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Stress Relief: Can Continuous Culture in a Low-Lactate Culture Medium Reduce Numerical Chromosomal Abnormalities and Therefore Improve Euploidy Rates?

Authors: VerMilyea, M.D., C. Rios, A. Abu Maizar, R.M. James, A. Picou, H. Werland, R. Marrs, K. Silverberg

Study question: We wanted to compare PGT-A results from embryos cultured in a new formulation of culture medium against those embryos cultured in a sequential or single-step culture system.

Summary answer: This study was a retrospective analysis of embryos created from 2016 to 2018 in two separate IVF laboratories. Embryos were either cultured to the blastocyst stage in a sequential culture system (G-Series™, Vitrolife), Continuous Single Culture® (CSCM) or Continuous Single Culture®- NX (CSCM-NX) (Irvine Scientific®). CSCM-NX contains a lower concentration of lactate than traditional culture media. All embryos were cultured in 6% CO2 in reduced oxygen. A sequential media change was performed with embryos cultured in G-Series™ on Day 3 (from G1™ to G2™), whereas embryos cultured in both CSCM and CSCM-NX were cultured undisturbed, in the same medium for seven days. Trophectoderm biopsy was performed on either Day 5, 6 or 7 of blastocyst development and embryo ploidy status was determined by PGT-A through NextGen Sequencing by the Illumina MiSeq platform (Ovation Genetics). Embryos reported as normal had no detectable copy number aberration, at a threshold of ≤30%.

Study design, size, duration: 1,573 embryos cultured in the sequential culture system were biopsied for PGT-A, while 3,417 and 1,665 embryos were biopsied following culture in CSCM and CSCM-NX respectively. 48% of embryos cultured in CSCM-NX were identified as euploid, compared to 43% of embryos cultured in the sequential system. This difference was significant (p<0.05). When comparing biopsied embryos cultured in CSCM vs. CSCM-NX low-lactate medium, 46% were euploid compared to 58%, respectively. This difference was also highly significant (P<0.001).

Results: An excess of lactate present in culture medium may be a contributing factor to unwarranted stress on an embryo. This strain on metabolic efficiency can subsequently alter embryo development and cellular integrity which may increase the occurrence of mitotic aneuploidy by affecting spindle assembly and chromosome segregation in dividing cells. For the first time, we report a highly significant difference in euploidy rates from embryos cultured in a low lactate, single-step culture media. Our results show that by simply changing our selection of culture media we experienced a 10% increase in euploid embryos. Stimulation protocols, the PGT-A testing platform and overall embryo culture protocols remained consistent. Further assessment of subsequent pregnancy outcomes is currently ongoing.