辅助生殖技术中卵巢过度刺激综合征发生发展预测指标的研究

目的　寻找辅助生殖技术 (ART)中卵巢过度刺激综合征 (OHSS)发生发展的预测指标。方法　比较1998～ 2 0 0 3年ART治疗后 4 5例OHSS和 4 0例非OHSS患者的妊娠结局 ;并根据OHSS发生时间分早发、晚发两组 ,比较组间特征和实验室资料 ,回归分析筛查OHSS发生发展预测指标。结果　HCG注射后发生OHSS的平均时间为 (9 3± 4 7)d。早发组 (尤合并妊娠者 )比晚发组年轻、促性腺激素用量少、多囊卵巢病例多、HCG注射日中小卵泡评分高 ,差异有显著性意义。回归分析发现 :仅中小卵泡评分与OHSS发生时间相关 ;用中小卵泡评分 >2 0分预测早发组OHSS发生的阳性、阴性预测值 ,敏感性、特异性分别为 90 0 %、92 0 %、81 8%、95 8%。OHSS持续时间与是否妊娠或多胎妊娠有关 ,用OHSS持续时间 >7d、≤ 7d、≥ 12d可分别预测早发组妊娠、晚发组未孕和多胎妊娠。结论　早发OHSS与卵巢对外源性HCG过度反应有关 ,HCG日中小卵泡评分可预测OHSS的发生 ;晚发OHSS更多与胚胎种植后产生的内源性HCG有关 ,OHSS持续时间可判断妊娠情况     

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。     

IVF/ICSI-ET周期hCG注射次日雌二醇(E_2)水平变化的意义

目的:探讨体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)周期中hCG注射次日血清雌二醇(E2)水平较hCG注射日的增幅对超促排卵临床结局的预测价值。方法:回顾性分析362例行黄体中期长方案IVF/ICSI-ET患者的临床资料。hCG注射次日E2增幅=(hCG注射次日血清E2水平-hCG注射日E2水平)/hCG注射日E2水平×100%。根据增幅的不同分成4组:A组增幅20%,B组增幅为0.1%~20%间,C组为-20%~0%间,D组增幅-20%。分析4组患者基本临床资料、超促排卵情况以及临床结局各项指标。结果:各组患者的取卵年龄、不孕年限、基础FSH(bFSH)值、降调节剂量、rFSH天数、hCG用量、hCG注射日LH值、2原核(2PN)胚胎数、优质胚胎数、冷冻胚胎数各组间差异均无统计学意义。各组患者的Gn启动剂量、Gn总用量、hCG注射日P值差异均有统计学意义(P0.05),且各值随着E2增幅的降低逐渐升高。A组的临床妊娠率(56.30%)显著高于B、C、D组(40.27%、42.85%和20.00%),差异有统计学意义(P0.05)。A组的胚胎种植率(33.86%)虽高于B、C、D组(26.23%、28.65%和16.67%),但差异无统计学意义(P0.05)。结论:监测黄体中期长方案垂体降调节IVF/ICSI-ET患者hCG注射次日E2增幅水平对临床结局有预测意义,E2水平在hCG注射次日较hCG注射日增幅高达20%以上时,临床结局较好。     

卵泡刺激素刺激后血清抑制素B和雌二醇预测体外受精周期中卵巢的反应性及其相关性

目的 探讨以经重组卵泡刺激素（rFSH）刺激后体外受精（IVF）周期中不同时间血清抑制素B（INHB）、雌二醇（E2）的动态变化,预测不孕患者卵巢的反应性,为选择最佳的超促排卵方案提供理论依据。方法 采用酶联免疫吸附试验,测定57例不孕患者（年龄〈40岁）于IVF周期中的不同时问,即月经第3天、注射rFSH前、注射rFSH后1d,及注射rFSH后5d的血清INHB、E2水平,并与反映卵巢反应性的2个指标——获卵数／rFSH总量、（卵泡数／rFSH总量）的平方根进行相关性分析。根据本研究中卵泡数及获卵数、是否发生卵巢过度刺激综合征（OHSS）的情况,将57例患者分为低反应组、过度刺激组及正常反应组,比较3组注射rFSH后INHB及E2水平的变化。结果 （1）注射rFSH后1、5d,其血清INHB及E：水平均与卵巢反应性呈显著正相关（INHB：rS=0．69—0．73,E2：rS=0．60～0．73;P=0．000）。（2）低反应组、正常反应组及过度刺激组注射rFSH后5d,患者血清INHB水平分别为164．7、696．2及1263．5ng／L,E2水平分别为303．2、1709．5及4261．0pmol／L,低反应组明显低于正常反应组,正常反应组明显低于过度刺激组,3组分别比较,差异均有统计学意义（P（0．01）。结论 经rFSH刺激后,血清INHB及E2水平能较敏感地预测卵巢对rFSH刺激的反应性,且INHB比E2更敏感。INHB及E2水平降低,可预测卵巢的低反应性;反之,可预测发生OHSS。     

来曲唑/FSH促排卵中GnRHa与hCG诱发卵泡成熟效果的比较

目的:比较曲普瑞林和hCG在来曲唑(LE)/FSH促排卵行IVF-ET治疗中诱发卵泡成熟的效果。方法:391个IVF-ET治疗周期随机分成促性腺激素激动剂(GnRHa)组(n=267)和hCG组(n=124),所有患者均采用LE/FSH促排卵方案,当主导卵泡平均直径达18～20mm时,GnRHa组患者采用达菲林0.1mg诱导卵泡成熟,hCG组采用hCG10000IU诱导卵泡成熟,比较组间的获卵数、MII卵率、受精率、卵裂率、优胚率、临床妊娠率和中-重度卵巢过度刺激综合症(OHSS)发生率。同时比较两组患者诱导日(d0)、取卵日(d2)、胚胎移植前日(d4)和胚胎移植后第4日(d9)的血清E2、P、LH水平。结果:hCG组Gn使用总量、MII卵率、卵裂率、中-重度OHSS发生率显著高于GnRHa组(P<0.05)。Gn使用天数、获卵数、受精率、种植率、临床妊娠率、流产率组间无统计学差异(P>0.05)。GnRHa组d0LH、d2LH、d9LH水平显著高于hCG组(P<0.05),而d2P、d4E2、d4P、d4LH、d9E2、d9P水平显著低于hCG组(P<0.05)。结论:在LE/FSH促排卵方案中可以用GnRHa替代hCG诱导卵泡成熟,而不影响IVF结局,并显著降低OHSS发生率。GnRHa诱导卵泡成熟的IVF周期其黄体期存在黄体功能不全,需适当补充外源性hCG加强黄体支持。     

hCG注射日雌二醇(E_2)增幅及每成熟卵泡E_2水平对控制性促排卵hCG扳机的影响

目的:探讨控制性促排卵(COS)hCG注射日雌二醇(E2)在hCG扳机时的作用。方法:接受长方案垂体降调节IVF/ICSI-ET助孕的不孕症患者1 811例,测量COS周期中E2水平,计算E2增幅[E2增幅=(hCG注射日E2值-hCG注射前日E2值)/hCG注射前日E2值]。按照E2的增幅分为5组:A1组E2增幅≤-10%,A2组E2增幅为-9%~10%,A3组E2增幅为11%~50%,A4组E2增幅为51%~100%,A5组E2增幅100%;另按hCG注射日每卵泡E2水平分为5组:B1组E2≤200 pg/ml,B2组E2为201~300 pg/ml,B3组E2为301~400 pg/ml,B4组E2为401~500 pg/ml,B5组E2500 pg/ml。比较各组间一般临床特征及IVF-ET的临床结局。结果:①A1组hCG注射日直径≥14 mm卵泡数、获卵数及2PN数较其他4组高,hCG注射日直径≥18 mm卵泡比例,较其他4组低,差异均有统计学意义(P0.05),临床妊娠率偏低,但与其余4组间无统计学差异(P0.05);②A5组hCG注射日P水平、hCG注射日直径≥14 mm卵泡数、获卵数、2PN数、临床妊娠率和胚胎着床率均较其他4组低,差异有统计学意义(P0.05);③B2组临床妊娠率和胚胎着床率较其他4组高,差异有统计学意义(P0.05)。结论:hCG注射日E2增幅介于-9%~100%、每成熟卵泡E2值介于201~300 pg/ml之间是hCG扳机的最佳时机。     

