宫腔灌注富血小板血浆对薄型子宫内膜反复移植失败患者子宫内膜厚度及临床结局的影响

Effect of Uterine Cavity Perfusion with Platelet-rich Plasma on Endometrial Thickness and Clinical Outcome in Patients with Thin Endometrial Repeated Implantation Failure

目的探讨宫腔灌注富血小板血浆(PRP)对薄型子宫内膜反复移植失败(RIF)患者子宫内膜厚度及临床结局的影响。方法选取2018年1月至2019年1月唐山市妇幼保健院收治的薄型子宫内膜RIF患者167例,按照治疗方法不同分为对照组(84例)和PRP组(83例)。对照组在月经周期第3天给予戊酸雌二醇2 mg/d,早晚各1 mg;同时注射生长激素4 U,每日1次,治疗10 d后应用阴道超声监测子宫内膜的厚度。PRP组将5 ml PRP做宫腔灌注,保留15 s后取出人工受精管,在宫腔灌注PRP 72 h后采用阴道超声监测子宫内膜厚度。比较两组患者治疗前后子宫内膜容积、子宫内膜厚度、子宫内膜下螺旋动脉血流变动力学指标[血流阻力指数(RI)、搏动指数(PI)、收缩期末与舒张期末最高血流速率比值(S/D)]、血清辅助性T细胞(Th)1细胞因子[白细胞介素(IL)-2、肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)]、Th2细胞因子(IL-4、IL-6、IL-10)水平以及临床结局。结果治疗后,两组子宫内膜容积、子宫内膜厚度均大于治疗前(P<0.05),且PRP组大于对照组[(5.30±1.00)ml比(4.52±0.86)ml、(8.69±0.98)mm比(7.86±0.70)mm](P<0.01)。治疗后,两组患者RI、PI、S/D均低于治疗前,且PRP组低于对照组(0.65±0.02比0.72±0.08、0.80±0.09比0.92±0.10、2.13±0.15比2.68±0.25)(P<0.01)。治疗后两组患者Th1细胞因子(IL-2、TNF-α、IFN-γ)表达水平均低于治疗前,且PRP组低于对照组[(1.68±0.52)ng/L比(2.35±0.55)ng/L、(1.00±0.32)ng/L比(1.86±0.52)ng/L、(4.02±0.52)ng/L比(5.23±0.52)ng/L](P<0.01);Th2细胞因子(IL-4、IL-6、IL-10)表达水平均高于治疗前,且PRP组高于对照组[(3.32±1.03)ng/L比(2.16±0.99)ng/L、(16.35±2.39)ng/L比(12.20±1.06)ng/L、(3.26±0.52)ng/L比(2.00±0.15)ng/L](P<0.01)。PRP组周期取消率低于对照组,生化妊娠率、临床妊娠率高于对照组(P<0.05)。结论宫腔灌注PRP可明显增加薄型子宫内膜RIF患者子宫内膜厚度,改善Th1/Th2细胞失衡状态,临床结局理想。

Objective To analyze the influence of intrauterine infusion of platelet-rich plasma(PRP)on endometrial thickness and clinical outcome of patients with thin endometrial repeated implantation failure(RIF).Methods A total of 167 patients with thin endometrial RIF admitted to Tangshan Maternal and Child Health Hospital from Jan.2018 to Jan.2019 were included and divided into a control group(84 cases)and a PRP group(83 cases)according to treatment methods.In the control group,2 mg/d of estradiol valeric acid was given on the third day of the menstrual cycle,1 mg each in the morning and evening;4 U of growth hormone was injected once daily,and vaginal ultrasound was used to monitor the endometrial thickness after 10 d of treatment;in the PRP group,intrauterine perfusion of 5 ml PRP was given and the artificial fertilized tube was removed after 15 s,and the endometrial thickness was monitored by vaginal ultrasound 72 h after intrauterine perfusion of PRP.The endometrial volume,endometrial thickness,hemorheological dynamics indexes of subendometrial spiral artery[resistance index(RI),pulsatility index(PI),systolic peak velocity/diastolic flow velocity(S/D)],levels of serum helper T cell(Th)1 cytokines[interleukin(IL)-2,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)]and Th2 cytokines(IL-4,IL-6,IL-10)before and after treatment,as well as the clinical outcomes of the two groups were compared.Results After treatment,the endometrial volume and endometrial thickness in the two groups were higher than before treatment(P<0.05),and the PRP group higher than the control group[(5.30±1.00)ml vs(4.52±0.86)ml,(8.69±0.98)mm vs(7.86±0.70)mm](P<0.01).After treatment,RI,PI and S/D in both groups were lower than before treatment,and the PRP group lower than the control group(0.65±0.02 vs 0.72±0.08,0.80±0.09 vs 0.92±0.10,2.13±0.15 vs 2.68±0.25)(P<0.01).After treatment,the expression levels of Th1 cytokines(IL-2,TNF-α,IFN-γ)in both groups were lower than before treatment,and the PRP group lower than the control group[(1.68±0.52)ng/L vs(2.35±0.55)ng/L,(1.00±0.32)ng/L vs(1.86±0.52)ng/L,(4.02±0.52)ng/L vs(5.23±0.52)ng/L](P<0.01);the expression levels of Th2 cytokines(IL-4,IL-6,IL-10)were higher than those before treatment,and PRP group higher than the control group[(3.32±1.03)ng/L vs(2.16±0.99)ng/L,(16.35±2.39)ng/L vs(12.20±1.06)ng/L,(3.26±0.52)ng/L vs(2.00±0.15)ng/L](P<0.01).The cycle cancellation rate of the PRP group was lower than that of the control group,and the biochemical pregnancy rate and clinical pregnancy rate were higher than those of the control group(P<0.05).Conclusion Uterine perfusion of PRP can significantly increase the thickness of endometrium in patients with thin endometrium RIF,improve the imbalance of Th1/Th2 cells,and the clinical outcome is ideal.