养精种玉汤治疗反复移植失败肾阴虚证的疗效及对LIF,VEGF,IL-1β,MCP-1的影响
|
摘要
目的:探讨养精种玉汤治疗反复移植失败肾阴虚证的临床效果,探讨其机制。方法:选择山东中医药大学附属医院中西医结合生殖与遗传中心行体外受精-胚胎移植(IVF-ET)的反复种植失败(RIF)肾阴虚证患者70例,随机分为观察组、对照组,各35例。所有患者均行常规长方案进行超促排卵,观察组于移植前1个月的月经周期第5～14天服用养精种玉汤,并于移植当月月经周期第5天继续服用至移植日,对照组不服用中药。观察两组治疗后的中医证候积分;两组人体绒膜促性腺激素(HCG)日子宫内膜厚度、分型、子宫动脉搏动指数(PI)和阻力指数(RI);子宫内膜分泌物白血病抑制因子(LIF),血管内皮生长因子(VEGF),白细胞介素-1β(IL-1β)和单核细胞趋化蛋白-1(MCP-1);获卵数、受精率及胚胎移植结果。结果:治疗后,观察组中医证候积分较单纯西药组明显改善(P <0. 05);治疗后两组子宫内膜厚度差异无统计学意义,A型内膜占比观察组明显高于对照组(P <0. 05); PI两组间差异无统计学意义; RI观察组明显低于对照组(P <0. 05);移植日观察组VEGF,IL-1β及LIF水平均高于对照组,MCP-1水平低于对照组(P <0. 05);两组获卵数、受精率比较差异无统计学意义;观察组临床妊娠率明显高于对照组(P <0. 05)。结论:养精种玉汤可显著缓解RIF肾阴虚证患者的临床症状,有效提高了RIF患者A型子宫内膜形态,降低子宫动脉血流阻力,优化子宫内膜种植条件,显著提高临床妊娠率。
Objective:To explore the clinical efficacy of Yangjing Zhongyu Tang in treating kidney-Yin deficiency due to repeated implantation failure(RIF).Method:Totally 70 patients with kidney yin deficiency due to repeated implantation failure(RIF)who received the periodic Frozen thawed embyo(FET)after in vitro fertilization(IVF)embryo cryopreservation were selected from the Integrative Medicine Reproductive and Genetics Center of Affiliated Hospital of Shandong University of Traditional Chinese Medicine(TCM).They were randomly divided into observation group and control group,with 35 cases in each group.All patients were received long protocol controlled ovarian hyperstimulation.Observation group was given Yangjing Zhongyu Tang from the 5~(th)day to the 14~(th)day of the menstrual cycle 1 month before transplantation,and continued to take it on the 5~(th)day of the menstrual cycle in the month of the transplantation.Control group did not given TCM.After treatment,TCM syndrome scores,endometrial thickness,typing,uterine artery pulsation index(PI)and resistance index(RI)of HCG,endometrial secretion leukemia inhibitory factor(LIF),blood vessels endothelial growth factor(VEGF),interleukin-1β(IL-1β)and monocyte chemoattractant protein-1(MCP-1),number of eggs obtained,fertilization rate and embryo transfer results were observed.Result:After treatment,the scores of TCM syndromes in observation group were significantly improved,with statistically significant difference(P<0.05).There was no significant difference in endometrial thickness between two groups after treatment.The type of endometrium in observation group was significantly higher than that of control group(P<0.05).There was no significant difference in PI between two groups.The RI value of observation group was significantly lower than that of control group(P<0.05).VEGF,IL-1βand LIF of observation group were higher than those of control group,and the MCP-1 was lower than that of control group(P<0.05).There was no significant difference in the number of eggs obtained and the fertilization rate between two groups.The clinical pregnancy rate of observation group was significantly higher than that of control group(P<0.05).Conclusion:Yangjing Zhongyu Tang can significantly alleviate the clinical symptoms of patients with kidney-Yin deficiency due to RIF,effectively improve the type A endometrial morphology of RIF patients,reduce the uterine artery blood flow resistance,optimize endometrial implantation,and significantly improve the clinical pregnancy rate.
