Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology

Abstract

Advanced glycation end-products (AGE) are pivotal in aging and diabetes. Aging and polycystic ovary syndrome, a diabetes-associated disease, often cause infertility. We examined how AGE accumulation affects assisted reproductive technology (ART) outcomes. In this retrospective analysis, toxic AGE (TAGE), pentosidine (Pent) and carboxymethyl lysine (CML) in blood and follicular fluid (FF) were measured in 157 ART-patients. We analyzed associations of AGE with ART outcomes and pre-ART clinical factors. TAGE, Pent and CML in FF and TAGE in serum, showed significant negative correlations with estradiol and numbers of follicles larger than 12 mm in diameter, retrieved oocytes, fertilized oocytes and embryos. AGE, Pent in FF and TAGE in serum showed significant negative correlations with ongoing pregnancy. Areas under receiver-operating characteristic curves for AGE (0.709), Pent in FF (0.686) and TAGE in serum (0.667) were significantly larger than for the reference (0.5). Women with serum TAGE above 7.24 U/ml showed decreased oocyte numbers and ongoing pregnancy rates, even with younger age or lower Day-3 FSH. Serum TAGE correlated positively with leptin (R = 0.51), BMI, low-density lipoprotein, triglyceride, glucose, homeostasis model assessment-insulin resistance and insulin. Serum TAGE and FF Pent accumulations correlated highly with poor follicular and embryonic development and with a lower likelihood of ongoing pregnancy. Serum TAGE predicts poor ART outcomes independent of age and Day-3 FSH.