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。     

IVF中GnRH拮抗剂给药对多囊卵巢综合征患者VEGF的影响

目的 探讨IVF—ET中GnRH antagonist治疗多囊卵巢综合征（PCOS）对血清及卵泡液中VEGF的影响。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：治疗组18人（GnRH antagonist多荆方案）和对照组24人（GnRH agonist长方案），在超促排卵周期的取卵日留取卵泡液，采用EusA方法检测血清和卵泡液内VEGF的水平，同时比较两组间的获卵数、成熟卵母细胞数、卵裂数、受精率、植入率、临床妊娠率及流产率。结果 两组hCG日血清E2、LH水平及HCG日相对采卵日血清VEGF水平差异有统计学意义（P均〈0．05），着床率和妊娠率经Х^2检验，结果差异有统计学意义（P〈0．05），hCG日卵泡液VEGF水平，两组Gn的用量及用药天数，获卵数，成熟卵母细胞数，受精率，卵裂率相比较均无显著差异。结论 GnRH antagonist治疗PCOS不会改变卵泡液的VGEF水平，不会影响卵泡的发育及卵母细胞的受精率和卵裂率，而妊娠率和着床率均升高，E2水平明显降低可能是影响着床率和妊娠率的主要因素。治疗组OHSS的发生率是下降的。GnRH antagonist用药是安全和高效的。     

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。     

垂体降调节天数对PCOS患者体外受精胚胎移植结局的影响

目的探讨多囊卵巢综合征患者IVF-ET中促性腺激素（Gn）用药前最佳降调节天数。方法将2006年3月～2008年8月在本中心接受体外受精-胚胎移植（IVF-ET）和卵泡浆内单精子显微注射（ICSI）的多囊卵巢综合征患者146例,按照Gn用药前垂体降调节天数的不同分为3组：A组≤10d,B组11～14d,C组≥15d。回顾性分析比较不同垂体降调节天数对获卵数、优质胚胎率、临床妊娠率、OHSS发生率的影响。结果3组患者年龄、基础内分泌水平（E2、FSH、LH、P）、hCG注射日E2、LH、P水平及内膜厚度没有明显差异（P〉0.05）;C组Gn用药天数、剂量明显高于A组、B组,（P〈0.05）;3组获卵数、OHSS发生率没有明显差异（P〉0.05）;受精率、优质胚胎率、A组与C组、B组与C组之间之间没有明显差异（P〉0.05）,但B组与A组差异明显（P〈0.05）。临床妊娠率B组高于C组,C组高于A组但三者没有统计学意义。结论Gn用药前垂体降调节天数对妊娠结局有一定的影响,降调节天数≥15d时需增大Gn用量及天数,降调节天数11～14d时可得到较高的受精率和优质胚胎率。     

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。     

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。     

子宫内膜异位症不孕患者采用不同方案IVF—ET的结局分析

目的：分析采用不同方案对子宫内膜异位症不孕患者进行体外受精-胚胎移植（Invitrofertilization-embryotransfer,IVF_ET）助孕治疗结局的影响。方法：回顾性分析77例（80个周期）子宫内膜异位症患者经口服避孕药＋短方案（A组）和长方案（B组）治疗,对IVF-ET妊娠结局的影响。结果：与长方案组相比口服避孕药＋短方案组获卵数、受精率、卵裂率无显著变化（P〉0．05）,但促性腺激素（Gonadotropin,Gn）用量显著减少,临床妊娠率、胚胎植入率显著提高（P〈0．05）。结论：子宫内膜异位症患者采用口服避孕药＋短方案进行超促排卵可以提高IVF-ET的成功率。     

对比不同用药方案在多囊卵巢综合征患者行IVF-ET中的临床效果对比

目的比较促性腺激素释放激素类似物(GnRH-a)联合小剂量HCG、低剂量HCG和中剂量HCG三种药物方案对行IVF-ET助孕的PCOS患者的临床效果。方法回顾性分析2015年10月至2017年10月于华中科技大学同济医学院附属协和医院行IVF-ET助孕的120例PCOS患者,根据HCG日扳机药物不同分为A、B、C三组,分别使用GnRH-a联合2000U、8000 U以及10000 U HCG诱导卵泡成熟。观察患者的优胚率、可移植胚胎数、获卵数、受精率、卵裂率及OHSS发生率。结果三组患者年龄、BMI、不孕年限、基础FSH、基础LH、基础E2、基础窦卵泡数等一般资料均无统计学差异(P0.05),且三组患者Gn用量、Gn天数、获卵数、受精率、卵裂率、卵子成熟率、HCG日E2水平均无统计学差异(P0.05)。A、B组患者可移植胚胎数均显著高于C组,且A组优胚率显著高于B、C组(P0.05);三组患者多胎妊娠率、流产率、取消移植行全胚胎冷冻率比较均无统计学差异(P0.05),A组患者临床妊娠率显著高于B、C组(P0.05),而OHSS总发生率显著低于B、C组(P0.05)。结论对于行IVF-ET助孕的PCOS患者而言,GnRH-a联合小剂量HCG诱导卵泡成熟有利于提高可移植胚胎数和优胚率,提高妊娠率和临床妊娠率,降低OHSS的发生率。     

