The Effect Of GnRH-Ant Protocol On Follicular Fluid And Serum IGF-â… , IGFBP-â…  And Sex Hormone

Objective:To discuss the effect of different doses of GnRH-ant on follicular fluid,serum insulin-like growth factor I,insulin-like growth factor-binding protein Iestrogen,progesterone to study if there were difference in the intrafollicular microenvironment caused by different doses and protocols for invitro ertilization and embryo transfer patients. To offer the basic theory for reasonable apply of GnRH-ant.Methods:We performed a prospective analysis of IVF/ICSI-ET patients’ data(due to tubal factor) in the second hospital, hebei medical university from October 2013 to January 2015.The inclusion criteria:①under 35 years old,regular pattern menstrual period(25 to 35d),spontaneously ovulation;②body mass index 18 to 24kg/m2; ③normal bilateral ovaries;④Serum prolactin in the normal range, the ovarian reserve function is normal(basal FSH ≤ 10 mlU / mL,basic sinus follicle count > 10, basal E2 level ≤ 50 pg / mL, FSH / LH <3.6).The eclusion criteria: ① History of tuberculosis(TB),radiotherapy or chemotherapy previous medical history;②Abnormal chromosome karyotype;③ hormone was applied in a short period of time(3 months);④Uterine malformation(such as uterus septum and uterus unicornis), submucous myoma, endometrial polyp and polycystic ovary syndrome; ⑤ have dependent on narcotic drugs.The patient information according to stimulate ovulation scheme is divided into three groups as follows:Group A(GnRH antagonists scheme 0.25 mg group)n=30:On the second day of menstrual period,We assessment ovarian basic state by transvaginal ultrasound and serum FSH,LH,E2 levels,opened in menstruation 2-3 days gonadotropin(Gn) controlled ovarian stimulation.When the dominant follicle reached about 14 mm or LH level about 5 mIU/ml or E2 level > 600 pg / ml GnRH-ant 0.25 mg / d were added,until the HCG injection day.Group B(GnRH antagonists scheme 0.125 mg group)n=30:On the second day of menstrual period,We assessment ovarian basic state by transvaginal ultrasound and serum FSH,LH,E2 levels,opened in menstruation 2-3 days gonadotropin(Gn) controlled ovarian stimulation.When the dominant follicle reached about 14 mm or LH level about 5 mIU/ml or E2 level > 600 pg / ml GnRH-ant 0.125 mg / d were added,until the HCG injection day.Group C:(GnRH agonist long protocol)n=30:fter exclusion of mid-luteal pregnancy,GnRH agonist 0.1 mg/d was used.until pituitary drop standard(FSH level < 5 mIU/mL,LH level < 5 mIU/mL E2 level ≤ 50 pg / mL)gonadotropin(Gn) controlled ovarian stimulationhe.We compared serum IGF-I,IGFBP-I,E2,P levels and E2/P on the day of HCG administration and follicular fluid IGF-I,IGFBP-I levels and their relationships on the day of ovum pick up,dosage of gonadotrophin,duration of stimulation,number of follicles above 16 mm in both ovaries and oocytes retrieved,mild to moderate OHSS,ICSI follicles maturation rate,fertilization rate,full-embryo cryopreserved rate,embryos cryopreserved rate,implantation rate,fresh cycle clinical pregnancy rate,fresh cycle live birth rate,the first cycle clinical pregnancy rate,the first cycle chemical pregnancy rate,the first cycle early abortion rate.The effect of different doses of antagonists on clinical outcomes were analyzed.Results:There was no significant difference between three programs in the BMI, the number of basal follicles,age,basal luteinizing hormone levels, basal ollicle-stimulating hormone levels,blood-based estradiol levels(P>0.05).Gonadotropin application time,gonadotropin application count,number of the follicles above 16 mm in ovaries,oocytes retrieved,endometrial thickness on the day of HCG,implantation rate,full-embryo cryopreserved rate,embryos cryopreserved rate,implantation rate,fresh cycle clinical pregnancy rate,fresh cycle live birth rate,the first cycle clinical pregnancy rate,the first cycle chemical pregnancy rate,the first cycle early abortion rate,compared three groups,there was no statistically significant difference(P>0.05).The ICSI follicles maturation rate of A group(88.77%)and of B group(83.90%) are higher than C group(71.79%)(P<0.05),while there was no difference between A group and B group(P>0.05).The fertilization rate of A group was higher than that in C group(P<0.05),and B group(P<0.05),while there was no difference between B group and C group(P> 0.05).Mild to moderate OHSS in C group(56.67%)was higher than that in A group(23.33%)(P< 0.05) and B group(3.33%)(P< 0.05),while there was no significant difference between A group with and B group(P> 0.05).Serum IGF-I levels on HCG day(70.65±18.56ng/L),serum IGFBP-I levels on HCG day(81.64±14.03ng/L),serum IGF-I levels on OPU day( 68.47±19.07ng/L),serum IGFBP-I levels on OPU day(104.68±14.13ng/L),follicular fluid IGF-I levels on OPU day(90.63±15.04ng/L),follicular fluid IGFBP-I levels on OPU day(145.66±32.80ng/L) in A group was significantly higher than B group and C group, data of B group was higher than the C group(P<0.05).Conclusion:1 The use of GnRH-ant can increase fertilization rate and the maturation rate of follicles,and serum IGF-I and IGFBP-I levels on HCG day and OPU day was increased,the follicular fluid IGF-I and IGFBP-I levels was increased on OPU day, and the rise of IGF-I IGFBP-I levels are positively correlate with alter the dose of GnRH antagonist. GnRH antagonists scheme can influence the microenvironment of inside the follicle,making the change in the direction of the benefits the egg development,but this change is not enough to affect clinical final outcome.2 Three groups of controlled ovarian hyperstimulation scheme have no effect on the full-embryo cryopreserved rate,embryos cryopreserved rate,implantation rate,clinical pregnancy rate,the first cycle early abortion rate,fresh cycle live birth rate.But application Gn RH antagonists solution(using antagonist) reduces the risk of OHSS occurred.