Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
Hum Reprod. 2012 Jul;27(7):1977-84. doi: 10.1093/humrep/des097. Epub 2012 Apr 4.
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.
尽管 ICSI 取得了成功，但在所有 ICSI 周期中仍有 1-3%发生完全受精失败（TFF）。ICSI 后辅助卵母细胞激活（ICSI-AOA）可以恢复受精，在精子相关受精缺陷的情况下效率最高。当精子激活卵母细胞的能力被认为正常时，ICSI-AOA 的指征就不那么明显了，这可以通过异种 ICSI 模型（如鼠卵母细胞激活试验（MOAT））来证明。在这项研究中，我们验证了 ICSI-AOA 是否对怀疑卵母细胞激活缺陷的患者有益。
一项前瞻性研究纳入了在我们中心（院内病例，n=2）或其他中心（院外病例，n=12）出现 TFF 或常规 ICSI 后低受精（LF）史的患者。所有病例均通过 MOAT 排除了精子缺陷。在下一个治疗周期中，一半的姐妹中期 II 卵母细胞进行 ICSI-AOA，其余卵母细胞进行常规 ICSI（“半 ICSI-AOA 周期”）。主要结局参数为受精率、妊娠率和活产率。
总体而言，ICSI-AOA 能够提高疑似卵母细胞相关受精问题患者的受精率，与常规 ICSI 相比，ICSI-AOA 后受精率为 74.2%，而常规 ICSI 后为 43.5%（P<0.001）。累积妊娠率和活产率分别为 35.7%和 14.3%。仅考虑院外患者，与常规 ICSI 相比，有 TFF 史的患者中 ICSI-AOA 的受精率更高（P<0.001）。有趣的是，对于在其他中心经历过低受精但并非零受精的院外患者，ICSI-AOA 不能提高受精率。对于两名因常规 ICSI 后 LF 而就诊的院内患者，ICSI-AOA 程序分别提高了平均受精率（分别为 25%和 75%）。
对于通过异种 ICSI 模型诊断为疑似卵母细胞激活缺陷的患者，ICSI-AOA 的适应证仍存在争议。我们的数据表明，ICSI-AOA 对疑似卵母细胞激活缺陷且既往常规 ICSI 后 TFF 的患者非常有效。相比之下，当在另一个中心有 LF 史时，应谨慎行事，并在一半的姐妹卵母细胞上测试 ICSI-AOA 的效率，因为 ICSI-AOA 并不总是对既往 LF 且疑似卵母细胞激活缺陷的患者有益。对于这些患者，使用姐妹卵母细胞的半 ICSI-AOA 周期可以帮助区分分子卵母细胞激活缺陷和既往的技术或其他生物学失败。此外，这种半 ICSI-AOA 策略使我们能够为未来的治疗周期制定适当的策略。现在需要对更大的患者群体进行进一步的研究。
