比较GnRH拮抗剂与GnRHa短方案在卵巢低反应患者超促排卵中的应用

目的比较促性腺激素释放激素拮抗剂（GnRH-ant）方案与GnRHa短方案对卵巢低反应患者超促排卵行体外受精一胚胎移植（IVF-ET）结局的影响。方法72名卵巢低反应要求行IVF一ET治疗的患者,随机分为GnRH拮抗剂组共29个周期和GnRH激动剂短方案共43个周期。比较两组患者的周期取消率、Gn使用天数和剂量、获卵数、受精率、胚胎种植率、临床妊娠率。结果两组患者Gn使用天数和剂量、获卵数、受精率,胚胎种植率、临床妊娠率等比较均无显著统计学差异（P〉0.05）。GnRH拮抗剂组患者周期取消率、hCG日血清E2水平、LH水平显著低于GnRHa短方案组,差异有显著统计学意义（P〈O.05）。结论对卵巢低反应的患者促超排卵后行IVF-ET结局而言,GnRH拮抗剂方案并不优于GnRHa短方案,但为了减少周期取消率,可以考虑采用GnRH拮抗剂方案促排卵。     

GnRH拮抗剂在体外受精-胚胎移植中的应用

目的探讨促性腺激素释放激素（GnRH）拮抗剂方案在体外受精-胚胎移植（IVF—ET）促超排卵中的应用效果。方法回顾性比较分析本中心2006年8月～2007年8月接受ⅣF—ET助孕治疗的患者中采用GnRH拮抗剂方案的54例患者和采用GnRH激动剂长方案的135例患者，观察其临床效果。结果两组Gn用量、HCG日内膜厚度、受精率、卵裂率之间比较无显著性差异；两组患者Gn使用天数、HCG日E2值、获卵数、冷冻率、种植率、妊娠率、OHSS发生率之间比较有显著性差异。结论GnRH拮抗剂联合促性腺激素促超排卵方案缩短用药时间，减少费用，并可显著降低OHSS的发生率，但冷冻率、妊娠率较GnRH激动剂长方案偏低。     

比较HMG、基因重组促卵泡素组合拮抗剂方案对卵巢低反应体外受精结局影响

目的探讨促性腺激素释放激素拮抗剂（GnRH拮抗剂）分别配伍HMG与基因重组促卵泡素方案对卵巢低反应患者控制性超排卵的效果,并比较两种不同组合对体外受精一胚胎移植结局是否存在差异。方法纳入研究对象为前次IVF—ET治疗失败,证明是卵巢低反应,要求再次IVF—ET治疗的患者,随机分为2组,A组使用GnRH拮抗剂＋HMG方案．共40周期,B组使用GnRH拮抗剂＋果纳芬,共40个周期。将两组患者的年龄、不孕年限、不孕类型、不孕原因、基础FSH水平、周期取消率、hCG日血清E2水平、LH水平、受精方式、自然流产率、临床妊娠率、胚胎种植率等进行比较。结果两组患者年龄、不孕年限、不孕类型、不孕原因、基础FSH水平、受精方式、周期取消率、自然流产率等比较差异均无显著性（P〉0．05）。两组患者的hCG日血清E2水平、LH水平、临床妊娠率、胚胎种植率等比较差异均有显著性（P〈0．05）,上述指标以GnRH拮抗剂＋HMG组为高。结论GnRH拮抗剂与HMG配伍,对卵巢低反应的患者是一种有效的超排卵治疗方案,与GnRH拮抗剂与基因重组促卵泡素组合相比,可以提高IVF—ET的临床妊娠率和胚胎种植率,并且费用低廉。     

不同促排卵方案在高龄不孕患者IVF-ET中的临床应用

目的对比不同促排卵方案在年龄≥40岁不孕女性体外受精/卵母细胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)助孕中的临床疗效。方法回顾性分析2010年1月至2013年8月于我院生殖中心以促性腺激素释放激素激动剂(Gn RH-a)长方案、Gn RH-a短方案和促性腺激素释放激素拮抗剂(Gn RH-ant)方案促排卵行IVF/ICSI助孕的40岁及以上患者334例,比较各组的IVF结局。结果三组患者的一般情况、HCG日激素水平、受精率、优质胚胎率、周期取消率和临床妊娠率差异均无统计学意义(P0.05);长方案组获卵数、促性腺激素(gonadotropin,Gn)使用天数和总量显著高于其他两组,差异有统计学意义(P0.05)。结论高龄不孕患者应用长方案获卵数更高,Gn用量也较大;短方案临床结局较差;拮抗剂方案Gn用量较小但具有较好的临床结局,对于高龄患者可优先考虑。     

