L26/P-149 Impact of extended in vitro maturation on oocyte developmental potential: a matched-pair analysis of 65,167 oocytes

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Abstract Study question Does in vitro completion of nuclear maturation in MI-derived oocytes prior to ICSI affect fertilization and blastocyst development compared with in vivo–matured MII oocytes? Summary answer MI-derived oocytes maturing in vitro show significantly poorer fertilization and blastocyst development, although their use may still increase cumulative blastocyst yield in selected patients. What is known already Oocytes retrieved at metaphase I (MI) can complete nuclear maturation in vitro and reach metaphase II (MII) before ICSI, but their true developmental competence remains controversial. In clinical practice, these oocytes are frequently discarded at denudation due to uncertainty regarding their fertilization and developmental potential and concerns that delayed nuclear maturation may not be accompanied by adequate cytoplasmic maturation. Previous studies have reported inconsistent outcomes, often limited by small sample sizes, heterogeneous laboratory protocols, and inadequate control of key confounders such as female age, oocyte origin, and center-related variability. Consequently, large, well-controlled multicenter studies focusing on MI-derived oocytes are scarce. Study design, size, duration Retrospective multicenter matched-pair cohort study including 65,167 oocytes from IVF/ICSI cycles performed between 2019 and 2026. Propensity score matching generated 1,689 balanced pairs comparing in vivo–matured MII oocytes with MI-derived oocytes completing maturation in vitro prior to ICSI. Participants/materials, setting, methods After retrieval, oocytes were incubated with cumulus cells, then denuded and cultured until ICSI. MI oocytes were classified as in vitro–matured MII only if first polar body extrusion was observed immediately before ICSI. Matching accounted for female age, oocyte origin (own or donor), oocyte type (fresh or vitrified), and center. Fertilization, degeneration, and blastocyst development were analyzed using McNemar, paired Wilcoxon, and Cochran’s Q tests, with odds ratios calculated from discordant pairs. Main results and the role of chance After matching, groups were identical across all covariates. MI-derived oocytes maturing in vitro showed significantly higher non-fertilization rates compared with in vivo–matured MII oocytes (27.8% vs. 13.4%; adjusted OR [aOR]=2.5, 95% CI 2.0–3.0) and increased abnormal fertilization (9.8% vs. 8.8%; aOR=1.4, 95% CI 1.1–1.9). Normal fertilization was significantly reduced (53.6% vs. 67.9%). Post-ICSI degeneration rates did not differ significantly between groups (9.8% vs. 8.9%; aOR=1.2, 95% CI 0.9–1.6). Blastocyst formation was markedly lower in in vitro–matured oocytes (19.8% vs. 36.3%), with a higher risk of failure to reach the blastocyst stage (aOR=2.4, 95% CI 2.0–2.8). All global tests were statistically significant (p < 0.001), except degeneration. The consistency between crude and adjusted estimates and the narrow confidence intervals indicate robust findings unlikely to be explained by chance. Limitations, reasons for caution The retrospective design precludes causal inference. Although extensive matching minimized confounding, unmeasured biological factors related to oocyte competence may persist. Strict matching criteria reduced the analytical sample, potentially limiting generalizability. Wider implications of the findings Although MI-derived oocytes maturing in vitro show significantly poorer outcomes at a statistical level, their clinical use may still be justified in selected patients, as insemination of these oocytes can increase the total number of available blastocysts and potentially improve cumulative reproductive chances. Trial registration number No

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