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 4 1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 0 5 ) ,注射后OHSS组VEGF水平明显升高 (P <0 0 1) ,显著高于对照组和非OHSS组 (P <0 0 1) ;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 0 1) ,显著高于对照组 (P <0 0 1) ,但非OHSS组变化不明显 (P >0 0 5 )。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。     

不同黄体支持方法对体外受精-胚胎移植结果的影响

目的:探讨三种黄体支持方法对体外受精-胚胎移植(IVF-ET)结果的影响。方法:回顾性分析195个IVF-ET周期的结果,根据注射hCG当天的血E2水平、B超示直径≥14 mm卵泡数目及所用的黄体支持方法分组。A组:112例,E2<2 000 pg/mL,直径≥14 mm的卵泡数<10个,hCG进行黄体支持;对E2≥2 000 pg/mL,卵泡数目≥10个者,随机分为两组,B组,46例,单用黄体酮进行黄体支持;C组,37例,黄体酮加雌激素进行黄体支持。结果: 三组间妊娠率、种植率、流产率、OHSS发生率差异均无显著性,P>0.05。结论:hCG用于IVF黄体支持并不优于黄体酮,但在一定程度上可避免某些患者由于注射黄体酮产生的痛苦。黄体酮+雌激素进行黄体支持应该是黄体支持较合理的方案,还需进一步研究。     

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.     

控制性超促排卵中人绒毛膜促性腺激素最佳扳机时间的探讨

本文综合分析了hCG注射日LH、E2、P、E2/P水平,及hCG注射日卵泡大小、每卵泡血清E2水平等各因素与hCG注射时机的相互关系,并指出hCG扳机时机需在卵泡大小达到一定程度,大卵泡达到一定比例,每卵泡E2水平达到200~350 pg/ml之间时,兼顾各激素水平及内膜情况进行综合考虑。     

卵巢过度刺激综合征患者血管内皮生长因子的变化

目的:探讨卵巢过度刺激综合征(OHSS)发病过程中血管内皮生长因子(VEGF)的作用机理。方法:ELISA法测定hCG注射日、胚胎移植日血清及取卵日卵泡液VEGF浓度;半定量RT-PCR技术检测取卵日颗粒细胞VEGF mRNA的表达。结果:OHSS组与非OHSS组血清VEGF浓度相比,hCG注射日未见显著性差异(102.5±40.8比90.23±34.62 pg/mL,P>0.05),胚胎移植日则差异显著(150.93±59.91,104.18±20.76 pg/mL,P<0.01);两组卵泡液相比有显著性差异(782.86±136.87比362.5±231.85 pg/ml,p<0.05)。OHSS组hCG注射日与胚胎移植日血清VEGF浓度有显著性差异,而对照组则未见差异。半定量RT-PCR结果显示,两组VEGF/β-actin之比有显著差异(0.54±0.24比0.27±0.12,P<0.01),OHSS组VEGF mRNA表达明显增强。结论:VEGF在OHSS发病机理中起一定作用。卵泡液及胚胎移植日血清VEGF浓度与OHSS的发生有着密切的关系。     

Hormonal and ultrasonic characteristics of 23 clomiphene citrate stimulated cycles resulting in pregnancies after in vitro fertilization and embryo transfer

In vitro fertilization (IVF) and embryo transfer (ET) were successful in 24 clomiphene citrate stimulated cycles in 22 patients. Ovarian follicular growth was monitored by ultrasound (US) and serum estradiol (E2) concentrations in order to determine the most favorable time for the induction of ovulation by administration of human chorionic gonadotropin (hCG). The day of the hCG injection was considered day 0. After an almost linear growth the mean diameter of the dominant follicle reached 19.3 +/- 2 mm on day 0. Serum E2 concentrations also increased in almost linear fashion up to a maximum of 1,037 +/- 322 pg/ml on day +1. On day 0 the mean serum E2 concentration was 862 +/- 279 pg/ml. A mean serum E2 concentration per dominant and codominant follicle of 328 +/- 100 pg/ml was found on day 0. There was no linear correlation between the follicular diameters and the serum E2-values on the same day. The time of ovum recovery was often different to the time at which ovulation would have been expected in a normal cycle.     

