Improving embryo selection by the development of a laboratory-adapted time-lapse model

Abstract

Objective: To study whether a powerful, in-house, embryo-selection model can be developed for a specific in vitro fertilization (IVF) laboratory where embryos were already selected for transfer using general models. Design: In total, 12,944 fertilized oocytes were incubated in an EmbryoScope (Vitrolife, G€ oteborg, Sweden) at our laboratory. Embryos were selected for transfer or freezing using general models. There were 1,879 embryos with known implantation data (KID), of which 425 had positive KIDs. For the outcome, we set 3 endpoints for KID's definition: gestational sac, clinical pregnancy, and live birth. Results of a comparison between KID-positive and -negative embryos for cell division timings were analyzed separately for intracytoplasmic sperm injection (ICSI) and IVF embryos in patients aged 18-41 years. Setting: IVF center. Patients: The study included 1,075 women undergoing IVF or ICSI treatment between June 2013 and February 2019. Intervention(s): None. Main Outcome Measure(s): The KID-positive and -negative embryos were analyzed for statistical differences in cell division timing and cell cycle intervals. We used the EmbryoScope Stats software (Unisense FertiliTech, Aarhus, Denmark) for model development. The statistically different timing parameters were tested for their contribution to scoring in the model. The algorithms were tested for area under the receiver operating characteristic curve (AUC) in the KID embryos for developing day-2, -3, and -5 embryo-selection models. The validation of these algorithms was performed using calibration/validation procedures. Results: Because significant differences in morphokinetics were found between the KID-positive and KID-negative embryos in our laboratory, it was possible to use our specific KID data to develop an in-house model. The algorithms were developed for embryo selection on days 2, 3, and 5 in the ICSI embryos. In most cases, AUC was >0.65, which indicated that these models were valid in our laboratory. In addition, these AUC values were obtained from all gestational sac, clinical pregnancy, and live birth KID embryo databases tested. An increase in the predictability of the models was observed from days 2-3 to day 5 models. The AUC test results ranged between 0.657 and 0.673 for day 2 and day 3, respectively, and 0.803 for the day 5 model. Conclusion:A model based on laboratory-specific morphokinetics was found to be complementary to general models and an important additive tool for improving single embryo selection. Developing an in-house laboratory-specific model requires many stages of sorting and characterization. Many insights were drawn about the model developing process. These may facilitate and improve the process in other laboratories. (Fertil Steril Sci Ò 2021;2:176-97. Ó2021 by American Society for Reproductive Medicine.

Evaluation of fragmented embryos implantation potential using time‐lapse technology

“…By using the cell division timing grouped quartiles (previously published by our group and presented in Table S1), 24 we found that fragmentation and morphokinetics were independent variables for clinical pregnancy in embryos which had up to 32% final fragmentation. We were able to show that there was no correlation between morphokinetics and degree of fragmentation up to 32% fragmentation.…”

“…Following embryo scoring by KIDScore D5 v.3 model, the embryos were examined also by our in‐house model 24 . For some severely fragmented embryos it was not possible to recognize all their division times and therefore to perform a full annotation.…”

“…Several studies showed that there is a need for an individual laboratory‐adapted model for embryo selection in addition to the general models 24 . We developed a laboratory‐adapted model based on our known implantation data (KID) embryos.…”

Embryo fragmentation – Is it really a detrimental factor?

“…The different quartiles represent different implantation potential. Embryos with t2 and with tSB in quartile 1 (Q1) had a higher chance to implant than embryos with t2 and tSB in quartile 4 [24]. The t2 and tSB of most of the fragmented embryos were equally distributed in the rst 3 quartiles (Table 1A) and were not concentrated in quartile 3 or 4 as one may assume.…”

“…Lately, morphokinetic time-lapse evaluation of embryos is a widespread tool used for embryo selection. We previously reported that the different morphokinetic quartiles are in correlation with clinical pregnancy and that shorter division timings yielded a signi cantly higher pregnancy rate [24]. Rhenman et al found that the degree of fragmentation is an independent signi cant predictor for success rate.…”