The Predictive Value Of VEGF EG-VEGF IL-6 IL-18 On The Occurrence Of Ovarian Hyperstimulation Syndrome

Research background and purpose:In recent years,with the increasing of infertility patients,assisted reproductive technology(ART)has been widespread used.Ovarian stimulation by exogenous gonadotropins is the key to success of ART,but its side effects will lead to ovarian hyperstimulation syndrome(OHSS),which is one of the most serious complications.According to literature reports,the incidence of moderate and severe OHSS is 3%-10%,and for women with high risk factors,the incidence of OHSS is as high as 20%.At present,we can prevent OHSS through coasting therapy,GnRH-a trigger,whole embryo freezing,drug intervention and so on,but the basis of prevention is prediction,and there is no reliable index to predict it.Therefore,it is particularly important to clarify the OHSS prediction indicators.However,FF is the internal environment of oocyte growth and development,and the biological factors appearing in FF may be related to the occurrence and development of OHSS,or may be predictors of the OHSS.The purpose of this study was to explore the predictive value of OHSS by vascular endothelial growth factor(VEGF),endocrine gland-driven vascular endothelial growth factor(EG-VEGF),interleukin-6(IL-6),interleukin-18(IL-18)in FF on the day of oocyte retrieval in patients of high ovarian response.Materials and Methods:A total of 106 patients with high ovarian response who accepted IVF/ICSI in the center of assisted reproductive medicine of Sichuan Provincle People's Hospital from January to August 2019 were collected.FF was collected and centrifuged.Then the supernatant fluid were placed 2ml for storage at-80?.Enzyme linked immunosorbent assay(ELISA)was used for detection within 6 months.The patients were divided into OHSS group(76 people)and non OHSS group(30 people)according to the occurrence of OHSS.The differences of the general situation and the concentrations of VEGF,EG-VEGF,IL-6 and IL-18 in FF between the two groups were compared,and whether the above four biological factors had predictive value for the occurrence of OHSS was analyzed.At the same time,according to the severity of OHSS,patients in OHSS group were divided into mild group(43 people),moderate group(18 people)and severe group(15 people).The differences of concentration levels of four factors among the three groups were compared to analyze whether they have predictive value for the severity of OHSS.Result:1.The study included 106 patients with high ovarian response,30 patients without OHSS(non OHSS group),76 patients with OHSS(OHSS group),including 43 patients in mild OHSS group,18 in moderate OHSS group and 15 in severe OHSS group.2.Basic data of patients in OHSS group and non OHSS group:There was no significant difference in characteristics between OHSS patients and non OHSS patient,including age,duration of infertility,body mass index,basal follicle stimulating hormone(bFSH),basal estrogen(bE2),basal luteinizing hormone(bLH),number of MII oocytes,number of 2PN,total gonadotropin(Gn)dose and gonadotropin(Gn)duration.However number of oocytes retrievaled,the level of anti-mullerian hormone(AMH),antral follicle count(AFC)and estrogen(E2)on the day of HCG were higher in the OHSS group compared to that in the non OHSS group,the difference is statistically significant(P<0.05).3.Comparison of promotion ovulation programs between OHSS group and non OHSS group:There was no significant difference between OHSS group and non OHSS group in the composition ratio of GnRH-a programs and GnRH-A program(c2=0.2,P=0.905).4.Comparison of factors concentration in FF between OHSS group and non OHSS group:The concentrations of VEGF,EG-VEGF,IL-6 and IL-18 in FF of OHSS group were significantly higher than those of non OHSS group(P < 0.05).5.Comparison of factors concentration in FF of OHSS patients with different severity:The concentrations of EG-VEGF,IL-6 and IL-18 in FF increased with the severity of OHSS,but there was no significant difference between the groups(P > 0.05).The concentration of VEGF in FF of mild OHSS group was higher than that of moderateOHSS group and severe OHSS group,but there was no significant difference(P >0.05).6.Comparison of the concentrations of four factors in FF between OHSS group and non OHSS group with different promotion ovulation programs:Both OHSS group and non OHSS group,the concentrations of VEGF,EG-VEGF,IL-6 and IL-18 in the FF of GnRH-A program were lower than those of GnRH-a programs,but the difference was not statistically significant(P > 0.05).7.Correlation of VEGF,EG-VEGF,IL-6,IL-18 in FF:There was no correlation between the concentrations of VEGF,EG-VEGF,IL-18 in FF and the level of E2 in serum on trigger day(r = 0.113,P = 0.247;r = 0.162,P =0.098;r = 0.139,P = 0.155),while the concentration of IL-6 in FF was weakly correlated with the level of E2(r = 0.211,P = 0.03).The concentrations of VEGF,EG-VEGF,IL-6 and IL-18 in FF were all positively correlated,among which the correlation between EG-VEGF and IL-6 was the strongest(r = 0.901,P < 0.001).8.The predictive value of VEGF,EG-VEGF,IL-6,IL-18 in FF for OHSS:The AUC of VEGF,EG-VEGF,IL-6 and IL-18 in FF respectively were 0.759,0.773,0.759 and 0.741,which indicated that the four factors had a high predictive value for the occurrence of OHSS.Conclusion:1.The concentrations of VEGF,EG-VEGF and IL-18 in FF had no correlation with the serum E2 level on the day of trigger,while the concentration of IL-6 had weak correlation with the E2 level.2.There was significant correlation among VEGF,EG-VEGF,IL-6 and IL-18 in FF,among which IL-6 and EG-VEGF had the highest correlation.3.The concentrations of VEGF,EG-VEGF,IL-6 and IL-18 in FF were significantly increased in OHSS patients,which may be related to the occurrence of it,and have a high predictive value for the occurrence of OHSS,but can not predict the severity.