■卵泡生成中的血管生成有助于自然和体外受精(IVF)周期中的卵母细胞发育能力。因此,卵泡发生过程中卵泡液(FF)中关键血管生成因子的鉴定具有临床意义,对体外受精具有重要意义。这项研究旨在确定FF中关键的血管生成因子,以预测体外受精过程中的卵母细胞成熟度。
■招募了40名在首次体外受精治疗中使用GnRH拮抗剂方案进行卵巢刺激的参与者。每个病人,两个卵泡样本(一个排卵前卵泡,>18毫米;一个中窦卵泡,<14mm)在卵母细胞取出过程中没有潮红的情况下收集。总的来说,从40名患者收集了80份FF样品。通过Luminex高性能测定分析FF中血管生成相关蛋白的表达谱。记录的患者数据包括窦卵泡计数,抗苗勒管激素,年龄,BMI。在月经周期第2天,触发日收集血清样本,和取卵日。通过化学发光法测量激素浓度,包括第2天的FSH/LH/E2/P4,触发天的E2/LH/P4和取回天的E2/LH/P4。
■10种血管生成因子在FF中高表达:eotaxin,Gro-α,IL-8,IP-10,MCP-1,MIG,PAI-1(Serpin),VEGF-A,CXCL-6和HGF。eotaxin的浓度,IL-8、MCP1、PAI-1、VEGF-A在排卵前卵泡明显高于中腔卵泡,排卵前卵泡中Gro-α和CXCL-6的表达水平低于中腔卵泡(p<0.05)。Logistic回归和受试者工作特征(ROC)分析显示,VEGF-A,eotaxin,和CXCL-6是卵母细胞成熟度的三个最强预测因子。VEGF-A和CXCL-6的组合比其他组合以更高的灵敏度(91.7%)和特异性(72.7%)预测卵母细胞成熟度。
■我们的研究结果表明VEGF-A,eotaxin,FF中的CXCL-6浓度与从窦中期到排卵前期的卵母细胞成熟度密切相关。VEGF-A和CXCL-6的组合在体外受精过程中显示出相对较好的卵母细胞成熟度预测率。
Angiogenesis in folliculogenesis contributes to oocyte developmental competence in natural and in vitro fertilization (IVF) cycles. Therefore, the identification of key angiogenic factors in follicular fluid (
FF) during folliculogenesis is clinically significant and important for in vitro fertilization. This study aims to identify the key angiogenic factors in
FF for predicting oocyte maturity during in vitro fertilization.
Forty participants who received ovarian stimulation using a GnRH antagonist protocol in their first in vitro fertilization treatment were recruited. From each patient, two follicular samples (one preovulatory follicle, > 18 mm; one mid-antral follicle, < 14 mm) were collected without flushing during oocyte retrieval. In total, 80
FF samples were collected from 40 patients. The expression profiles of angiogenesis-related proteins in
FF were analyzed via Luminex high-performance assays. Recorded patient data included antral follicle count, anti-müllerian hormone, age, and BMI. Serum samples were collected on menstrual cycle day 2, the trigger day, and the day of oocyte retrieval. Hormone concentrations including day 2 FSH/LH/E2/P4, trigger day E2/LH/P4, and retrieval day E2/LH/P4 were measured by chemiluminescence assay.
Ten angiogenic factors were highly expressed in
FF: eotaxin, Gro-α, IL-8, IP-10, MCP-1, MIG, PAI-1 (Serpin), VEGF-A, CXCL-6, and HGF. The concentrations of eotaxin, IL-8, MCP1, PAI-1, and VEGF-A were significantly higher in preovulatory follicles than those in mid-antral follicles, while the Gro-α and CXCL-6 expressional levels were lower in preovulatory than in mid-antral follicles (p < 0.05). Logistic regression and receiver operating characteristic (ROC) analysis revealed that VEGF-A, eotaxin, and CXCL-6 were the three strongest predictors of oocyte maturity. The combination of VEGF-A and CXCL-6 predicted oocyte maturity with a higher sensitivity (91.7%) and specificity (72.7%) than other combinations.
Our findings suggest that VEGF-A, eotaxin, and CXCL-6 concentrations in FF strongly correlate with oocyte maturity from the mid-antral to preovulatory stage. The combination of VEGF-A and CXCL-6 exhibits a relatively good prediction rate of oocyte maturity during in vitro fertilization.