Critical analysis of blastocyst culture in in-vitro fertilization and embryo transfer

The world is moving towards extended embryo culture (Day 5 - Blastocyst Culture) and transfer of human embryos in IVF/ICSI cycles instead of the traditional day 2/3 (cleavage stage) transfer to improve pregnancy rates in patients seeking treatment for infertility. Due to the Embryo protection law preventing embryo selection, it is standard in Germany to perform day 2/3 (Cleavage) transfers and seldom, the German Middle Way is adopted to perform blastocyst transfers. Although the outcome of an ART cycle depends on a multitude of clinical and laboratory factors, this study pursued to critically explore the various advantages and disadvantages of changing the protocol in a German lab to international standards where blastocyst culture is the norm. Analysis of 1126 ART cycles that were performed from 2014 to 2018 in the University Reproductive Medical Unit of UKSH, Kiel showed that there was an improvement in pregnancy rates from 2014 to 2018 in both cleavage stage transfer and blastocyst transfer with a 1.4 time increase every year. There was a significant rise in the pregnancy rates with blastocyst transfer compared to cleavage stage transfer as a direct result of increase in the number of morphologically ideal blastocysts cultured in the lab due to improvement in the lab culture conditions by shifting from conventional incubators which had atmospheric oxygen tension (21%) to the sustained stable culture conditions (temperature and pH) of bench-top and time-lapse incubators which had 5% oxygen. The improvement in culture conditions had a higher impact on day 5 rather than day 2/3 culture as it could be speculated that the blastocyst stage is more susceptible to changes in the culture environment than cleavage stage. Hence, it would be logical in situations where there are sub-optimal conditions in the lab that a cleavage stage transfer should be opted for over a blastocyst transfer. Regardless of age, significantly more patients had an ideal day 5 embryos compared to a day 2/3 embryos possibly because in the blastocyst transfer group, 4 or more embryos were left in culture to identify the one with the best development potential for transfer whereas in the cleavage group only 1, 2 or 3 embryos were left in culture which were then transferred irrespective of their development potential. While ideal day 5 embryos were an excellent tool to assess the culture system in the lab and were associated with higher pregnancy rates, not-ideal cleavage stage embryos were associated with higher abortion rates. Although we had significant improvement in our pregnancy rates with changeover to blastocyst transfers, they were not as high as those in the UK. Perhaps because unlike the German law, culture of all the fertilized oocytes gave the ART Lab the liberty to choose the best embryos for transfer and freeze or discard extra embryos. The limitation of this study was that the sample size of blastocyst group was relatively small and a larger randomized controlled study should be carried out in the future to further confirm these findings. In conclusion, if an IVF Unit would want to improve its pregnancy rates by shifting to blastocyst culture, it would be advisable to monitor and to improve its culture systems till the ideal blastocyst rate is >60% before its wider application. Furthermore, a change in the German Law to support wider application of Blastocyst culture would definitely have a greater impact on overall pregnancy rates.


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