Predictive value of cytoplasmic granulation patterns during in vitro fertilization in metaphase II oocytes: Part I, poor-prognosis patients

Objective: To determine whether 4 cytoplasmic granulation patterns of human metaphase II oocytes have a predictive value for in vitro fertilization outcomes. Design: A retrospective cohort study. Setting: An academically affiliated private clinical infertility and research center. Patient(s): A total of 2,690 consecutive fresh autologous oocytes collected from women aged 41.2 ± 5.0 years between 2017 and 2019. Intervention(s): Determination of granulation pattern in every oocyte during intracytoplasmic sperm injection as fine, central, dispersed, and newly introduced uneven granulations. Main Outcome Measure(s): Fertilization outcomes (2 pronuclei [2PN], <2PN, and >2PN rates), pregnancy, and live birth rates for different granulation patterns at different ages. Result(s): Fine granulation produced the highest 2PN rate, followed by central, uneven, and dispersed granulation (91.8%, 83.9%, 77.9%, and 54.8%, respectively). Differences in fertilization were surprisingly relatively independent of age and other variables. Overall, compared with fine granulation, dispersed granulation resulted in lower pregnancy rates (4.6% vs. 10.7%) and known-outcome analysis (1.3% vs. 5.6%) as well as lower live birth rates (3.0% vs. 8.9%) and known-outcome analysis (0.6% vs. 5.6%). The known-outcome analysis demonstrated that uneven granulation had lower live birth rates than fine granulation (2.3% vs. 5.6%). Unexpectedly, the ooplasm granulation patterns were largely disassociated from embryo morphologic grades. Conclusion(s): We, for the first time, demonstrated that 4 distinct cytoplasmic granulation patterns in metaphase II oocytes had, largely independent of age and other variables, a predictive value for fertilization, pregnancy, and live birth outcomes in in vitro fertilization cycles of poor-prognosis patients. These data suggest that upstream ooplasm granulation patterns deserve closer attention in terms of embryo selection.