Abstract

Abstract Study question Are the clinical outcomes of an ICSI cycle impacted by the proportion of oocytes with smooth endoplasmatic reticulum aggregates (SERa)? Summary answer In terms of fertilization, blastocyst formation and live birth there is no difference between SERa- and SERa+ cycles, regardless of the proportion of SERa+ oocytes. What is known already It is not certain yet whether the presence of oocytes with SERa may impact the clinical outcome of an ICSI cycle. The majority of studies compare the outcome of SERa positive (SERa+) versus SERa negative (SERa-) cycles. It is not clear whether the proportion of SERa+ oocytes may play a role on cycles overall outcome, and which patients are at risk of harvesting a higher proportion of SERa+ oocytes. Limited data suggests that the duration of stimulation, the total dose of gonadotropins, the serum hormone levels and the number of oocytes are positively correlated with the presence of SERa+ oocytes. Study design, size, duration Retrospective study (2016-2019), including data from 2468 ovum pick-ups, performed in a tertiary university-based referral center. Results from fresh plus cryopreserved embryo transfers are included. In total, 2097 SERa- and 371 SERa+ cycles are included in the analysis. Participants/materials, setting, methods Cases are categorized based on the rate of SERa+ oocytes compared to the total number of metaphase II oocytes: SERa- (N = 2097), low SERa + (<30%) (N = 262), and high SERa + (≥30%) (N = 109). Baseline patient characteristics, treatment cycle parameters and clinical outcome per cycle are compared between the groups. According to the local protocol, SERa+ oocytes are not used for ICSI. Main results and the role of chance Women with high SERa+ proportion are older (36.15y for the SERa+ group vs. 34.49y for the high SERa- group, p < 0.001), have lower anti mullerian hormone levels (AMH) (1.60ng/ml vs. 2.28ng/ml, p < 0.001), received a higher total dose of gonadotropins (3227.01IU vs. 2858IU, p = 0.003), have fewer oocytes retrieved (9.13 vs. 11.08, p < 0.001), have a lower number of good quality day 5 blastocysts (1.17 vs. 2.33, p < 0.001) and face more often transfer cancellation (23.7% vs. 47.7%, p < 0.001). Compared to women with SERa- cycles, women with <30% SERa oocytes are younger (33.76y, p = 0.04), have higher AMH levels (2.56ng/ml, p < 0.001), have more oocytes retrieved (15.11, p < 0.001), have a higher number of good quality day 5 blastocysts (3.17, p < 0.001) and less transfer cancellations (14.9%, p < 0.001). A multivariate regression model adjusted for age, progesterone level at ovulation trigger and the type of pituitary suppression shows that cycles with a high proportion of SERa+ still have a lower amount of day 5 blastocysts (p < 0.001), a higher chance of transfer cancellation (p < 0.001), but no difference in the amount of retrieved oocytes (p = 0.097), fertilization (p = 0.813), blastocyst formation rate (0.975), implantation (p = 0.105) and live birth rate (p = 0.615). Limitations, reasons for caution The SERa+ oocytes in this analysis were not used for ICSI, which could have affected the result between SERa+ and SERa- cycles. Wider implications of the findings A low proportion of SERa+ oocytes (<30%) is common in young and high responders, without hampering clinical outcome. Contrary, >30% SERa+ oocytes leads to a higher risk of transfer cancellation, when these oocytes are not used for ICSI. Therefore, the inclusion of SERa+ oocytes for ICSI should be further investigated. Trial registration number not applicable

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