P-520 Factors associated with embryonic mosaicism: a systematic review and meta-analysis
Authors: Cascales A , Lledó B , Ortiz J.A , Morales R , Castro A , Ten J , Bernabeu A , Bernabeu R 
Published: June 2022

Abstract

Study question
What factors are involved in chromosomal mosaicism in human blastocysts?

Summary answer
Progenitors’ age and embryo biopsy day are associated with mosaicism rate.

What is known already
Chromosomal abnormalities are common in embryos analyzed in preimplantation genetic testing for aneuploidy (PGT-A) cycles. Mosaicism is a usual event in embryos derived from IVF cycles.
With the development of Next-Generation Sequencing (NGS) techniques, the ability to detect mosaicism in embryos has been improved.
Several studies show that mosaic embryos have reduced potential to reach term compared to euploid. Furthermore, the existing scientific evidence regarding the cause of embryonic mosaicism is scarce with conclusions generating considerable controversy.

Study design, size, duration
A systematic review and meta-analysis were conducted following the PRISMA guidelines on Medline and Google Scholar (January 2016 to December 2021).
Studies addressing factors associated with embryo mosaicism were comprehensively analyzed. As inclusion criteria: mosaicism should have been detected from a blastocyst trophectoderm biopsy on day 5,6 o 7 and analyzed by NGS.
Embryo quality, maternal and paternal age, day of biopsy and seminal quality were the outcomes variables included for analysis.

Participants/materials, setting, methods
A comprehensive database search resulted in 195 articles, 18 of which were included for abstract reading. Search, screen, and data extraction were performed by two reviewers independently based on inclusion criteria.
The study by meta-analysis of the effect of the different factors associated with embryonic mosaicism was carried out using the inverse variance method. Depending on the existence of heterogeneity between studies, the fixed effects method or the random effects method were used.

Main results and the role of chance
After critically and thoroughly reading the selected papers, 10 of them were included in the meta-analysis. Data from our reproductive clinic were also enclosed in the analysis (2513 cycles, 7242 embryos).
The results of the meta-analysis show that neither embryo quality nor seminal quality (male factor) were related to mosaic embryo rate (OR: 1.15; 95%CI: 0.98-1.35 and OR: 1.01; 95%CI: 0.80-1.27, respectively).
In contrast, a positive association with embryo mosaicism was observed for the variable “biopsy day” (OR: 1.06; 95% CI: 1.01-1.11): in embryos biopsied on day 6 or 7 of embryonic development, a small increase in the mosaicism rate was observed, in comparison with day 5. A significative positive association was also observed when we studied “paternal age” factor (OR: 1.13; 95% CI: 1.02-1.26): embryo mosaicism increases with paternal age.
On the other hand, maternal age showed a negative association with mosaicism (OR: 0.84; 95% CI: 0.74-0.95). Interestingly, in opposite to what happens with the aneuploidy rate, embryo mosaicism is higher in young women.

Limitations, reasons for caution
The main limitation is the low number of papers analyzed in the meta-analysis. Limitations also include the retrospective design and heterogeneity of studies, limiting comparison and pooling of data. Nonetheless, our conclusions were based on studies with low risk of bias.

Wider implications of the findings
Our result, combined with the body of medical evidence available suggest that embryo mosaicism rate is influenced by trophectoderm biopsy day and maternal and paternal age. This information will add in the knowledge for elucidating the uncertainties surrounding the factors by which mosaicism is generated in embryos.

Trial registration number
Not applicable