Follicular Fluid Levels of Adrenomedullin 2, Vascular Endothelial Growth Factor and its Soluble Receptors Are Associated with Ovarian Response During ART Cycles

Abstract

Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes. Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits. Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and − 0.366, respectively). Based on the ROC curve, the cutoff value for ADM2 as a non-responder predictor was 348.55 (pg/ml) with a sensitivity of 67.7% and a specificity of 94.6%. Conclusions For the first time we measured FF ADM2 levels to determine the relationship to VEGF and its soluble receptors. We suggest that ADM2 could be a potential predictive marker for non-responders. Although the exact function of ADM2 in ovarian angiogenesis is not yet understood, our study may shed light on the possible role of ADM2 in folliculogenesis and ovulation.

S100 protein family and embryo implantation

“…[17][18][19][20] Several factors are involved in effective implantation. [21][22][23][24][25][26][27][28] One of the most important is calcium. Certainly, Ca 2+ balance is critical in successful pregnancy.…”

Exosome‐based intercellular communication in female reproductive microenvironments

“…FF is derived from both follicular cells secretion and blood plasma. The granulosa and theca cells secret different proteins, hormones, and antiapoptotic factors into the FF (da Silveira, Veeramachaneni, Winger, Carnevale, & Bouma, 2012;Nejabati, Mota, et al, 2017;Ranjbaran et al, 2019;Revelli et al, 2009). Bidirectional communication between the gamete and the cumulus cells, as the nurse cells, plays the crucial role for nuclear meiosis regulation in the oocyte; this communication also regulates the development and differentiation of follicles and containing granulosa cells.…”

Investigating apoptotic, inflammatory, and growth markers in poor responders undergoing natural in vitro fertilization cycles: a pilot study

“…Another extensively examined growth factor is VEGF, which is actively secreted into FF by granulosa cells 29–32 . Increased levels of VEGF were observed in FF originating from in vitro fertilization (IVF) patients with low (or even no) response to controlled ovarian stimulation (COS) 33–36 . Contradictory data indicate both a positive 37,38 and a negative association of high levels of FF VEGF with the number and size of follicles, along with the number of mature oocytes 33–35,39–42 …”