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

During in vitro fertilization, cytoplasmic granulation patterns of metaphase II oocytes are predictive of fertilization, pregnancy, and live birth, suggesting an approach toward embryo selection, including ooplasm granulations.

VOLUME 116, ISSUE 2, P431-443


Jianjun Hu, M.D., Emanuela Molinari, Ph.D., Sarah Darmon, Ph.D., M.S., Lin Zhang, M.D., Pasquale Patrizio, M.D., M.S., David H. Barad, M.D., M.S., Norbert Gleicher, M.D.



To determine whether 4 cytoplasmic granulation patterns of human metaphase II oocytes have a predictive value for in vitro fertilization outcomes.


A retrospective cohort study.


An academically affiliated private clinical infertility and research center.


A total of 2,690 consecutive fresh autologous oocytes collected from women aged 41.2 ± 5.0 years between 2017 and 2019.


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.


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.


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.