Exploring the potential of metaphase I oocytes unresponsive to rescue IVM: fertilization, embryo development, and pregnancy outcomes

BACKGROUND: The aim of this prospective cohort study was to evaluate the developmental potential of metaphase I (MI) oocytes that failed to mature following rescue in vitro maturation (IVM), and to investigate the roles of artificial oocyte activation (AOA) and meiotic spindle presence in fertilization and early embryo development. METHODS: A total of 49 patients were included in the analysis. The study population was divided into 2 groups: an AOA group (28 patients, 42 MI oocytes) undergoing intracytoplasmic sperm injection (ICSI) followed by calcium ionophore-mediated activation, and a non-AOA control group (21 patients, 40 MI oocytes) undergoing ICSI without activation. Fertilization, embryo development, and clinical outcomes were compared between the groups. In addition, meiotic spindle presence was assessed using polarized light microscopy, and patients were categorized as spindle-positive or spindle-negative. RESULTS: Fertilization occurred in 23 of 42 MI oocytes (54.7%) in the AOA group, compared with 1 of 40 (2.5%) in the non-AOA group (p < 0.001). In the control group, fertilization was observed only in a spindle-positive patient, and the resulting embryo arrested before transfer. In contrast, embryos derived from AOA-treated oocytes were able to progress to the transfer stage. Among AOA-treated patients, fertilization rates were higher in the spindle-positive group than in the spindle-negative group (71.4% vs. 50.0%), although this difference did not reach statistical significance. A total of eight embryos reached the transfer stage, resulting in one biochemical pregnancy and one clinical pregnancy leading to a live birth. CONCLUSION: MI oocytes that fail to mature after rescue IVM appear to retain limited developmental potential. The use of artificial oocyte activation was associated with higher fertilization rates and enabled embryo development to progress to transferable stages in this cohort. The presence of a meiotic spindle may be associated with improved developmental competence and could represent a potential non-invasive marker; however, this observation requires further validation. Given the limited sample size and exploratory nature of the study, these findings should be interpreted with caution, and larger studies are needed to confirm their clinical relevance.