O-066 CSCM-NXC media containing a low lactate concentration seems to benefit expansion grade compared to traditional continuous media
Authors: Moreno Moya J M , Mansell S , Alland I , Øverlie I , Sørdal T , Finset M 
Published: June 2022

Abstract

Study question
Does lactate presence in the culture medium have an effect on embryo development, specifically during blastocyst formation? Is it an age related effect?

Summary answer
There is a statistical significative reduction of early blastocyst formation and a trend towards higher proportion of expanded and hatching blastocysts in lower lactate concentration.

What is known already
Embryos after embryonic genome activation start an active consumption of glucose to convert it into pyruvate and lactate for ATP production through the TCA cycle. Conversion from pyruvate to lactate to produce NADH through LDH (lactate dehydrogenase) can be counterbalanced by increased amounts of lactate, which then can alter the NAD+/NADH ratio resulting in a higher oxidative stress and reduced metabolic activity. Recently, a new commercial media formulation with a substantial reduction of lactate has come in to the market reporting increased efficiency of blastocyst formation and amount of euploid embryos compare to its version with a traditional lactate concentration.

Study design, size, duration
From September to November 2021 embryos were cultured in two different continuous media (SAGE 1-STEP and FUJIFILM IRVINE SCIENTIFIC CSCM-NXC). A total of 260 correctly fertilized embryos were allocated in both types of media (119 in 1-STEP and 141 in CSCM-NXC). Patients containing more than one zygote had their embryos allocated as equally as possible in both types of media.

Participants/materials, setting, methods
Age of participants ranged from 24-45 years. The embryos were cultured in embryoscope+ and their destination was assigned as Transfer, Vitrification or Discard (if by day 6 they did not reach a good quality blastocyst). Morphokinetic parameters were measured and Gardner's grading system for blastocyst quality annotated. For blastocyst quality comparison, only day 5 was considered. Variables studied were utilisation and blastocyst formation rates, expansion grade, ICM and TE quality, patient age, and pregnancy rates.

Main results and the role of chance
Incubation of embryos in reduced lactate concentration reduced significantly (p-value=0.013) the proportion of embryos with expansion grade 1 (14.3% 1STEP vs 3.4% CSCM-NXC), in contrast, a trend towards higher expansion grades, more importantly grade 5 (7.8% 1STEP vs 14.9% CSCM-NXC) was observed. A slight reduction in proportion of discarded embryos (47.52% CSCM-NXC vs 54.62% 1STEP) and increased proportion of vitrified embryos (34.75% CSCM-NXC vs 27.73% 1STEP) was also observed. Regarding ICM and TE qualities, in general there was also a trend in benefit of use of CSCM-NXC medium (55.3% CSCM-NXC vs 50.7% 1STEP for grade A in ICM; 36.8% CSCM-NXC vs 30.1% 1STEP for grade A in TE). Morphokinetic parameters were not different between groups, except T3 which showed to be significative (p-value=0.026) earlier in 1STEP than CSCM-NXC (37.13 h vs 38.71 h respectively). Age subgroups of patient showed no difference in utilisation rates for ages &lt; 37 years old, however, for ages ≥37 there was a higher proportion of utilised embryos (56.3 CSCM-NXC vs 41.9% 1STEP for 37-40 years old; 60% CSCM-NXC vs 42.3% 1STEP for &gt;40 years old). Finally, pregnancy rates were equal for those fresh transfers between both groups.

Limitations, reasons for caution
The study has a reduced sample size, so statistical power is reduced. Furthermore, it cannot be discarded that the effect is not a contribution to other differences in formulation of both media. Time to birth or cumulated pregnancy parameter would be more indicative of benefits.

Wider implications of the findings
Two main hypotheses that require further validation: First, excess of certain metabolites in culture can impair development of preimplantation embryos. Second, embryos may be more sensitive to certain medium composition depending on age, so medium designed according to this may be a near future direction to improve IVF outcomes.

Trial registration number
NA