Impact of low lactate embryo culture medium on live birth and perinatal outcome

Pre-implantation development is a critical period of developmental plasticity, which could have effects on both treatment success rates (LBR) and perinatal outcomes. This study aimed to determine the impact of low-lactate concentration in continuous embryo culture media on first embryo transfer and cumulative live birth rates and perinatal outcomes. From 2019 to 2020, 896 IVF or ICSI cycles had embryos cultured in either standard-lactate [Continuous Single Culture Complete CSCM-C (446)] or low-lactate continuous culture media [Continuous Single Culture-NX; CSCM-NX (450)] at a multicentre clinic (5 clinics) during a prospective clinical validation. CSCM-NX (Fuijifilm Irvine Scientific) contains a lower concentration of lactate compared to CSCM-C (Fuijifilm Irvine Scientific). The primary outcomes were live birth after first embryo transfer and cumulative live birth, both per retrieval. Secondary outcomes included first transfer miscarriage rate and perinatal outcomes. Multivariate logistic regression was used to assess the association between two groups, adjusting for maternal age, clinic ID, IVF/ICSI and number of oocytes. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) are reported. Percentage of cycles with fresh transfer, freeze-all, and no transfer were similar for CSCM-C vs CSCM-NX, respectively (44 vs 44%, 46 vs 47%, 10 vs 9%). Live birth rate after first transfer (aOR: 1.32, 95% CI: 1.00-1.70) was higher for CSCM-NX (43.3% vs 36.6%). Miscarriage rate (aOR: 1.13, 95% CI: 0.68-1.90) and cumulative live birth rate (aOR: 1.15, 95% CI: 0.87-1.51) were similar between CSCM-C (8.0%, 54.0%) and CSCM-NX (10.3%, 57.8%). There were no significant differences in perinatal outcomes: birth weight (3328 g vs 3333 g); preterm birth-37 weeks (8.1% vs 10.5%); very preterm -<32 wks (2.7% vs 2.5%); low birth weight-<2500 g (8.5% vs 8.4%); high birth weight (2.3% vs 1.1%); and neonatal death (0.3% vs 0.9%). This prospective clinical validation of standard versus low lactate embryo culture media indicates that culture with low lactate results in a higher live birth rate on first transfer though a similar cumulative live birth rate. No differences were detected in perinatal outcomes, providing evidence that culturing with low lactate does not have long-term consequences.