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。     

促性腺激素释放激素类似物方案对胚胎冻融移植结局的影响

目的分析促性腺激素释放激素拮抗剂（GnRH-A）方案和促性腺激素释放激素激动剂（GnRH-a）长方案后的胚胎冻融移植（FET）周期的结局,探讨GnRH类似物方案对FET结局的影响。方法回顾性分析2009年1月至12月在本中心采用GnRH-A方案和GnRH-a长方案后的FET周期,比较其妊娠结局。结果 GnRH-A/GnRH-a方案随后的FET周期比较,GnRH-A方案患者年龄较大（33.24 vs.30.12）,两组胚胎复苏率（85.57%vs.80%）无差异（P〉0.05）,临床妊娠率（48.89%vs.42.37%）、种植率（28.57%vs.26.73%）和抱婴回家率（37.78%v.s34.46%）均无显著差异（P〉0.05）。FET周期中,妊娠组和未妊娠组相比,临床妊娠组ET胚胎评分显著高于未妊娠组（P〈0.05）,其余特征均无差异。结论取卵周期GnRH类似物方案对FET周期妊娠结局无明显影响。     

GnRH antagonist治疗多囊卵巢综合征的IVF-ET结局

目的探讨GnRH antagonist治疗PCOS病人的IVF—ET结局。方法将2006年4月至6月42例临床诊断为PCOS的病人随机分为两组：GnRH antagonist治疗组18人和GnRH agonist长方案对照组24人，记录促性腺激素的用量及其用药天数，获卵数，受精率，卵裂率，HCG日子宫内膜厚度和雌激素水平，周期取消率，妊娠率，OHSS发生率等。结果两组促性腺激素的用量及其用药天数、获卵数、受精率和卵裂率相比较均无显著差异。在hCG日的雌激素水平明显降低，子宫内膜是增厚的，其差异有统计学意义（P均＜0．05），妊娠率和着床率经X^2。检验，结果差异有统计学意义（P＜0．05）。结论GnRH antagonist治疗PCOS妊娠率和着床率均升高的，而卵泡的发育、卵母细胞的受精率和卵裂率不受影响。E2水平明显低于对照组可能为影响着床率和妊娠率的主要因素，GnRH antagonist用药是安全和高效的，为促排卵提供了新选择。     

GnRH拮抗剂与GnRH激动剂短方案IVF-ET结局的比较

目的比较GnRH antagonist与GnR Hagonist短方案的IVF-ET结局。方法2006年8月至2007年8月GnR Hantagonist治疗组54人和GnR Hagonist短方案对照组132人,记录促性腺激素的用量及其用药天数、hCG日子宫内膜厚度和激素水平、获卵数、受精率、卵裂率、优胚率、妊娠率和OHSS发生率等指标。结果两组促性腺激素的用量及其用药天数、获卵数、受精率、卵裂率、着床率和妊娠率相比较均无显著差异（P〉0.05）。GnR Hantagonist组在hCG日激素水平低,与对照组比较其差异有统计学意义。结论行GnR Hantagonist方案IVF-ET助孕治疗与传统的GnR Hagonist短方案比较,其hCG日雌激素水平下降可能是OHSS发生率显著下降的主要因素;但卵泡的发育、卵母细胞的受精率、卵裂率及妊娠率和着床率均不受影响。GnR Hantagonist的使用为IVF-ET助孕药物提供了一种新的选择。     

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。     

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。     

促性腺激素释放激素拮抗剂方案比激动剂长方案获得更多可利用胚胎

目的 分析促性腺激素释放激素(GnRH)拮抗剂方案与传统激动剂长方案,哪种方案能获得更好的胚胎。方法 纳入自2016年1月至2019年12月首次在北京朝阳医院生殖中心进行促排卵的病例,其中传统长方案组1 095例,拮抗剂方案组1 511例,并对相应的指标进行回顾性比较分析,包括受精率、胚胎质量、妊娠结局等。结果 拮抗剂方案组可利用胚胎率(29.94%vs 31.59%)、双原核(2PN)优质胚胎率(44.67%vs 46.86%)、每取卵周期可利用囊胚数/OPU(1±2 vs 1±2)及可利用囊胚率(25.62%vs 29.66%)均显著高于长方案组。结论 与传统长方案相比,拮抗剂方案能给患者带来更多可利用胚胎,加之与长方案类似的妊娠结局以及较低的卵巢过度刺激(OHSS)风险,拮抗剂方案正逐渐成为临床控制性促排卵(卵巢刺激)(COS)方案的首选。     

