The Higher Response of Vascular Endothelial Growth Factor and Angiotensin-II to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome

Junwei Qu, Yena Che, Pei Xu, Yanjie Xia, Xiaoke Wu, Yong Wang, Junwei Qu, Yena Che, Pei Xu, Yanjie Xia, Xiaoke Wu, Yong Wang

Abstract

Background: This research investigated the response of vascular active factors, vascular endothelial growth factor (VEGF) and angiotensin-II (AT-II) to ovarian stimulation during 24 hours in patients with polycystic ovary syndrome (PCOS).

Materials and methods: In this clinical trial study, 52 patients with PCOS and 8 control cases were stimulated with human chorionic gonadotropin (HCG) on the 4(th) to 7(th) day of the patients' natural or induced menstrual cycles. We measured VEGF and AT-II by radioimmunoassay before the injection (0 hour) and 3, 8, 12, 18 and 24 hours after the stimulation.

Results: After ovarian stimulation, there was substantially higher level of VEGF in typical PCOS patients than the other three groups at the 3 hour time point (p<0.05), while there were no significant differences in VEGF at all the other time points among the four groups. As for AT-II, before and at all time points after the ovarian stimulation, it seemed that the AT-II levels in patients' sera with different phenotypes of PCOS by the Rotterdam criteria were all higher than in the control group although the differences were not statistically significant. The level of AT-II in typical PCOS patients was also significantly higher than the other three groups at the 3 hour time point (p<0.05), while no significant differences at all the other time points among the four groups were observed.

Conclusion: The response to the stimulation varied among patients with different phenotypes of PCOS according to the Rotterdam criteria. Serum VEGF and AT-II were possible contributors to an increased risk of developing ovarian hyperstimulation syndrome (OHSS) in patients with typical PCOS during the early follicular phase (3 hours) after ovarian stimulation (

Registration number: NCT02265861).

Keywords: Angiotensin-II; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Vascular Endothelial Growth Factor.

Figures

Fig 1
Fig 1
Vascular endothelial growth factor (VEGF) (A) and angiotensin II (AT- II) (B) response to stimuli during the ovarian stimulation test. The level of VEGF and AT- II in typical polycystic ovary syndrome (PCOS) patients (group 1) was substantially higher than the other three groups at the 3 hour time point. Note: Logarithmic transformation of data was performed for measures that were not normally distributed. All results are expressed as Log10 (x ± s). *; P<0.05, PCO; Polycystic ovarian morphology and HA; Hyperandrogenism.

