Abstract

Abstract Study question Are there any predictive factors supporting the decision of inseminating delayed-matured oocytes? Summary answer Patients with ≤59% mature oocytes at retrieval and/or Anti-Mullerian-Hormone (AMH) >2.52 ng/ml have increased chances of obtaining a euploid embryo from delayed-matured oocytes. What is known already Approximately 15% of oocytes retrieved after ovarian stimulation are immature, at metaphase I (MI) or germinal-vesicle (GV) stages at the time of oocyte denudation. Performing IVM in those oocytes could permit an increase on the number of usable embryos. Nevertheless, the utility of delayed-matured oocytes varies greatly among IVF laboratories with relatively low success rates, hence its practice in daily routine might be counter-productive. Determining which patient population could benefit from such strategy is valuable thereof to the clinical practice. Moreover, data comparing euploid rates of embryos derived from delayed-matured oocytes with its mature sibling oocytes are needed. Study design, size, duration This observational study was performed at ART Fertility Clinics, Abu Dhabi, UAE, between January 2019 and June 2021. A total of 5454 cumulus oocytes complexes (COC) were retrieved from 469 ovarian stimulation cycles. Out of the retrieved COCs, 3473 oocytes were immediate at metaphase II (MII-D0), and 915 were delayed-metaphase II oocytes (MII-D1). Participants/materials, setting, methods Patients with primary and secondary infertility undergoing Controlled ovarian stimulation (COS) in standardized protocols for IVF/ICSI treatment were included. Ovum pick up performed 34-36h post final oocyte maturation trigger shot (TS). Insemination was done 39-41h post TS for the MII-D0, while MII-D1 ICSI was performed 63-68h post TS. All cycles were planned for Preimplantation Genetic Testing for Aneuploidies (PGT-A) at blastocyst stage using Next Generation Sequencing (NGS). Main results and the role of chance Fertilization rates significantly differed between MII-D0 and MII-D1 oocytes (69.54% vs 55.96%, p < 0.001, respectively). Blastocyst utilization rates were significantly higher in MII-D0 group compared to MII-D1 group (59.47% vs 18.52%, p < 0.001). However, no difference was observed in the rate of euploid blastocysts between MII-D0 and MII-D1 (46.3% vs 39.0%, p = 0.163). As identified by univariant logistic regression analysis, the following parameters augmented the chances of obtaining at least 1 blastocyst for biopsy when MII-D1 were injected: AMH (OR 1.15, p < 0.001), number of COCs collected (OR: 1.03, P = 0.005), maturation rate on day0 (OR: 0.19, P = 0.001). When the multivariant analysis model was applied, AMH and maturation rate on day0 remained significant factors predicting the success of inseminating delayed-matured oocytes (OR:1.15, [CI:1.00-1.32], p = 0.045); OR:0.06, [CI:0.03-0.31], p < 0.001, respectively), with cut off values of AMH >2.52 ng/ml and maturity rate of ≤ 59%, being identified by ROC analysis. Limitations, reasons for caution ICSI of MII-D1 was performed with the fresh or frozen sperm samples from the previous day. Exact timing of polar body extrusion of delayed-matured MI/GV was not identified. Wider implications of the findings The results of this study might provide guidance to the IVF laboratories for targeting the patient population who would benefit from MII-D1 ICSI without adhering to unnecessary costs and workload. Trial registration number not applicable

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