Smooth endoplasmic reticulum aggregates in human oocytes are related to female infertility etiology and diminished reproductive outcomes

Smooth endoplasmic reticulum aggregates (SERa) are a type of dysmorphism in oocytes derived from controlled ovarian stimulation (COS). The effect of SERa on assisted reproductive techniques (ART) outcomes is debatable. Based on some evidence, SERa-positive (SERa+) oocytes cause complications including newborn demise, and compromise the outcome of the unaffected oocytes of the same cycle. While other reports demonstrated equal developmental competence between SERa+and SERa-negative (SERa-) oocytes/cycles. We conducted a prospective cross-sectional study on 315 women candidates for ART and compared the outcome among SERa+ (N=73) and SERa- cycles (N=217). Furthermore, for the first time, we investigated the prevalence of SERa+cycles in women with various infertility etiologies. Our results indicated that SERa+patients presented higher levels of Estradiol on the day of ovulation triggering (p=0.02). Regarding the ART outcome, there were no differences in the number of retrieved oocytes, oocyte maturation and fertilization rates among the groups. However, the quality of the unaffected oocytes (p=0.03), the rates of day-3 top-quality embryos (p=0.01, and p=0.03 for grades A and B, respectively), and clinical pregnancy (p=0.05) in SERa+group were significantly reduced. Moreover, the prevalence of SERa+cycles gradually increased among endometriosis, POI/POR, PCOS, normal women, tubal factor, and idiopathic groups. Our study suggests that suboptimal situations such as elevated levels of Estradiol can increase the occurrence of SERa+oocytes. This suboptimal phenomenon can negatively influence the outcome of the cycle. Thus, optimization of COS, particularly in vulnerable groups such as women with idiopathic infertility may lower the SERa+cycle occurrence, improving the ART outcome.