Calcium Ionophore–Assisted Oocyte Activation Is Associated with Higher Fertilization Outcomes in Women with Endometriosis Undergoing ICSI: A Prospective Observational Study

Background and Aim: Endometriosis may impair oocyte competence and calcium-mediated activation, limiting fertilization after ICSI. This study evaluated whether calcium ionophore-assisted oocyte activation (AOA) associated with improved fertilization and embryological outcomes in women with endometriosis undergoing fresh ICSI cycles. Patients and Methods: This prospective observational cohort included 108 women with endometriosis-associated infertility at Cairo University Hospital. Fifty-four underwent ICSI followed by calcium ionophore AOA using GM508 Cult-Active, and 54 underwent standard ICSI. The primary outcome was fertilization rate. Secondary outcomes included normal fertilization, cleavage, blastocyst formation, high-quality embryos, implantation, and clinical pregnancy. Results: AOA significantly increased normally fertilized oocytes (3.41 ± 0.92 vs 2.87 ± 0.80; p=0.003) and fertilization rate (75.99 ± 12.79% vs 59.10 ± 15.94%; p<0.001). It also improved cleaved embryos, blastocyst number, blastocyst formation rate, and high-quality embryos. Adjusted analysis confirmed higher normal fertilization (adjusted OR 2.34, 95% CI 1.80–3.05), blastocyst formation (adjusted OR 1.40, 95% CI 1.08–1.82), and high-quality embryo production (adjusted IRR 1.43, 95% CI 1.28–1.60). Clinical pregnancy was higher but not significant (33.3% vs 24.1%; p=0.288). Conclusion: Calcium ionophore AOA was associated with higher fertilization and embryo-development outcomes in selected endometriosis ICSI cycles but did not significantly improve implantation or clinical pregnancy. Because allocation was non-randomized, residual indication bias cannot be excluded. These findings apply mainly to young women with surgically confirmed endometriosis, acceptable ovarian reserve, normal semen parameters, and fresh ICSI cycles, and require confirmation in larger randomized trials assessing pregnancy and live birth.