COMPARISON OF TIME LAPSE AND CONVENTIONAL INCUBATORS WITH LABORATORY PERFORMANCE INDICATORS AND EUPLOIDY RATES: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract

Objectives

We aim to investigate whether time-lapse incubation systems have a favorable euploidy yield and day 5 embryo performances compared to conventional incubation.

Material and Methods

MEDLINE and Scopus databases were searched electronically till January 2024, using combinations of the relevant MeSH terms, keywords, and word variants for “time-lapse” AND “assisted reproductive technology”. The risk of bias in the included studies was assessed using the Cochrane RoB v2.0 for randomized trials. Only RCTs reporting the results of d5 embryos were included in the final analysis. The primary outcomes were blastulation and high-quality d5 embryo rates. The secondary outcome was the euploidy rate per biopsied embryo. After all abstracts and full texts (n=35) were reviewed independently by two authors (C.B., E.K.), 17 studies were selected for the final analysis. Analysis of the extracted data was performed with RStudio. A random-effects model with the Mantel-Haenszel method for pooling studies was used. ORs with 95% CIs were obtained, and variance between studies was tested using the I-squared statistic. Publication bias was explored using funnel plots and asymmetry tests (i.e. rank correlation).

Results

Random effect model in meta-analysis demonstrates favorable blastulation rates per embryo for TLS compared to conventional incubators [RR = 1.088, 95%CI = 1.01 to 1.17; 4 studies, 4923 fertilized eggs observed; p= 0.0189]. High embryo quality (HEQ) was defined as a higher grade than 3BB based on the Gardner classification system in all included studies. HEQ rate per fertilized embryo shows a positive trend for TLS compared to conventional incubators (CI), but there was no significance [RR = 1.10, 95%CI = 0.96 to 1.25; 6 studies, 5339 high-quality embryos in 11382 fertilized eggs, p= 0.178]. Only two sibling studies were found for the euploidy rate per biopsied embryo outcome, and a significant favorable tendency was found in TLS compared to CI [RR = 1.17, 95%CI = 1.02 to 1.35; 2 studies, 450 euploid embryos with 914 biopsies, p= 0.02]. Except for HQB rates, moderate heterogeneity was found in the other two outcomes. Risk of Bias assessment showed that in each study, there was at least one high-risk domain (e.g., assignment to intervention) in all included studies.

Conclusion

Time-lapse incubation systems may improve euploidy and blastulation rates compared to conventional ones, but the evidence is limited and inconclusive regarding significant overall benefits in embryo development. The low-to-moderate quality of evidence requires cautious interpretation. The scarcity of studies randomizing women in ploidy status assessment, relying predominantly on sibling oocyte randomization, significantly limits our understanding of these assessments' broader applicability and effectiveness.