Vascular endothelial growth factor, interleukin-6 and interleukin-2 in serum and follicular fluid of patients with ovarian hyperstimulation syndrome

BACKGROUND: The pathogenesis of ovarian hyperstimulation syndrome (OHSS) is not completely understood. OBJECTIVE: To investigate the presence of VEGF, IL-6 and IL-2, in serum and follicular fluid, in patients developing severe OHSS. STUDY DESIGN: We enrolled 101 women undergoing in vitro fertilization. Eight patients developing severe OHSS were compared with 43 high risk patients and 50 controls. We analyzed VEGF and IL-6 in serum collected before hCG administration, and in both serum and follicular fluid on the day of oocyte retrieval. RESULTS: OHSS patients presented follicular fluid IL-6 levels higher than both the patients at risk and controls (P<0.05). On the day of the oocyte retrieval the patients developing OHSS showed serum and follicular VEGF values higher than the ones of the patients at risk (P<0.05). Serum and follicular fluid IL-2 levels showed no differences between the examined groups. IL-2, IL-6 and VEGF values were not correlated with each other. CONCLUSIONS: Angiogenesis and inflammation processes are both present in severe OHSS.     

Monitoring of follicles by ultrasonography during induction with HMG-HCG treatment--especially on the prevention of side effects

Estrogen levels are a useful indicator to use in predicting of ovarian hyperstimulation syndrome (OHSS) which is one of the side effects of HMG-HCG therapy. However, the quantitative assay of estrogens entails cumbersome time-consuming procedures. The present study represents our attempt to establish criteria for predicting the occurrence of OHSS by the use of ultrasonography (USG), a diagnostic procedure that can be performed quickly and conveniently. The subjects were 40 anovulatory women (79 cycles) receiving HMG-HCG therapy. Each patient had USG performed at the time of switching to HCG in a regimen of sequentially administered gonadotropins and was measured for maximum follicular diameter (FD) and total of vertical follicular area (FA) to correlate measurements of these parameters with simultaneously determined serum estradiol (E2) levels. A study was also made of relationships of FD and FA with ovulation and OHSS. The results are summarized as follows: No distinct correlation was observed between FD and E2 (r = 0.3794). It should be noted, however, that the therapy was successful in inducing ovulation in those cases in which the patient was switched to HCG from HMG when FD was 18mm or above. There was a significant correlation between FA and E2 (r = 0.8113, p less than 0.001). FA was thus proven to well reflect E2 levels and hence to be a parameter of the predictive value for OHSS. All but one (with moderate OHSS) of 26 cases showing evidence of OHSS had FA values of more than 6.0cm2, while those developing severe OHSS invariably.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment.

