Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

The Association of Soluble VEGFR-1 Serum Level and Genetic (rs7993418) Polymorphism with In Vitro Fertilization and Embryo Transfer Outcome in the Population of Northern Iran

Authors
Sadegheh Moeinfar 1
Farhad Mashayekhi 1
Mohammad Hadi Bahadori 2
Roya Faraji 3
Zivar Salehi 1
1 Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
2 Cellular and Molecular Research Center, Guilan University of Medical Sciences, Rasht, Iran
3 Department of Community Medicine and Biostatistics, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
10.18502/jri.v24i1.11904
Abstract
Background: Vascular endothelial growth factor receptors (VEGFRS) play an important role in embryo implantation. The aim of the present study was to examine the association of VEGFR1 circulating level and gene polymorphism with in vitro fertilization and embryo transfer (IVF-ET) outcome. Methods: In this case–control study, 120 women who had unsuccessful IVF (IVF – ) history and 120 women who had successful IVF outcome (IVF + ) as controls were included. Genomic DNA was extracted from blood samples. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The serum levels of soluble VEGFR1 (sVEGFR1) were measured by ELISA. ANOVA test was used for statistical analysis. Results: The frequency of T and C alleles in IVF + individuals were 87.5%, 12.5% and among IVF - were 75.5%, 24.5%, respectively (p=0.0006). The minor allele (C) was associated with an increased risk of IVF failure based on results from codominant (OR=3.86, 95%CI 1.19-12.47), dominant (OR=2.32, 95%CI 1.31-4.10), recessive (OR=3.22, 95%CI 1.00-10.29), and allele models (OR=2.28, 95%CI 1.40-3.69). We also showed that there is a significant decrease in serum sVEGFR1 levels in IVF as compared to IVF+ (p=0.006) groups. Moreover, TT genotype is significantly associated with increased serum sVEGFR1 concentration in IVF group (TT, CT, and CC serum levels were 106.55±11.04, 94.33±10.75, and 83.33±9.13 ng/ml, and in IVF + group were 156.11±18.08, 120.66±16.51, and 84.66±20.31 ng/ml, respectively). Conclusion: The results of this study indicate that VEGFR1 polymorphism and sVEGFR1 circulating levels are associated with IVF-ET outcome. Moreover, CC genotype is associated with decreased sVEGFR-1 serum concentration and IVF-ET failure.
Keywords
ELISA
ET
Iran
IVF failure
RFLP
Vascular Endothelial Growth Factor A
VEGFA
  1. Plaseska-Karanfilska D, Noveski P, Plaseski T, Maleva I, Madjunkova S, Moneva Z. Genetic causes of male infertility. Balkan J Med Genet. 2012;15(Sup-pl):31-4.
  2. Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International committee for monitoring assisted reproductive technology (ICMART) and the World health organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009;92(5):1520-4.
  3. Wright VC, Chang J, Jeng G, Chen M, Macaluso M, Centers for Disease Control and Prevention. Assisted reproductive technology surveillance-United States, 2004. MMWR Surveill Summ. 2007;56(6):1-22.
  4. Mahajan N, Kaur S, Alonso MR. Window of implantation is significantly displaced in patients with adenomyosis with previous implantation failure as determined by endometrial receptivity assay. J Hum Reprod Sci. 2018;11(4):353-8.
  5. van Mourik MS, Macklon NS, Heijnen CJ. Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment. J Leukoc Biol. 2009;85(1):4-9.
  6. Lai TH, Vlahos N, Shih IeM, Zhao Y. Expression patterns of VEGF and Flk-1 in human endometrium during the menstrual cycle. J Reprod Infertil. 2015;16(1):3-9.
  7. Cottrell HN, Wu J, Rimawi BH, Duran JM, Spencer JB, Sidell N, et al. Human endometrial stromal cell plasticity: Reversible sFlt1 expression negatively coincides with decidualization. Hypertens Pregnancy. 2017;36(2):204-11.
