The effect of follicle size and homogeneity of follicular development on the morphokinetics of human embryos.

PURPOSE: Our aim was to investigate follicular size (large, ≥17 mm and small, <17 mm) at the time of OPU and homogeneity of follicular development (homogenous development: follicles being present in a homogenous spread of all sizes; heterogeneous: a predominance of small and large follicles) by analysing the morphokinetics of embryo development. METHODS: In this prospective cohort study, 2526 COCs belonging to 187 patients were cultured to day 5. Embryos were evaluated morphokinetically. Four subgroups were defined: large follicles from heterogeneous cycles (LHet) and homogenous cycles (LHom) and small follicles from heterogeneous cycles (SHet) and homogenous cycles (SHom). RESULTS: Rates of fertilization, blastocyst formation and top and good quality blastocysts were found to be significantly higher in embryos from the LHom group (p < 0.001; p < 0.001; p < 0.001). Small follicles from both homogenous and heterogeneous cycles had significantly lower blastocyst formation and top and good quality blastocyst rates (p < 0.001; p < 0.001). Embryos from SHet had significantly more direct cleavages (p = 0.011). Time to reach blastocyst was shorter in SHom than LHet and LHom (p = 0.002; p = 0.027, respectively). However, once the blastocyst stage was achieved, implantation rates were not significantly different between subgroups, the highest rate being observed in the LHom group. Multivariable analysis revealed that homogeneity of follicular development and follicular size had a significant effect on blastocyst development and quality (p = 0.049; p < 0.001, respectively). CONCLUSION: Follicular dynamics, illustrated by follicular size and homogeneity of follicular development, influence early human embryo development. Patterns of follicular growth have an impact on embryo quality and viability which is reflected in morphokinetic variables.

Relative kinetic expressions defining cleavage synchronicity are better predictors of blastocyst formation and quality than absolute time points.

PURPOSE: Morphology alone is not enough for the selection of the embryo (s) with the highest implantation potential and time-lapse imaging has added embryo development kinetics as another selection criterion. Therefore, a combination of morphology with kinetics has inspired a new field termed "morphokinetics", providing a new way of evaluating and selecting embryos. The aim of the study was to identify a criterion solely based on morphokinetic data and available up to the 8-cell stage (t8) to predict blastocyst formation and quality. METHODS: The study included 3,354 embryos, with annotations up to t8, and cultured until day 5 from 626 infertile patients. A total of 17 kinetic expressions, either absolute cleavage timings and time intervals or time ratios were tested retrospectively for the prediction of blastocyst formation and quality. RESULTS: Relative timings (t8-t5, the cleavage synchronicity from 4 to 8 cells and from 2 to 8 cells) were found to be better indicators of blastocyst formation and quality when compared to absolute time-points. Especially, the cleavage synchronicity from 2 to 8 cells (CS2-8) = ((t3-t2) + (t5-t4))/(t8-t2)) was found to be the best predictor available on day 3 for blastocyst formation and quality (AUC:0.786; sensitivity: 83.43; specificity: 62.46). CONCLUSIONS: Time intervals and relative ratios based on selected cleavage cycles defining synchronicity allowed a specific analysis providing high predictivity of blastocyst formation and quality.