倾向性得分匹配分析卵巢储备功能减退人群拮抗剂方案延迟启动的效果

Propensity score matching analysis of delayed start protocol with gonadotropin-releasing hormone antagonist in patients with diminished ovarian reserve

目的:探讨卵巢储备功能减退人群采用拮抗剂方案延迟启动时间的临床效果及费效比。方法:回顾性队列研究分析2017年7月至2019年12月期间在宜春市妇幼保健院生殖科采用拮抗剂方案促排卵后行体外受精/卵胞质内单精子显微注射(in vitro fertilization/intracytoplasmic sperm injection,IVF/ICSI)的卵巢储备功能减退患者,根据启动时机分为延迟启动组和正常启动组,其中延迟启动组共43个周期,启动时间为月经第7~10日,正常启动组共333个周期,启动时间为月经第2~4日,比较两组患者控制性卵巢刺激(controlled ovarian sitmulation,COS)的促排卵情况、临床结局及费效比。将两组患者的年龄、不孕年限、体质量指数、启动日卵泡刺激素(follicle-stimulating hormone,FSH)、窦卵泡数(antral follicular count,AFC)、抗苗勒管激素(anti-Müllerian hormone,AMH)及促性腺激素(gonadotropin,Gn)启动剂量进行倾向性得分匹配(propensity score matching,PSM),匹配后再次分析,以减少数据分组不均带来的误差。结果:PSM前Gn使用时间[(8.0±2.0)]d、Gn使用总量[(1740.1±561.2)IU]、人绒毛膜促性腺激素(human chorionic hormone,hCG)注射日雌二醇[(1371.2±1203.3)ng/L]、获卵数[(5.1±5.1)枚]、M_(II)卵数[(4.4±4.3)枚]延迟启动组低于正常启动组[(9.0±2.0)d,P<0.001;(2055.1±634.7)IU,P<0.001;(1853.5±1351.5)ng/L,P=0.03;(7.0±5.5)枚,P=0.03;(6.1±4.8)枚,P=0.03],正常受精率(71.7%±32.1%)高于正常启动组(58.9%±31.2%,P=0.01),每一启动周期总费用[(14179.9±2909.4)元]低于正常启动组[(16003.6±2543.1)元,P<0.001]。PSM后两组比较hCG注射日雌二醇、获卵数、M_(II)卵数差异均无统计学意义(P均>0.05),延迟启动组Gn使用时间[(7.9±2.0)d]、Gn使用总量[(1729.8±563.8)IU]低于正常启动组[(8.8±1.5)d,P=0.03;(2021.5±726.1)IU,P=0.04],正常受精率(71.0%±32.2%)高于正常启动组(55.4%±37.5%,P=0.04),每一启动周期总费用[(14232.5±2923.9)元]低于正常启动组[(15590.2±3116.9)元,P=0.04]。PSM前后新鲜胚胎移植率、周期取消率和临床妊娠率两组差异均无统计学意义(P>0.05)。结论:卵巢储备功能减退人群拮抗剂方案延迟启动时间可以改善正常受精率,减少Gn使用时间和Gn使用总量,降低每一启动周期总费用。

Objective To explore the clinical effect and cost-effectiveness of a delayed start protocol with gonadotropin-releasing hormone(GnRH)antagonist in patients with diminished ovarian reserve(DOR).Methods A retrospective study was performed in 376 cycles of DOR patients undergoing in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)from July 2017 to December 2019 in Reproductive Center of Yichun Maternal and Child Health Hospital who had GnRH antagonist protocol to ovarian stimulation.According to the start time,those patients were divided into two groups,the delayed start group including 43 cycles(the start time at day 7-10 of menstruation),the conventional start group including 333 cycles(start normally at day 2-4 of menstruation).The ovulation induction results,clinical outcomes and cost-effectiveness ratio of the two groups with controlled ovarian sitmulation(COS)were compared.Propensity score matching(PSM)was performed on age,duration of infertility,body mass index,follicle-stimulating hormone(FSH)level on the first day of gonadotropin(Gn)used,the dosage of Gn used on the first day,antral follicle count(AFC),anti-Müllerian hormone(AMH)were analyzed again after PSM to reduce the influence of unequal characters between the two groups.Results Before matching,the conventional start protocol patients'FSH level of the first day of Gn used was lower than that of the delayed start protocol,the results of ovarian stimulation such as the total duration of Gn used[(8.0±2.0)d],the total dosage of Gn used[(1740.1±561.2)IU],estradiol level on human chorionic hormone(hCG)injection day[(1371.2±1203.3)ng/L],total number of oocytes retrieved(5.1±5.1),number of M_(II) oocytes retrieved(4.4±4.3)were lower[(9.0±2.0)d,P<0.001;(2055.1±634.7)IU,P<0.001;(1853.5±1351.5)ng/L,P=0.03;7.0±5.5,P=0.03;6.1±4.8,P=0.03],but the two pronuclei fertilization rate(71.7%±32.1%)was higher than that in the conventional start protocol patients(58.9%±31.2%,P=0.01).We also found the total costs of per cycle[(14179.9±2909.4)yuan]was less than that of the conventional protocol[(16003.6±2543.1)yuan,P<0.001].After matching,the two groups had the same estradiol level on hCG injection day,total number of oocytes retrieved,number of M_(II) oocytes retrieved(P>0.05),but the total duration of Gn used[(7.9±2.0)d],the total dosage of Gn used[(1729.8±563.8)IU],the total cost per cycle[(14232.5±2923.9)yuan]of delayed protocol remain lower and the two pronuclei fertilization rate(71.0%±32.2%)was also higher than those of the conventional protocol[(8.8±1.5)d,P=0.03;(2021.5±726.1)IU,P=0.04;(15590.2±3116.9)yuan,P=0.04;55.4%±37.5%,P=0.04].There was no difference in the fresh embryo transfer rate,the cycle cancellation rate and the clinical pregnancy rate between the two groups neither before nor after PSM.Conclusion The delayed start antagonist protocol maybe improve the normal fertilization rate and reduce the total days of Gn used,the total dosage of Gn used so as to have less total cost of each cycle in patients with DOR.