体外受精-胚胎移植中卵巢低反应的治疗研究进展

卵巢低反应(poor ovarian response,POR),是超排卵过程中出现的卵巢对促性腺激素(gonadotropin,Gn)刺激反应不良的一种状态。随着女性生育的年龄的不断升高,卵巢功能呈现不可逆的下降趋势。POR患者对Gn的低反应可导致周期取消率升高、获卵数少、卵母细胞质量差、可供移植胚胎数减少,极少有冷冻胚胎或无冷冻胚胎,继而导致妊娠结局不良。本文对低反应卵巢的最佳刺激方案的探讨做一总述。     

促性腺平抑因子在女性生殖方面的研究进展

促性腺平抑因子(GnSAF)是由卵泡刺激激素(FSH)刺激卵巢产生的一种可以降低垂体对促性腺激素释放激素(GnRH)反应的蛋白分子,其主要作用是抵抗雌激素,从而负反馈调节黄体生成激素(LH)合成与分泌,参与卵泡募集、生长发育、排卵,并与卵巢反应性、子宫内膜容受性及控制性超促排卵(COH)结局等女性生殖活动密切相关。     

雌二醇对大鼠颌下腺GnRH、GH生成的影响

目的　研究雌二醇 (estradiol- 17β,E2 )对颌下腺促性腺激素释放激素 (gonadotropin releasing hor-mone,Gn RH)和生长激素 (growth factor,GH )生成的影响。方法　采用免疫组织化学的 ABC法。结果　雌二醇促进颌下腺 Gn RH的生成而对 GH的产生有抑制作用。结论　雌二醇可能对颌下腺 Gn RH和 GH的合成起重要的调节作用     

长效和短效GnRH—a在控制性超排多卵长方案中的应用比较

目的探讨长效和短效促性腺激素释放激素激动剂（GnRH—a,达菲林）在控制性超排卵长方案中的应用及其对临床结局的影响。方法回顾性分析长方案控制性超排卵362例患者的临床资料,按使用达菲林剂型的不同分为两组：A组170例采用长效达菲林1．O-1．5mg单次注射降调节;B组192例采用短效达菲林0．1mg／d降调节,比较两组间降调情况,促性腺激素（Gn）用量,Gn天数,获卵数,优胚率,妊娠率,种植率,流产率,卵巢过度刺激综合征（OHSS）发生率等。结果两组间对比,Gn用量,受精率,优胚率,临床妊娠率,流产率均无统计学差异（P〉0．05）,A组降调时间,Gn天数,获卵数,胚胎种植率,OHSS发生率均高于B组,差异有统计学意义（P〈0．05）。结论在控制性超排卵长方案中应用长效和短效GnRH—a均能达到有效的降调节,获得相似的妊娠率,但长效GnRH—a垂体抑制更深,Gn刺激时间长,OHSS风险增高。     

雌二醇对大鼠凳下腺GnRH,GH生成的影响

目的 研究雌二醇（estradiol17β,E2)对颌下腺促性腺激素释放激素（gonadotropin relesaing hormoe GnRH)和生长激素（growth factor,GH)生成的影响。方法 采用免疫组织化学的ABC法。结果 雌二醇促进颌下腺GnRH的生成而对GH的产生有抑制作用。结论 雌二醇可能对颌下腺GnRH和GH的合成起重要的调节作用。     

发现一种具有生长激素释放活性的新肽

三十多年前Harris首次提出下丘脑神经细胞分泌的化学物质调节垂体前叶功能的假说。最近,发现一种肽能特异地强烈刺激生长激素(GH)分泌,该肽不象促甲状腺释放激素(TRH)、促性腺激素释放激素(GnRH)、促皮质激素(CRH)和生长素释放抑制因子那样来源于下丘脑,而得自两例病人的胰腺肿瘤。其中1例有垂体肿大,经蝶鞍作手     