  8. Shibuya M. Structure and dual function of vascular endothelial growth factor receptor-1 (Flt-1). Int J Biochem Cell Biol. 2001;33(4):409-20.
  9. Xiong Y, Huo Y, Chen C, Zeng H, Lu X, Wei C, et al. Vascular endothelial growth factor (VEGF) receptor- tyrosine 1175 signaling controls VEGF-induced von Willebrand factor release from endothelial cells via phospholipase C-gamma 1- and protein kinase A-dependent pathways. J Biol Chem. 2009;284(35):23217-24.
  10. Millauer B, Wizigmann-Voos S, Schnürch H, Martinez R, Møller NP, Risau W, et al. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell. 1993;72(6):835-46.
  11. Clark DE, Smith SK, Sharkey AM, Charnock-Jones DS. Localization of VEGF and expression of its receptors flt and KDR in human placenta throughout pregnancy. Hum Reprod. 1996;11(5):1090-8.
  12. Halder JB, Zhao X, Soker S, Paria BC, Klagsbrun M, Das SK, et al. Differential expression of VEGF isoforms and VEGF (164)-specific receptor neuropilin-1 in the mouse uterus suggests a role for VEGF (164) in vascular permeability and angiogenesis during implantation. Genesis. 2000;26(3):213-24.
  13. Karimlo FK, Mashayekhi F, Sorouri ZZ, Bahador MH, Salehi Z. Association of GSTM1 and GSTT1 gene polymorphisms and in-vitro fertilisation outcome in a population in northern Iran. J Obstet Gynaecol. 2015;35(1):46-8.
  14. Alipour M, Mashayekhi F, Salehi Z. Association of leukemia inhibitory factor gene polymorphism and in vitro fertilization outcome in a population in northern Iran. Cell Mol Biol (Noisy-le-grand). 2017;63(3):58-61.
  15. Shabanipour S, Mashayekhi F, Bahadori MH, Soruri ZZ. The relationship between MMP-9 promoterpolymorphism and IVF outcome. Cell Mol Biol (Noisy-le-grand). 2015;61(1):64-7.
  16. De Geyter C. Assisted reproductive technology: Impact on society and need for surveillance. Best Pract Res Clin Endocrinol Metab. 2019;33(1):3-8.
  17. Crawford G, Ray A, Gudi A, Shah A, Homburg R. The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis. Hum Reprod Update. 2015;21(2):275-84.
  18. Goodman C, Jeyendran RS, Coulam CB. Vascular endothelial growth factor gene polymorphism and implantation failure. Reprod Biomed Online. 2008;16(5):720-3.
  19. Zarezade N, Saboori Darabi S, Ramezanali F, Amirchaghmaghi E, Khalili G, Moini A, et al. mRNA expression of VEGF and its receptors in fallopian tubes of women with ectopic pregnancies. Int J Fertil Steril. 2015;9(1):55-64.
  20. Kim CH, Ahn JW, Kim SH, Chae HD, Kang BM. Effects on in vitro fertilization-embryo transfer outcomes of vascular endothelial growth factor receptor-1, -2 and -3 in eutopic endometrial tissue of women with endometriosis. J Obstet Gynaecol Res. 2011;37(11):1631-7.
  21. Amirchaghmaghi E, Rezaei A, Moini A, Roghaei MA, Hafezi M, Aflatoonian R. Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J. 2015;16(4):538-45.
  22. Fasouliotis SJ, Spandorfer SD, Witkin SS, Liu HC, Roberts JE, Rosenwaks Z. Maternal serum vascular endothelial growth factor levels in early ectopic and intrauterine pregnancies after in vitro fertilization treatment. Fertil Steril. 2004;82(2):309-13.
