Comparison Of Ectopic Pregnancy Risk Among Transfers Of Embryos Vitrified On Day 3,day 5 And Day 6

Objective To compare ectopic pregnancy risk among transfers of embryos vitrified on day 3,day5 and day 6.Methods Data of patients undergoing 31,871 frozen-thawed embryo transfer(FET)cycles of in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)(13,853 pregnancies)in the Department of Assisted Reproduction,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine from March 2003 to May 2015 were collected and retrospectively analysed.Patients with uterine abnormities,patients having a simultaneous transfer of embryos vitrified on different days,patients getting embryos cryopreserved by slow freezing transferred,patients using rather than the three typical endometrial preparations,patients using embryos vitified on other days than day 3,day 5and day 6,and patients with cycle records with core data missing were not used.Finally,a total of10,908 pregnancies following 24,233 FET cycles of IVF/ICSI were included in our study.The ectopic pregnancy rate was compared by patient and treatment characteristics.In order to account for the correlation between all pregnancies reported by the same woman,goodness of fit was used to specify the best fitted generalized estimated equation regression models to calculate unadjusted and adjusted odds ratios(a OR)and 95% confidence intervals(CIs)for the association between ectopic pregnancy and significant characteristics selected from the univariate analysis(P<.20)plus year of treatment.To control for the impact of the significant characteristics on the overall chance of pregnancy,both the univariate and multivariate analyses were repeated using the number of transfers instead of the number of clinical pregnancies as the denominator to calculate the ectopic pregnancy rate.Results 1.Calculations with number of pregnancies as denominator:In the univariate analyses,the ectopic preganancy rates of the subgroups of patients transferred embryos vitrified on day 3,day5 and day 6 were 3.1%、1.9% and 0.6% respectively(P<0.05).In the univariate analyses,the ORs and 95% CIs for patients transferred embryos vitrified on day3,day 5 and other days compared with those transferred embryos vitrified on day 6 were 5.13(2.28-11.54)and 3.14(1.16-8.55)respectively,and the a OR and 95% CIs was 5.38(2.39-12.10)and2.88(1.05-7.87)respectively.2.Calculations with number of cycles as denominator:In the univariate analyses,the ectopic preganancy rates of the subgroups of patients transferred embryos vitrified on day 3,day 5 and day 6were 1.4%、1.1% and 0.3% respectively(P<0.05).In the univariate analyses,the ORs and 95% CIs for patients transferred embryos vitrified on day3,day 5 and other days compared with those transferred embryos vitrified on day 6 were 4.22(1.86-9.60)and 3.33(1.22-9.14)respectively,and the a OR and 95% CI was 4.09(1.85-9.06)and 3.17(1.16-8.65)respectively.Conclusion Day 6 vitrified embryo transfers are associated with a significantly lower risk of ectopic pregnancy both than day 3 and day 5 vitrified embryo transfers.The reduced ectopic pregnancy risk in day 6 vitrified embryo transfers indicates embryo factors may play important roles in the pathogenesis of ectopic pregnancy,and more individualized timing of embryo transfer in FET cycles may be needed to decrease the risk of ectopic pregnancy.