体外受精- 胚胎移植超促排卵周期中金属蛋白酶3、肿瘤坏死因子、血管内皮生长因子的表达与卵巢反应性的研究

Relationships of MMP-3, TNF and VEGF in serum and follicular fluid with ovarian response during IVF-ET cycles

摘要:

目的 分析在体外受精-胚胎移植（IVF-ET）超促排卵周期中不孕妇女血清及卵泡液中的金属 蛋白酶3（MMP-3）、肿瘤坏死因子（TNF）、血管内皮生长因子（VEGF）的表达，了解MMP-3、VEGF 及 TNF 在其中的分布特点，分析其与卵巢反应的相关性。方法 收集2013 年3 月-2015 年10 月行IVF-ET 治 疗的413 例超促排卵周期的患者，不孕原因均为输卵管因素，年龄22 ～ 38 岁，依据患者获卵数分为高反应组 （获卵数≥ 20 个）、正常反应组（获卵数6 ～ 19 个）及低反应组（获卵数≤ 5 个），分别用酶联免疫方法测定 各组在促性腺激素（Gn）起始注射日、绒毛膜促性腺激素（hCG）注射日血清及卵泡液中VEGF、TNF 及 MMP-3 的水平，分析组间的差异。结果 在3 组患者的基本情况差异无统计学意义的情况下：① 3 组患者 hCG 日血清MMP-3 和VEGF 的表达均高于Gn 启动日（P <0.05）；② 3 组患者hCG 日血清中TNF 的表达 低于Gn 启动日（P <0.05）；③高反应组患者卵泡液中MMP-3 的表达均高于正常反应组和低反应组（P <0.05）； ④高反应组患者卵泡液中VEGF 和TNF 的表达均低于正常反应组和低反应组。（P <0.05）。结论 ①随着促 排卵过程中卵泡的发育，血清中VEGF 和MMP-3 的表达增多，TNF 则随着卵泡的发育逐渐减少；②经超排 卵后患者卵泡液中MMP-3 表达与卵巢反应呈正相关，而VEGF 和TNF 与卵巢反应呈负相关。

Abstract:

Objective To study of the levels of matrix metalloproteinase 3 (MMP-3), tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF) in serum and follicular fluid during in vitro fertilization-embryo transfer (IVF-ET) cycles and their relationships with ovarian response. Methods Totally 413 infertile female patients were under investigation. According to the number of eggs obtained, they were divided into high reaction group (eggs obtained ≥ 20), normal reaction group (6-19 eggs obtained) and the low reaction group (eggs obtained ≤ 5). The levels of MMP-3, TNF and VEGF in serum and follicular fluid were measured by ELISA on the gonadotropin (Gn) initial injection day and the human chorionic gonadotropin (hCG) injection day. The differences among the groups were analyzed. Results The serum expressions of MMP-3 and VEGF on the hCG injection day were significantly higher than those on the Gn initial injection day in all the 3 groups (P < 0.05). The serum expression of TNF on the hCG injection day was lower than that on the Gn initial injection day in the 3 groups (P < 0.05). The level of MMP-3 in the follicular fluid of the high reaction group was higher than that of the normal reaction group and the low reaction group (P < 0.05). The levels of VEGF and TNF in the follicular fluid of the high reaction group were lower than those of the normal reaction group and the low reaction group (P < 0.05). Conclusions With the development of follicles during ovulation promotion, the serum expressions of VEGF and MMP-3 increase and TNF gradually decreases. After hyperstimulation of ovulation the expression of MMP-3 in follicular fluid is positively correlated with ovarian response, while VEGF and TNF are negatively correlated with ovarian response.