There are no current standardized methods for outcomes based quality control monitoring of embryo culture media.
Probably the best option to evaluate embryo culture media quality and performance is to look at the percentage of oocytes that go on to become a blastocyst. We also need to account for embryos that are transferred on day 3 and embryos that are transferred as fresh day 5 morula stage embryos (just before the blastocyst stage). We can account for these embryos that are transferred before the blastocyst stage by converting all embryos to day 5 blastocyst equivalents. We then divide the total number of day 5 blastocyst equivalents for a cohort of oocytes (a group of oocytes all retrieved at the same time) by the total number of oocytes retrieved. This gives us day 5 blastocyst equivalents per oocyte. We want to use the same denominator for ICSI and conventional insemination cases so we are actually using the number of cumulus-oocytes complexes retrieved as the denominator. This includes immature oocytes. This is a good metric because it is also the metric used to compare performance of method of fertilization (ICSI vs conventional insemination) and incubator performance.
Here is data from our center for embryo cultures from 9/1/2024 though 3/3/2025. The data can be plotted on a quantile-quantile plot which shows that the data are normally distributed without any outliers indicating similar quality performance of each batch of culture media.
In November of 2023 our center had 17 cohorts of oocytes affected by the CooperSurgical embryo culture media recall which was issued in December of 2023. The recall was issued for discovery of low magnesium in the media. There were a total of 252 oocytes among the 17 embryo cultures affected (average of 14.8 oocytes per cohort). The blastulation rate per cumulus-oocyte complex was 15% and there was an average of 0.14 day 5 blastocyst equivalents per oocyte (cumulus-oocyte complex). This was slightly lower than all of the other culture media batches we’ve analyzed at our center.
10 of the 17 embryo cultures used ICSI fertilization (59%) while 7 of 17 used conventional insemination (41%). Conventional insemination starts with placing the oocytes with the sperm in fertilization media for 16-18 hours before the oocytes are denuded and transferred to culture media. Time spent in the fertilization media (which was unaffected) seemed to have a protective affect since the conventional insemination cycles were less affected. For ICSI cycles the oocytes are immediately placed in affected culture media after sperm injection.
For the 7 conventional insemination cycles the blastulation rate per oocyte was 20% and there were 0.22 day 5 blastocyst equivalents per oocyte.
For the 10 ICSI cycles the blastulation rate per oocyte was 11% and there were 0.08 day 5 blastocyst equivalents per oocyte.
In addition to low rates of blatocyst formation, we saw a shift from day 5 to day 7 blastocysts. We typically see 52% of blastocysts formed on day 5, 41% on day 6, and 7% on day 7. For the 17 affected embryo cultures we saw 6% of blastocysts form on day 5, 43% on day 6, and 51% on day 7.
The shift from day 5 to day 7 blastocysts was seen in both the convenational insemination and ICSI groups.
Conventional Insemination: 4% day 5, 42% day 6, and 54% day 7
Intracytoplastmic Sperm Injection: 10% day 5, 43% day 6, and 48% day 7
Thankfully these types of incidents are rare. In this case CooperSurgical worked with our center to reach out to affected patients and offer compensation. Hopefully standardized ongoing assessment of culture media performance can be incorporated in the workflow of all IVF labs and culture media manufacturers.
This research has been approved by the Christ Hospital IRB (protocol #25-030).