两种促性腺激素释放激素激动剂降调节方案晚卵泡期孕酮升高的临床结局分析

Analysis of clinical pregnancy outcome of progesterone elevation with two kinds of down-regulation methods using gonadotropin-releasing hormone agonist

目的探讨卵泡期长效长方案和黄体期短效长方案晚卵泡期孕酮升高对临床结局的影响。方法回顾性队列研究分析2015年1月至2018年12月期间在郑州大学第一附属医院生殖医学中心接受新鲜卵裂期胚胎移植助孕并采用卵泡期长效长方案或黄体期短效长方案的体外受精/卵胞质内单精子显微注射(in vitro fertilization/intracytoplasmic sperm injecion,IVF/ICSI)的患者临床资料。对上述患者周期进行针对年龄、基础卵泡刺激素(follicle-stimulating hormone,FSH)和移植胚胎数的倾向性评分匹配(propensity score matching,PSM),采用卵泡期长效长方案患者(A组)1748例,采用黄体期短效长方案患者(B组)1751例。根据人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)注射日孕酮水平再分别将A组、B组患者分为4个亚组:<1.00μg/L组(1亚组),1.00~1.25μg/L组(2亚组),1.25~1.75μg/L组(3亚组)和1.75~3.00μg/L组(4亚组)。比较A、B组内各亚组临床妊娠率、流产率等各项指标。结果A组的临床妊娠率高于B组[65.5%(1145/1748)比53.6%(938/1751),P<0.001],活产率高于B组[55.7%(973/1748)比44.0%(770/1751),P<0.001],差异均有统计学意义。A组中A4亚组临床妊娠率[56.6%(82/145)]显著低于A1亚组[(66.8%(725/1086),P=0.01]和A2亚组[69.3%(167/241),P=0.008];B组中B3和B4亚组临床妊娠率[43.6%(68/156),30.8%(12/39)]显著低于B1亚组[55.4%(728/1315)]和B2亚组[55.2%(127/230)],差异均具有统计学意义(B3比B1亚组:P=0.003;B4比B1亚组:P=0.002;B3比B2亚组:P=0.016;B4比B2亚组:P=0.004)。调整混杂因素后,多因素logistics分析结果显示,A组中其他亚组与A1亚组相比,对临床妊娠率影响差异无统计学意义(A2亚组比A1亚组,OR=1.090,95%CI=0.787~1.509,P=0.606;A3亚组比A1亚组,OR=0.809,95%CI=0.588~1.114,P=0.194;A4亚组比A1亚组,OR=0.675,95%CI=0.456~1.000,P=0.050);B组中与B1亚组相比,B4亚组临床妊娠率明显下降(OR=0.410,95%CI=0.199~0.843,P=0.015)。结论经过PSM匹配后,卵泡期长效长方案临床妊娠率、活产率优于黄体期短效长方案。卵泡期长效长方案对高孕酮负面影响的耐受性优于黄体期短效长方案。

Objective To evaluate the clinical pregnancy outcomes of progesterone elevation cycles with follicular phase gonadotropin-releasing hormone agonist(GnRH-a)long-acting protocol and luteal phase GnRH-a short-acting protocol.Methods In this retrospective cohort study,data of patients who received in vitro fertilization/intracytoplasmic sperm injecion(IVF/ICSI)treatment with fresh cleavage phase embryo transferred and follicular phase GnRH-a long-acting protocol or luteal phase GnRH-a short-acting protocol at the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2018 were analyzed.We matched the above patient cycles with age,basal follicle-stimulating hormone(FSH)and number of transplanted embryos using propensity score matching(PSM).There were 1748 cases received long-acting protocol(group A)and 1751 cases received short-acting protocol(group B).According to the different concentrations of progesterone on human chorionic gonadotropin(hCG)injection day,patients were divided into four subgroups:<1.00μg/L(group 1),1.00-1.25μg/L(group 2),1.25-1.75μg/L(group 3)and 1.75-3.00μg/L(group 4).We compared the different items among subgroups in group A and group B including clinical pregnancy,miscarriage rate,and so on.Results The clinical pregnancy rate of group A was higher than that of group B[65.5%(1145/1748)vs.53.6%(938/1751),P<0.001],and the live birth rate of group A was higher than that of group B[55.7%(973/1748)vs.44.0%(770/1751),P<0.001],both of the differences were statistically significant.The clinical pregnancy rate of subgroup A4[56.6%(82/145)]was significantly lower than that of subgroup A1[66.8%(725/1086),P=0.010]and subgroup A2[69.3%(167/241),P=0.008].In group B,the clinical pregnancy rate of subgroup B3 and subgroup B4[43.6%(68/156),30.8%(12/39)]was significantly lower than that of subgroup B1[55.4%(728/1315)]and subgroup B2[55.2%(127/230)],the differences were statistically significant(subgroup B3 vs.subgroup B1,P=0.003;subgroup B4 vs.subgroup B1,P=0.002;subgroup B3 vs.subgroup B2,P=0.016;subgroup B4 vs.subgroup B2,P=0.004).Adjusted for confounding factors,the results of multi-factor logistics analysis showed that:compared with subgroup A1,other subgroups(subgroup A2:OR=1.090,95%CI=0.787-1.509,P=0.606;subgroup A3:OR=0.809,95%CI=0.588-1.114,P=0.194;subgroup A4:OR=0.675,95%CI=0.456-1.000,P=0.050)in group A had no statistically significant difference in clinical pregnancy rate.Compared with subgroup B1,the clinical pregnancy rate of subgroup B4 was significantly lower in group B(OR=0.410,95%CI=0.199-0.843,P=0.015).Conclusion After PSM matching,the clinical pregnancy rate and the live birth rate of follicular phase GnRH-a long-acting protocol were better than those of luteal phase GnRH-a short-acting protocol.The follicular phase GnRH-a long-acting protocol had better tolerance to the negative effects of high progesterone than that of luteal phase GnRH-a short-acting protocol.