References

    1. Wang Y, Wu X, Cao Y, Yi L, Chen J. A microsatellite polymorphism (tttta)n in the promoter of the CYP11a gene in Chinese women with polycystic ovary syndrome. Fertil Steril. 2006;86(1):223–226.
    1. Wang Y, Wu X, Cao Y, Yi L, Fan H, Chen J. Polymorphisms of the peroxisome proliferator-activated receptor-gamma and its coactivator-1alpha genes in Chinese women with polycystic ovary syndrome. Fertil Steril. 2006;85(5):1536–1540.
    1. Xu P, Shen SM, Zhang XL, Liang F, Xie GB, Yi L, et al. Haplotype analysis of single nucleotide polymorphisms in anti-Müllerian hormone gene in Chinese PCOS women. Arch Gynecol Obstet. 2013;288(1):125–130.
    1. Speca S, Napolitano C, Tagliaferri G. The pathogenetic enigma of polycystic ovary syndrome. J Ultrasound. 2007;10(4):153–160.
    1. Zackova T, Jarvela IY, Tapanainen JS, Feyereisl J. Assessment of endometrial and ovarian characteristics using three dimensional power Doppler ultrasound to predict response in frozen embryo transfer cycles. Reprod Biol Endocrinol. 2009;7:151–158.
    1. Dahl SK, Cannon S, Aubuchon M, Williams DB, Robins JC, Thomas MA. Follicle curetting at the time of oocyte retrieval increases the oocyte yield. J Assist Reprod Genet. 2009;26(6):335–339.
    1. Escobar-Morreale HF, Luque-Ramirez M, Gonzalez F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril. 2011;95(3):1048–1058.
    1. Harada M, Peegel H, Menon KM. Expression of vascular endothelial growth factor A during ligand-induced down-regulation of luteinizing hormone receptor in the ovary. Mol Cell Endocrinol. 2010;328(1-2):28–33.
    1. Julio-Pieper M, Lozada P, Tapia V, Vega M, Miranda C, Vantman D, et al. Nerve growth factor induces vascular endothelial growth factor expression in granulosa cells via a trkA receptor/mitogen-activated protein kinase-extracellularly regulated kinase 2-dependent pathway. J Clin Endocrinol Metab. 2009;94(8):3065–3071.
    1. Tokuyama O, Nakamura Y, Muso A, Fujino Y, Ishiko O, Ogita S. Vascular endothelial growth factor concentrations in follicular fluid obtained from IVF-ET patients: a comparison of hMG, clomiphene citrate, and natural cycle. J Assist Reprod Genet. 2002;19(1):19–23.
    1. Gard PR. Implications of the angiotensin converting enzyme gene insertion/deletion polymorphism in health and disease: a snapshot review. Int J Mol Epidemiol Genet. 2010;1(2):145–157.
    1. Alphan Z, Berberoglu Z, Gorar S, Candan Z, Aktas A, Aral Y, et al. Increased total Renin levels but not Angiotensin-converting enzyme activity in obese patients with polycystic ovary syndrome. Med Princ Pract. 2013;22(5):475–479.
    1. Sohrabvand F, Ansaripour S, Bagheri M, Shariat M, Jafarabadi M. Cabergoline versus coasting in the prevention of ovarian hyperstimulation syndrome and assisted reproductive technologies outcome in high risk patients. Int J Fertil Steril. 2009;3(1):35–40.
    1. Gomez R, Ferrero H, Delgado-Rosas F, Gaytan M, Morales C, Zimmermann RC, et al. Evidences for the existence of a low dopaminergic tone in polycystic ovarian syndrome: implications for OHSS development and treatment. J Clin Endocrinol Metab. 2011;96(8):2484–2492.
    1. Hill MJ, Chason RJ, Payson MD, Segars JH, Csokmay JM. GnRH antagonist rescue in high responders at risk for OHSS results in excellent assisted reproduction outcomes. Reprod Biomed Online. 2012;25(3):284–291.
    1. Vural P, Kusku-Kiraz Z, Dogru-Abbasoglu S, Cil E, Karadag B, Akgul C, et al. Vascular endothelial growth factor -2578 A/C, -460 T/C and +405 G/C polymorphisms in polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2009;147(1):57–60.
    1. Qiao J, Feng HL. Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update. 2011;17(1):17–33.
    1. Bates DO. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res. 2010;87(2):262–271.
    1. El Behery MM, Diab AE, Mowafy H, Ebrahiem MA, Shehata AE. Effect of laparoscopic ovarian drilling on vascular endothelial growth factor and ovarian stromal blood flow using 3-dimensional power Doppler. Int J Gynaecol Obstet. 2011;112(2):119–121.
    1. Brogan RS, Mix S, Puttabyatappa M, VandeVoort CA, Chaffin CL. Expression of the insulin-like growth factor and insulin systems in the luteinizing macaque ovarian follicle. Fertil Steril. 2010;93(5):1421–1429.
    1. Pundir J, Sunkara SK, El-Toukhy T, Khalaf Y. Meta-analysis of GnRH antagonist protocols: do they reduce the risk of OHSS in PCOS? Reprod Biomed Online. 2012;24(1):6–22.
    1. Beigi Boroujeni M, Beigi Boroujeni N, Salehnia M, Marandi E. Ultrastructural changes of corpus luteum after ovarian stimulation at implantation period. Iran Biomed J. 2012;16(1):33–37.
    1. Battaglia C, Mancini F, Persico N, Zaccaria V, de Aloysio D. Ultrasound evaluation of PCO, PCOS and OHSS. Reprod Biomed Online. 2004;9(6):614–619.
    1. Hayden MR, Sowers KM, Pulakat L, Joginpally T, Krueger B, Whaley-Connell A, et al. Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus. Cardiorenal Med. 2011;1(3):193–210.
    1. Arefi S, Mottaghi S, Sharifi AM. Studying the correlation of renin-angiotensin-system (RAS) components and insulin resistance in polycystic ovary syndrome (PCOs) Gynecol Endocrinol. 2013;29(5):470–473.
    1. Milsted A, Underwood AC, Dunmire J, DelPuerto HL, Martins AS, Ely DL, et al. Regulation of multiple renin-angiotensin system genes by Sry. J Hypertens. 2010;28(1):59–64.
    1. Cherry JA, Hou X, Rueda BR, Davis JS, Townson DH. Microvascular endothelial cells of the bovine corpus luteum: a comparative examination of the estrous cycle and pregnancy. J Reprod Dev. 2008;54(3):183–191.
    1. Alper MM, Smith LP, Sills ES. Ovarian hyperstimulation syndrome: current views on pathophysiology, risk factors, prevention, and management. J Exp Clin Assist Reprod. 2009;6:3–3.
    1. Davis JS, Rueda BR, Spanel-Borowski K. Microvascular endothelial cells of the corpus luteum. Reprod Biol Endocrinol. 2003;1:89–89.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever