P-735 Are there any differences in preimplantation blastocyst chromosomal abnormalities between polycystic ovary syndrome patients and controls? A multi-center retrospective cohort study

Abstract Study question Are there possible differences in the preimplantation blastocyst chromosome aberrations between polycystic ovary syndrome (PCOS) patients and controls? Summary answer PCOS lowers aneuploidy risk but increases mosaicism risk in preimplantation embryos, and PCOS-related insulin resistance should be investigated as a potential cause. What is known already PCOS is thought to alter granulosa cell functions and effects on oocyte development, potentially leading to chromosomal abnormalities and increasing the risk of pregnancy loss. However, few studies have compared the chromosomal status of preimplantation embryos from PCOS patients to those from healthy controls. Study design, size, duration This was a multi-center retrospective cohort study conducted at 3 IVF centers. A total of 707 blastocysts from 147 PCOS patients and 3006 blastocysts from 821 control women receiving preimplantation genetic testing (PGT) between 2015 and 2021. Participants/materials, setting, methods PGT was performed using next-generation sequencing (NGS). Differences in the chromosome aberrations were compared. Multivariate and subgroup analyses were conducted to control for confounders. Influences of insulin resistance and PCOS phenotype on the risks of specific chromosomal abnormalities were also examined. Main results and the role of chance Compared to controls, blastocysts from PCOS patients demonstrated lower aneuploidy rate (14.7% vs. 25.4%, P < 0.001) but greater mosaicism rate (16.5% vs. 8.7%, P < 0.001). Multivariable analysis adjusting for age, IVF center, body mass index (BMI), total gonadotropin (Gn) dose, and peak serum estradiol (E2) on trigger day, identified PCOS as an independent protective factor against embryonic aneuploidy (adjusted OR = 0.56, 95% CI, 0.42–0.76, P<0.001) but a risk factor for embryonic mosaicism (adjusted OR = 2.05, 95% CI 1.48–2.85, P<0.001). These differences in chromosomal spectrum were also observed in subgroups stratified by age, IVF center and BMI. Further multivariate analysis suggested that insulin resistance could be responsible for the increased risk of embryonic mosaicism among PCOS patients (OR = 1.89, 95% CI, 1.06–3.34, P=0.03). Limitations, reasons for caution The main limitation is the retrospective design. Besides, methodological uncertainties still exist in detecting mosaicism in current reproductive medicine. A longer-term, multiple-center prospective study with greater methodological standardization is warranted to confirm the present results. Wider implications of the findings These results suggest that PCOS pathology may increase the risk of mitosis errors but not the risk of meiosis errors during oocyte development, and PCOS-related insulin resistance should be investigated as a potential cause. Trial registration number 2020[325]