促性腺激素释放激素拮抗剂方案比激动剂长方案获得更多可利用胚胎

目的 分析促性腺激素释放激素(GnRH)拮抗剂方案与传统激动剂长方案,哪种方案能获得更好的胚胎。方法 纳入自2016年1月至2019年12月首次在北京朝阳医院生殖中心进行促排卵的病例,其中传统长方案组1 095例,拮抗剂方案组1 511例,并对相应的指标进行回顾性比较分析,包括受精率、胚胎质量、妊娠结局等。结果 拮抗剂方案组可利用胚胎率(29.94%vs 31.59%)、双原核(2PN)优质胚胎率(44.67%vs 46.86%)、每取卵周期可利用囊胚数/OPU(1±2 vs 1±2)及可利用囊胚率(25.62%vs 29.66%)均显著高于长方案组。结论 与传统长方案相比,拮抗剂方案能给患者带来更多可利用胚胎,加之与长方案类似的妊娠结局以及较低的卵巢过度刺激(OHSS)风险,拮抗剂方案正逐渐成为临床控制性促排卵(卵巢刺激)(COS)方案的首选。     

GnRH拮抗剂在卵巢反应不良患者中的应用

目的探讨促性腺激素释放激素（GnRH）拮抗剂在卵巢反应不良患者中的应用。方法对既往应用体外受精-胚胎移植（IVF-ET）技术治疗过程中发生卵巢反应不良或取消周期的60例不孕患者随机对照分为两组,GnRH拮抗剂组和GnRH激动剂方案组,观察激素水平、获卵数、受精率、妊娠率等。结果拮抗剂组获卵数多于激动剂组（3.36±1.97 vs 2.43±0.92,P=0.038）,两组患者在HCG日LH水平、E2水平和P水平没有明显差异,在〉14mm的卵泡数、妊娠率分别为（3.04±1.33 vs 2.73±0.87,P=0.082）、（24%vs 14.3%,P=0.291）,两组患者均没有出现LH峰值。结论GnRH拮抗剂方案对卵巢反应不良的患者不失为可尝试的治疗方法。     

三种方法治疗未破裂卵泡黄素化综合征的疗效分析

目的 比较3种方法治疗未破裂卵泡黄素化综合征（LUFS）疗效。方法 将34个病例56个治疗周期随机分成3个治疗组：A组（HCG组），B组（单次GnRH—a组），C组（GnRH—a＋HCG组），观察3组患者的妊娠率，排卵率，并分别于HCG／达必佳注射日及排卵后7日抽取外周血测LH，P，观察各组有无差异。结果 3种治疗方法的排卵率有统计学差异（P〈0．05），C组的排卵率显著高于B组，A组。而3组的妊娠率则无明显差异（P〉0．05）。HCG／达必佳注射日3组血LH有统计学差异（P〈0．05），C组低于A组与B组，而血P值则3组之间无统计学差异（P〉0．05）。排卵后7日血P值3组之间亦有统计学差异（P〈0．05），A组高于C组，C组高于B组。结论 GnRH—a＋HMG方案能有效的降低HCG注射日LH值。提高LUFS患者的排卵率，但妊娠率无明显改善。     

Comparison of GnRH agonists and antagonists in assisted reproduction cycles of patients at high risk of ovarian hyperstimulation syndrome

