胰岛素样生长因子结合蛋白-3与促排卵结局的相关研究
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摘要
目的探讨胰岛素样生长因子结合蛋白-3(IGFBP-3)在不同控制性超促排卵(COH)方案中的动态变化及其与COH结局的相关性。方法收集76例在白求恩国际和平医院首次行IVF/ICSI治疗患者COH过程中的血清及卵泡液,分为长方案组(38例)及非降调方案组(38例),酶联免疫吸附方法(ELISA)检测血清及卵泡液中IGFBP-3水平并进行相关分析。结果 1.两组基础血清IGFBP-3无统计学差异,长方案组降调过程中血清IGFBP-3明显下降,且Gn启动日长方案组IGFBP-3明显低于非降调组(P=0.029)。2.Gn启动后两组血清IGFBP-3水平继续下降,取卵后2天升高;两组Gn启动后的IGFBP-3无统计学差异;且Gn第5天IGFBP-3水平与COH结局具有较,好的相关性(P<0.05)。3.两组FFIGFBP-3水平随卵泡增大而升高,大中卵泡IGFBP-3水平无统计学意义(P>0.05),但非降调组小卵泡IGFBP-3水平明显高于长方案组(P=0.037);且大卵泡IGFBP-3水平与COH结局相关性最好。结论血清及大中FFIGFBP-3水平可能对卵巢反应性及COH结局具有好的预测价值。
Objective:To investigate the dynamic changes of insulin-like growth factor-binding protein-3(IGFBP-3)in different controlled hyperstimulation(COH)protocols and its correlation with the outcome of COH. Methods:The serum and follicular fluid of 76 patients treated with IVF/ICSI for the first time in Bethune International Peace Hospital were collected and divided into downregulation protocol(DRP)group(38 cases)and undownregulation protocol(NDRP)group(38 cases). The level of IGFBP-3 was detected by ELISA and the correlation was analyzed. Results:1.There was no significant difference in serum IGFBP-3 between the two groups. The level of serum IGFBP-3 decreased significantly in DRP group and lower than that in NDRP group on Gn starting day(P=0. 029). 2. After Gn administration,IGFBP-3 in the two protocols began to decrease,and went up on one day after hCG injection(P<0.05). There were no statistical differentces about IGFBP-3 in the two protocols after Gn stimulation(P>0.05). In addition,IGFBP-3 on the fifth day of stimulation had a better correlation with COH outcomes. 3. IGFBP-3 in follicles was positive with folliclar sizes. There were no statistical differences about IGFBP-3 in big and middle follicles(P>0.05). However,significant difference was found in small follicles(P=0.037). IGFBP-3 in big follicles had the strongest correlation with COH outcomes. Conclusion:IGFBP-3 in serum and big,mid-follicles are good predictors for ovarian response and COH outcomes.
Objective:To investigate the dynamic changes of insulin-like growth factor-binding protein-3(IGFBP-3)in different controlled hyperstimulation(COH)protocols and its correlation with the outcome of COH. Methods:The serum and follicular fluid of 76 patients treated with IVF/ICSI for the first time in Bethune International Peace Hospital were collected and divided into downregulation protocol(DRP)group(38 cases)and undownregulation protocol(NDRP)group(38 cases). The level of IGFBP-3 was detected by ELISA and the correlation was analyzed. Results:1.There was no significant difference in serum IGFBP-3 between the two groups. The level of serum IGFBP-3 decreased significantly in DRP group and lower than that in NDRP group on Gn starting day(P=0. 029). 2. After Gn administration,IGFBP-3 in the two protocols began to decrease,and went up on one day after hCG injection(P<0.05). There were no statistical differentces about IGFBP-3 in the two protocols after Gn stimulation(P>0.05). In addition,IGFBP-3 on the fifth day of stimulation had a better correlation with COH outcomes. 3. IGFBP-3 in follicles was positive with folliclar sizes. There were no statistical differences about IGFBP-3 in big and middle follicles(P>0.05). However,significant difference was found in small follicles(P=0.037). IGFBP-3 in big follicles had the strongest correlation with COH outcomes. Conclusion:IGFBP-3 in serum and big,mid-follicles are good predictors for ovarian response and COH outcomes.
引文
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[15] Gene G,Yilmaz N,Uygur D,et al. The effect of intrafollicular IGF-1 and IGFBP-3 on IVF outcome in patients using different gonadotropins:a prospective study[J]. J Assist Reprod Genet,2011,28(4):405-410.