Objective:To explore the clinical efficacy of Yangjing Zhongyu Tang in treating kidney-Yin deficiency due to repeated implantation failure(RIF).Method:Totally 70 patients with kidney yin deficiency due to repeated implantation failure(RIF)who received the periodic Frozen thawed embyo(FET)after in vitro fertilization(IVF)embryo cryopreservation were selected from the Integrative Medicine Reproductive and Genetics Center of Affiliated Hospital of Shandong University of Traditional Chinese Medicine(TCM).They were randomly divided into observation group and control group,with 35 cases in each group.All patients were received long protocol controlled ovarian hyperstimulation.Observation group was given Yangjing Zhongyu Tang from the 5~(th)day to the 14~(th)day of the menstrual cycle 1 month before transplantation,and continued to take it on the 5~(th)day of the menstrual cycle in the month of the transplantation.Control group did not given TCM.After treatment,TCM syndrome scores,endometrial thickness,typing,uterine artery pulsation index(PI)and resistance index(RI)of HCG,endometrial secretion leukemia inhibitory factor(LIF),blood vessels endothelial growth factor(VEGF),interleukin-1β(IL-1β)and monocyte chemoattractant protein-1(MCP-1),number of eggs obtained,fertilization rate and embryo transfer results were observed.Result:After treatment,the scores of TCM syndromes in observation group were significantly improved,with statistically significant difference(P<0.05).There was no significant difference in endometrial thickness between two groups after treatment.The type of endometrium in observation group was significantly higher than that of control group(P<0.05).There was no significant difference in PI between two groups.The RI value of observation group was significantly lower than that of control group(P<0.05).VEGF,IL-1βand LIF of observation group were higher than those of control group,and the MCP-1 was lower than that of control group(P<0.05).There was no significant difference in the number of eggs obtained and the fertilization rate between two groups.The clinical pregnancy rate of observation group was significantly higher than that of control group(P<0.05).Conclusion:Yangjing Zhongyu Tang can significantly alleviate the clinical symptoms of patients with kidney-Yin deficiency due to RIF,effectively improve the type A endometrial morphology of RIF patients,reduce the uterine artery blood flow resistance,optimize endometrial implantation,and significantly improve the clinical pregnancy rate.
引文
[1]Coughlan C, Ledger W, WANG Q. Recurrent implantation failure:definition and management[J].RBMO,2014,28(1):14-38.
[2]张倩,李芷舒,张宇明,等.反复移植失败患者子宫内膜容受性的超声评价[J].中国医科大学学报,2018,47(4):350-354.
[3]江晓玲,李桂荣,樊桂玲,等.辅助生殖中反复种植失败相关对策研究进展[J].华北理工大学学报:医学版,2017,19(1):75-79.
[4]田海英,徐祥波,王蔼明,等.反复移植失败伴慢性子宫内膜炎不同检测方法比较及高危因素分析[J].中国计划生育学杂志,2017,25(4):263-266.
[5]施政,陈丽萍,朱闽波,等.子宫内膜微刺激术对反复移植失败患者再次移植结局的影响[J].现代实用医学,2018,30(2):221-223.
[6]刘杰,郑洁,雷亚兰,等.宫腔灌注基因重组人绒毛膜促性腺激素联合静脉注射阿托西班在反复着床失败冻融周期囊胚移植中的临床效果[J].中国生育健康杂志,2017,28(4):378-381.
[7]张琦,张勤华.温肾活血方对反复移植失败患者种植窗子宫内膜形态及血流的影响[J].生殖医学杂志,2017,26(12):1217-1222.
[8]廖风娇,苏靖,黎洁,等.浅析中医名方养精种玉汤[J].黑龙江中医药,2015,44(1):6.
[9]付凤真.养精种玉汤对不孕症患者黄体中期子宫内膜胰岛素样生长因子-Ⅱ的影响[J].亚太传统医药,2015,11(8):118-119.
