High embryo yield (and not oocyte yield) despite low ovarian stimulation dose correlates with cumulative livebirth rate in normal-high responders undergoing IVF/ICSI

Abstract Study question Does a good response i.e., high oocyte or embryo yield with low ovarian stimulation correlate with cumulative live birth outcome in IVF/ ICSI treatment? Summary answer High ovarian sensitivity to stimulation (embryos to gonadotropin dose ratio) positively predicts cumulative live birth in IVF, while oocytes to stimulation dose ratio does not. What is known already The conventional belief that the higher the number of eggs retrieved, the better for IVF outcome has been challenged. Oocyte yield fails to predict fresh-cycle live birth in presence of high ovarian response. Ovarian sensitivity index (OSI) which is an expression of inherent ovarian responsiveness to stimulation remained overlooked as a predictor of success in IVF. We explore whether attention should be on the oocyte or embryo yield as a function of ovarian stimulation (OSI) can predictor of positive outcomes in IVF. Study design, size, duration Retrospective analysis of 750 patients who underwent IVF/ ICSI treatment with ≤150 IU of gonadotropin in an antagonist protocol due to predicted normal or high response. This is a further analysis of a previously published study covering a period between 1 January 2016 to 31 Dec 2018. Participants/materials, setting, methods Multi-centre study within a group company using the same treatment protocols. Participants were normal or high responders of IVF/ ICSI, predicted poor responders (according to Bologna criteria) were excluded. All patients received ≤150 IU daily dose of gonadotropin (FSH) in an antagonist cycle. Cumulative LBR calculated. Univariate and multivariate (regression) analysis, adjusting for all significant variables were done to find the predictors of cumulative livebirth. Main results and the role of chance When the women who achieved a livebirth were compared with those who did not, there was no difference in the mean BMI (23.7 vs 23.6, p = 0.81), antral follicle counts (p = 0.33), Anti-mullerian hormone levels (p = 0,89), mean starting (149.5 vs 140.5 IU/ day, p = 0.16), and total gonadotropin doses (1360.7 vs 1342.8 IU, p = 0.62). Women’s age (33.5 vs 35.3 years, p < 0.0001) and the number of embryos transferred (p < 0.0001) had significantly correlation with LBRs. There was no difference in the mean number of oocyte (9.1 vs 8,6, p = 0.21) or oocyte yield per unit of gonadotropin (7.4 vs 6.7, p = 0.32).. The mean number of embryos (5.4 vs 4.1, p < 0.0001), transferable embryos (2.5 vs 1.9, p = 0.0006) and embryo yield per unit of gonadotropin (4.1 vs 3.2, p < 0.0001) were significantly higher in the livebirth group. After adjusting for woman’s age and the number of embryos transferred, the embryo yield (both total (p < 0.0001) and transferable (p = 0.01) embryos and embryo yield per gonadotropin unit (p = 0.0007) were predictors of cumulative livebirth whereas oocyte yield and oocyte number per unit of gonadotropin were not. The above findings remained the same when only IVF cycles excluding male infertility or only the cycles with a fixed 150 IU/d gonadotropin dose were analysed. Limitations, reasons for caution A moderate-sized study population. The poor responders have been excluded to minimise variations in the protocol and stimulation dose. Wider implications of the findings Our study is a proof of concept of ‘ovarian sensitivity index’ indicating the inherent ovarian responsiveness rather than the strength of stimulation determines the IVF/ICSI outcome. Embryo yield appeared to be a predictor of cumulative livebirth while oocyte yield is not, in normal and high responders of IVF. Trial registration number Not applicable