From atypical fertilization to last-chance success: the real clinical value of 1PN-embryos in IVF

Abstract

Study question: Which is the contribution of 1PN-derived embryos to the cumulative live birth rate per oocyte retrieval (cLBR) in IVF? Summary answer: The use of 1PN-derived embryos as last chance involves ≥3% and ≥19% relative-increase in cLBR among cycles with ≥1PN-zygote and ≥1 1PN-derived embryo, respectively. What is known already: 1PN-zygotes display reduced developmental competence compared with 2PN-zygotes, but when reaching the blastocyst stage show comparable clinical outcome. In fact, cumulative evidence, including over 1000 transfers worldwide, suggests reassuring implantation and obstetric outcomes with no increase in adverse events. On this basis, ESHRE and Alpha, in the updated Istanbul consensus, support a cautious clinical use of 1PN zygotes, ideally combined with blastocyst culture and PGT-A for biparental diploidy assessment. Nevertheless, most data derive from single-center studies, and true 1PN status is often not confirmed through time-lapse imaging. Study design, size, duration: Retrospective observational multi-center study at 8 private IVF clinics in Sweden and Iceland between 2016 and 2024. All 46886 cycles included by 15600 couples (mean age:35.4yr, mean BMI:24.6Kg/m2; 19% characterized by severe-male-factor) underwent time-lapse culture. 1PN-zygotes were systematically cultured and, if developing into viable embryos, they were transferred as last-chance option. We assessed the relative contribution of 1PN-derived embryos to the cLBR overall, per cycle with ≥1 1PN-zygote and with ≥1 1PN-derived viable embryo. Participants/materials, setting, methods: All oocytes retrieved were inseminated by IVF and/or ICSI and cultured in time-lapse-incubators. Only untested single embryo-transfers were performed. First transfers, if fresh, were either at the cleavage- or blastocyst-stage (≥3BB). Only blastocysts (≥3BB) were vitrified. Multivariable mixed-effects logistic-regressions tested associations with live-birth in 1PN-embryos vs 2PN-embryos unmatched and matched per confounders. The relative-contribution of 1PN-embryos to cLBR was calculated as additional cycles with ≥1 LB divided by cycles that achieved ≥1 LB with 2PN-embryos. Main results and the role of chance: Overall, 448049 cumulus-oocyte-complexes were retrieved (mean:10.2 in 46886 cycles). The 218876 2PN-zygotes obtained (mean:5) resulted into 94482 useable 2PN-embryos (mean:2.2; 43.2% blastulation-rate) in 35054 cycles, while 13412 1PN-zygotes (mean:0.3) resulted into 1355 useable 1PN-embryos (mean:0.03 overall and 0.13 among cycles with ≥1 1PN-zygote cultured; 10.1% blastulation-rate, p