The Effect Of Gonadotropin Dosage,Peripheral Th1/Th2 Cytokines Profile On Pregnancy Outcomes After Assisted Reproductive Technology

Chapter 1The effect of gonadotropin dosage on blastocyst aneuploidy and live-birth ratesBackground The administration of gonadotropins in ovarian stimulation leads to supraphysiological steroid concentrations compared with those seen during natural cycles.It has been theorised that ovarian stimulation with exogenous gonadotropins(Gn)interferes in the natural selection of dominant follicles,increasing the rate of embryonic aneuploidy.Objective The study aims to determine whether an association exists between the total dose of exogenous gonadotropins and blastocyst aneuploidy,live-birth rates in the Han Chinese population.Materials and methods This is a retrospective study using anonymized data on preimplantation genetic testing for aneuploidy(PGT-A)cycles perfonned in China from 2013 to 2017.Data from 1088 PGT-A cycles and 3219 embryos were analyzed by array-comparative genomic hybridization(array-CGH).The study included 944 women who underwent PGT-A cycles with COH.Cycles were analyzed by the total dose of exogenous gonadotropins(<1500 IU,1500-3000 IU and>3000 IU),patient age(<35 and ?35 y.o.)and number of oocytes retrieved(1-5,6-10,11-15 and>15 oocytes).Outcomes In the group of younger women(<35 y.o.,537 PGT-A cycles),the incidence of aneuploidy ranged from 36.9%to 43.4%when data was stratified by gonadotropins dose.The adjusted logistic regression model showed that the dose of exogenous Gn was not correlated with the embryo aneuploidy rate.Similar results were shown in the group of women with advanced maternal age(?35 y.o.,551 PGT-A cycles),with no statistic difference in the rate of blastocyst aneuploidy in different gonadotropins dose groups(<1500 IU,58.0%;1500-3000IU,59.8%;and>3000 IU,59.8%;P=0.86).The live-birth rates after single cryopreserved blastocyst transfers were also not significantly associated with the gonadotropins dose.Conclusions This study demonstrates that the total dose of exogenous gonadotropins used for ovarian stimulation was not associated with embryo aneuploidy or live birth rates in PGT-A cycles.The finding suggests that the high doses of gonadotropins used in assisted reproductive technology(ART)cycles may be safe.Chapter 2Predictive value of peripheral Thl/Th2 cytokines on HCG day for embryo implantationBackground Assisted reproduction technology has been rapidly developed in the world,but there are still some problems have not been solved.Reproductive experts and patients pay attention to the problem of how to improve the implantation rate.It is believed that the percentage and function of circulating lymphocyte subsets may change during ovarian stimulation,some of these alterations may be correlated with embryo implantation in patients undergoing assisted reproduction technology.Objective To investigate the predictive value of circulating Thl/Th2 cytokines on HCG day regarding embryo implantation.Materials and methods Fifty-two peripheral blood samples were obtained on the day of HCG,from women who underwent in vitro fertilization-embryo transfer(IVF-ET)or intracytoplasmic sperm injection-embryo transfer(ICSI-ET)treatment.And according to the pregnancy outcome,patients were divided into the non-pregnancy group(nPG,N=29)and the successful pregnancy group(sPG,N=23).The peripheral cytokines including tumor necrosis factor-alpha(TNF-a),interferon-gamma(IFN-,?),interleukin 2(IL-2),interleukin 4(IL-4),interleukin 6(IL-6)and interleukin 10(IL-10).All cytokines were measured by flow cytometry.Outcomes The level of IFN-? was statistically higher in nPG than sPG.But no statistic difference was identified in the level of IL-2,IL-4,IL-6.IL-10 and TNF-?between the two groups.No significant change was found in the ratios of TNF-?/IL-4,TNF-?/IL-10,IFN-?/IL-4,IFN-?/IL-10,IL-6/IL-4 and IL-6/IL-10 between the nPG and sPG.The receiver operating characteristic curve analysis showed an area of 0.678 for serum IFN-y level in differentiating from implantation to non-implantation(95%confidence interval 0.529-0.826,P<0.05).The other Th1/Th2 cytokines had no significant predictive value for implantation.Conclusions The increased level of IFN-y on the day of HCG increased the risk of non-implantation after embryo transfer,which might be helpful to predict embryo implantation.However,the ratios of anti-inflammatory cytokines and pro-inflammatory cytokines was not helpful to predict embryo implantation.