Between-laboratory reproducibility of time-lapse embryo selection using qualitative and quantitative parameters: a systematic review and meta-analysis

Abstract

Purpose To investigate the between-laboratory reproducibility of embryo selection/deselection effectiveness using qualitative and quantitative time-lapse parameters. Methods A systematic search was performed on MEDLINE, EMBASE, and the Cochrane Library (up to February 2020) without restriction on date, language, document type, and publication status. Measuring outcomes included implantation, blastulation, good-quality blastocyst formation, and euploid blastocyst. Results We detected 6 retrospective cohort studies externally validating the first clinical time-lapse model (Meseguer) emphasizing quantitative parameters, of which 3 (including one involving 2 independent centers) were included for the pooled analysis. Receiver operating characteristics analysis showed reduced predictive power of the model when either including or not including sister clinic validation. Fifteen cohort studies evaluating qualitative parameters were included for meta-analysis, and the mean Newcastle-Ottawa Scale was 5.3. Overall, meta-analysis showed significantly adverse association between the presence of ≥ 1 cleavage abnormalities and embryo implantation rates (11 studies, n = 7266; RR = 0.39[0.28, 0.55] 95% CI ; I 2 = 57%). Further analysis showed adverse impacts of direct cleavage (7 studies, n = 7065; RR = 0.28 [0.15, 0.54] 95% CI ; I 2 = 46%), reverse cleavage (2 studies, n = 3622; RR = 0.16 [0.03, 0.75] 95% CI ; I 2 = 0%), chaotic cleavage (2 studies, n = 3643; RR = 0.11 [0.02, 0.69] 95% CI ; I 2 = 24%), and multinucleation (5 studies, n = 2576; RR = 0.59 [0.50, 0.69] 95% CI ; I 2 = 0%), but not the < 6 intercellular contact points at the 4-cell stage (1 study, n = 185; RR = 0.17 [0.02, 1.15] 95% CI ). Conclusions Qualitative time-lapse parameters are reliably associated with embryo developmental potential among laboratories, whereas the reproducibility of time-lapse embryo selection model that emphasizes quantitative parameters may be compromised when externally applied.

Change in the Strategy of Embryo Selection with Time-Lapse System Implementation—Impact on Clinical Pregnancy Rates

“…), stimulation protocol, embryo culture techniques (fertilization method, culture media, gas composition), and embryo status (embryo quality and ploidy) [ 23 ]. Various authors report a lack of reproducibility between algorithms [ 24 ] or centers [ 25 ] and emphasise the need for either external validation of the models [ 26 ] or development of in-house algorithms based on the laboratory’s own data [ 27 ]. Nonetheless, the KIDScore™ (Vitrolife, Västra Frölunda, Sweden), a predictive model designed for EmbryoScope based on a large set of Known Implantation Data (KID) originating from a wide range of IVF clinics, would be universal and independent of culture conditions and fertilization methods [ 17 ].…”

Time-lapse monitoring technologies for the selection of bovine <i>in vitro</i> fertilized embryos with high implantation potential

“…Recent information on human embryo selection algorithms has been summarized in several systematic reviews [ 33 , 34 , 36 , 59 ]. Several human studies have indicated that blastocyst formation can be predicted by several quantitative parameters, such as the duration of the second cleavage [ 28 , 32 , 60 ], the duration of the second synchronization (time between 3-cells to the 4-cells stage) [ 31 , 32 , 61 ], the time to 2-cell [ 61 , 62 ], and the time to 5-cells [ 60 , 61 ].…”

Non-invasive evaluation of embryo quality for the selection of transferable embryos in human in vitro fertilization-embryo transfer

“…However, a recent meta-analysis reported that TLMS interventions were effective [101]. Two randomized controlled clinical trials demonstrated the efficacy of TLMS in various conditions in the last 6 years [102,103].…”