Abstract
Abstract Study question Does oocyte central granularity (CG) compromise post-ICSI live birth achievement? Are morphologically normal oocytes obtained from CG cycles also affected? Summary answer Oocytes with CG, but not morphologically normal oocytes obtained from cycles providing CG oocytes, present lower competence to achieve a live birth. What is known already Ooplasm central granularity (CG) is associated with alterations in the actin cytoskeleton and meiotic spindle potentially affecting meiotic accuracy, fertilisation dynamics and embryo development. We have recently reported lower fertilisation rates and slower morphokinetics associated with CG. However, to clarify whether CG does affect oocyte developmental competence and if it is associated with endocrine alterations that may also impinge on the performance of morphologically normal oocytes obtained in the same cycle, adequately powered studies assessing the clinical outcomes of cycles transferring embryos derived from CG oocytes or from their morphologically normal companions are needed. Study design, size, duration Retrospective analysis including 866 control ICSI cycles/patients providing only morphologically normal oocytes (NO) and 211 CG cycles/patients providing NO and CG oocytes, from July 2014 to August 2021. Clinical outcomes were compared (1) between cycles providing CG oocytes (CG) or not (Control 1), and (2) among cycles achieving a fresh transfer in which only NO were obtained (Control-T), CG oocytes were obtained but NO-derived embryos were transferred (NOT), and CG-derived embryos were transferred (CGT). Participants/materials, setting, methods Patients undergoing their first ICSI cycle (n = 866; Control) or their first ICSI cycle providing CG oocytes (n = 211; Treatment-groups) were included. Cycle characteristics and outcomes were compared using the Fisher’s exact test and the Wilcoxon sum rank test. Multivariate analyses were performed to assess the potential interference of maternal age, infertility cause, number of embryos transferred and day of embryo transfer on the relationship between CG and live birth. Main results and the role of chance Patients providing CG oocytes (n = 211) presented higher maternal age (37.6± 4.5 vs. 36.5± 4.3; p= p < 0.001), higher basal FSH (8.5± 3.8 vs. 7.9± 4.1 IU/L; p = 0.03), lower AMH (2.2± 2.2 vs. 3.2± 3.5 ng/mL; p < 0.001), higher incidence of ovarian infertility (17.5% vs. 4.9%; p < 0.001) and higher FSH total dose (2255.3± 866.4 vs. 1825.6± 752.3 IU; p < 0.0001), compared to controls (n = 866). Implantation, abortion and live birth rates did not differ between cycles providing (CG) or not (Control) CG oocytes (22.7% vs. 24.9%, 17.1% vs. 27.7%, 25.8% vs. 22.9%, respectively). Nevertheless, implantation and live birth rates were lower in cycles in which CG-derived embryos were transferred (CGT; n = 87) compared to cycles in which CG oocytes were obtained but only NO-derived embryos were transferred (NOT; n = 57), or to cycles in which CG oocytes were not obtained (Control-T; n = 595). Implantation rates were 11.4%, 30.9% and 24.9%, while live birth rates were 10.5%, 30.2% and 22.9% for CGT, NOT and Control-T, respectively (p < 0.001 for implantation rates in CGT vs. NOT and CGT vs. Control-T; p < 0.04 for live birth rates in CGT vs. NOT and CGT vs. Control-T). No significant differences were observed between NOT and Control-T. Limitations, reasons for caution Our study is subjected to the limitations of a retrospective analysis and thus the data may be affected by other variables that were not controlled for. Moreover, the intrinsic difficulty in obtaining a higher number of cycles in which only CG-derived embryos are transferred, limits the power of the analysis. Wider implications of the findings Our findings shed light on a still unsolved question in ICSI practice. The present data indicate that CG is associated with markedly reduced oocyte developmental competence, while the presence of CG oocytes in a cycle does not affect the quality of the companion normal oocytes. Trial registration number not applicable
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