BACKGROUND: During IVF or ICSI cycles, ovarian hyperstimulation syndrome (OHSS) is a major problem. The aim of this prospective, multicentre, comparative study (using historical controls) was to assess the efficacy of a GnRH antagonist protocol in preventing OHSS in selected patients who had experienced OHSS or had been at risk of OHSS in their previous IVF/ICSI attempt. METHODS AND RESULTS: Patients underwent a new cycle where the same gonadotrophin protocol was used [same dose of recombinant FSH (rFSH)] but a different protocol was used for pituitary desensitization: cetrorelix 0.25 mg multiple-dose antagonist instead of GnRH agonist long protocol. Cetrorelix 0.25 mg was administered daily, starting when the leading follicle reached a diameter of 14 mm. In other words, rFSH was administered in the new cycle according to the dosage and the step-up or step-down modalities used during the previous cycle, independently of ultrasound findings and serum estradiol (E(2)) levels. Eighty-seven patients entered the study. Out of the 87 cycles involving GnRH agonists, 49 (56.3%) were cancelled and out of the 87 involving GnRH antagonists 28 (32.2%) were cancelled [McNemar's test; 95% confidence interval (CI) -35.8% to -11.2%; P < 0.001]. After GnRH agonist cycles, we recorded 24 cases of OHSS (18 moderate and six severe; 27.6%), whereas after the GnRH antagonist cycles there were 10 cases of OHSS (nine moderate and one severe; 11.5%) (95% CI-26.4% to -5.7%; P = 0.006). There was a statistically significant reduction in the total number of follicles with a diameter >10 mm (Wilcoxon's test; Z = 6.1; P < 0.001) and of E(2) levels on the day of HCG administration (2538 versus 4322.4 pg/ml; P < 0.001) in the GnRH antagonist cycles versus GnRH agonist cycles. Twenty-nine patients had an embryo transfer in the first cycle (76.3% of oocyte retrievals) and 57 in the cycle using GnRH antagonist (96.6%). This 20.3% difference was also significant (Z-test; 95% CI 6.8-36.0%; P = 0.003). After the antagonist cycles, 18 pregnancies (20.7 per initiated cycle; 31.6% per embryo transfer) were obtained. CONCLUSIONS: Although this study presents some limitations owing to the use of historical controls, our data show a favourable effect of GnRH antagonists in reducing the incidence of OHSS and the number of assisted fertilization cycles cancelled because of the risk of OHSS in high responder patients. As a consequence, GnRH antagonist plus gonadotrophin administration could also increase the percentage of oocyte retrievals and embryo transfers in this high risk group of patients.     

IVF获卵数、全胚冷冻与体外受精胚胎移植妊娠结局的关系

目的探讨控制超排卵（COH）中获卵数对体外受精一胚胎移植（IVF—ET）妊娠结局的影响,及为避免重度OHSS全胚冷冻的效果。方法接受常规IVF助孕治疗的不孕症患者358例（除外ICSI,Half—ICSI,Re—ICSI）。根据获卵数不同分为3组,其中获卵数1～10者122例（I组）,获卵数11～20者183例（II组）,获卵数〉20者53例（Ⅲ组）;358例中发生OHSS48例全胚冷冻,其中I组无全胚冷冻,Ⅱ组全胚冷冻28例,Ⅲ组全胚冷冻20例。结果全胚冷冻组与新鲜移植组比较：年龄及优胚率无明显差异,着床率及临床妊娠率无明显差异;新鲜移植第Ⅲ组着床率及临床妊娠率低于全胚冷冻第Ⅲ组,差异有显著性。结论OHSS时全胚冷冻保证了妊娠结局,尤其对获卵数〉20的患者有利。     

GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis

Triggering final oocyte maturation with GnRH agonist during ovarian stimulation is feasible when inhibition of premature LH surge is performed with GnRH antagonists, and we aimed to systematically collate evidence on the clinical efficacy of GnRH agonist triggering in patients undergoing assisted reproduction in GnRH antagonist protocols. Twenty-three publications were identified by a comprehensive literature search that included PubMed, Embase and the Cochrane Library. Three publications out of 23 fulfilled the inclusion criteria for meta-analysis, which were (i) prospective, randomized controlled study design; (ii) stimulation with gonadotropins for induction of multifollicular development; (iii) suppression of endogenous LH by a GnRH antagonist; (iv) triggering of final oocyte maturation with GnRH agonist; (v) control group randomized to receive HCG for final oocyte maturation and (vi) any means of luteal phase support other than HCG. The participants were normoovulatory women undergoing IVF. The outcomes assessed were clinical pregnancy per randomized patient; number of oocytes retrieved; proportion of metaphase II oocytes; fertilization rate; embryo quality score; first trimester abortion rate; ovarian hyperstimulation syndrome (OHSS) incidence. Results are presented as combined standardized differences of the mean and combined odds ratios, as appropriate, with 95% confidence intervals. No significant difference was found for the number of oocytes retrieved (-0.94, -0.33-0.14), proportion of metaphase II oocytes (-0.03, -0.58-0.52), fertilization rate (0.15, -0.09-0.38) or embryo quality score (0.05, -0.18-0.29). No OHSS occurred in two of the studies, whereas in one study OHSS incidence was not reported. Thus from the available data, no conclusion can be drawn as regards OHSS incidence after GnRH agonist triggering. In comparison to HCG, GnRH agonist administration is associated with a significantly reduced likelihood of achieving a clinical pregnancy (0.21, 0.05-0.84; P = 0.03). The odds of first trimester pregnancy loss is increased after GnRH agonist triggering; however, the confidence interval crosses unity (11.51, 0.95-138.98; P = 0.05). In conclusion, the use of GnRH agonist to trigger final oocyte maturation in IVF, where inhibition of premature LH surge is achieved with GnRH antagonists, yields a number of oocytes capable to undergo fertilization and subsequent embryonic cleavage, which is comparable to that achieved with HCG. However, the likelihood of an ongoing clinical pregnancy after GnRH agonist triggering is significantly lower as compared to standard HCG treatment.     

Embryo implantation and GnRH antagonists: GnRH antagonists do not activate the GnRH receptor

Recent suggestions that gonadotrophin-releasing hormone (GnRH) antagonists activate the GnRH receptor are discussed. Most of the studies cited in support of this suggestion are in-vitro studies, testing supra-pharmacological doses of GnRH analogues in cancer cell lines, whereas GnRH antagonists, e.g. ganirelix or cetrorelix, do not affect the steroidogenesis of human granulosa cells in vitro. In patients treated with GnRH antagonists prior to IVF or intracytoplasmic sperm injection (ICSI), oocyte maturity and fertilization rates are equal to those achieved following a long protocol of GnRH agonists. Although there is a tendency towards a lower pregnancy rate (not statistically significant) in the initial trials using GnRH antagonist with either recombinant FSH or human menopausal gonadotrophin (HMG) for ovarian stimulation, this new treatment option of GnRH antagonists facilitates short and simple treatment and improves the convenience and safety for the patient. As with GnRH agonists in the past, the clinical outcome of GnRH antagonist treatment will improve with time as more clinical experience is gained (learning curve) and the treatment protocol is optimized. Moreover, a GnRH agonist instead of human chorionic gonadotrophin (HCG) may be used for triggering ovulation and will decrease the cancellation rate and minimize the risk for developing ovarian hyperstimulation syndrome (OHSS).     

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。     

Will GnRH antagonists provide new hope for patients considered 'difficult responders' to GnRH agonist protocols?

We have assessed the use of cetrorelix, a gonadotrophin releasing hormone (GnRH) antagonist, in conjunction with clomiphene citrate and gonadotrophin in 31 in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) cycles for 25 difficult responders. Group I included 18 poor responders (24 cycles) with no live birth in 23 previous IVF cycles with GnRH agonists. Group II included seven patients (seven cycles) with polycystic ovaries. Thirteen previous IVF/GIFT cycles with GnRH agonists had resulted in one live birth and three of these patients had developed ovarian hyperstimulation syndrome (OHSS). The treatment protocol involved a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections from cycle day 2. Cetrorelix 0.25 mg/day was started when the leading follicle reached 14 mm. The outcome in both groups was favourable compared to previous treatment with GnRH agonists. In group I the abandoned cycle rate was 29 versus 57% (P = 0.06). More oocytes were produced (6.4 versus 4.7 oocytes/cycle) at a lower dose of follicle-stimulating hormone (FSH) (709 versus 1163 IU/oocyte; P = 0.08) and two live births resulted (11.8%). In group II fewer oocytes were produced (10.2 versus 14.5 oocytes/cycle), using a lower dose of gonadotrophin (170 versus 189 IU/oocyte) and resulted in one ongoing pregnancy. No patients experienced OHSS. This report is preliminary and a further controlled randomized study is required.