[10]王欣,吴维城.养精种玉汤治疗女性肾亏血虚型不孕的疗效机制分析[J].中医临床研究,2017,9(11):122-123.
[11]Engmann L,Sladkevicius P,Agrawal R,et al. The pattern of changesin ovarian stromal and uterine artery blood flow velocities during in vitro fertilization treatment and its relationship with outcome of the cycle[J].Ultrasound Obst Gyn,1999,13(1):26-33.
[12]国家中医药管理局.中医病症诊断疗效标准[M].北京:中国医药科技出版社,2012:215-216.
[13]罗颂平.中医妇科学[M].北京:高等教育出版社,2008:117.
[14]中华人民共和国卫生部.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002:253-258.
[15]王晨晔,丁彩飞,张伟,等.中药三步治疗对反复移植失败患者再次激素替代冻融胚胎移植妊娠率影响的临床研究[J].中国性科学,2018,27(8):90-93.
[16]辛明蔚,何军琴.从"胞络者系于肾"探讨温肾养血法提高子宫内膜容受性[J].现代中西医结合杂志,2018,27(20):2203-2205.
[17]Casado-Vela J,Rodriguez-Suarez E,Iloroi I,et al.Comprehensive proteomic analysis of human endometrial fluid aspirate[J]. J Proteome Res,2009,8(10):4622-4632.
[18]Boomsma C M,Kavelaars A,Eijkemans M J C,et al.Endome-trial secretion analysis identifies a cytokine profile pre-dictive of pregnancy in IVF[J]. Hum Reprod,2009,24(6):1427-1435.
[19]Rahiminejad M E,Moaddab A,Ebrahimi M,et al. The relationship between some endometrial secretion cytokines and in vitro fertilization[J]. Iran J Reprod Med,2015,13(9):557-562.
[20]李瑞玉.宫腔镜子宫内膜微创术对子宫内膜容受性因子表达的影响[J].中国医药导刊,2016,18(6):569-571.
[21]叶瑶,牛志宏,谷瑞环,等.种植窗期宫腔液单核细胞趋化蛋白(MCP)-1预测冻融胚胎移植妊娠结局[J].生殖与避孕,2015,35(3):154-58.
[22]GONG X,TONG Q,CHEN Z,et al. Microvascular density and vascular endothelial growth factor and osteopontin expression during the implantation window in a controlled ovarian hypersti-mulation rat model[J]. Exp Ther Med,2015,9(3):773-779.
[23]Meduri G,Bausero P,Applanat M,et al,Expression of vascular endothelial growth factor receptors in the human endometrium:modulation during menstrual cycle[J].Biology Reprod,2000,62(2):439-447.
[24]Bourgain C,Devroey P. The endometrium in stimulated cycles for IVF[J]. Hum Reprod Update,2003,9(6):515-522.
[25]Geisert R,Fazleabas A,Lucy M,et al. Interaction of the conceptus and endometrium to establish pregnancy in mammals:role of interleukin 1beta[J]. Cell Tissue Res,2012,349(3):825-838.
[26]马蓉,王新梅,朱小莉.补肾调冲方对肥胖型多囊卵巢综合征不孕患者疗效及对子宫内膜容受性的影响[J].中国实验方剂学杂志,2018,24(5):188-192.
[2]张倩,李芷舒,张宇明,等.反复移植失败患者子宫内膜容受性的超声评价[J].中国医科大学学报,2018,47(4):350-354.
[3]江晓玲,李桂荣,樊桂玲,等.辅助生殖中反复种植失败相关对策研究进展[J].华北理工大学学报:医学版,2017,19(1):75-79.
[4]田海英,徐祥波,王蔼明,等.反复移植失败伴慢性子宫内膜炎不同检测方法比较及高危因素分析[J].中国计划生育学杂志,2017,25(4):263-266.
[5]施政,陈丽萍,朱闽波,等.子宫内膜微刺激术对反复移植失败患者再次移植结局的影响[J].现代实用医学,2018,30(2):221-223.
