Binucleated and micronucleated blastomeres in embryos derived from human assisted reproduction cycles

Abstract

This prospective sequential, cohort study examined the two most common multinucleation phenotypes observed in the authors' clinic, binucleated (BN) and micronucleated (MN) blastomeres, and included all intracytoplasmic sperm injection (ICSI) patients <40 years of age with at least one multinucleated embryo in the cohort as observed on day 2 of development. Eighty ICSI cycles of 560 consecutive cycles had multinucleated embryos (14.3%). Of the 80 cycles, 770 embryos were derived; 183 (23.8%) were observed to be multinucleated. Blastocyst rates were significantly higher with BN than MN embryos. MN embryos were more often derived from embryos with poor pronuclear morphology (41/81 = 50.6%). Transferred mononucleated sibling embryos from the BN group had an ongoing pregnancy rate of 48% (12/25) compared with 15.4% (4/26 from the group with MN embryos (P = 0.03). The implantation rate for sibling embryos from the BN group was higher than for those from the MN group. Fluorescence in-situ hybridization (FISH) analysis showed that BN embryos had normal blastomeres significantly more frequently than MN embryos (9/28 (32.1%) versus 1/27 (3.7%), P = 0.016). Time-lapse photography showed that the nuclei of both morphologies dissolved independently before the next mitotic division and that BN blastomeres definitely have two distinct nuclei. These observations indicate two diverse morphologies and causal mechanisms. Time-lapse photography showed that both were subject to independent dissolution of their nuclear membrane suggesting an asynchrony between the nuclei and a possible interruption in proper nuclear and cell division. Multinucleation should definitely be looked for during IVF assessment. Excluding these embryos from transfer is prudent practice.