口服避孕药预治疗对多囊卵巢综合征患者体外受精-胚胎移植结果的影响

目的探讨多囊卵巢综合征(PCOS)患者应用口服避孕药预治疗对体外受精-胚胎移植(IVF-ET)结局的影响。方法 192例PCOS患者IVF-ET周期随机分成两组:研究组IVF-ET前先用口服避孕药(妈富隆或达英35)预治疗93例,对照组99例。比较两组年龄、促性腺激素(Gn)用量、获卵数、受精率、植入率、妊娠率、流产率和卵巢过度刺激综合征(OHSS)的发生率。结果两组年龄、Gn用量、获卵数、受精率无明显差异,预治疗组的植入率、妊娠率显著高于对照组(P0.05)。流产率和卵巢过度刺激综合征(OHSS)的发生率对照组(9.1%)显著高于研究组(5.2%)。结论 PCOS患者IVF-ET前先用口服避孕药顸治疗可提高植入率和妊娠率,降低OHSS的发生率。     

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).     

The leuprolide flare regime for in-vitro fertilization/gamete intra-fallopian transfer and embryo cryopreservation.

Gonadotrophin releasing hormone agonists (GnRHa) are now well established as adjuvant agents for in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) but several different modes of usage have been proposed. Our experience with 328 cycles of leuprolide used in a flare regime is reviewed. An endocrinologically proven flare effect was associated with a reduction of human menopausal gonadotrophin (HMG) usage (10 versus 16 ampoules) and a lower cycle cancellation/conversion rate (7.4 versus 11.3%). Overall, satisfactory rates of oocyte recovery (93%, mean number of oocytes 7.0), clinical pregnancy (24.4% per oocyte recovery) and pregnancy from frozen/thawed embryo transfers (14%) were achieved. The flare protocol appears to be a satisfactory choice for the majority of subjects but careful monitoring is required to avoid the potential for ovarian hyperstimulation.     

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.     

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.     

GnRH antagonist in single-dose applications

Previous studies on ovarian stimulation have confirmed the efficacy of a single dose of the gonadotrophin-releasing hormone (GnRH) antagonist, Cetrorelix, in preventing premature LH surges. The single-dose protocol is easy to use and assures patient compliance. When compared with the long protocol using a depot administration of the GnRH agonist, triptorelin, the IVF results in patients treated with Cetrorelix showed a shorter treatment duration, reduced amount of human menopausal gonadotrophin (HMG) required and a lower occurrence of ovarian hyperstimulation syndrome (OHSS). The pregnancy rates did not differ significantly between the two treatments. The use of Cetrorelix in natural cycles associated with gonadotrophins reduced the rate of premature LH surges and, therefore, the cancellation rate. The stimulation was minimal and the preliminary pregnancy rates were satisfactory. If a larger study confirms the results of the natural cycle with HMG support, the single-dose administration of GnRH antagonist could represent an interesting first-choice IVF treatment in selected indications. The tolerance of Cetrorelix was excellent in all patients, with only mild and transitory reactions at the injection site. New GnRH antagonists are already available for clinical use in some countries, and they will certainly change ovarian stimulation protocols. If the pregnancy rates are confirmed, the main advantages of these new compounds are the reduction in side-effects and complications of the stimulation protocol; a clear benefit to the 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 versus GnRH antagonist in oocyte donation cycles: a prospective randomized study

BACKGROUND: The specific role of LH in folliculogenesis and oocyte maturation is unclear. GnRH antagonists, when administered in the late follicular phase, induce a sharp decrease in serum LH which may be detrimental for IVF outcome. This study was performed to evaluate whether the replacement of GnRH agonist (triptorelin) by a GnRH antagonist (ganirelix; NV Organon) in oocyte donation cycles has any impact on pregnancy and implantation rates. METHODS: A total of 148 donor IVF cycles was randomly assigned to use either a GnRH antagonist daily administered from the 8th day of stimulation (group I) or a GnRH agonist long protocol (group II) for the ovarian stimulation of their donors. The primary endpoints were the pregnancy and the implantation rates. RESULTS: The clinical pregnancy rate per transfer (39.72%, 29/73 versus 41.33%, 31/75) based on transvaginal scan findings at 7 weeks of gestation, the implantation rate (23.9 versus 25.4%) and the first trimester abortion rate (10.34 versus 12.90%) were similar in the two groups. CONCLUSION: In oocyte donation cycles the replacement of GnRH agonist by a GnRH antagonist appears to have no impact on the pregnancy and implantation rates when its administration starts on day 8 of stimulation.     

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。