Another ASRM is over with lots of interesting new science presented. As always the programme covered a large variety of topics. In this blog I will highlight some of the studies and sessions which I found of particular interest.
Time-lapse for IVF continues to be strong
The field of time-lapse continues to be strong both in terms of studies showing efficacy and possibility for improved evaluation and time-lapse is being increasingly used as a trusted tool to investigate the effect of other clinic procedures and for doing interesting research.
The use of time-lapse in USA was investigated in a survey-study conducted with 204 US IVF clinics out of which 35 had time-lapse technology (P-560). 71% of clinics with time-lapse access use this technology for embryo selection before transfer and 57% offer time-lapse technology to all of their patients. The study showed that users of the technology are more likely than others to believe that time-lapse will become standard of care. This is in concordance with the feedback we often see with time-lapse users; time-lapse users generally are very reluctant to go back to traditional evaluation as they feel that essential information about embryo development is lost without dynamic monitoring.
How can a clinic benefit from integrating time-lapse information in their selection procedures? This ASRM showed many examples of these benefits. The benefit of time-lapse in embryo selection is very much related to identifying developmental traits that would otherwise be missed and to digitizing information about embryo development. Looking into the developmental features of 1599 embryos, Zhang et al (P-664) showed that features like time of syngamy and the exhibition of abnormal features like MN and/or direct cleavage could have the potential to be predictive about the ability of an embryo to make it to 8-cell, blast stage or implantation. Such traits can only be properly deduced with time-lapse and this study is in agreement with several previous reports and publications.
Blastocyst dynamics was the topic of several studies as this is a relatively new assessment measure made possible by time-lapse surveillance of embryos. In one study Saura et al. (P-180) confirmed their previous data showing that blastocyst collapse is a negative feature of embryo development and should be identified through assessment of the video sequence. In this study implantation rate was significantly affected by the exhibition of at least one blastocyst collapse. In another study, Dr. Huang investigated blastocyst expansion dynamics by performing hourly cross sectional measurements of the expanding blastocysts and thereby was able to identify an optimal rate of expansion (P-559).
Can the embryo repair itself?
In recent years a potential embryo “self-repair” mechanism has been the focus of several studies. In this hypothesis an embryo may be able to recover partial aneuploidy (mosaicism) by exclusion of cell(s) during morula and/or blastocyst formation. This hypothesis explains at least in part how embryos with a negative PGS result can show subsequent good competence. Dr. Sadowy showed an analysis of cell exclusions during blastulation (O-43). In this analysis all excluded cells were chromosomally abnormal and excluded cells were not representative of blastocyst ploidy. This highlights the importance of a careful biopsy process taking specific notice to biopsy an appropriate part of the embryo.
A potential reason for the embryo to self-repair by cell exclusion was addressed by Dr. Zaninovic (P-655) who found a strong correlation between the exclusion of cells during blastulation and the exhibition of direct unequal cleavages (DUC) and karyokinesis without cytoplasmic division (NUK). This group has previously defined direct unequal cleavage as the phenomenon of one cell dividing into more than two daughter cells at any stage during the first three cleavage cycles. Analyzing 5300 embryos from PGS cycles, 16.5% of embryos excluded blastomere(s) during blastulation. The related occurrence of DUC/NUK and blastomere exclusion was significant and most often in embryos exhibiting DUC/NUK the excluded cells were descendants of the DUC/NUK cells (85.2% / 53.1%). These findings may explain a potential source of mosaicism, and also account, at least in part, for the observation that embryos with abnormal division kinetics sometimes implant. Interestingly, blastomere exclusion was most prominent in younger women.
The trend towards increased genetic testing with new and more sensitive tools is clearly evident, however along with this trend there is also growing recognition that there needs to be clearer guidelines on counseling patients when the results are not black and white.
As with all technologies, time-lapse information must be applied and interpreted properly. One of the oral presentations at ASRM showed that humans are still better than machines at annotating embryos (O-224). In this study, an automated annotation system was compared to manual annotation and shown to incorrectly annotate cell numbers in 30% of cases leading to an altered morphokinetic scoring of the embryos. The automatic system was unable to perform annotation of 11% of embryos which was significantly higher than the case for manual annotation. This highlights the importance of proper annotation and the need for a human set of eyes when looking at the complexities of dynamic embryo development.
How to minimise drama in the embryology laboratory
An interesting interactive session focused on the importance of having procedures to control workflow, risk analysis and communication on order to be “Minimizing drama in the Embryology Laboratory”. Chairmen Dr. Kelk and Dr. Wiemer presented various measures and procedures that were useful to ensure best practice in the clinic. These included having time-outs when things are busy to stop and think before continuing, asking the right questions if things seem out of place, teaching staff that is OK to ask for help or admit if they have made an error and even celebrating identification of errors, and having an end of day checklist to ensure that no mistakes have been made and that the lab is ready for the next busy day.
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Written by Dr. Tine Qvistgaard Kajhøj
Tine did her PhD in the stem cell field. One of her responsibilities at Vitrolife is holding workshops where clinics both get started with and develop their skills in using time-lapse technology, in order to improve their results.