Metaphase I-arrest oocyte with agar-like zona pellucida, abandon or not abandon?

BACKGROUND: The morphological appearance of zona pellucida (ZP) is considered to be predictive of the quality of the oocytes and embryos. Agar-like ZP represents a common type of ZP abnormality, which is usually associated with significant defects in oocyte maturation and typically leads to unfavorable assisted reproductive technology (ART) outcomes. Currently, the intrinsic properties of agar-like ZP oocytes remain unclear, and effective strategies to improve the ART outcomes for such patients are still lacking. METHODS: We explored the intrinsic characteristics of metaphase I (MI)-arrest oocytes with agar-like ZP through RNA sequencing, immunofluorescence, and polarization microscope. Preemptive intracytoplasmic sperm injection (Pre-ICSI), i.e., performing ICSI on MI-arrest oocytes with agar-like ZP, was attempted, and its clinical outcomes were evaluated. What's more, we analyzed the potential mechanism of the effectiveness of Pre-ICSI. RESULTS: We uncovered the intrinsic nature of MI-arrest oocytes with agar-like ZP, revealing that these oocytes have inherently achieved nuclear and cytoplasmic maturation and should not be abandoned. Based on the fertilization and developmental potential of MI-arrest oocytes with agar-like ZP, we proposed Pre-ICSI as a targeted therapeutic strategy for such oocytes. Clinical results confirmed Pre-ICSI enabled the successful fertilization and development of these oocytes into available embryos, significantly improving the ART outcomes for patients with agar-like ZP. Further mechanical properties detection showed that the stiffness of agar-like ZP and narrow perivitelline space mechanically restrained the first polar body (PB) separating from the cytoplasm in space during the first meiosis. The mechanical intervention of Pre-ICSI, along with the dynamic changes in the cytoplasm post-insemination, provided space for the extrusion of PBs, thus facilitating the fertilization process. CONCLUSIONS: MI-arrest oocytes with agar-like ZP possess intact nuclear and cytoplasmic maturation, representing a highly viable and valuable gamete pool rather than inherently defective discards. When managed with the targeted Pre-ICSI strategy, these oocytes can be successfully rescued, significantly improving the yield of available embryos and the overall success rate of IVF for these patients.