The Impact of BMI on PCOS Patients and Transcriptome Profiling and Bioinformatic Analysis of Granulosa Cells in PCOS Patients with High and Low BMI

Purpose: To explore the impact of high body mass index (BMI) on the embryo quality and clinical outcomes of polycystic ovary syndrome (PCOS) patients, and the possible genes involved.

Methods: Patients who underwent in-vitro fertilization (IVF) treatment and embryo transfer in our center from November 2014 to September 2023, were divided into low BMI PCOS (LBP) group, high BMI PCOS (HBP) group, and high BMI control (HBC) group. Transcriptome sequencing was performed in eight PCOS patients' granulosa cells (GCs).

Results: A total of 812 IVF/intracytoplasmic sperm injection (ICSI) cycles in the embryo part; and 489 fresh, 634 frozen-warmed embryo transfer (FET) cycles from the clinical part were included. The ICSI normal fertilization rate of HBP group was decreased compared to LBP and HBC groups (p = 0.013&0.008). The IVF blastocyst development rate in HBP group was lower than LBP group (p = 0.01). The preterm birth rate in HBP group was higher than in LBP (30.66% vs. 16.48%, p = 0.041) and HBC groups (30.66% vs. 11.34%, p = 0.002), the adjusted OR (AOR) of preterm birth and BMI was 1.124 (p = 0.023) in FET cycles. Transcriptome sequencing result of GCs showed that differentially expressed miRNAs/lncRNA/circRNA/mRNAs in two PCOS groups were 61, 450, 83, and 568, respectively. The hub genes analysis, enrichment analysis and competing endogenous RNA network revealed that cell cycle, oocyte maturation, systemic lupus erythematosus, oxidative phosphorylation, and mitogen-activated protein kinases (MAPK) signaling pathways had important roles in the embryo development and pregnancy process.

Conclusions: The combined effect of PCOS and obesity reduced oocyte quality and embryonic development potential, finally led to poorer clinical outcomes.