Efficacy of Calcium Chloride Dihydrate Supplementation at ICSI on Patient Outcomes

Abstract

Background: ICSI typically results in fertilisation rates of >65% however patients may still have low or no fertilisation despite the oocyte and sperm quality appearing normal. After entry of the sperm into the oocyte, a cascade of reactions facilitates calcium release and subsequent oocyte activation. In cases of poor or failed fertilisation it is possible that this cascade fails and therefore different methods of artificial oocyte activation are used to try and induce calcium release. Aim: To determine if calcium chloride dihydrate supplementation in the PVP (5mM) at the time of ICSI (ICSI-Ca) improves fertilisation, utilisation and clinical pregnancy rates compared to ICSI alone, particularly in patients with a history of low fertilisation (<50%). Methods: Retrospective study between 2016-2021 at Monash IVF Victoria on a paired cohort of patients (n=178 patients) where an ICSI cycle was analysed coupled with the subsequent ICSI-Ca cycle. The paired cohort was further subdivided into a low-fertilisation cohort (<50% fertilisation on previous cycles: n=66 patients) compared to the remaining patients with normal-fertilisation ([Formula: see text] 50%; n=122). Exclusion criteria included donor cycles, PGT patients, surgical sperm retrieval, women [Formula: see text] 45 years old, patients with >6 cycles and [Formula: see text] 5 inseminated oocytes. Results: Calcium supplementation increased both fertilisation (28.8% ICSI vs 49.7% ICSI-Ca, p<0.0001) and clinical pregnancy rate (4.9% ICSI vs 25.0% ICSI-Ca: p<0.05) in the low-fertilisation cohort but not in the normal-fertilisation cohort. Interestingly, utilisation rate increased in the normal-fertilisation cohort (32.6% ICSI vs ICSI-Ca: 44.9%, p<0.01) but not in the low-fertilisation cohort, although the number of extra embryos utilised per patient after ICSI-Ca increased in both groups. Conclusion: Calcium supplementation appears not to be a detrimental addition to ICSI and may improve IVF outcomes, particularly for patients with a history of low fertilisation. Further investigations including prospective case matched studies or RCT are required to confirm these findings.