薄型子宫内膜患者血管内皮生长因子基因多态性对胚胎种植成功率的影响

Influence of vascular endothelial growth factor gene polymorphism on success rate of embryo implantation in patients with thin endometrium

目的分析薄型子宫内膜患者血管内皮生长因子(VEGF)基因多态性对胚胎种植成功率的影响。方法选择2022年6月—2023年12月本院妇科门诊及住院的100例薄型子宫内膜患者为研究组,另选择同期本院体检部的健康成年女性100例为对照组。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)测定VEGF基因4个不同位点的单核苷酸多态性,利用等位基因特异性PCR(AS-PCR)分析2组VEGF相应位点基因型及等位基因频率的分布情况。研究组均接受冻融胚胎移植(FET),并在30~35 d后利用超声明确其妊娠情况;根据妊娠结局将研究组分为妊娠成功组、妊娠失败组,比较2组VEGF基因多态性情况。采用Logistic回归分析探讨VEGF基因多态性对薄型子宫内膜患者妊娠结局的影响;绘制受试者工作特征(ROC)曲线,分析VEGF基因多态性预测薄型子宫内膜患者妊娠失败的价值。结果相较于-2578C/A位点AA+CA基因型,携带CC基因型薄型子宫内膜的发病风险增加1.412倍(95%CI:1.004~1.985),等位基因C突变可使发病风险增加1.526倍(95%CI:1.066~2.186);与-1154G/A位点GA+AA基因型相比,携带GG基因型薄型子宫内膜的发病风险增加1.467倍(95%CI:1.011~2.128),等位基因G突变可使发病风险增加1.531倍(95%CI:1.026~2.284);2组VEGF基因-460C/T、+936C/T位点基因型、等位基因分布情况比较,差异无统计学意义(P>0.05)。研究组100例薄型子宫内膜患者FET后,40例妊娠成功。妊娠成功组与妊娠失败组VEGF基因-2578C/A、-1154G/A位点基因型分布情况比较,差异有统计学意义(P<0.05)。经Logistic回归分析发现,携带VEGF基因-2578C/A位点CC基因型与-1154G/A位点GG基因型是影响薄型子宫内膜患者妊娠结局的危险因素(OR>1,P<0.05)。ROC曲线显示,VEGF基因-2578C/A、-1154G/A位点基因多态性预测薄型子宫内膜患者妊娠失败的曲线下面积(AUC)为0.801(95%CI:0.552~0.838)。结论携带-2578C/A位点CC基因型、-1154G/A位点GG基因型会增加薄型子宫内膜患者发病风险,降低薄型子宫内膜患者妊娠成功率,且VEGF基因-2578C/A、-1154G/A位点基因多态性可有效预测薄型子宫内膜患者妊娠失败风险。

Objective To analyze the influencing of vascular endothelial growth factor(VEGF)gene polymorphism on success rate of embryo implantation in patients with thin endometrium.Methods A total of 100 patients with thin endometrium from the gynecological outpatient and inpatient departments of the hospital from June 2022 to December 2023 were selected as study group,and another 100 healthy adult women from the physical examination department in the same period were selected as control group.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to determine the single nucleotide polymorphism at four different loci of the VEGF gene.Allele-specific PCR(AS-PCR)was used to analyze the distribution of VEGF genotypes and allele frequencies at the corresponding loci in both groups.The study group underwent frozen-thawed embryo transfer(FET),and their pregnancy conditions were confirmed by ultrasound 30 to 35 days later.Based on pregnancy outcomes,the study group was divided into successful pregnancy group and failed pregnancy group,and VEGF gene polymorphism between the two groups was compared.Logistic regression analysis was conducted to investigate the influence of VEGF gene polymorphism on pregnancy outcomes in patients with thin endometrium.Receiver operating characteristic(ROC)curve was plotted to assess the predictive value of VEGF gene polymorphism for pregnancy failure in patients with thin endometrium.Results Compared with the AA+CA genotype at the-2578C/A locus,patients carrying the CC genotype had increased risk of developing thin endometrium by 1.412 times(95%CI,1.004 to 1.985),and the allelic mutation C showed increased risk by 1.526 times(95%CI,1.066 to 2.186).Similarly,compared with the GA+AA genotype at the-1154G/A locus,patients carrying the GG genotype had increased risk of developing thin endometrium by 1.467 times(95%CI,1.011 to 2.128),and the allelic mutation G showed increased risk by 1.531 times(95%CI,1.026 to 2.284).There were no significant differences in VEGF gene genotypes and allele distributions at the-460C/T and+936C/T loci between the two groups(P>0.05).Among the 100 patients with thin endometrium in the study group,40 cases had successful pregnancies after FET.There were significant differences in the distribution of VEGF gene genotypes at the-2578C/A and-1154G/A loci between the successful pregnancy group and the failed pregnancy group(P<0.05).Logistic regression analysis revealed that carrying the CC genotype at the-2578C/A locus and the GG genotype at the-1154G/A locus were risk factors for pregnancy outcomes in patients with thin endometrium(OR>1,P<0.05).The ROC curve showed that the area under the curve(AUC)for predicting pregnancy failure in patients with thin endometrium based on VEGF gene polymorphisms at the-2578C/A and-1154G/A loci was 0.801(95%CI,0.552 to 0.838).Conclusion Carrying the CC genotype at the-2578C/A locus and the GG genotype at the-1154G/A locus can increase the risk of developing thin endometrium and reduce the success rate of pregnancy in patients with thin endometrium.Moreover,VEGF gene polymorphisms at the-2578C/A and-1154G/A loci can effectively predict the risk of pregnancy failure in patients with thin endometrium.