比较早卵泡期长效长方案和拮抗剂方案在不明原因不孕人群中的应用

Comparison of the early follicular long-term protocol and antagonist protocol in unexplained infertility patients

目的:探讨不明原因不孕人群进行早卵泡期长效长方案和拮抗剂方案诱导排卵的临床效果及妊娠结局。方法:检索南京医科大学第一附属医院生殖医学科临床辅助生殖技术管理系统软件数据库,收集2018年1月至2019年1月期间进行体外受精/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)的不明原因不孕患者临床资料共642例,根据促排卵方案不同分为拮抗剂方案组(记为拮抗剂组,共359例)和早卵泡期长效长方案组(记为早长组,共283例)。通过回顾性队列研究分析两组患者的临床妊娠率、活产率、胚胎种植率以及其他诱导排卵临床指标及实验室指标。在此基础上,进一步针对患者年龄、体质量指数(body mass index,BMI)分别进行分层分析。结果:①拮抗剂组患者BMI[(22.17±2.96)kg/m 2]高于早长组患者[(21.68±2.29)kg/m 2,P=0.018],其余指标差异均无统计学意义(P均>0.05)。②早长组患者促性腺激素(gonadotropin,Gn)启动剂量[(149.74±36.24)IU]显著低于拮抗剂组[(177.97±38.85)IU,P<0.001],Gn使用时间[(11.93±2.26)d]、Gn使用总量[(1908.35±632.36)IU]显著高于拮抗剂组[(8.86±1.45)d,(1638.57±497.23)IU,P均<0.001]。两组患者行卵裂期胚胎移植早长组胚胎种植率[57.14%(152/266)]、临床妊娠率[66.48%(121/182)]、活产率[59.89%(109/182)]均显著高于拮抗剂组[39.53%(68/172),P<0.001;51.72%(60/116),P=0.011;40.52%(47/116),P=0.001],中重度卵巢过度刺激综合征发生率组间比较差异无统计学意义(P>0.05)。多因素logistic回归分析结果显示治疗方案、年龄均是卵裂期胚胎移植临床妊娠、活产的危险因素[2.261(95%CI=1.333~3.836),P=0.002;0.928(95%CI=0.869~0.991),P=0.026;2.598(95%CI=1.535~4.397),P<0.001;0.906(95%CI=0.849~0.967),P=0.003]。③<35岁患者行早长方案新鲜胚胎周期移植临床妊娠率、活产率均高于拮抗剂组,但差异均无统计学意义(P均>0.05)。35~39岁患者早长方案新鲜胚胎周期移植种植率、临床妊娠率、活产率均高于拮抗剂组,但差异均无统计学意义(P均>0.05)。④正常BMI人群中早长组种植率[55.71%(122/219)]、临床妊娠率[63.58%(96/151)]、活产率[58.94%(89/151)]均显著高于拮抗剂组[37.82%(45/119),P=0.002;46.99%(39/83),P=0.014;39.76%(33/83),P=0.005]。超重人群中,早长组种植率[68.09%(32/47)]、临床妊娠率[81.25%(26/32)]均显著高于拮抗剂组[43.40%(23/53),P=0.013;57.14%(20/35),P=0.034],但活产率差异无统计学意义(P>0.05)。结论:与拮抗剂方案相比,给予不明原因不孕症患者进行早卵泡期长效长方案促排卵可获得较满意的IVF新鲜周期移植临床妊娠结局,但其增加患者降调节时间及Gn使用时间、总剂量。

Objective To investigate the clinical effects and pregnancy outcomes of the early follicular long-term protocol and antagonist protocol in the treatment of unexplained infertility patients.Methods From January 2018 to January 2019,642 cases of unexplained infertility patients with early follicular long-term protocol and antagonist protocol in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET)were collected using the clinical assisted reproductive technologies management system software database of the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University.Patients were divided into early follicular long-term protocol(n=283)and antagonist protocol(n=359)groups.The clinical outcomes of the two groups were analyzed retrospectively,including the implantation rate,the clinical pregnancy rate,and the live birth rate.Furthermore,the pregnancy outcomes of different age and body mass index(BMI)patients were further analyzed.Results 1)The BMI in the antagonist protocol group was higher than that in early follicular long-term protocol group[(22.17±2.96)kg/m^(2)vs.(21.68±2.29)kg/m^(2),P=0.018].The other based data did not exhibit remarkable difference between the two groups(P>0.05).2)The starting dosage of gonadotropin(Gn)in early follicular long-term protocol group was less than that of antagonist group[(149.74±36.24)IU vs.(177.97±38.85)IU,P<0.001].While the total duration and dosage of Gn used in early follicular long-term protocol group were significantly higher than those in antagonist group[(11.93±2.26)d vs.(8.86±1.45)d,P<0.001;(1908.35±632.36)IU vs.(1638.57±497.23)IU,P<0.001).The cleavage embryo implantation rate,the clinical pregnancy rate and the live pregnancy rate in fresh cycle in early follicular long-term protocol group were significantly higher than those in the antagonist group[57.14%(152/266)vs.39.53%(68/172),P<0.001;66.48%(121/182)vs.51.72%(60/116),P=0.011;59.89%(109/182)vs.40.52%(47/116),P=0.001].The incidence of moderate and severe ovarian hyperstimulation syndrome between the two groups were not statistically different(P>0.05).Multivariate logistic regression analysis showed that different protocols and age were both risk factors for clinical pregnancy and live birth of cleavage embryo transfer[2.261(95%CI=1.333-3.836),P=0.002;0.928(95%CI=0.869-0.991),P=0.026;2.598(95%CI=1.535-4.397),P<0.001;0.906(95%CI=0.849-0.967),P=0.003].3)In patients under 35 years old,the clinical pregnancy rate and the live birth rate in early follicular long-term protocol group were higher than those of the antagonist group,but there was no statistical difference(all P>0.05).The fresh embryo cycle implantation rate,the clinical pregnancy rate and the live birth rate of 35-39 years old patients in the early follicular long-term protocol group were higher than those in the antagonist group,but there was no statistical difference(all P>0.05).4)In normal BMI group,the implantation rate,the clinical pregnancy rate and the live birth rate in early follicular long-term protocol group were significantly higher than those in the antagonist group[55.71%(122/219)vs.37.82%(45/119),P=0.002;63.58%(96/151)vs.46.99%(39/83),P=0.014;58.94%(89/151)vs.39.76%(33/83),P=0.005].In the overweight population,the implantation rate and the clinical pregnancy rate in early follicular long-term protocol group were significantly higher than those in the antagonist group[68.09%(32/47)vs.43.40%(23/53),P=0.013;81.25%(26/32)vs.57.14%(20/35),P=0.034],but there was no statistically significant difference in the live birth rate(P>0.05).Conclusion Compared with the antagonist protocol,early follicular long-term protocol for unexplained infertility patients may achieve higher clinical pregnancy outcomes in IVF fresh cycle,but it could increased the duration of descending,the duration and dosage of Gn used.