Time-lapse embryo monitoring: does it add to standard in-vitro fertilization/intracytoplasmic sperm injection?

CAPSULE: This commentary is a collaborative effort of Professor Christine Wyns (Brussels, Belgium) and Dr. Yoshiharu Morimoto (Osaka, Japan). 

This paper underlines the evolution of time-lapse technology (TLT) in IVF translating from traditional incubators to incubators using built-in or not imaging systems to capture sequential images of the embryo during culture and allow the embryologist to closely monitor the embryonic development process in vitro without opening the incubator. Based on extensive morpho-kinetic data of the developing embryo various algorithms were developed and analyzed to help predict ART outcomes.

Technical parameters of several commercially available time-lapse systems (TLSs) such as type of illumination, single or grouped embryo culture and dishes, single or multiple planes of view and possibility or not to be used in conventional incubators are summarized in this paper.

This review further presents the current knowledge on TLT with regards to embryo blastulation and clinical outcomes:

❖ The possibility to discriminate between embryos with a higher likelihood to develop into a blastocyst was analyzed in multicentric studies, including thus different culture conditions and fertilization methods. Overall, these studies pointed to the need for further validation of the observations, although fastercleaving embryos seemed to have a better chance to reach the blastocyst stage.

❖ Among studies aiming to identify embryos with better clinical outcomes it was shown that euploid blastocysts developing after a morulation time of less than 80 hours post-insemination and having a high trophectoderm quality resulted in a significantly higher live birth rate, although in the specific culture conditions used.

❖ Meta-analyses including randomized controlled trials found controversial results on clinical outcomes when using TLSs versus conventional morphological assessment, most likely related to the high heterogeneity between studies, notably with regards to TLSs, culture conditions and day of embryo transfer.

❖ Two of the meta-analyses showed improvements in live birth rates and decreased miscarriage rates while one meta-analysis of ten RCTs concluded in the absence of a difference for ongoing pregnancy and live birth rates. Furthermore, the latest Cochrane published in 2019 did not find differences between use of TLSs or not in terms of live birth, clinical pregnancy, cumulative pregnancy, miscarriage, or

stillbirth rates.

❖ Based on a systematic review of 13 studies, none of the morpho-kinetic parameters appeared to be strongly associated with embryo ploidy and the current evidence is thus not in favor of using TLSs to select euploid embryos.

Besides some practical advantages of TLSs such as reduction in time spent by embryos outside the incubator conditions, a lower risk of human errors or collision of dishes, a reduced workload for lab technicians due to use of single-step media, need for fewer culture dishes and automation of embryo scoring, the authors point to laboratory team skills required to correctly position the embryos in the wells and to the need of some training for data interpretation. High costs related to purchase of the equipment, software and specific consumables are also highlighted.

Expert opinion:

❖ TLT allows to collect continuous and more accurate embryo evaluation by contrast to conventional fixed- timepoint microscopic observation.

❖ Aiming at a better embryo selection using TLT is in line with efforts to promote single embryo transfer but so far validated predictive morpho-kinetic criteria and algorithms that may allow improved clinical outcomes have not been identified.

❖ While it seems obvious that there is less disruption in culture conditions in TLSs, current recommendations are in favor of the need to have an internal lab validation of embryo morphokinetic parameters able to predict clinical outcomes, taking thus into account center specific culture conditions.

❖ Based on inconsistencies between available studies, discarding embryos based only on TLSs’ evaluation should currently be discouraged.

❖ Future efforts to obtain reliable and consistent data using TLT could be facilitated by the integration of artificial intelligence imaging diagnostic tools.

❖ Data collection and storage using TLT could promote data sharing and facilitate open science.

Acknowledgment: This commentary was co-authored by Professor Christine Wyns (Belgium) and Dr. Yoshiharu Morimoto (Japan). We gratefully acknowledge the time and effort invested in summarizing this article.