A novel cytokine panel can better predict oocyte competency in overweight patients

Abstract

Body composition affects outcomes in fertility treatments, however there is no clear correlation between measurement of body composition (BMI, lean/fat ratio and waist/hip ratio) and outcomes. This study aimed at creating a panel of metabolites to predict oocyte quality and competency in overweight patients. A retrospective cohort of biobanked follicular fluid (FF) samples collected between April 2017-December 2018 at a university-affiliated fertility clinic. Consented patients were included if they were undergoing IVF, did not have a female factor related diagnosis, and had a BMI≥25. Luminex Multiplex Bead Assays (R&D Systems) were performed on FF from 14 patients. The analytes were chosen based on an a priori literature review which highlighted metabolites previously correlated with fertility treatment outcomes in overweight patients. The tested metabolites were adipokines (resistin, leptin and adiponectin), pro-inflammatory cytokines (IL6, IL18 and TNFɑ), the anti-inflammatory cytokine IL10, the acute inflammation marker CRP, and factors associated with fat and glucose homeostasis (insulin, prolactin and chemerin). All samples and standards were assayed in duplicate (MACSQuant Analyzer). Absolute quantification was performed by comparing fluorescence of the samples to standard curves using Flowjo (v10). Linear regression determined the impact changes in these metabolites have on embryology outcomes, while controlling for demographic features (R v3.5.1). Patients were similar in terms of age (35.6±1.1 years), BMI (30.9±1.0 kg/m2) and AMH (18.3±1.7 pmol/L). The mean maturation rate was 70.6%, fertilization rate was 82.5%, cleavage rate was 99.2% and blastulation rate was 50.9%. Of all analysed factors, TNFɑ and IL18 were negatively associated with BMI and positively affected fertilization rate. Notably, leptin and CRP were not associated with BMI. However, increased leptin concentration negatively affected maturation rate, and increased CRP levels showed a tendency towards decreasing blastulation rate. Interestingly, several factors were negatively associated with blastocyst quality, including: IL6, IL18, chemerin, prolactin and insulin (all p<0.01). To our knowledge, this is the most comprehensive study to examine the effect multiple adipokines and cytokines have on metrics of oocyte and embryo quality in humans. While some cytokines that affect oocyte quality and embryology outcomes in fertility treatments correlate with BMI in overweight patients, others do not. Notably, IL6, IL18, TNFɑ, CRP, chemerin, prolactin, insulin and leptin all affect different aspects of oocyte and embryo development. Therefore, they should be considered as potential biomarkers to predict success in fertility treatments of overweight patients. Such biomarkers could help delineate patients of similar BMI with differing fertility potential. Further research should focus on larger-scale studies exploring these relationships in non-obese patients and determining if patients’ serum can be utilized to predict fertility treatment success.