Abstract

Abstract Study question What are the developmental competence and clinical value in ICSI cycles of retrieved metaphase-I oocytes matured in vitro (rescued-MI) to the metaphase-II (MII) stage? Summary answer Rescued MI-oocytes showed lower developmental but similar post-implantation competence than their sibling MII-oocytes, thereby contributing to a + 9.5% relative-increase in the cumulative-live-birth rate per completed-cycle. What is known already MI-oocytes are typically excluded from ICSI. Nevertheless, some authors reported their use in cancer or poor responder patients. On average, 15-20% of the oocytes retrieved in IVF are immature, but 45% of them may mature within a few hours of culture. These rescued-oocytes showed lower developmental, chromosomal and reproductive competence. Regardless, they might be valuable for some patients. To date, most of the studies were conducted including patients using own oocytes, thus implicitly involving the bias of infertility and poor prognosis. Here we aimed at outlining the clinical value of rescued-MI oocytes in the context of egg donation cycles. Study design, size, duration Observational study conducted at a private IVF center including 284 fresh oocyte donation cycles (Jan-2020 to Dec-2021). Two hours after oocyte-retrieval, all MI-oocytes identified after denudation were cultured for 1-2 additional hour(s). If reaching the MII-stage, they were inseminated via ICSI with ejaculated sperm, as for sibling MII-oocytes. Single culture in continuous media was conducted. MI- and MII-derived embryonic cohorts were monitored and compared. One-hundred-fifty-three cycles in the same period had no MI-oocyte available. Participants/materials, setting, methods Two-hundred-eighty-four cycles were conducted from 272 recipients (42.1±4.0 years) with fresh oocytes retrieved from 215 donors (25.5±5.0 years). All sperm samples were ejaculated (42.3% fresh; 15% oligoasthenoteratozoospermic). The number of MI- and MII-oocytes after denudation was 2.2±1.3 (range:1-7) and 7.5±1.6 per cycle, respectively. 1.7±1.2 (0-6) MI-oocytes matured in vitro (rescue-rate: 78.1±33.4%) and were inseminated. Embryological data were compared between sibling MI- and MII-derived cohorts. Clinical data and relative contributions of MI-oocytes were also reported. Main results and the role of chance The mean fertilization rate per cohort of inseminated MI- and MII-oocytes were 54.3±43.0% and 74.4±18.1%, respectively (paired t-test<0.01). The mean blastulation rate per cohort of MI- and MII-derived zygotes were 53.1±44.4% and 59.1±25.9%, respectively (paired t-test=0.1). Overall, 0.5±0.7 (0-4) MI-derived blastocysts were obtained adding up to the 3.2±1.7 MII-derived ones, thereby resulting in a + 20.8±40.1% (0 to + 300%) relative increase per cycle. Overall, 268 (94%), 247 (89.7%), and 188 (66.2%) cycles had ≥1, ≥2 and ≥3 MII-derived blastocyst(s), respectively. These rates showed a + 1.1% (N = +3), +4.9% (N = +12) and +7.4% (N = +24) relative increase due to MI-derived blastocysts use. To date, 19 out of 63 MI-derived blastocysts transferred resulted in a live-birth (30.2%, 95%CI 19.6-43.2) versus 124 out of 399 MII-derived ones (31.1%, 95%CI 26.6-35.9; p = 0.99). We reported 4 miscarriages out of 27 clinical pregnancies (14.8%, 95%CI 4.8-34.6) versus 38 out 162 (23.5%, 95%CI 17.3-30.9, p = 0.45), respectively. To date, 70% (N = 199/284) of the cycles was concluded, with a cumulative-live-birth-rate of 61.3% (N = 122/199). This rate showed a + 9.5% (N = +18) relative increase due to MI-derived blastocysts use. Among 85 non-completed cycles, 19 (22.4%) have MI-derived blastocysts still available. Limitations, reasons for caution Retrospective study. A cost-effectiveness analysis is warranted, especially because MI-oocytes clinical use involves additional workload and costs. 31% (N = 44/140) of patients with ≥1 live-birth have supernumerary cryopreserved MI-derived blastocysts. Many cycles are not concluded. Gestational/perinatal outcomes were not reported. More data with own eggs and/or including chromosomal testing are needed. Wider implications of the findings Rescuing MI-oocytes might increase the number of blastocysts available per cycle, and possibly the cumulative-live-birth-rate. Nevertheless, this practice involves a higher workload and the production of more supernumerary blastocysts. Mostly poor prognosis couples might benefit from their use; therefore a couple-specific decision-making process is desirable. Trial registration number n/a

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