OBJECTIVE: To overview the world literature on ovarian hyperstimulation syndrome (OHSS) and modes of prevention and treatment of OHSS. STUDY SELECTION: All the pertinent literature on OHSS, its prevention, and strategies for treatment were reviewed. PREVENTION: Key to prevention is proper identification of the population at risk, which includes women with either the hormonal or the morphological signs of polycystic ovarian disease, high serum estradiol (E2) before human chorionic gonadotropin (hCG) administration (E2 greater than 4,000 pg/mL), multiple follicular response (greater than 35), younger age, and lean habitus. When a high risk situation is recognized, ovulatory dose of hCG may be reduced, avoided (with cycle cancellation), or substituted by gonadotropin-releasing hormone or its agonist. Luteal support with hCG is to be bypassed. To minimize risk of OHSS, endogenous pregnancy-drived hCG may be eluded by judicious cryopreservation of all embryos. Last, follicular aspiration will allow higher levels of E2 and larger number of follicles to be matured with lesser risk of OHSS than conventional ovulation induction without follicular aspiration. TREATMENT: In-house for the severe and intensive care for the critical form. Meticulous fluid and electrolyte balance using both crystalloids and colloids (albumin) until hemoconcentration abates. Paracentesis is indicated for tight ascites, deteriorating kidney functions, and symptomatic relief. Diuretics may be prudently used once hemodilution is achieved. Dopamine drip may be used as a renal rescue, whereas heparin is indicated for thromboembolic phenomena and surgery reserved for abdominal catastrophies. Therapeutic interruption of an early gestation may be lifesaving when all other measures have failed. CONCLUSIONS: Although severe and critical OHSS may not be completely avoided, early recognition of high-risk factors, judicious prevention schemes, and treatment strategies should reduce the complication and long-term sequelae of this iatrogenic syndrome.     

Coexistent hemoconcentration and hypoosmolality during superovulation and in severe ovarian hyperstimulation syndrome: a volume homeostasis paradox

OBJECTIVE: To investigate the concomitant time courses of the changes in osmolality and calculated blood volume during the genesis of ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study. SETTING: IVF-ET program in a university-based assisted reproductive technology center. PATIENT(S): Thirty women undergoing superovulation for IVF-ET. INTERVENTION(S): Blood and urine samples were obtained on seven occasions from the start of FSH stimulation until a pregnancy test. Five women with severe OHSS had daily blood and urine tests during hospitalization. MAIN OUTCOME MEASURE(S): Changes in serum and urine osmolality, serum electrolytes, albumin, hemoglobin, and hematocrit. RESULT(S): Blood volume in women with OHSS decreased significantly by 20% from days hCG +2 to +4, followed by a sustained increase of 30% above baseline from days hCG +8 to +12. There was no statistically significant change in blood volume in women without OHSS. There was a sharp decrease in serum osmolality in women without OHSS between days 0 and hCG +2, which recovered toward baseline from day 4 after hCG. In women with OHSS, there was an unexpected increase in osmolality of 6 mOsm/kg between days hCG -2 and 0, followed by a decrease of 8 mOsm/kg by day hCG +2; this was sustained until day hCG +12. Patients with OHSS demonstrated a concentration and dilution of their urine during the acute and recovery phases of the syndrome, respectively, despite persistence of the hypoosmolar state. CONCLUSION(S): Decreased osmolality in severe OHSS is maintained despite significant decreases and increases in blood volume, suggestive of fundamental alterations in osmoregulation.     

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.     

Unilateral follicular aspiration and in-vitro maturation before contralateral oocyte retrieval: a method to prevent ovarian hyperstimulation syndrome

Background: Five women undergoing intracytoplasmatic sperm injection (ICSI) considered to be at high risk of developing an ovarian hyperstimulation syndrome (OHSS) from March to July 2002 underwent unilateral follicular aspiration. Methods: When ≥15 follicles of 12–15 mm diameter in each ovary and a serum estrodial level ≥2500 pg/ml was present, follicular aspiration was performed unilaterally without hCG administration. Ovarian stimulation was continued for 1–3 days in four women before human chorionic gonadotrophin (hCG) was given. In one woman hCG injection was administered at the evening after unilateral follicular aspiration. The oocyte retrieval from the contralateral ovary was performed 36 h after hCG injection. By unilateral follicular aspiration two to six germinal vesicle (GV) oocytes could be retrieved. After in-vitro maturation of those oocytes ICSI was performed. Results: In four women one to two oocytes were fertilized and cryopreserved. In one case only one triploid pronucleus (3PN) was observed. At the contralateral ovum-pick up after hCG injection a median of 10 could be retrieved. After transfer of a median of 3 embryos, no pregnancy was achieved. Four of five patients developed a severe OHSS and were hospitalized for a median of 3 days. Conclusion: Unilateral follicular aspiration and continuation of stimulation therefore can not be recommended for the prevention of OHSS.