Germinal vesicle oocytes' rescue: a worthless treatment or a patient-centred approach? Eight years of clinical experience in poor prognosis patients.

study questionDoes germinal vesicle (GV) rescue by IVM provide a meaningful clinical benefit in patients with unexpectedly low mature oocyte yield, and which patient profiles are most likely to benefit? SUMMARY ANSWER: Especially in patients with more GV oocytes obtained, GV rescue increased the number of mature oocytes, zygotes, blastocysts, and euploid embryos per cycle, reduced transfer cancellation, and contributed to a 20% relative increase in cumulative live birth rate. WHAT IS KNOWN ALREADY: Immature oocytes retrieved during controlled ovarian stimulation are traditionally discarded due to their reduced developmental competence. Previous studies suggest that GV rescue may increase usable oocytes, but its clinical value, especially within a Pre-implantation Genetic Testing for Aneuploidies (PGT-A) framework, remains unclear. STUDY DESIGN, SIZE, DURATION: This retrospective clinical study analysed 8 years of GV rescue experience in a single centre (January 2017-December 2024), including 47 women (<39 years) undergoing ICSI with PGT-A who displayed suboptimal mature oocyte recovery (Metaphase II oocytes (MII) ≤6, maturity rate <80% relative to ≥14 mm follicles at ovulation trigger, and ≥4 GV oocytes). A sub-analysis of available time-lapse videos of rescued GV oocytes and sibling control MII oocytes was conducted to outline morphometric and morphodynamic determinants of rescue and blastulation. PARTICIPANTS/MATERIALS, SETTING,

methodsAll retrieved MII oocytes underwent ICSI, whereas GV oocytes were cultured in time-lapse systems for additional 24 h; those rescued (rMII) were inseminated. Outcomes included fertilization, blastulation, morphological quality, euploidy rates, and clinical outcomes after vitrified-warmed euploid blastocyst transfer. Patients' benefit was defined as obtaining ≥1 euploid blastocyst from rMII. Morphometric features (relevant areas, diameters, perimeters) and morphodynamic parameters (timing of GV breakdown [GVBD], metaphase-I duration and first polar body (PB1) extrusion, second polar body (PB2) extrusion, pronuclei appearance, juxtaposition and fading, and cleavage) were annotated. MAIN RESULTS AND THE ROLE OF CHANCE: Among 266 GV oocytes, 53.7% matured to MII, increasing the available MII yield per patient by 75%. Fertilization rates were comparable between MII and rMII, while blastulation was significantly lower for rMII. Nevertheless, rMII-derived blastocysts showed similar morphology and euploidy to controls and contributed ≥1 additional euploid embryo in 11 patients. These patients exhibited higher total cumulus-oocyte complexes, GV count, and superior rMII fertilization and blastulation, although the demographics and basal parameters as well as the sibling control MII competence were comparable. GV rescue contributed to an 8% relative increase in the number of patients with euploid blastocysts and to a 20% relative increase in the number of patients with a live birth. Successfully rescued GV oocytes were substantially larger and underwent faster GVBD. rMII oocytes were significantly smaller than sibling control MII oocytes. Among the former, earlier pronuclear juxtaposition and shorter cleavage timings were associated with successful blastocyst development. LIMITATIONS, REASONS FOR CAUTION: The design is retrospective at a private IVF centre. The sample size is small, although this is the consequence of purposely strict inclusion criteria. Findings apply to patients with unexpectedly low MII yield undergoing PGT-A cycles in experienced laboratories. WIDER IMPLICATIONS OF THE

findingsGV rescue represents a patient-centred strategy that can increase cumulative IVF success in cycles with limited mature oocyte yield. Further refining of patient selection criteria and standardizing this approach may enhance its clinical utility in future appraisals. The definition of artificial intelligence-powered pipelines to extract relevant morphometric/morphodynamic features to inform future predictive tools along with improvements in rescue protocols represent important upcoming innovations in this area of research. STUDY

fundingThe study was partially supported by the ESHRE Research Grant 2024. DISCLOSURES: The authors declare no conflict of interest related with the content of this manuscript. TRIAL REGISTRATION NUMBER: Not applicable.