Effect modification by developmental stage of embryos on the association between late follicular phase progesterone elevation and live birth in fresh transfers

Background Late follicular phase progesterone elevation (LFPE) during ovarian stimulation is associated with reduced live birth rates (LBRs) after cleavage-stage embryo transfer. However, due to better synchronization with a stimulated endometrium, prior studies shown that LFPE had no effect on transferring embryos at blastocyst stage. The study aim to exam whether the developmental stage of embryos and serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration jointly affect the odds of live birth in fresh fresh IVF/intracytoplasmic sperm injection (ICSI) cycles. Methods The single-center retrospective cohort study included a total of 4,471 fresh embryo transfer cycles with 2,342 at cleavage stage versus 2,129 at blastocyst stage. Patients underwent IVF/ICSI with ovarian stimulation in gonadotropin-releasing hormone antagonist protocol. The serum progesterone level was examined both as a continuous variable and as a categorical variable by quartiles. Analysis was performed using the generalized estimating equations framework and multivariate regression models. Results LBRs were inversely associated with progesterone as a continuous variable on the day of hCG in both the cleavage-stage (crude OR 0.87, 95%CI 0.73–1.03; adjusted OR 0.80, 95% CI 0.65–0.98) and the blastocyst-stage (crude OR 0.66, 95%CI 0.56–0,78; adjusted OR 0.61, 95%CI 0.50–0.73) groups. The interaction testing was highly significant ( P = 0.018) indicating an effect modifying role of stage of embryos transferred on the association of pregesterone values with the LBRs in fresh cycles. A similar pattern for a greater reduction in ORs for live birth in cycles with blastocysts transfer was also observed when progesterone was analyzed by interquartile ranges. The findings remained unchanged in subgroup analysis stratified by types of ovarian response. Conclusions In fresh cycles, detrimental effect of late follicular phase progesterone elevation on live birth was more prominent in blastocyst-stage group compared with that in clevaged-stage group.