  23. Asimakopoulos B, Nikolettos N, Papachristou DN, Simopoulou M, Al-Hasani S, Diedrich K. Follicular fluid levels of vascular endothelial growth factor and leptin are associated with pregnancy outcome of normal women participating in intracytoplasmic sperm injection cycles. Physiol Res. 2005;54(3):263-70.
  24. Gupta P, Deo S, Jaiswar SP, Sankhwar PL. Case control study to compare serum vascular endothelial growth factor (VEGF) level in women with recurrent pregnancy loss (RPL) compared to women with term pregnancy. J Obstet Gynaecol India. 2019;69(Suppl 2):95-102.
  25. Garrido N, Navarro J, Remohí J, Simón C, Pellicer A. Follicular hormonal environment and embryo quality in women with endometriosis. Hum Reprod Update. 2000;6(1):67-74.
  26. Chen H, Zheng JB, Wang DM, Xing H, Wang H. Association between vascular endothelial growth factor and clinical outcomes of IVF-ET/ICSI. J Coll Physicians Surg Pak. 2019;29(1):19-23.
  27. Boudjenah R, Molina-Gomes D, Wainer R, de Mazancourt P, Selva J, Vialard F. The vascular endothelial growth factor (VEGF) +405 G/C polymorphism and its relationship with recurrent implantation failure in women in an IVF programme with ICSI. J Assist Reprod Genet. 2012;29(12):1415-20.
  28. Jung YW, Ahn EH, Kim JO, An HJ, Cho SH, Kim YR, et al. Association of genetic polymorphisms in VEGF -460, -7 and -583 and hematocrit level with the development of idiopathic recurrent pregnancy loss and a meta-analysis. J Gene Med. 2018;20(9):e3048.
  29. Sajjadi MS, Ghandil P, Shahbazian N, Saberi A. Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage. J Obstet Gynaecol Res. 2020;46(3):369-75.
  30. Vagnini LD, Nascimento AM, Canas Mdo C, Renzi A, Oliveira-Pelegrin GR, Petersen CG, et al. The relationship between vascular endothelial growth factor 1154G/A polymorphism and recurrent implantation failure. Med Princ Pract. 2015;24(6):533-7.
  31. Goodman C, Jeyendran RS, Coulam CB. Vascular endothelial growth factor gene polymorphism and implantation failure. Reprod Biomed Online. 2008;16(5):720-3.
  32. Cobos E, Recalde S, Anter J, Hernandez-Sanchez M, Barreales C, Olavarrieta L, et al. Association between CFH, CFB, ARMS2, SERPINF1, VEGFR1 and VEGF polymorphisms and anatomical and functional response to ranibizumab treatment in neovascular age-related macular degeneration. Acta Ophthalmol. 2018;96(2):e201-12.
  33. Beuselinck B, Jean-Baptiste J, Schöffski P, Couchy G, Meiller C, Rolland F, et al. Validation of VEGFR1 rs9582036 as predictive biomarker in metastatic clear-cell renal cell carcinoma patients treated with sunitinib. BJU Int. 2016;118(6):890-901.
  34. Cardoso JV, Abrão MS, Vianna-Jorge R, Ferrari R, Berardo PT, Machado DE, et al. Combined effect of vascular endothelial growth factor and its receptor polymorphisms in endometriosis: a case-control study. Eur J Obstet Gynecol Reprod Biol. 2017;209:25-33.
  35. Park SJ, Ki KD, Lee HW, Lee YB, Lee KS, Huh CY, et al. The follicular fluid and serum concentrations of vascular endothelial growth factor in patients during IVF-ET cycles. Korean J Obstetr Gynecol. 2006;49:1941-8.
  36. Bansal R, Ford B, Bhaskaran S, Thum M, Bansal A. Elevated levels of serum vascular endothelial growth factor-A are not related to NK cell parameters in recurrent IVF failure. J Reprod Infertil. 2017;18(3):280-7.
Journal of Reproduction & Infertility
Volume 24, Issue 1
Winter 2023
Pages 11-17