ABSTRACT
CONTEXT: The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment. OBJECTIVE: The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve. DESIGN, SETTING, AND PARTICIPANTS: Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women. An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured. MAIN OUTCOME MEASURES: Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocytes retrieved were measured. RESULTS: In the serum, sRAGE levels were negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not with age or serum AMH. The higher the FF sRAGE, the lower the number of international units of gonadotropin needed per cycle independent of age, BMI, or day 3 FSH level (r = -0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and the total dose of gonadotropins, FF sRAGE predicted the number of oocytes retrieved (R(2) = 0.27, P = .045). FF sRAGE positively correlated with FF AMH levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF sRAGE and AMH or AMHR-II mRNA levels. CONCLUSION: These data support a relationship between FF sRAGE and measures of ovarian reserve. The pathological significance of the harmful inflammatory AGEs in follicular health clearly requires further investigation. Targeting AGEs might offer potential therapeutic options for the treatment of diminished ovarian response.
Subject(s)
Follicular Fluid/metabolism , Granulosa Cells/metabolism , Oocytes/metabolism , Receptors, Immunologic/metabolism , Adult , Age Factors , Anti-Mullerian Hormone/blood , Biomarkers/metabolism , Body Mass Index , Female , Follicle Stimulating Hormone/blood , Humans , Oocyte Retrieval , Oocytes/cytology , Ovarian Follicle/metabolism , Ovulation Induction , Receptor for Advanced Glycation End Products , Receptors, Immunologic/blood , Receptors, Immunologic/geneticsABSTRACT
OBJECTIVE: To evaluate the impact of multinucleation of a sibling blastomere of day 2 embryos on the rate of aneuploidy detected by day 3 preimplantation genetic screening (PGS) biopsy and the effect on subsequent implantation and pregnancy rates. DESIGN: Retrospective cohort study. SETTING: University-based IVF center. PATIENT(S): A total of 141 couples undergoing their first IVF-PGS cycle for idiopathic recurrent pregnancy loss (RPL) or multiple failed IVF implantations. INTERVENTION(S): Biopsy of single-nucleated blastomeres for PGS analysis of chromosomes X, Y, 13, 15, 16, 17, 18, 21, and 22 by fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): Aneuploidy, implantation, and pregnancy rates. RESULT(S): PGS revealed an increased incidence of aneuploidy when comparing multinucleated day 2 embryos with single-nucleated embryos (85% vs. 78%; relative risk 0.92 (95% confidence interval 0.84-1.00). Transfer of single-nucleated euploid embryos resulted in clinical pregnancy and implantation rates of 28% and 24%. Transfer of multinucleated euploid embryos resulted in no implantations. CONCLUSION(S): The presence of multinucleated blastomeres on day 2 of embryo development, 1 day before biopsy, predicts an increase of aneuploidy and poor pregnancy outcomes in IVF-PGS cycles.
