ICSI in non-male factor infertility patients does not alter metabolomic signature in sibling embryos as evidenced by sensitivity enhanced nuclear magnetic resonance (NMR) spectroscopy.

Intracytoplasmic sperm injection (ICSI) was developed to overcome male factor infertility, however, there recently has been an increasing trend in ICSI usage irrespective of the etiology, demonstrating an overuse of this insemination technique. There is a limited knowledge on the behaviour of ICSI derived embryos in non-male factor infertility patients. Metabolomic assessment of preimplantation embryos in conjunction with morphological evaluation can provide better understanding of embryonic behaviour. Hence, this study was undertaken to explore if there are any metabolomic differences between IVF and ICSI derived sibling day-5 blastocysts from non-male factor infertility patients. This prospective study included nineteen couples with non-male factor infertility undergoing Assisted Reproductive Technology. The sibling oocytes retrieved from each patient were randomly assigned to two groups and inseminated either by IVF or ICSI. Spent culture media (SCM) in which embryos were cultured up to day 5 were collected and investigated using sensitivity enhanced NMR based metabolite profiling utilizing high resolution (800 MHz) NMR equipped with cryogenically cooled micro-coil (1.7 mm) probe. The metabolomic signature between IVF and ICSI derived sibling blastocysts was assessed. A significant reduction in the concentrations of pyruvate, citrate, glucose and lysine were observed in both IVF and ICSI sibling embryos compared to medium control (P< 0.05-0.001). Further, histidine and valine level was found lower in ICSI embryos compared to medium control (P<0.05) during 96 hours of in vitro culture. Notably, between IVF and ICSI SCM, no significant difference in the concentration of the metabolites was found. Our results suggest that ICSI in non-male factor does not alter the SCM metabolomic signature during 96 hours of embryonic development.

PloS one. 2022 Sep 23*** epublish ***

Ameya Jijo, Aswathi Cheredath, Shubhashree Uppangala, Vani Lakshmi R, David Joseph, Huidrom Yaiphaba Meitei, Gitanjali Asampille, Pratap Kumar, Nagana Gowda G A, Guruprasad Kalthur, Borut Kovacic, Satish Kumar Adiga

Department of Reproductive Science, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India., Department of Data Science, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India., NMR Research Centre, Indian Institute of Science, Bangalore, India., Department of Reproductive Medicine and Surgery, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India., Northwest Metabolomics Research Center, Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States of America., Department of Reproductive Medicine, University Medical Centre Maribor, Maribor, Slovenia.