IVF-ET中自然周期和随后的超排周期子宫内膜周期变化的观察

目的探讨体外受精-胚胎移植技术中,自然周期和随后的超排周期子宫内膜的周期变化与治疗结局的关系,以寻找影响胚胎着床的相关因素.方法 162个体外受精-胚胎移植(IVF-ET)周期,其中包括单精子胞浆内注射(ICSI)48个周期,按治疗结局分为妊娠组和非妊娠组,用阴道超声监测其自然周期和随后的超排周期子宫内膜的厚度及特征,分析对治疗结局的影响.结果自然周期排卵日(排卵型病例)及超排周期注射hCG日子宫内膜厚度,超排周期子宫内膜的生长速率,两组间比较,差异无显著性,P＞0.05.自然周期排卵日(排卵型病例)子宫内膜特征,两组间比较,差异无显著性,P＞0.05,而超排周期注射hCG日则有显著性差异,P＜0.05.注射hCG日子宫内膜特征为A型,周期妊娠率高.结论自然周期子宫内膜的生长发育状态不影响治疗结局,超排周期注射hCG日子宫内膜特征是影响治疗结局的因素.     

抗苗勒管激素对卵巢低反应预测价值的研究

目的探讨抗苗勒氏管激素(AMH)在辅助生殖技术(ART)中对控制性超排卵(COH)卵巢低反应的预测价值。方法利用ELISA法对181例首次接受IVF/ICSI-ET治疗的不孕症患者基础血清AMH蛋白水平(bAMH)进行检测。根据患者COH卵巢反应将患者分为2组:卵巢低反应组20例(获卵数≤5个)和卵巢反应良好组161例(获卵数>5个)。比较bAMH与年龄、获卵数、基础FSH等的相关性。结果①181例不孕症患者bAMH水平与获卵数呈显著正相关(r=0.709,P<0.05);②卵巢低反应组(获卵数≤5个)与反应良好组(获卵数>5个)的bAMH水平比较,差异有统计学意义(P<0.05);③受试者工作特征(ROC)曲线分析显示,bAMH水平的曲线下面积(AUC)为0.949。当bAMH截断值≤3.65ng/ml时,灵敏度为86.3%,特异度为90.0%。结论 AMH与卵巢反应性有关,可以在辅助生殖技术中作为评价预测COH中卵巢低反应的血清学标记物。     

Controlled ovarian hyperstimulation (COH) parameters associated with euploidy rates in donor oocytes

Although oocyte donors are young and are expected to provide a high rate of euploid oocytes, significant differences of euploidy rates for donor embryos exist between different IVF centers (1). Laboratory conditions can lead to differences of euploidy (2,3,4,5,6,7); but, the role of COH has not been investigated. In this study, we investigated whether euploidy rates in the embryos created from donor oocytes are influenced by controlled ovarian hyperstimulation parameters used during assisted reproduction. Euploidy rates in egg donor cycles undergoing PGT-A (N = 423) were examined retrospectively for associations with donor age, gonadotropin doses (dose per day), the fraction of gonadotropin provided by hMG (F(hMG)), days of stimulation, estradiol per mature oocyte on day of trigger, number of mature oocytes retrieved, number of embryos biopsied, incidence of euploidy and physician of record. Differences in euploidy rates between physicians were examined using analysis of variance. The proportion of euploid embryos per donor cycle was examined for associations with COH parameters using pairwise post-hoc comparisons, adjusting for multiple testing. The set of variables from this analysis was then submitted to a principal component analysis. Linear regression analysis was used to assess the relationships between stimulation parameters and the incidence of euploidy (the dependent variable). Euploidy rates and cycle parameters varied significantly among treating physicians. Euploidy rates (expressed as a fraction of biopsied embryos) were associated (p = 0.01) only with the F(hMG) but not with the number of MII retrieved or other variables. On the other hand, the number of euploid embryos (in contrast to the euploidy rate) was associated with the number of MII produced. Donor euploidy rates are significantly associated with the fraction of total gonadotropin comprising human menopausal gonadotropin (or F(hMG)) during controlled ovarian hyperstimulation but are not associated with other cycle parameters. The study provides the first suggestion that patient stimulation parameters can affect the incidence of euploidy in embryos generated through the use of standard assisted reproductive techniques. The study is limited by its retrospective approach and because the aCGH analysis used is less sensitive than more recent NGS technology. Further, it provides a suggestion that the use of hMG is beneficial for obtaining euploid embryos.     

腹腔镜联合人工授精治疗子宫内膜异位症不孕的临床观察

目的探讨子宫内膜异位症（EMs）不孕患者腹腔镜术后行夫精人工授精妊娠率的影响因素。方法回顾性分析164例腹腔镜术后的EMs不孕患者进行的318个人工授精周期的临床资料。以年龄、不孕年限、腹腔镜术后时间、用药情况、周期数、是否促排卵、r-AFS分期、IUI时机分别进行妊娠率的比较。结果 EMs不孕患者术后人工授精的周期妊娠率为13.21%。年龄≤35岁的周期妊娠率高于35岁以上者（χ2=6.687,P〈0.05）,不孕年限≤5年的妊娠率高于5年以上者（χ2=5.430,P〈0.05）,腹腔镜术后1年内行人工授精的妊娠率高于1年以上者（χ2=6.005,P〈0.05）,Ⅰ～Ⅱ期患者的妊娠率高于Ⅲ～Ⅳ期患者（χ2=8.264,P〈0.05）,加用促排卵治疗的妊娠率高于自然周期者（χ2=4.569,P〈0.05）,3周期内人工授精的妊娠率高于3周期以上者（χ2=4.031,P〈0.05）,双次IUI者妊娠率高于单次者（χ2=4.371,P〈0.05）,差异均有统计学意义。而术后是否使用GnRH-a则与妊娠率无关。结论 EMs不孕患者腹腔镜术后行人工授精治疗的最佳时间是术后1年内3周期内有较高的妊娠率,建议同时加用促排卵治疗。     

改良超长降调节方案用于体外受精-胚胎移植卵巢低反应患者的临床研究

目的探讨改良超长降调节方案在既往体外受精一胚胎移植失败的卵巢低反应患者中的应用效果。方法回顾性分析本中心58例连续两周期行体外受精一胚胎移植术的卵巢低反应患者,其中第一周期采用拮抗剂方案,第二周期采用改良超长方案。自身对照比较两组临床及实验室结果。结果第二周期获得了38．2％的临床妊娠率,两组Gn启动剂量、HCG日E2、LH及P值、HCG日子宫内膜厚度、获卵数、移植胚胎数比较无统计学差异（P〉0．05）,可移植胚胎数、冷冻胚胎数第二周期均较第一周期高,但无统计学差异（P〉0．05）;Gn天数、优质胚胎率、周期取消率第二周期组较第一周期组高,均有统计学差异（P〈0．05）。结论对于既往采用拮抗剂方案失败的卵巢低反应患者,再次行体外受精-胚胎移植可尝试采用改良超长降调节方案。     

辅助生殖技术中卵巢低反应影响因素与妊娠结局研究

目的探讨辅助生殖技术（ART）中卵巢对控制性超排卵（COH）低反应的影响因素以及低反应患者的妊娠结局。方法回顾性分析327名首次接受IVF/ICSI-ET治疗的不孕症患者的资料。根据患者COH卵巢反应分为卵巢低反应组（n=137例,获卵数≤5个）和卵巢反应良好组（n=190例,获卵数〉5个）,分析年龄、基础卵泡刺激素（bFSH）、窦卵泡数等对COH的影响。结果①单因素分析显示影响卵巢低反应发生的因素有年龄、基础卵泡刺激素水平、基础FSH/LH值和窦卵泡数;Logistic多因素回归分析显示：年龄与卵巢反应性呈负相关,窦卵泡数与卵巢反应性呈正相关,且相关程度窦卵泡数〉年龄。②卵巢低反应组与卵巢反应良好组的临床妊娠率分别为27.83%和39.16%,两组间临床妊娠率差异有统计学意义（P〈0.05）。结论年龄和窦卵泡数可用于预测卵巢的反应性,其中窦卵泡数为最敏感的指标。卵巢低反应影响妊娠结局。     

Immunoglobulins and cytokines level in follicular fluid in relation to etiology of infertility and their relevance to IVF outcome

OBJECTIVE: The aims of the present study were to (i) determine the presence and concentration of albumin fractions (alpha1, alpha2, beta, gamma), immunoglobulins (IgA, IgG, IgM) and cytokines [interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF)] in periovulatory ovarian follicular fluid (FF) of in vitro fertilization (IVF) patients, (ii) examine the relationship between these parameters and the etiology of infertility as well as the IVF outcome and (iii) find out if these parameters in FF could be used as a predictive factor of IVF outcome. DESIGN: The levels of albumin fractions, immunoglobulin and cytokines were measured from women who underwent IVF therapy for various indications and the results were compared between the patient groups and IVF outcome. MATERIALS AND METHODS: Follicular fluid was obtained from 160 IVF patients. A total of 79 patients underwent controlled ovarian hyperstimulations (COH) either with follicle-stimulating hormone (FSH) or HMG. Whereas, the HMG was used for the second set of patients (n=81) - after down regulation with gondotropin-releasing hormone agonists (Gn-RHa) - the protein fractions were determined using electrophoresis separation. Immunoglobulins were measured using a commercial kits and the concentration of cytokines was determined by the highly sensitive enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: The stimulation regimens used have no effect on albumin (alpha1, alpha2, beta, gamma) and immunoglobulin (IgA, IgG, IgM) concentrations, as no significant difference was observed between the two groups. Besides, no specific relationship was found between the concentration of these investigated parameter in FF and etiology of infertility or fertilization, cleavage and pregnancy rate. Besides, there were no significant differences between the groups for any cytokine investigated. Moreover, there were no correlations between the concentration of IL-6, IL-8 and GM-CSF in FF and steroid hormone concentration in the blood at the day of oocytes retrieval or IVF outcome. IN CONCLUSION: Total protein, albumin fraction, immunoglobulins and cytokines level in FF of patients undergoing COH for IVF therapy for various etiology of infertility could not be a useful parameter for predicting IVF outcome.     

