Abstract

Abstract Study question Are morphokinetic embryo behavior and embryo quality as per Known Implantation Diagnosis Score (KIDScore) assessment related to oocyte dimorphism in intracytoplasmic sperm injection (ICSI) cycles? Summary answer Morphokinetic embryo behavior and embryo quality as per KIDScore assessment are positively related with oocyte dimorphisms, which was demonstrated by delayed cell cleavage and blastulation. What is known already As a routine procedure in intracytoplasmic sperm injection (ICSI) cycles, denudation of retrieved oocytes allows the determination of maturation status and the assessment of morphological features of the cytoplasm, perivitelline space (PVS) and zona pellucida. Oocytes presenting extra and intracytoplasmic dimorphisms have been correlated to impaired embryo developmental potential and implantation. 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 relationship between oocyte dimorphisms an embryo morphokinetic events. Study design, size, duration This cohort study, performed in a private university-affiliated IVF center from Mar/2019-Dec/2021, included 156 ICSI cycles and 1158 injected oocytes cultured in a TLI incubator (EmbryoScope+). The presences of intracytoplasmic dimorphisms (granulation clusters, smooth endoplasmic reticulum (SER), dark cytoplasm and vacuoles), and extracytoplasmic dimorphisms (large perivitelline space (PVS), PVS granulation, polar body (PB) fragmentation and abnormal zona pellucida) were recorded, and their potential association with embryo morphokinetic events were investigated considering clustering of data. Participants/materials, setting, methods Evaluated kinetic markers were timing to pronuclei appearance (tPNa) and fading (tPNf), to two, three, four, five, six, seven, and eight cells (t2 - t8), to morulation (tM), start of blastulation (tSB) and blastulation (tB). Durations of the second (t3-t2) and third (t5-t3) cell cycles (cc2 and cc3) and timing to complete synchronous divisions s1 (t2-tPNf), s2 (t4-t3), and s3 (t8-t5) were calculated. The KIDScore ranking was recorded. The post hoc power was > 95.0%. Main results and the role of chance Morphologically normal oocytes (n = 747) reached tPNa (6.0 ± 0.1h vs. 6.4 ± 0.1h), t3 (36.5 ± 0.3h vs. 37.5 ± 0.2h), t6 (50.9 ± 0.5h vs. 52.1 ± 0.3h), tM (88.3 ± 0.8h vs. 91.6 ± 1.2h), tSB (97.4 ± 0.8h vs. 108.8 ± 3.6h), tB (104.7 ± 0.8h vs. 109.3 ± 0.5h) and cc2 (10.0 ± 0.3h vs 10.7 ± 0.2h) significantly faster than oocytes showing intracytoplasmic dimorphisms (n = 411). Significantly faster t5 (48.4 ± 0.3h vs. 50.5 ± 0.8h), t6 (51.5 ± 0.3h vs. 53.0 ± 0.7h), t7 (54.0 ± 0.3h vs. 57.1 ± 0.8h), t8 (57.9 ± 0.4h vs. 60.5 ± 0.9h), tB (107.9 ± 0.5h vs. 113.2 ± 1.1h) and cc3 (11.6 ± 0.2h vs. 13.5 ± 0.5h) were observed in normal oocytes compared to oocyte showing extracytoplasmic dimorphisms (n = 162). The incidence of extracytoplasmic dimorphisms per cohort was associated with decreased implantation (B: −23.9, CI: −37.8 – −10.1) and odds of pregnancy (OR: 0.360, CI: 0.163 – 0.796). KIDScore ranked significantly different between normal oocytes and those presenting ZP (3.8 ± 0.8 vs. 2.7 ± 0.8) and shape dimorphisms (4.1 ± 0.7 vs. 2.4 ± 1.0), and non-resistant membranes (4.4 ± 0.1 vs. 2.8 ± 0.1). Limitations, reasons for caution Despite the use of a nested statistical analysis that accounted for the fact that embryos from the same patient share comparable developmental behavior, this study has limitations, such as the retrospective design and small sample size, though an adequate power has been achieved. Wider implications of the findings This study adds to knowledge of oocyte quality role in embryo development. Dimorphic oocytes may have inefficient biological machinery. Significant differences, that could not have been noticed in a conventional incubator, were observed in embryo morphokinetic development when normal and abnormal oocytes were compared. Trial registration number N/A

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