毓麟珠方加减对反复移植失败患者非移植周期子宫内膜容受性的影响

Effect of Modified Yulinzhu Prescription on Endometrial Receptivity in Patients with Repeated Transplantation Failure in Non-transplantation Cycle

目的探讨毓麟珠方加减对反复移植失败(RIF)患者子宫内膜容受性影响的作用机制。方法选取2017年1月—2019年5月于浙江省中西医结合医院生殖医学科门诊或住院治疗的肾虚型RIF非移植周期患者30例为RIF治疗组,欲行人工受精曾有妊娠史的育龄期女性30例为对照组。RIF治疗组予中药毓麟珠方加减口服,从月经第5天开始,连续服用21天为1个疗程,治疗3个疗程。对照组不予任何药物治疗。观察RIF治疗组治疗前后肾虚证候评分,测定两组黄体中期血清mi RNA-31水平及子宫内膜Foxp3、eNOS miRNA表达。结果治疗组治疗后中医证候评分较治疗前显著降低[(12.23±2.01)分比(17.97±3.59)分],差异有统计学意义(P<0.01)。RIF治疗组治疗前黄体中期血清mi RNA-31水平显著高于对照组[(1.79±0.11)比(1.01±0.10)],RIF治疗组治疗后黄体中期血清miRNA-31水平显著低于治疗前[(1.28±0.13)比(1.79±0.11)],差异均有统计学意义(P均<0.01)。RIF治疗组治疗前子宫内膜Foxp3、eNOS miRNA水平均显著低于对照组[(0.38±0.08)比(0.56±0.13),(0.33±0.06)比(0.73±0.12)],RIF治疗组治疗后子宫内膜Foxp3、eNOS miRNA水平均显著高于治疗前[(0.48±0.10)比(0.38±0.08),(0.55±0.13)比(0.33±0.06)],差异均有统计学意义(P均<0.01)。治疗组和对照组的血清mi RNA-31与子宫内膜Foxp3、eNOS miRNA水平均呈负相关关系(P均<0.05)。结论毓麟珠方加减治疗RIF患者非移植周期,可改善其肾虚临床症状及体征,可能通过降低血清mi RNA-31水平,增强种植窗口期子宫内膜Foxp3、eNOS miRNA表达。

Objective To investigate the mechanism of the effect of Modified Yulinzhu Prescription on endometrial receptivity in patients with repeated transplantation failure(RIF).Methods Thirty patients with kidney deficiency RIF in non-transplant cycle who were treated in outpatient or inpatient treatment at Department of Reproductive Medicine of Zhejiang Integrated Traditional Chinese and Western Medicine Hospital from January 2017 to May 2019,were selected as the RIF treatment group,and 30 women of childbearing age who were about to undergo artificial insemination and had a history of pregnancy were selected as the control group.In the RIF treatment group,Yulinzhu Prescription was added or reduced orally,and it was taken continuously for 21 days from the 5th day of menstruation for 1 course of treatment and 3 courses of treatment.The control group received no drug therapy.The renal deficiency syndrome scores were observed before and after treatment in the RIF treatment group,and the serum miRNA-31 levels and the endometrial Foxp3 and eNOS miRNA expressions in the two groups were detected in the middle luteal phase.Results After treatment,the scores of TCM syndromes in the treatment group were significantly lower than those before treatment[(12.23±2.01)vs(17.97±3.59)],and the difference was significant(P<0.01).The serum miRNA-31 level in mid-luteal phase before treatment in RIF treatment group was significantly higher than that in control group[(1.79±0.11)vs(1.01±0.10)],while the serum miRNA-31 level in mid-luteal phase after treatment in RIF treatment group was significantly lower than that before treatment[(1.28±0.13)vs(1.79±0.11)],and the differences were significant(P<0.01).The levels of Foxp3[(0.38±0.08)vs(0.56±0.13)]and eNOS[(0.33±0.06)vs(0.73±0.12)]miRNA in endometrium of RIF treatment group before treatment were significantly lower than those of control group,the levels of Foxp3[(0.48±0.10)vs(0.38±0.08)]and eNOS[(0.55±0.13)vs(0.33±0.06)]miRNA in endometrium of RIF treatment group after treatment were significantly higher than those before treatment,and the differences were significant(P<0.01,respectively).Serum miRNA-31 in treatment group and control group was negatively correlated with Foxp3 and eNOS miRNA levels in endometrium(P<0.05,respectively).Conclusion Modified Yulinzhu Prescription can improve the clinical symptoms and signs of kidney deficiency in RIF patients during non-transplantation period,and may increase the expression of Foxp3 and eNOS miRNA in endometrium during implantation window by reducing the level of serum miRNA-31.