Artificial oocyte activation improves ICSI outcomes following unexplained fertilization abnormalities

Abstract

Research Question: Is Artificial Oocyte Activation (AOA) effective for patients with unexplained low or no fertilisation following IVF/ICSI? Design: All IVF/ICSI cases resulting in total fertilisation failure or fertilisation rate ≤25% at Ninewells Assisted Conception Unit, Dundee, Scotland January 2014 - December 2021 (n=231) were reviewed contemporaneously. After exclusion of obvious stimulation, egg, sperm and/or ART laboratory factors, patients with ≥1 cycle of IVF/ICSI resulting in apparently unexplained fertilisation abnormalities were offered research investigations, including sperm immunocytochemistry for phospholipase C zeta protein expression (ethical approval 22/SS/0104). This retrospective case-controlled cohort study evaluated laboratory and clinical outcomes for 39 couples (15 attended for sperm studies research) that subsequently undertook ICSI-AOA with Ca2+ ionophore (GM508 Cult-Active 1; Gynemed). Results: Comparing preceding IVF/ICSI and subsequent ICSI-AOA for each patient, number of eggs collected was similar, however ICSI-AOA resulted in a significantly improved fertilisation rate (57.2% vs. 7.1%; p<0.0001). The uplift was even more profound for a subset identified with PLCζ deficiency (66.3% vs. 4.6%; p<0.0001). Overall, ICSI-AOA resulted in a higher number of fresh embryo transfers (94.6% vs. 33.3%; p<0.0001), significantly higher clinical pregnancy rate (CPR) and live birth rate (LBR; 17.9% vs. 2.6%; p=0.025), as well as a significant increase in cycles with surplus embryos suitable for cryostorage (43.6% vs. 0%; p<0.0001) and increased cumulative CPR (30.8% vs. 2.6%; p<0.0001) and LBR (28.8% vs. 2.6%; p=0.0002). Conclusion: AOA is a powerful tool that can transform clinical outcomes for couples experiencing apparently unexplained fertilisation abnormalities. PLCζ assays have the potential to be valuable diagnostic tools to determine patient selection for ICSI-AOA and research efforts should continue to focus on their development.