Time-lapse technology in the IVF laboratory. Assessing safety and human embryo development

Background: Time-lapse monitoring of human embryos is becoming increasingly utilized in clinical IVF laboratories. This technology allows for uninterrupted, continuous observation of embryo development without having to remove embryos from the controlled environment inside the incubator. Additional information about embryo development can be obtained and combined with traditional morphological evaluations. However, few randomized controlled trials have been performed investigating the efficacy and safety of closed culture systems utilizing time-lapse technology. Aim: To investigate in a randomized controlled trial (RCT) if the number of good quality embryos (GQEs) derived from culture in a closed system (the EmbryoScopeTM) was superior compared to culture in a conventional culture system. A further aim was to investigate if one or more morphokinetic variables could predict live birth after day 2 transfer, when analysed in combination with conventional morphology and patient variables. Materials and Methods: A total of 364 patients were randomized to culture until day 2 in either the EmbryoScope (n=240) or in a conventional incubator (n=124) at atmospheric O2 and 6% CO2. Only first cycle patients treated with ICSI (intracytoplasmic sperm injection) were included. In paper I the mean number of GQEs in each group was the primary endpoint. In paper II, time-lapse images of 207 transferred embryos from patients achieving the same number of live born children as transferred embryos, or no live birth, were analysed by logistic regression to determine predictors of live birth among morphological-, morphokinetic- and patient variables. Results: In Paper I, no significant difference was found in the mean ± SD number of GQEs between the groups cultured for two days in a closed (n=240), compared to a conventional (n=124) culture system (2.41±2.27 vs. 2.19±1.82, p=0.34). In Paper II, early cleavage and fragmentation grade were the only variables that independently could predict live birth (OR 4.84 (95% CI: 2.14-10.96) p=0.0002) and (OR 0.46 (95% CI: 0.25-0.84) p=0.012), respectively), early cleavage as a positive predictor and fragmentation grade as a negative predictor of live birth. No morphokinetic variables were independently predictive of live birth. Limitations: The primary outcome of the RCT, number of GQEs on day 2, was a surrogate variable for live birth (paper I). In addition, only ICSI patients were included, and different culture dishes for the time-lapse incubator and the conventional incubator were used. Conclusion: No benefit was found for the time-lapse system over the conventional system, with regards to the number of GQEs on day 2. None of the included morphokinetic variables were predictive of live birth