应用PPOS与拮抗剂方案的20~50岁患者每取卵周期累积活产率比较:一项倾向性评分匹配研究

Cumulative live birth rate per oocyte retrieval cycle in patients aged 20-50 years using PPOS versus GnRH antagonist protocol:a propensity score matching study

目的比较拮抗剂方案和高孕激素状态下促排卵(progestin-primed ovarian stimulation,PPOS)方案在20~50岁患者中的每取卵周期累积活产率。方法回顾性队列研究分析2017年1月至2021年4月期间在同济大学附属上海市第一妇婴保健院生殖医学科接受体外受精/卵胞质内单精子注射-胚胎移植(in vitro fertilization/intracytoplasmic sperm injection and embryo transfer,IVF/ICSI-ET)助孕并采用拮抗剂方案或PPOS方案的20~50岁不孕症患者3752例,使用倾向性评分匹配(propensity score matching,PSM)方法按1∶1匹配均衡两组间的变量后,比较两组的基本特征、临床/实验室指标及助孕结局等。通过多因素logistic回归分析对混杂因素进行校正后对比两种促排卵治疗的每取卵周期累积活产率;通过分层分析比较两种促排卵方案在不同类型患者中的临床疗效。结果匹配后,1466例患者(每组各733例)纳入分析,两组患者的年龄、体质量指数、不孕类型、不孕病因、不孕年限、取卵次数、基础卵泡刺激素、窦卵泡计数和授精方式构成比等差异均无统计学意义(均P>0.05)。拮抗剂方案组扳机日雌二醇水平[1700.30(1011.76,2580.50)ng/L]及黄体生成素(luteinizing hormone,LH)水平[1.95(1.07,5.27)U/L]显著低于PPOS方案组[2056.50(884.08,3601.59)ng/L,P=0.010;3.00(1.51,5.00)U/L,P<0.001],差异均有统计学意义。PPOS方案组周期取消率[30.56%(224/733)]显著高于拮抗剂方案组[18.83%(138/733),P<0.001];而获卵数、可利用胚胎数及优质胚胎数与拮抗剂方案组相似(均P>0.05)。PPOS方案组的胚胎种植率[16.97%(207/1220)]、每移植周期临床妊娠率[21.78%(188/863)]、每移植周期持续妊娠率[16.11%(139/863)]和每移植周期活产率[15.06%(130/863)]均明显低于拮抗剂方案组[21.42%(266/1242),P=0.010;27.38%(233/851),P=0.012;21.62%(184/851),P=0.004;20.80%(177/851),P=0.002];PPOS方案组累积活产率[17.74%(130/733)]显著低于拮抗剂方案组[24.15%(177/733)],差异有统计学意义(P=0.003)。多因素logistics回归分析调整混杂因素后显示卵巢刺激方案为影响每取卵周期累积活产率的独立危险因素(OR=1.42,95%CI:1.03~1.95,P=0.032)。分层分析结果显示,在年龄≤35岁与取卵次数≥2次的人群中,PPOS方案组的累积活产率[21.35%(111/520),7.85%(41/522)]显著低于拮抗剂方案组[28.93%(151/522),P=0.005;12.23%(62/507),P=0.019]。结论与PPOS方案相比,拮抗剂方案可改善20~50岁不孕症患者的每取卵周期累积活产率,且在女方年龄≤35岁及非首次取卵的患者中更为显著。

Objective To compare the cumulative live birth rate(CLBR)per oocyte retrieval cycle between gonadotropin-releasing hormone(GnRH)antagonist protocol and progestin-primed ovarian stimulation(PPOS)protocol in patients aged 20-50 years.Methods A retrospective cohort study was conducted to analyze 3752 infertile patients aged 20-50 years who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET).They used either GnRH antagonist protocol or PPOS protocol at the Center of Assisted Reproduction in Shanghai First Maternity and Infant Hospital from January 2017 to April 2021.One to one propensity score matching(PSM)was used to match the population characteristics.Baseline,clinical and laboratory characteristics,as well as pregnancy outcomes were compared between the two groups.The differences of CLBR was analyzed by multivariate logistic regression and subgroup analysis.Results After matching,1466 patients(733 in each group)were included in the analysis.No significant differences were detected in age,body mass index,infertility type,cause and duration of infertility,number of stimulation cycles,basal follicle-stimulating hormone,number of antral follicles and composition ratio of insemination methods between the two groups(P>0.05).Serum estradiol level[1700.30(1011.76,2580.50)ng/L]and luteinizing hormone(LH)level[1.95(1.07,5.27)U/L]on trigger day were significantly lower in GnRH antagonist group than in PPOS group[2056.50(884.08,3601.59)ng/L,P=0.010;3.00(1.51,5.00)U/L,P<0.001].The cycle cancellation rate of PPOS group[30.56%(224/733)]was significantly higher than that of GnRH antagonist group[18.83%(138/733),P<0.001].The numbers of oocytes obtained,available embryos and good-quality embryos were similar to those in GnRH antagonist group(all P>0.05).For each embryo transfer cycle,the implantation rate[16.97%(207/1220)vs.21.42%(266/1242)],the clinical pregnancy rate[21.78%(188/863)vs.27.38%(233/851)],the onging pregnancy rate[16.11%(139/863)vs.21.62%(184/851)]and the live birth rate[15.06%(130/863)vs.20.80%(177/851)]were significantly lower in PPOS group than in GnRH antagonist group(P=0.010,P=0.012,P=0.004 and P=0.002,respectively).The CLBR of PPOS group was significantly lower than that of GnRH antagonist group[17.74%(130/733)vs.24.15%(177/733),P=0.003].Multivariate logistic regression analysis showed that ovarian stimulation protocol was an independent risk factor for CLBR[OR=1.42,95%CI:1.03-1.95,P=0.032].The results of subgroup analysis showed that the CLBR of PPOS group was significantly lower than that of GnRH antagonist group in the population aged≤35 years and underwent non-first IVF/ICSI cycle[21.35%(111/520)vs.28.93%(151/522),P=0.005;7.85%(41/522)vs.12.23%(62/507),P=0.019].Conclusion Compared with PPOS regimen,antagonist regimen can improve the CLBR per oocyte cycle in infertile patients aged 20-50 years,and is more significant in women aged≤35 years and non-first oocyte collection patients.