安徽医科大学学报

目的 聚焦不明原因反复种植失败(URIF)患者，比较粒细胞集落刺激因子(G-CSF)不同给药方式对该类患者在冻融胚胎移植周期中的临床治疗效果。方法 采用回顾性病例对照分析，研究对象为接受诊疗的187例URIF患者，根据患者在冻融胚胎移植周期内膜转化日是否使用G-CSF，以及G-CSF的给药方式，将研究对象分为3组：对照组(未使用G-CSF, n=71)、皮下注射组(皮下注射G-CSF, n=72)和宫腔灌注组(宫腔灌注G-CSF,n=44)。研究过程中，对3组URIF患者的妊娠结局进行对比分析，并开展Logistic回归分析。结果 3组患者生化妊娠率差异显著(P<0.05)，提示总体比较差异有统计学意义，就数值趋势而言，生化妊娠率表现为皮下注射组>宫腔灌注组>对照组。进一步进行两两比较发现，仅皮下注射组与对照组差异有统计学意义(P<0.017)，其余组间差异均无统计学意义(P > 0.017)。3组患者早期流产率的总体比较同样显示差异显著(P<0.05)，提示组间分布差异有统计学意义，数值趋势为宫腔灌注组>皮下注射组>对照组。两两比较结果显示，仅宫腔灌注组与对照组差异有统计学意义(P<0.017)，其余任意两组比较差异均无统计学意义(P > 0.017)。多因素Logistic回归分析结果显示：在生化妊娠结局方面，转化日子宫内膜厚度、移植胚胎数以及皮下注射G-CSF为生化妊娠率升高的独立影响因素，而年龄为生化妊娠率降低的独立影响因素；在临床妊娠结局方面，转化日子宫内膜厚度、移植胚胎数以及皮下注射G-CSF同样为临床妊娠率升高的独立影响因素，而身体质量指数为临床妊娠率降低的独立影响因素。结论 皮下注射G-CSF治疗URIF患者，仅提高了生化妊娠率，多因素Logistic回归分析中皮下注射G-CSF是URIF临床妊娠率的提高因素，但3组患者妊娠结局比较，临床妊娠率无显著提高。妊娠结局比较及多因素Logistic回归分析结果均提示宫腔灌注G-CSF对治疗URIF患者无明显疗效。

Objective To focused on patients with unexplained repeated implantation failure(URIF) and compare the clinical efficacy of different administration routes of granulocyte colony-stimulating factor(G-CSF) in patients undergoing frozen-thawed embryo transfer cycles.Methods A retrospective case-control study was conducted. A total of 187 patients with URIF who received medical treatment were enrolled in this study. According to whether G-CSF was used on the day of endometrial transformation and its administration route in frozen-thawed embryo transfer cycles, the patients were divided into three groups: control group(without G-CSF, n=71), subcutaneous injection group(subcutaneous G-CSF, n=72), and intrauterine infusion group(intrauterine G-CSF infusion, n=44). The pregnancy outcomes among the three groups were compared, and Logistic regression analysis was performed.Results There were significant differences in biochemical pregnancy rates among the three groups(P<0. 05), indicating statistical significance in the overall comparison. In terms of numerical trend, the biochemical pregnancy rate was in the order: subcutaneous injection group > intrauterine infusion group > control group. Further pairwise comparison showed that only the difference between the subcutaneous injection group and the control group was statistically significant(P<0. 017), while no significant differences were found between the other groups(P>0. 017). The overall comparison of early miscarriage rates among the three groups also showed a significant difference(P<0. 05), indicating a statistically significant difference in the distribution among the groups. The numerical trend was: intrauterine perfusion group > subcutaneous injection group > control group. Pairwise comparison results showed that only the difference between the intrauterine perfusion group and the control group was statistically significant(P<0. 017), while there was no statistically significant difference between any other two groups(P>0. 017). Multivariate Logistic regression analysis showed that endometrial thickness on the day of transformation, number of transferred embryos, and subcutaneous G-CSF injection were independent factors associated with an increased biochemical pregnancy rate, where as age was an independent factor for a decreased biochemical pregnancy rate. For clinical pregnancy outcome, endometrial thickness on the day of transformation, number of transferred embryos, and subcutaneous G-CSF injection were also independent factors for an increased clinical pregnancy rate, while BMI was an independent factor for a decreased clinical pregnancy rate.Conclusion Subcutaneous injection of G-CSF only improved the biochemical pregnancy rate in URIF patients. Multivariate Logistic regression analysis showed that subcutaneous G-CSF injection was a favorable factor for clinical pregnancy rate in URIF patients; however, no significant improvement in clinical pregnancy rate was observed among the three groups. Both the comparison of pregnancy outcomes and the results of multivariate logistic regression analysis indicates that intrauterine perfusion of G-CSF has no significant therapeutic effect in the treatment of patients with URIF.