GnRH超短激动剂联合拮抗剂方案在POSEIDON低预后患者中的应用效果分析

Application of controlled ovarian hyperstimulation with agonist-antagonist protocol in POSEIDON group 3 and group 4 patients with low prognosis

目的探讨促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)超短激动剂联合拮抗剂(agonist-antagonist protocol,AAP)方案与标准拮抗剂方案相比,是否可以改善波塞冬(Patient-Oriented Strategies Encompassing Individualized Oocyte Number,POSEIDON)分类标准低预后患者的临床结局。方法采用病例对照研究,回顾性分析2016年1月至2018年5月期间就诊于北京大学第三医院妇产科生殖医学中心,接受体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)的低预后患者(POSEIDON 3组、4组)646个周期的临床资料。使用AAP方案的,记为AAP组(323个周期),对照组按照1∶1选择同时期年龄匹配、应用标准拮抗剂方案患者,比较两组患者的一般资料、促排卵周期指标及临床结局。结果AAP组窦卵泡计数(antral follicle count,AFC)偏少[3.00(2.00,4.00)比4.00(2.00,5.00),P<0.001],抗苗勒管激素(anti-Müllerian hormone,AMH)水平两组相似[0.51(0.25,0.83)μg/L比0.53(0.31,0.81)μg/L,P>0.05],AAP组促性腺激素(gonadotropin,Gn)使用时间更短[10.00(8.00,11.00)d比10.00(9.00,11.00)d,P=0.020],Gn用量更低[2675.00(2100.00,3300.00)U比3075.00(2550.00,3750.00)U,P<0.001],两组获卵数相当[3.00(2.00,5.00)枚比4.00(2.00,6.00)枚,P>0.05]。在受精方案比例(常规受精/卵胞质内单精子注射受精)相当的情况下,AAP组有更高的受精率[74.15%(955/1288)比69.13%(918/1328),P=0.004]和优质胚胎率[62.57%(585/935)比56.94%(509/894),P=0.014],且最终有更高的胚胎着床率[22.31%(87/390)比15.84%(64/404),P=0.020]、累积临床妊娠率[32.50%(78/240)比22.86%(56/245),P=0.018]和累积活产率[25.83%(62/240)比17.96%(44/245),P=0.036]。结论对于POSEIDON低预后3组、4组患者,AAP方案较常规拮抗剂方案有更佳的临床结局。

Objective By comparing standard gonadotropin-releasing hormone antagonist regimen and gonadotropin-releasing hormone agonist-antagonist protocol(AAP regimen)in Patient-Oriented Strategies Encompassing Individualized Oocyte Number(POSEIDON)group 3 and group 4 patients with low prognosis,to study if AAP regimen could improve the clinical outcomes in low prognosis patients.Methods A case-control study was performed,the clinical data of 646 cycles of prospective poor ovarian response(POR)patients(POSEIDON group 3 and 4)who received in vitro fertilization and embryo transfer(IVF-ET)in Peking University Third Hospital Department of Obstetrics and Gynecology,Reproductive Medical Center from January 2016 to May 2018 were retrospectively analyzed.The total number of AAP cycle was 323,and control group was selected from the database with 1∶1 matching of contemporaneous prospective POR patients(POSEIDON group 3 and group 4)with similar age and approaching date of oocyte retrieval.Patients'general information,ovarian stimulation indexes and clinical outcomes were compared.Results AAP group had fewer antral follicle count(AFC)[3.00(2.00,4.00)vs.4.00(2.00,5.00),P<0.001]and similar anti-Müllerian hormone(AMH)level[0.51(0.25,0.83)μg/L vs.0.53(0.31,0.81)μg/L,P>0.05]compared with control group.AAP group had shorter duration of gonadotropin(Gn)used[10.00(8.00,11.00)d vs.10.00(9.00,11.00)d,P=0.020]and lower dosage of Gn used[2675.00(2100.00,3300.00)U vs.3075.00(2550.00,3750.00)U,P<0.001]than control group.AAP group had similar number of oocytes obtained[3.00(2.00,5.00)vs.4.00(2.00,6.00),P>0.05]compared with control group.Under the same proportion of fertilization schemes(routine or intracytoplasmic sperm injection methods),AAP group had higher fertilization rate[74.15%(955/1288)vs.69.13%(918/1328),P=0.004]and good-quality embryo rate[62.57%(585/935)vs.56.94%(509/894),P=0.014],and ultimately had higher embryo implantation rate[22.31%(87/390)vs.15.84%(64/404),P=0.020],cumulative clinical pregnancy rate[32.50%(78/240)vs.22.86%(56/245),P=0.018]and cumulative live birth rate[25.83%(62/240)vs.17.96%(44/245),P=0.036].Conclusion For POSEIDON patients with low prognosis and POR,controlled ovarian hyperstimulation with AAP regimen had better clinical outcomes compared with conventional antagonist regimen.