to suggest practical guidelines usefull for the prevention and treatment. Although the incidence of thrombosis varies from 0.2% among in vitro fertilization (IVF) cycles and up to 10% for severe cases of the syndrome, it represents the most dangerous complication of OHSS. Different changes in haemostatic markers have been found to create a state of hypercoagulability, but no single standard test is available to estimate the state of thrombosis. The role of markers for thrombophilia is controversial. Thromboses are mostly venous (67–75%) involving upper limbs and neck, then arterial (25–33%) which are mainly intracerebral. The predominant sites of venous thromboembolism in the upper part of the body may be explained by higher concentrations of estrogens drained through lymphatic ducts from ascites and by compression of rudimentary branchyal cysts. Once early diagnosis is established, it is crucial to use an anticoagulant treatment with heparin proceeded with thromboprophylaxis. However, identification of patients at risk and preventive measures of OHSS are the best means in reducing the risk of thrombosis after ovarian stimulation.     

Association of thrombophilia and polycystic ovarian syndrome in women with history of recurrent pregnancy loss

Purpose: To evaluate the prevalence of thrombophilic disorders in polycystic ovarian syndrome (PCOS) women with history of recurrent pregnancy loss (RPL). Materials and methods: This study was carried out in 184 women with history of RPL, of which 92 of them were diagnosed with PCOS and 92 patients were without known PCOS. The prevalence of thrombophilic disorders was compared between the two mentioned groups. Results: According to the findings, 70.7% of PCOS women with history of RPL had thrombophilic disorders. The prevalence of protein C deficiency was significantly higher in PCOS group compared to the non-PCOS group (21.7% vs. 10.9%, p = 0.04). There was a trend toward higher prevalence of protein S deficiency in PCOS group compared to the control group, but the difference did not reach statistical significance (23.9% vs. 13%, p = 0.05). The prevalence of other thrombophilic disorders such as antithrombin III deficiency, homocysteine elevation, antiphospholipid antibody and Factor V Leiden was comparable between groups. Conclusion: The prevalence of thrombophilic disorders was more common in PCOS women than the normal group. The protein C deficiency is associated with PCOS in women with history of RPL. There was a trend toward higher prevalence of protein S deficiency in PCOS women, which needs further study.     

限制性促排卵方案预防卵巢过度刺激综合征的探索性研究

目的研究提前注射绒促性素（hCG）的促排卵方案,即限制性促排卵（LOS）方案,在预防卵巢过度刺激综合征（OHSS）发生中的作用。方法对10例OHSS高危的不孕患者,其中8例为多囊卵巢综合征（PCOS）患者,采用促性腺激素释放激素激动剂（GnRHa）长方案超排卵,当最大卵泡直径达到12．0～14．5mm时注射hCG10000U,36h后取卵,行常规体外受精或单精子卵母细胞质内注射及胚胎移植。结果10例患者均无OHSS发生,获卵11～35个,其中成熟卵4～28个,均在取卵周期行胚胎移植。胚胎移植后妊娠8例,其中输卵管妊娠1例。结论LOS方案可以使PCOS不孕患者在获得足够多的成熟卵、有效防止OHSS发生的同时不降低妊娠率。     

Comparison of bevacizumab and cabergoline in the treatment of ovarian hyperstimulation syndrome in a rat model

Abstract

The aim of this study is to investigate the effects of bevacizumab in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline. The study was performed with 24 rats in four main groups (one non-stimulated control and three OHSS treatment groups; bevacizumab, cabergoline and placebo). The rats were randomly assigned to four experimental groups (six rats per group). Efficacy of treatment was assessed on 29th day by measuring weight gain, number of eggs, presence of ascites and ovarian weight. Peritoneal fluid levels of vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay. Ovarian weights were significantly higher in the OHSS groups than the control group. Ovarian weights in OHSS placebo group were found to be higher than those in OHSS-treatment groups (p?=?0.002). VEGF levels were found increased in the OHSS-placebo group compared with the control group (p?<?0.05). This increase was not seen in the OHSS groups treated with either bevacizumab or cabergoline. We demonstrate in this study that bevacizumab can lower VEGF production and ovarian weight in rats treated with gonadotropins.     

多囊卵巢综合征大鼠脂肪组织中TNF-α的表达及其意义

目的研究由脱氢表雄酮（DHEA）诱导的多囊卵巢综合征（PCOS）SD大鼠动物模型的脂肪组织中TNF—α mRNA及蛋白的表达与其性激素变化及胰岛素抵抗（IR）的关系。方法以DHEA皮下注射21日龄SD雌性大鼠为研究组，观察其卵巢重量、光镜（HE染色）及透视电镜下改变，测定糖耐量、血清胰岛素、E2、T、P、PRL、FSH和LH水平，采用逆转录聚合酶链反应（RT—PCR）法及Western Blot技术检测其脂肪组织中TNF—α mRNA和蛋白的表达。结果实验组卵巢重量显著高于对照组（P〈0．05），实验组卵巢呈多囊样改变而黄体形成比例减少；实验组血清T、E2、空腹血糖和胰岛素水平明显高于对照组（P分别〈0．001、〈0．05、〈0．001和〈0．05），空腹血胰岛素与空腹血糖乘积的倒数（1／FINS×FGC）显著高于对照组（P〈0．05）；PCOS大鼠白色脂肪组织中TNF—α mRNA及蛋白表达均显著高于对照组（P〈0．05）。结论DHEA诱导的P—COS大鼠动物模型与PCOS患者相似，且有IR现象；由白色脂肪组织分泌的TNF—α在PCOS的发生机制中起着部分调节作用，从而加重PCOS患者的胰岛素抵抗。     

The role of cytokines in polycystic ovarian syndrome

Abstract

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Inflammation has been implicated in the metabolic disturbances and menstrual irregularities, which characterize this condition. Various inflammatory proteins have been investigated in women with PCOS including C-reactive protein, interleukin-6, interleukin-18 and tumor necrosis factor-alpha. The data is suggestive of the presence of a chronic low-grade inflammatory state, especially in case of obesity, insulin resistance and hyperandrogenism. Targeting this inflammatory process by means of anti-inflammatory agents might be a therapeutic alternative to the current treatment.