P-151 Embrionary self-correction by excluding multinucleated cells improve the euploidy rates
Authors: Munuera Puigvert A , Montalvo V , Massó J , García-Faura A , García F , Marquès B , López-Teijón M 
Published: June 2022

Abstract

Study question
Could the exclusion of multinucleated cells from an embryo be a mechanism to dispose of cells with aberrant genetic content?

Summary answer
Exclusion of multinucleated cells could be a self-correction mechanism that would allow some embryos to exclude aneuploid cells.

What is known already
Multinucleation represents a poor prognosis morphologic trait related to low blastocyst formation rates and implantation rates. Moreover, it has been correlated with an increased rate of aneuploidies and chromosomal abnormalities, thus increasing misscarriage rates. Traditional morphokinetics ensure that excluding blastomeres during the compaction, the embryo could reduce its potential to achieve an euploid blastocyst. According to our previous studies multinucleated embryos excluding multinucleated cells during the blastocyst formation increase their reproductive potential. These studies assessed the clinical outcomes based on the morphokinetics of multinucleated blastomeres, without taking into account the chromosomal status of these embryos.

Study design, size, duration
Retrospective cohort study involving data from 157 PGT-cycles, performed between 2017 and 2019, with at least one multinucleated embryo. This trial included 678 embryos cultured until blastocyst stage using one-step culture media in time-lapse incubators (Embryoscope, Vitrolife) up to D + 5/6 when PGT-A was performed by trophectoderm biopsy using the NGS analysis technique in good quality embryos (≥3BB) according to the Gardner Score. Chi-square test for a contingency table was performed to compare all groups.

Participants/materials, setting, methods
Two main groups were considered: Control Group (CG; n = 474), embryos without multinucleation and Multinucleation Group (MNC; n = 204), embryos with at least one blastomere multinucleated on D + 2/3. Multinucleation Group was subdivided in three groups according to the multinucleation cell location using time-lapse technology to track them. MNC-1 (N = 87), no cells excluded; MNC-2 (N = 31), mononucleated cells excluded; MNC-3 (N = 41), multinucleated cells excluded. We had to exclude from the study 45 embryos that could not be follow up.

Main results and the role of chance
We observed multinucleation in the 20.33% of the embryos. MNC-3 (43.9%) achieved the higher euploidy rate, equivalent to the CG (43.9%); p = 0.998. MNC-1 (26.4%) and MNC-2 (22.6%) had lower euploidy rates than Groups MNC-3 and GC; p &lt; 0.05. Regarding to the aneuploidy rates, MNC-2 (77.4%) showed a higher rate than of the other groups (MNC-1=52.9%; MNC-3=41.5%; CG = 42.0%), being significant compared to the CG and MNC-3; p &lt; 0.05.
The mosaicism rate of the MNC-1 (20.7%) is significantly higher than that of the CG (14.0%); p &lt; 0.05.

Limitations, reasons for caution
Limitations include the retrospective analysis of data, the wide difference on sample size between MNC and CG groups and the amount of embryos excluded due to the impossibility to be monitored.

Wider implications of the findings
These results prove that embryos excluding multinucleated cells reach equivalent euploidy values than embryos without multinucleation.
This outcome, together with previous studies, suggest a self-correction capacity that would allow some embryos to detect and expel cells with aneuploid genetic content, thus improving the global chromosomal status of the embryo.

Trial registration number
not applicable