生殖医学杂志

目的 探讨促性腺激素释放激素(GnRH)拮抗剂灵活方案中拮抗剂应用天数对新鲜周期体外受精/卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)临床结局的影响。方法 回顾性分析2019年10月至2022年10月于青岛大学附属妇女儿童医院生殖医学中心行IVF/ICSI-ET治疗的不孕症患者的临床资料，共1 632个周期。按照拮抗剂应用天数不同分为4组：A组(拮抗剂应用≤3 d)151个周期，B组(拮抗剂应用4 d)592个周期，C组(拮抗剂应用5 d)672个周期，D组(拮抗剂应用≥6 d)217个周期。比较4组患者的基础资料、促排卵情况、临床结局，应用单因素和多因素Logistic回归、多重线性回归分析临床结局的影响因素。结果 4组患者中，除A组的体质量指数(BMI)显著高于其他3组(P<0.05)外，其余各组间基础资料比较均无显著性差异(P>0.05)。促排卵情况比较发现，D组的Gn总用量、Gn总天数、扳机日P和E₂水平、子宫内膜厚度均显著高于其他3组(P<0.05),而扳机日LH水平显著低于其他3组(P<0.05)。4组的临床结局比较发现，移植胚胎类型中，A组移植卵裂期胚胎占比最大，C组移植囊胚占比最大，与其他组比较有显著性差异(P<0.05);D组患者正常受精率和优胚率均显著大于其他3组(P<0.05);C组患者囊胚形成率显著大于其他3组(P<0.05);而4组患者的种植率、临床妊娠率、早期流产率、活产率均无显著性差异(P>0.05)。Logistic回归分析显示，拮抗剂应用天数不是临床妊娠率的显著影响因素(P>0.05),HCG日LH水平、子宫内膜厚度、移植胚胎数均与临床妊娠率呈正相关(OR>1,P<0.05);多重线性回归分析显示，拮抗剂应用天数与HCG日LH水平呈负相关(P<0.05,B<0),与子宫内膜厚度呈正相关(P<0.05,B>0)。结论 GnRH拮抗剂应用天数不明显影响新鲜周期IVF/ICSI-ET的临床妊娠率及活产率，但拮抗剂应用天数与促排卵过程中激素水平、子宫内膜厚度和获卵数等临床指标的关系值得关注。

Objective:To investigate whether the duration of GnRH antagonist application affects the clinical outcomes of fresh IVF/ICSI-ET cycles in the flexible GnRH antagonist protocol.Methods:A retrospective analysis of data of infertility patients who underwent IVF/ICSI-ET treatment in Women and Children's Hospital, Qingdao University, from October 2019 to October 2022 was conducted. The respondents were divided into 4 groups based on the duration of antagonist application: group A(≤3 days of antagonist application, 151 cycles),group B(4 days of antagonist application, 592 cycles),group C(5 days of antagonist application, 672 cycles),group D(≥6 days of antagonist application, 217 cycles). Basic clinical characteristics, ovulation induction and clinical outcomes of the four groups were compared, and the influencing factors of clinical outcomes were analyzed by the univariate and multivariate logistic regression and multiple linear regression.Results:Among the four groups of patients, except for group A,whose body mass index(BMI) was significantly higher than those of the other three groups(P<0.05),there were no significant differences in the comparison of basic data among the other groups(P>0.05). Patients in group D had significantly higher total gonadotropin(Gn) dosage, total Gn days, progesterone and E₂ levels on the trigger day, and endometrial thickness than those of the other three groups(P<0.05),while LH levels on the trigger day were significantly lower than those of the other three groups(P<0.05). The clinical outcomes of the four groups were as follows. Patients in group A had the highest proportion of embryos transferred during the cleavage stage, group C had the highest proportion of embryos transferred during the blastocyst stage(P<0.05). Both the normal fertilization rate and the high-quality embryo rate of group D were significantly higher than those of the other three groups(P<0.05). The blastocyst formation rate in group C was significantly higher than those in the other three groups(P<0.05). However, there were no significant differences in the implantation rate, clinical pregnancy rate, early miscarriage rate, and the live birth rate among the four groups of patients(P>0.05). Logistic regression analysis showed that the duration of antagonist application was not a factor for the clinical pregnancy rate(P>0.05),and the LH level, endometrial thickness and the number of transplanted embryos on HCG day were positively correlated with the clinical pregnancy rate(OR>1,P<0.05). Multiple linear regression analysis showed that the duration of antagonist application was negatively correlated with LH level on HCG day(B<0,P<0.05),and positively correlated with endometrial thickness(B>0,P<0.05).Conclusions:The duration of GnRH antagonist application did not affect the clinical pregnancy rate and the live birth rate of fresh IVF/ICSI-ET cycles, but much more attention should be paid to the relationships between the duration of GnRH antagonist application as well as clinical indicators such as hormone levels, endometrial thickness and the number of oocytes retrieved during ovulation.