Assisted oocyte activation is not beneficial for all patients with a suspected oocyte-related activation deficiency

Abstract

Despite the success of ICSI, total fertilization failure (TFF) still occurs in 1-3% of all ICSI cycles. ICSI followed by assisted oocyte activation (ICSI-AOA) can restore fertilization, most efficiently in cases of sperm-related fertilization deficiency. The indication for ICSI-AOA is less obvious when the capacity of the sperm to activate oocytes is considered normal, as proved by a heterologous ICSI model, such as the mouse oocyte activation test (MOAT). In this study, we verified whether ICSI-AOA is beneficial for patients in whom an oocyte-related activation deficiency is suspected. A prospective study was conducted including patients presenting with a history of TFF or low fertilization (LF) following conventional ICSI in our centre (in-house cases, n= 2) or elsewhere (out-house cases, n= 12). In all cases a sperm deficiency was refuted by the MOAT. In a next treatment cycle, ICSI-AOA was performed on half of the sibling metaphase II oocytes and conventional ICSI on the rest ('split ICSI-AOA cycle'). The main outcome parameters were fertilization, pregnancy and live birth rates. Overall, ICSI-AOA was able to improve fertilization rates in couples with a suspected oocyte-related fertilization problem, with a mean fertilization rate of 74.2% following ICSI-AOA compared with 43.5% following conventional ICSI (P< 0.001). Cumulative pregnancy rate and live birth rate per cycle were 35.7 and 14.3%, respectively. Considering the out-house patients only, fertilization rates with ICSI-AOA were higher in couples with previous TFF than with conventional ICSI (P< 0.001). Interestingly, for out-house patients who had experienced low, but not zero, fertilization elsewhere, ICSI-AOA could not enhance the fertilization rate. For the two in-house patients, both suffering from previous LF following conventional ICSI, the ICSI-AOA procedure enhanced the mean fertilization rate (25 versus 75%, respectively). 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.