P-610 Lipid metabolism mediated the effect of glucose homeostasis and insulin resistance on IVF/ICSI outcomes in PCOS women

Abstract Study question To investigate the potential mediation role of lipid metabolism on the effect of glucose metabolism on IVF/ICSI outcomes in PCOS women. Summary answer Lipid metabolism indicators were possible mediators of the effect of glucose metabolism indicators on IVF/ICSI early reproductive outcomes in PCOS women. What is known already Women with PCOS have high incidences of dyslipidemia, obesity, impaired glucose tolerance (IGT), diabetes, and insulin resistance (IR) and are fragile to female infertility. The causality between dyslipidemia, glucose homeostasis dysregulation, and IR has been widely discussed. Dyslipidemia may be an intermediate biological mechanism for the associations between abnormal glucose metabolism and potential disorders of oocytogenesis and embryogenesis in PCOS women. Study design, size, duration We retrospectively analyzed 917 PCOS women aged between 20 – 45 years old who underwent their first fresh IVF/ICSI cycle with autologous oocytes during 2018 – 2020 at a reproductive center. Participants/materials, setting, methods Data on baseline reproductive and cycle characteristics were collected from the internal database derived from the electronic medical records. The pregnancy outcomes were collected by well-trained follow-up staff from telephone interviews. Associations between glucose and lipid metabolism indicators and IVF/ICSI outcomes were explored using multivariable generalized linear regressions. Mediation analyses were conducted to examine the role of lipid metabolism on the association between glucose metabolism and IVF/ICSI outcomes. Main results and the role of chance Significant dose-dependent relationships were found between glucose metabolism indicators and IVF/ICSI early reproductive outcomes, as well as between glucose metabolism indicators and lipid metabolism indicators (all P < 0.05). Also, we found significant dose-dependent relationships between lipid metabolism indicators and IVF/ICSI early reproductive outcomes (all P < 0.05). The mediation analysis indicated that elevated FPG, 2hPG, FPI, 2hPI, HbA1c, and HOMA2-IR were significantly associated with decreased retrieved oocyte count, MII oocyte count, normal fertilization count, normal cleavage count, high-quality embryo count, or blastocyst formation count after controlling for lipid metabolism indicators. Serum TG mediated 6.0 – 31.0% of the associations; serum TC mediated 6.1 – 10.8% of the associations; serum HDL-C mediated 9.4 – 43.6% of the associations; serum LDL-C mediated 4.2 – 18.2% of the associations; and BMI mediated 26.7 – 97.7% of the associations. Limitations, reasons for caution Given the retrospective nature, bias in data collection cannot be excluded. Besides, we did not consider any adjunctive therapy, including diet, exercise, or medication (i.e., metformin) before or during IVF treatment. The possible random errors in single measurements may also lead to certain imprecise estimates of association. Wider implications of the findings Our study emphasizes a mediation role of lipid metabolism in the impact of glucose metabolism on oocytogenesis and embryogenesis in PCOS women, suggesting that the monitoring and management of preconception lipid metabolism, glucose homeostasis, and IR are essential for improving the IVF/ICSI outcomes of PCOS women. Trial registration number Not Applicable