The Effect Of GnRH-ant Protocols On Follicular Fluid And Serum IGF-â…¡, VEGF, E₂and P Levels In IVF Patients And Its Clinical Significance

Objective: To study the effect of different doses of GnRH-ant onfollicular fluid and serum insulin-like growth factor II (IGF-II), vascularendothelial growth factor (VEGF), estrogen and progesterone levels toinvestigate whether there was any difference in the intrafollicularmicroenvironment caused by different doses and protocols for invitroertilization and embryo transfer (IVF-ET) patients. To provide a theoreticalbasis for the rational use of GnRH-ant.Methods: We performed a prospective analysis of IVF/ICSI-ET patients’(due to tubal factor) data from December2012to January2014.Inclusioncriteria: Age <35years; body mass index (BMI)18-25kg/m2; regularmenstrual cycle (25-35d); spontaneously ovulation; normal serum PRL levels;normal ovarian reserve (basal FSH≤10mlU/mL, basic sinus follicle count>10, basal E2level≤50pg/mL, FSH/LH <3.6); uterine abnormalities,bilateral ovaries. Exclusion criteria: polycystic ovary syndrome; endometriosis;systemic disease; endocrine or metabolic abnormalities; received hormonetherapy in previous three months; previous radiotherapy and chemotherapytreatment; smoking; narcotics addicts. according to the different protocols, allpatients were divided into three groups: GnRH agonist long protocol:afterexclusion of mid-luteal pregnancy, GnRH agonist of0.1mg/d were givenuntil patients’ hormone level reached our standard (FSH level <5mlU／mLLH level <5mlU／mL, E2level≤50pg/mL) before the start of Gn.0.125mg antagonist protocol: On the second day of menstruation, we assessed thestate of the ovary basis by vaginal ultrasound and serum FSH, LH, E2levels,and then Gn was applied for ovarian stimulation. When the dominant folliclereached about14mm or LH level>5mIU/ml or E2level>600pg/ml GnRH-ant0.125mg/d were given.0.25mg antagonist protocol: On thesecond day of menstruation, We assessed the state of the ovary basis byvaginal ultrasound and serum FSH, LH, E2levels, and then applicate Gn forovarian stimulation. When the dominant follicle reached about14mm or LHlevel about5mIU/ml or E2level>600pg/ml GnRH-ant0.125mg/d wereadded. We compared serum IGF-II, VEGF, E2, P levels and E2/P on the day ofHCG administration and follicular fluid IGF-II, VEGF levels and theirrelationships on the day of ovum pick up, dosage of gonadotrophin, durationof stimulation, number of follicles above16mm in both ovaries and oocytesretrieved, risk of OHSS, ICSI follicles maturation rate, fertilization rate,cleavage rate, avaliable embryos rate, fresh cycle clinical pregnancy rate, thefirst cycle (fresh and frozen cycles) chemical pregnancy rate, the first cycleclinical pregnancy rate, implantation rate, full-embryo cryopreserved rate,embryos cryopreserved rate. The effect of different doses of antagonists onclinical outcomes were analyzed.Results: There was no difference between three groups in the BMI, age,duration of infertility, number of basal follicles, blood-based FSH levels,blood-based LH levels, basal E2levels (P>0.05). There was no significantdifference of the three groups in the dosage of gonadotrophin, duration ofstimulation, number of follicles above16mm in ovaries and oocytes retrieved,cleavage rate, available embryo rate, fresh cycle clinical pregnancy rate, freshcycle live birth rate, the first cycle pregnancy rate, the first cycle biochemicalpregnancy rate, the first cycle early abortion rate, embryo implantation rate,embryo cryopreserved rate(P>0.05). The ICSI follicles maturation rate of0.25mg antagonist protocol and0.125mg antagonist protocol were higher thanthat in GnRH agonist long protocol(P<0.05), while there was no differencebetween0.25mg antagonist protocol and0.125mg antagonist protocol (X2=1.727P>0.05). The fertilization rate of0.25mg antagonist protocol washigher than that in GnRH agonist long protocol (X2=4.618P<0.05), and in0.125mg antagonist protocol (X2=5.394P<0.05), while there was nodifference between0.125mg antagonist protocol and GnRH agonist long protocol (X2=0.085P>0.05). The risk of OHSS of0.25mg antagonistprotocol was lower than that in GnRH agonist long protocol (X2=6.944P<0.05),0.125mg antagonist protocol was lower than that in GnRH agonist longprotocol (X2=20.317P<0.05), while there was no difference between0.25mg antagonist protocol and0.125mg antagonist protocol (X2=5.192P>0.05).The full-embryo cryopreserved rate of0.125mg antagonist protocol waslower than that in GnRH agonist long protocol (X2=4.800P<0.05), whilethere was no difference between0.25mg antagonist protocol and GnRHagonist long protocol (X2=1.905P>0.05),0.25mg antagonist protocol and0.125mg antagonist protocol (X2=0.784P>0.05). Serum IGF-II levels onHCG day, serum VEGF levels on HCG day, serum IGF-II levels on OPU day,serum VEGF levels on OPU day, follicular fluid IGF-II levels on OPU day,follicular fluid VEGF levels on OPU day in0.25mg antagonist protocol wassignificantly higher than0.125mg antagonist protocol and GnRH agonist longprotocol,0.125mg antagonist protocol was significantly higher than in GnRHagonist long protocol (P<0.05). There was no difference between three groupsof serum E2levels on HCG day, P levels on HCG day and E2/P value onHCG day (P>0.05).Conclusions: Application of GnRH-ant can elevate the ICSI folliclesmaturation rate, fertilization rate, and serum VEGF and IGF-II-II levels onHCG day and the follicular fluid and serum VEGF and IGF-II-II levelsincreased on OPU day, and the elevate of VEGF and IGF-II-II levelspositively correlated with increasing doses of GnRH-antagonist. But there wasno difference between three groups of serum E2levels on HCG day, P levelson HCG day and E2/P value on HCG day. There was no effect on cleavagerate, embryo available rate, clinical pregnancy rate, fresh cycle live birth rate,the first cycle pregnancy rate, embryo implantation rate, embryocryopreserved rate. But GnRH-antagonist can reduce the risk of OHSS.Antagonist protocol can change follicles microenvironment to the benefit ofoocytes development, but this change is insufficient to affect the outcome ofpregnancy.