HIGH OOCYTE IMMATURITY RATES IMPACT EMBRYO MORPHOKINETICS: LESSONS OF TIME-LAPSE IMAGING SYSTEM

Abstract

Up to 30% of the retrieved oocytes are still immature after controlled ovarian stimulation (COS). The ovarian asynchrony can be indicative of less responsiveness to COS, and oocyte immaturity rate may reflect the developmental competence of the entire cohort. Time-lapse imaging (TLI) systems allow for the mapping of morphological changes or events with the exact time-point of occurrence. The aim of this study was to investigate the impact of oocyte immaturity rate on morphokinetic events in a TLI system. This retrospective cohort study was performed in a private university-affiliated IVF center from March 2019 to December 2020 and included 3368 injected oocytes, cultured in a TLI incubator, from 474 ICSI cycles. Immature oocytes rates were defined as the number of germinal-vesicle (GV) plus Metaphase-I oocytes (MI) divided by the number of retrieved oocytes in each cycle. The effects of immature oocytes rates on morphokinetic events were investigated taking into account clustering of data (multiple embryos per cycle), using generalized mixed models. Evaluated kinetic markers were: pronuclei appearance (tPNa), timing to pronuclei fading (tPNf), timing to two (t2), three (t3), four (t4), five (t5), six (t6), seven (t7), and eight cells (t8), and timing to start of blastulation (tSB) and to blastulation (tB). Durations of the second and third cell cycles (cc2 and cc3, respectively) were also evaluated. The post hoc achieved power was > 95.0%. From 4120 retrieved oocytes, 3130 were mature (MII), and 990 were immature (660 GV and 330 MI). Positive relationships were observed between the rates of immature oocytes and slower tPNa (B: 0.053, CI: 0.045 – 0.061, p<0.001), tPNf (B: 0.081, CI: 0.070 – 0.093, p<0.001), t2 (B: 0.076, CI: 0.064 – 0.087, p<0.001), t3 (B: 0.070, CI: 0.056 – 0.084, p<0.001), t4 (B: 0.070, CI: 0.055 – 0.084, p<0.001), t5 (B: 0.083, CI: 0.063 – 0.102, p<0.001), t6 (B: 0.066, CI: 0.047 – 0.086, p<0.001), t7 (B: 0.076, CI: 0.055 – 0.098, p<0.001), t8 (B: 0.064, CI: 0.040 – 0.087, p<0.001), tSB (B: 0.090, CI: 0.014 – 0.165, p=0.020), tB (B: 0.043, CI: 0.011 – 0.075, p=0.009), and cc3 (B: 0.018, CI: 0.005 – 0.031, p=0.007). No significant associations were found between oocyte immaturity rate and clinical outcomes. Increasing oocyte immaturity rate correlates with delayed cell cleavage and blastulation. These findings highlight the importance of TLI for the identification and de-selection of slow-growing embryos for transfer, in cycles with high oocyte immaturity rate.