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[17] Zhang Q,Jiang Y,Miller M J,et al. IGFBP-3 and TNF-αregulate retinal endothelial cell apoptosis[J]. Invest Ophthal Visual Sci,2013,54(8):5376-5384.
[18] Zhang Q,Steinle JJ. IGFBP-3 inhibits TNF-αproduction and TNFR-2 signaling to protect against retinal endothelial cell apoptosis[J]. Microvascular Res,2014,95(1):76-81.
[19] Lee HJ,Lee JS,Hwang SJ,et al. Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrinβ4 expression[J]. Oncotarget,2015,6(17):15150-15163.
[2]刘小惠,吴小华.血清及卵泡液中抑制素B动态变化及其与促排卵结局的相关性研究[J].生殖与避孕,2016,36(11):897-903.
[3]吴小华,刘小惠,杨帅.血管内皮生长因子与抑制素B和促排卵结局的相关研究[J].中华生殖与避孕,2017,37(3):193-198.
[4]刘小惠,吴小华.胰岛素样生长因子-1与促排卵结局及抑制素B、血管内皮生长因子的相关研究[J].生殖医学杂志,2018(2):123-129.
[5] Firth SM,Baxter RC. Cellular actions of the insulin-like growth factor binding protein[J]. Endocrine Reviews,2002,23(6):824-854.
[6] Takaoka M,Harada H,Andl CD,et al. Epidermal growth factor receptor regulates aberrant expression of insulin-like growth factor-binding protein 3[J]. Cancer Res,2004,64(21):7711-23.
[7] Wang Q,et al. Genetic and dietary determinants of insulin-like growth factor(IGF)-1 and IGF binding protein(BP)-3 levels among Chinese women[J]. Plos One,2014,9(10):e108934.
[8] Yen YC,Hsiao JR,Jiang SS,et al. Insulin-like growth factorindependent insulin-like growth factor binding protein 3 promotes cell migration and lymph node metastasis of oral squamous cell carcinoma cells by requirement of integrinβ1[J]. Oncotarget,2015,6(39):41837-41855.
[9]徐嗣亮,刘嘉茵. LH调节女性雄激素生成的分子信号通路研究进展[J].国际生殖健康/计划生育杂志,2015,34(4):328-332.
[10] Zhou ZY,Li F,et al. Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 rehabilitated decreased testosterone concentrations in diabetic rats[J]. Med Sci Mon Int Med J Exp Clin Res,2015,21(10):94-99.
[11]蔡贺,张天真,等.生长激素对卵巢低反应患者卵泡液生长激素、胰岛素样生长因子-I及胰岛素样生长因子结合蛋白-3水平的影响[J].中国妇产科临床杂志,2016,17(4):328-332.
[12] Jin Q,Lee HJ,Min HY,et al. Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3[J]. Carcinogenesis,2014,35(10):2232-43.
[13] Hye JL,et al. Adipokines,insulin-like growth factor binding protein-3 levels,and insulin sensitivity in women with polycystic ovary syndrome[J]. Korean J Int Med,2013,28(4):456-63.
[14]吕芳,张保合,陈智英. IVF-ET患者IGFBP-3和IGF-1水平与卵泡发育、卵巢内分泌、胚胎质量及妊娠之间的关系[J].广东医学,2016,37(12):1836-1839.
[15] Gene G,Yilmaz N,Uygur D,et al. The effect of intrafollicular IGF-1 and IGFBP-3 on IVF outcome in patients using different gonadotropins:a prospective study[J]. J Assist Reprod Genet,2011,28(4):405-410.
[16] Sun OK,Bae UJ,Park BH. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3[J]. Sci Reports,2015,5:S23.
[17] Zhang Q,Jiang Y,Miller M J,et al. IGFBP-3 and TNF-αregulate retinal endothelial cell apoptosis[J]. Invest Ophthal Visual Sci,2013,54(8):5376-5384.
[18] Zhang Q,Steinle JJ. IGFBP-3 inhibits TNF-αproduction and TNFR-2 signaling to protect against retinal endothelial cell apoptosis[J]. Microvascular Res,2014,95(1):76-81.
[19] Lee HJ,Lee JS,Hwang SJ,et al. Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrinβ4 expression[J]. Oncotarget,2015,6(17):15150-15163.