[6]刘杰,郑洁,雷亚兰,等.宫腔灌注基因重组人绒毛膜促性腺激素联合静脉注射阿托西班在反复着床失败冻融周期囊胚移植中的临床效果[J].中国生育健康杂志,2017,28(4):378-381.
[7]张琦,张勤华.温肾活血方对反复移植失败患者种植窗子宫内膜形态及血流的影响[J].生殖医学杂志,2017,26(12):1217-1222.
[8]廖风娇,苏靖,黎洁,等.浅析中医名方养精种玉汤[J].黑龙江中医药,2015,44(1):6.
[9]付凤真.养精种玉汤对不孕症患者黄体中期子宫内膜胰岛素样生长因子-Ⅱ的影响[J].亚太传统医药,2015,11(8):118-119.
[10]王欣,吴维城.养精种玉汤治疗女性肾亏血虚型不孕的疗效机制分析[J].中医临床研究,2017,9(11):122-123.
[11]Engmann L,Sladkevicius P,Agrawal R,et al. The pattern of changesin ovarian stromal and uterine artery blood flow velocities during in vitro fertilization treatment and its relationship with outcome of the cycle[J].Ultrasound Obst Gyn,1999,13(1):26-33.
[12]国家中医药管理局.中医病症诊断疗效标准[M].北京:中国医药科技出版社,2012:215-216.
[13]罗颂平.中医妇科学[M].北京:高等教育出版社,2008:117.
[14]中华人民共和国卫生部.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002:253-258.
[15]王晨晔,丁彩飞,张伟,等.中药三步治疗对反复移植失败患者再次激素替代冻融胚胎移植妊娠率影响的临床研究[J].中国性科学,2018,27(8):90-93.
[16]辛明蔚,何军琴.从"胞络者系于肾"探讨温肾养血法提高子宫内膜容受性[J].现代中西医结合杂志,2018,27(20):2203-2205.
[17]Casado-Vela J,Rodriguez-Suarez E,Iloroi I,et al.Comprehensive proteomic analysis of human endometrial fluid aspirate[J]. J Proteome Res,2009,8(10):4622-4632.
[18]Boomsma C M,Kavelaars A,Eijkemans M J C,et al.Endome-trial secretion analysis identifies a cytokine profile pre-dictive of pregnancy in IVF[J]. Hum Reprod,2009,24(6):1427-1435.
[19]Rahiminejad M E,Moaddab A,Ebrahimi M,et al. The relationship between some endometrial secretion cytokines and in vitro fertilization[J]. Iran J Reprod Med,2015,13(9):557-562.
[20]李瑞玉.宫腔镜子宫内膜微创术对子宫内膜容受性因子表达的影响[J].中国医药导刊,2016,18(6):569-571.
[21]叶瑶,牛志宏,谷瑞环,等.种植窗期宫腔液单核细胞趋化蛋白(MCP)-1预测冻融胚胎移植妊娠结局[J].生殖与避孕,2015,35(3):154-58.
[22]GONG X,TONG Q,CHEN Z,et al. Microvascular density and vascular endothelial growth factor and osteopontin expression during the implantation window in a controlled ovarian hypersti-mulation rat model[J]. Exp Ther Med,2015,9(3):773-779.
[23]Meduri G,Bausero P,Applanat M,et al,Expression of vascular endothelial growth factor receptors in the human endometrium:modulation during menstrual cycle[J].Biology Reprod,2000,62(2):439-447.
[24]Bourgain C,Devroey P. The endometrium in stimulated cycles for IVF[J]. Hum Reprod Update,2003,9(6):515-522.
[25]Geisert R,Fazleabas A,Lucy M,et al. Interaction of the conceptus and endometrium to establish pregnancy in mammals:role of interleukin 1beta[J]. Cell Tissue Res,2012,349(3):825-838.
[26]马蓉,王新梅,朱小莉.补肾调冲方对肥胖型多囊卵巢综合征不孕患者疗效及对子宫内膜容受性的影响[J].中国实验方剂学杂志,2018,24(5):188-192.