A Study Of Intrauterine Infusion Of Growth Hormone And Granulocyte Colony Stimulating Factor In The Treatment Of Repeated Implantation Failure

Objective(s):Contrasting the efficiency of intrauterine infusing of growth hormone(GH)and granulo cytecolony stimulating factor(G-CSF)in the frozen embryo transfer(FET)outcome of repeated implantation failure(RIF).A control group with no treatment was set in this study.During the treatment,B-ultrasound examination was used to observe some relative items to seek the possible function mechanism of these two factors.Methods:This is a randomized controlled study,118 patients with RIF undergoing FET from September 2019 to January 2021 were included.They were randomly divided into three groups:G-CSF group(n=39),GH group(n=40)and blank control group(n=39).Intrauterine infusion of G-CSF or GH were given to patients in the study group on the 10th,12th and 14th day of the FET cycle,while no any other treatment was given to the patients in the control group.All patients were treated with hormone replacement protocol for the endometrial preparation before frozen thawed embryo transfer(FET),and tansvaginal ultrasound examination on the 10th day of the cycle and the day of endometrial transformation was performed.The Endometrial peristalsis wave,blood flow parameters,thickness and bilateral uterine artery blood flow parameters of the patients were observed.Endometrial transformation was performed after the endometrial thickness and hormone level reached the standard.Human chorionic gonadotropin(hCG)was detected on the 14th day after embryo transfer,and the gestational sac was detected by ultrasound on the 30th day.Finally,the statistical data were analyzed and its clinical significance was discussed.Results:The embryo implantation rates of G-CSF group,GH group and blank control group were 36.36%(28/75),48.05%(37/77)and 25.97%(20/77)respectively.Significantly Statistical difference was observerd(p=0.004)of the between GH group and control group,the embryo implantation rate of G-CSF group was higher than control group,but no statistical difference was also observed(p=0.091).Regarding to the clinical pregnancy rate,G-CSF group is 38.46%(15/39),GH group is 45.00%(18/40),blank control group is 28.21%(11/39),both of the study groups were higher than the control group,but the difference was not statistically significant(p=0.299).The highest clinical value of biochemical pregnancy was in G-CSF group at 15.38%(6/39),followed by 12.50%(5/40)in GH group,and 7.69%(3/39)in control group,and there was no statistical significance between the three groups(p=0.569).The endometrial blood flow parameters(PI 0.68 ± 0.12,RI 0.44±0.16,S/D1.87 ± 0.52)of GH group were lower than those in G-CSF group(PI 0.76±0.10,RI 2.18 ± 0.49,S/D 2.18 ± 0.49),blank control group(PI 0.74 ± 0.09,RI 0.09,RI)and G-CSF group(PI 0.76 ± 0.10,RI 2.18 ± 0.49,S/D 2.18±0.49),and blank control group(PI 0.74±0.09、RI 0.46±0.13、S/D2.15 ± 0.62).Significantly statistical difference of PI,S/D of the other two groups was observed(p<0.05).Regard to the endometrial peristalsis wave,the amplitude of peristalsis wave in G-CSF group was significantly lower than that of the other two groups(p=0.040),however,no statistical difference was observed on the frequency and direction of peristalsis wave among the three groups.Regard to endometrial thickness,no significant difference among the three groups was observed(p>0.05),which were 9.03 ± 1.80mm in G-CSF group,9.50 ± 2.31mm in GH group and 9.61 ±2.0mm in blank control group.Regard to the parameters of uterine artery blood flow among the three groups,no significant difference was observed on the day of endometrial transformation.Correlation analysis shows the indexes such as the parameters of endometrial blood flow,amplitude of peristalsis and age of patients,RIF times and pregnancy outcome,no statistically significant correlation was found between the indexes and the outcome of pregnancy.Conclusion(s):1.Intrauterine perfusion with GH for patients with RIF before embryo transfer can improve the embryo implantation rate;2.Intrauterine perfusion with GH can reduce the PI and S/D of endometrial blood flow in patients with RIF,which may improve the endometrial blood flow perfusion;3.Intrauterine perfusion with G-CSF can reduce the amplitude of endometrial peristalsis wave in patients with RIF,which may be conducive to embryo implantation.