Calcium ionophore improves embryonic development and pregnancy outcomes in patients with previous developmental problems in ICSI cycles

Abstract

Background Calcium (Ca2+) ionophores are now mainly considered as efficient treatments for fertilization failure. Recently, its application for rescuing poor embryo development was proposed but still non-routine. This study aimed to explore whether Ca2+ ionophore improves embryo development and pregnancy outcomes in patients with poor embryo development in previous intracytoplasmic sperm injection (ICSI) cycles. Methods This study included 97 patients undergoing assisted oocyte activation (AOA) with Ca2+ ionophore (calcimycin, A23187) treatment. Preimplantation embryonic development and clinical outcomes were compared between ICSI-AOA cycles (AOA group) and previous ICSI cycles of the same patients in which poor embryo developmental potential was present (non-AOA group). Subgroups stratified by maternal age (< 35, 35–40, ≥ 40 years, respectively) were analyzed separately. Results A total of 642 MII oocytes were collected in AOA group, and 689 in non-AOA group. Significantly higher day 3 good quality embryo rate (P = 0.034), good quality blastocyst formation rate (P < 0.001), and utilization rate (P < 0.001) were seen in AOA group. Similar results were seen in each subgroup. For pregnancy outcomes, there were significant differences in clinical pregnancy rate (P = 0.039) and live birth rate (P = 0.045) in total group. In subgroup aged < 35 years, biochemical (P = 0.038), clinical (P = 0.041), and ongoing pregnancy rate (P = 0.037) in AOA group were significantly higher than that in non-AOA group. No significant improvement for clinical outcomes for subgroups aged 35–40 and aged ≥40. Conclusion The study suggests that calcimycin could improve preimplantation development and pregnancy outcomes in patients aged < 35 years with embryo developmental problems in previous ICSI cycles.

The Effect of Artificial Oocyte Activation on Embryomorphokinetic Parameters and Blastulation Time

“…To the best of our knowledge, our sample population is the largest of any study conducted on this subject to date. Some clinical studies and meta-analyses have reported that AOA may help improve fertilization, embryonic development, and clinical pregnancy outcomes in many clinical conditions [21,23]. Therefore, we performed AOA mostly in patients with poor prognoses.…”

“…Researchers have attempted to improve the clinical outcomes of patients who experience fertilization failure or low fertilization rates using arti cial oocyte activation (AOA), including the use of PLCz and arti cial activators such as Ca ionomycin, Ca ionophore (A23187), strontium chloride, electrical pulse activation, and mechanical activation [20]. According to studies and meta-analyses, Ca ionophore (Cai) application signi cantly improves the overall fertilization rates in patients who experience fertilization failure [21][22][23]. Positive effects of Cai application have been detected at various embryonic development stages [19].…”

Minerals and the Menstrual Cycle: Impacts on Ovulation and Endometrial Health

“…Specifically, during these stages, calcium ions modulate the release of vital secondary messengers, including inositol trisphosphate (IP3) [33], cyclic adenosine monophosphate (cAMP) [34], and diacylglycerol (DAG) [35], which are essential for oocyte activation and its fusion with the spermatozoon [31,32]. In the early stages of embryonic development, a balanced calcium concentration is crucial for proper cellular division and the implantation of the embryo into the uterine lining [31,[200][201][202][203]. Consequently, an imbalance in calcium levels, whether due to a deficiency [204,205] or excess [206], can compromise fertility and reduce the likelihood of a successful pregnancy [207].…”

“…Furthermore, the Leukemia Inhibitory Factor (LIF) is another crucial molecule linked to embryo development [377]. Overall, these results indicate that an adequate calcium level in the body is a requirement for the successful implantation of the embryo and the initiation of pregnancy [45,203,370,378].…”