Failed fertilization after intracytoplasmic sperm injection (ICSI) can occur due to an oocyte activation defect. In these cases assisted oocyte activation (AOA) may help but efficiency is still unknown. Prior to AOA, the mouse oocyte activation test (MOAT) can be carried out by injecting human spermatozoa into mouse oocytes to evaluate their activating capacity. According to the MOAT activation percentage achieved, patients were classified into three groups: 0-20% (16 patients); 20-85% (seven patients); 85-100% (seven patients). For AOA, CaCl(2) was injected together with spermatozoa followed by a double Ca(2+) ionophore treatment. The fertilization rates before application of AOA in 50 cycles were 6%, 22% and 14% in, respectively, groups 1, 2 and 3 without any pregnancy. Fertilization and pregnancy rates after AOA in 61 cycles were significantly increased to 75% and 34% for group 1, 73% and 43% for group 2, and 75% and 17% for group 3 (P < 0.0001 and P < 0.004, respectively). Application of AOA results in normal fertilization and pregnancy rates in patients whose spermatozoa show deficient activation. When MOAT reveals no activation deficiency in spermatozoa, AOA still allows for high fertilization and acceptable pregnancy rates. The obstetric and neonatal outcomes after AOA were normal as no malformations were observed.

For patients with a suspected oocyte-related activation deficiency, as diagnosed by a heterologuous ICSI model, the indication for ICSI-AOA still remains debatable. Our data show that ICSI-AOA is very efficient in patients with a suspected oocyte-related activation deficiency and previous TFF after conventional ICSI. In contrast, when there was a history of LF in another centre, one should be careful and test the efficiency of ICSI-AOA on half of the sibling oocytes, because ICSI-AOA is not always beneficial for patients with previous LF and a suspected oocyte-related activation deficiency. For these patients, a split ICSI-AOA cycle using sibling oocytes can help to distinguish between a molecular oocyte-related activation deficiency and a previous technical or other biological failure. Moreover, this split ICSI-AOA strategy enables us to set the appropriate strategy for future treatment cycles. Further research with larger groups of patients is now required.

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Oocytes with absent spindles were associated with lower fertilization rates and advanced female age. Other important outcome parameters (embryo quality, pregnancy rates) were not correlated to spindle nor zona inner layer analysis. Interestingly, confocal imaging showed that polarized microscopy might be used as a qualitative predictive tool of human oocyte quality but no correlation could be demonstrated with quantitative polarized microscopy.

ClinicalTrials.gov: NCT01671644.

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