Intrauterine insemination and controlled ovarian hyperstimulation in cycles before GIFT

We have combined intrauterine insemination (IUI) and controlledovarian hyperstimulation (COH), for the treatment of infertilitydue to different aetiologies, prior to performing GUT. To date,we have treated 186 patients over a total of 489 cycles. Themean age of the patients was 34.1 ± 4 years and the meanduration of infertility was 4.8 ± 2.8 years. Folliculardevelopment was induced with human menopausal gonatrophin (HMG).Patients were monitored using serum oestradiol determinationsand ovarian ultrasound. Two intrauterine inseminations wereperformed 12 and 36 h after HCG injection. Semen samples wereprepared utilizing one of two techniques, swim-up or Percollgradient. A total of 33 pregnancies have occurred, the grosspregnancy rate being 17.7% per patient and 6.7% per cycle. Thecumulative pregnancy rate was 30%. Thirty-one pregnancies (94%)occurred within the first four cycles of treatment. During thesame period of time, the pregnancy rate per cycle in patientstreated with gamete intra-Fallopian transfer (GIFT) was 32.9%.Our data suggest that IUI combined with COH can result in pregnancyin a significant proportion of patients, but that the efficiencyper cycle of the technique is significantly lower than GIFT.     

卵巢低反应者体外受精-胚胎移植的临床结局分析

目的评估首次体外受精-胚胎移植时表现为卵巢低反应的患者接受再次体外受精-胚胎移植治疗的实际意义和调整临床处理过程的价值。方法回顾性分析2004年1月至12月间在北京大学第三医院生殖中心进行体外受精-胚胎移植的206个卵巢低反应病例,共288个周期的临床资料。结果206例卵巢低反应病例首次IVF-ET时临床妊娠率为22%。其中82例接受了再次IVF-ET,临床妊娠率为40.6%,高于首次IVF-ET,经统计学检验差异有显著性(P<0.05),再次IVF-ET的E2峰值,取卵数以及移植胚胎数均高于首次IVF-ET,经统计学检验差异有显著性(P<0.05)。结论首次IVF-ET卵巢低反应的患者经过调整促排卵方案,接受再次IVF-ET时临床妊娠率有所提高。     

C-reactive protein levels in patients undergoing controlled ovarian hyperstimulation for IVF cycle

BACKGROUND: The aim of the present study was to determine serum and follicular fluid C-reactive protein (CRP) levels in patients undergoing controlled ovarian hyperstimulation (COH) for IVF-embryo transfer cycle, and their possible correlation to COH variables. PATIENTS AND METHODS: The subjects were 16 consecutive patients undergoing our routine IVF long GnRH agonist protocol. Blood was drawn three times during the COH cycle: (i) the day on which adequate suppression was obtained (Day-S); (ii) the day of, or prior to HCG administration (Day-HCG); and (iii) the day of (and before) oocyte pick-up (Day-OPU). Levels of sex steroids and serum and follicular fluid CRP were compared among the three time points. Serum and follicular fluid CRP were measured with a commercial immunoturbidimetric assay. RESULTS: Serum levels of CRP were significantly higher on Day-OPU and Day-HCG than on Day-S, and significantly higher on Day-OPU than on Day-HCG. No difference was observed between follicular and serum CRP levels on Day-OPU. No significant correlations were found between serum and follicular fluid CRP, or between serum CRP-to-BMI ratio and serum sex steroid levels or IVF treatment variables. CONCLUSIONS: The significant increase in serum CRP levels during COH, especially after HCG administration, suggests that COH potentiates a state of systemic inflammation.