Abstract Study question Does an increase in usable blastocyst rates with low lactate culture medium lead to increased live birth rates? Summary answer Increased overall usable blastocyst rate correlates with an increased live birth rate following low lactate embryo culture. What is known already Lactate is essential to the oocyte and early embryo and while it is produced naturally through the normal glycolytic pathways of the same, it is nonetheless added to available embryo culture media. In embryo culture using a continuous culture medium containing only 1mM lactate, an increase in day 5 and overall usable blastocyst rates has been documented as compared to higher lactate (6-10mM) in a sequential media system. There are now also studies showing an increase in normal fertilization with a decrease in no fertilization and abnormal fertilization with oocytes placed in low lactate at oocyte retrieval. Study design, size, duration In a prospective interventional study of IVF cases between October 2020 and April 2021, patient oocytes were divided randomly amongst a control (Vitrolife G1/G2) and treatment (Continuous Single Culture Medium-NX Complete) group. Oocytes were split following oocyte retrieval and embryo culture proceeded in one of the two groups through day 6. Total oocytes in the control group, 258, and in the treatment group, 273. Patients of all ages and diagnosis’ were included. Participants/materials, setting, methods All cases were inseminated via intra-cytoplasmic sperm injection, blastocyst biopsy performed for next generation sequencing, and blastocysts vitrified with Vit Kit or Vit Kit–Freeze NX for frozen embryo transfer. All blastocysts were warmed with Vit Kit–Warm NX and transferred using SG/G2-Plus. Primary analysis included initial beta-HCG, clinical pregnancy rate (fetal cardiac activity) and live birth. Secondarily, fertilization rates were examined for comparison of normal (2PN), abnormal (1PN and 3PN), and no fertilization (0PN). Main results and the role of chance Chi-square analysis was applied on all considerations to assess statistical significance and p < 0.05 considered significant. In the analysis of fertilization parameters for the control versus treatment group, normal fertilization (69.0% vs 74.0%), abnormal fertilization (6.2% vs 8.0%) and no fertilization (19.8% vs 15.8%) rates were not significant. The initial beta HCG rates following frozen embryo transfer in the control and treatment groups were significant at 65.3% and 90.9%, respectively (p = 0.036). The rate of clinical pregnancy in the control was 38.5% and in the treatment group was 68.2% (p = 0.040). Live birth rate in the control versus treatment group was 30.8% and 59.1%, respectively (p = 0.049). There was no difference in the implantation rate between groups (control = 56.7%, treatment = 80.0%) (p = 0.065). In patients where the first embryo transfer did not result in clinical pregnancy, a subsequent transfer with an embryo from the opposite culture medium yielded a live birth rate of 11.1% (control) and 33.3% (treatment). Limitations, reasons for caution The pregnancy data in this particular study all result from frozen embryo transfers, with no fresh embryo transfers, and the possible effect or interference of the vitrification media, recovery medium and/or transfer medium cannot be accounted for, therefore, more study is needed. Wider implications of the findings The pregnancy and live birth rates in this analysis support previous findings that low lactate culture medium increases the instance of usable blastocysts and demonstrates that those increases can ultimately correlate with, and result in, a higher live birth rate for patients. Trial registration number Not Applicable
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