BACKGROUND: During ICSI, we occasionally observe pronucleus sized translucent vacuoles. We investigated why these vacuoles occur and determined the effect on pregnancy outcome. METHODS: Translucent vacuole‐positive oocytes and the corresponding cohort were examined by transmission electron microscopy (TEM) and histochemical staining with DiI and ER‐Tracker. Stimulation methods, hormonal levels, patients’ condition and grade of transferred embryos were compared between vacuole‐positive and vacuole‐negative cycles. RESULTS: By TEM, we confirmed that the vacuoles were tubular‐type smooth endoplasmic reticulum clusters (sERCs). Numerous small sERCs were also observed in the oocytes from the same cohort. Veeck’s grades of transferred embryos were higher in sERC‐positive cycles and fertilization rate was similar to those of sERC‐negative cycles. However, in sERC‐positive cycles, significantly lower pregnancy and higher biochemical pregnancy rates were shown. Serum estradiol levels on the day of hCG administration were significantly higher in sERC‐positive cycles. CONCLUSIONS: The presence of sERCs is associated with lower chances of successful pregnancy, even in sERC‐negative oocytes from the same cohort that are transferred along with the sERC‐positive oocytes. High estradiol levels could be one of the causes of sERC formation.