Intrafollicular soluble RAGE benefits embryo development and predicts clinical pregnancy in infertile patients of advanced maternal age undergoing in vitro fertilization

Abstract

Soluble receptor for advanced glycation end products (sRAGE) can decoy the toxic AGEs and is considered to be a protective factor. This study aimed to evaluate the correlation between intrafollicular sRAGE levels and clinical outcomes in infertile women of young or advanced maternal age (AMA) undergoing in vitro fertilization (IVF). A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study. The intrafollicular sRAGE concentration was measured to determine its association with the number of retrieved oocytes, fertilized oocytes, high-quality embryos or achievement of clinical pregnancy in young and AMA women, respectively. Besides, correlations between sRAGE and age or follicle-stimulating hormone (FSH) were examined. We found that the intrafollicular sRAGE levels were higher in young patients than those in AMA patients, suggesting that the sRAGE levels were inversely correlated with age. In young patients, sRAGE showed no correlation with the number of retrieved oocytes, fertilized oocytes, high-quality embryos or achievement of clinical pregnancy. But it was found that AMA patients with more retrieved oocytes, fertilized oocytes and high-quality embryos demonstrated higher sRAGE levels, which were a prognostic factor for getting clinical pregnancy independent of age or FSH level. In conclusion, the sRAGE levels decrease with age. Elevated intrafollicular sRAGE levels indicate good follicular growth, fertilization and embryonic development, and successful clinical pregnancy in AMA women, while in young women, the role of sRAGE may not be so predominant.

Keywords

soluble receptor for advanced glycation end products / infertile women / women of advanced maternal age / IVF outcomes

References

[1] InagiR. Inhibitors of advanced glycation and endoplasmic reticulum stress. Methods Enzymol, 2011, 491: 361-380 PMID: 21329810

[2] PiperiC, AdamopoulosC, DalagiorgouG, et al. . Crosstalk between advanced glycation and endoplasmic reticulum stress: emerging therapeutic targeting for metabolic diseases. J Clin Endocrinol Metab, 2012, 97(7): 2231-2242 PMID: 22508704

[3] YamagishiS, NakamuraK, ImaizumiT. Advanced glycation end products (AGEs) and diabetic vascular complications. Curr Diabetes Rev, 2005, 1(1): 93-106 PMID: 18220586

[4] KaleaAZ, SchmidtAM, HudsonBI. RAGE: a novel biological and genetic marker for vascular disease. Clin Sci, 2009, 116(8): 621-637 PMID: 19275767

[5] HudsonBI, CarterAM, HarjaE, et al. . Identification, classification, and expression of RAGE gene splice variants. FASEB J, 2008, 22(5): 1572-1580 PMID: 18089847

[6] FujiiEY, NakayamaM. The measurements of RAGE, VEGF, and AGEs in the plasma and follicular fluid of reproductive women: the influence of aging. Fertil Steril, 2010, 94(2): 694-700 PMID: 19376511

[7] FaddyM J, GosdenRG. A model conforming the decline in follicle numbers to the age of menopause in women. Hum Reprod, 1996, 11(7): 1484-1486 PMID: 8671489

[8] FaddyMJ, GosdenRG, GougeonA, et al. . Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod, 1992, 7(10): 1342-1346 PMID: 1291557

[9] TeVE, PearsonPL. The variability of female reproductive ageing. Hum Reprod Update, 2002, 8(2): 141-154

[10] StensenMH, TanboT, StorengR, et al. . Advanced glycation end products and their receptor contribute to ovarian ageing. Hum Reprod, 2014, 29(1): 125-134 PMID: 24256989

[11] TatoneC, AmicarelliF. The aging ovary—the poor granulosa cells. Fertil Steril, 2013, 99(1): 12-17 PMID: 23273984

[12] TatoneC, AmicarelliF, CarboneMC, et al. . Cellular and molecular aspects of ovarian follicle ageing. Hum Reprod Update, 2008, 14(2): 131-142 PMID: 18239135

[13] de BruinJP, DorlandM, SpekER, et al. . Age-related changes in the ultrastructure of the resting follicle pool in human ovaries. Biol Reprod, 2004, 70(2): 419-424 PMID: 14561658

[14] JinnoM, TakeuchiM, WatanabeA, et al. . Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology. Hum Reprod, 2011, 26(3): 604-610 PMID: 21233108

[15] MalickovaK, JarosovaR, RezabekK, et al. . Concentrations of sRAGE in serum and follicular fluid in assisted reproductive cycles—a preliminary study. Clin Lab, 2010, 56(9-10): 377-384 PMID: 21086782

[16] RamasamyR, YanSF, SchmidtAM. RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts. J Leukoc Biol, 2009, 86(3): 505-512 PMID: 19477910

[17] SharmaI, DhawanV, SahaSC, et al. . Implication of the RAGE-EN-RAGE axis in endometriosis. Int J Gynaecol Obstet, 2010, 110(3): 199-202 PMID: 20537326

[18] Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod, 2004,19(1):41–47

[19] Pr B. A textbook of in vitro fertilization and assisted reproduction. New York: The Parthenon Publishing Group Inc, 1999.

[20] DriancourtMA, ThuelB. Control of oocyte growth and maturation by follicular cells and molecules present in follicular fluid. A review. Reprod Nutr Dev, 1998, 38(4): 345-362 PMID: 9795980

[21] RevelliA, DellePL, CasanoS, et al. . Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod Biol Endocrinol, 2009, 7: 40 PMID: 19413899 PMCID: 2685803

[22] SantilliF, VazzanaN, BucciarelliLG, et al. . Soluble forms of RAGE in human diseases: clinical and therapeutical implications. Curr Med Chem, 2009, 16(8): 940-952 PMID: 19275604

[23] TamXH, ShiuSW, LengL, et al. . Enhanced expression of receptor for advanced glycation end-products is associated with low circulating soluble isoforms of the receptor in type 2 diabetes. Clin Sci, 2011, 120(2): 81-89 PMID: 20726839

[24] HorkaP, MalickovaK, JarosovaR, et al. . Matrix metalloproteinases in serum and the follicular fluid of women treated by in vitro fertilization. J Assist Reprod Genet, 2012, 29(11): 1207-1212 PMID: 23054355 PMCID: 3510381