Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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Cardiovascular risk may be increased in women with unexplained infertility

  • Verit, Fatma Ferda (Department of Obstetrics and Gynecology, Suleymaniye Maternity, Research, and Training Hospital) ;
  • Zeyrek, Fadile Yildiz (Department of Microbiology, Harran University Faculty of Medicine) ;
  • Zebitay, Ali Galip (Department of Obstetrics and Gynecology, Suleymaniye Maternity, Research, and Training Hospital) ;
  • Akyol, Hurkan (Department of Obstetrics and Gynecology, Suleymaniye Maternity, Research, and Training Hospital)
  • Received : 2016.06.29
  • Accepted : 2016.11.21
  • Published : 2017.03.31
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Abstract

Objective: Growing evidence suggests that increased cardiovascular disease (CVD) risk is associated with female infertility caused by conditions such as polycystic ovarian disease, obesity, thyroid dysfunction, and endometriosis. The aim of this study was to evaluate whether any relationship exists between CVD and unexplained infertility. Methods: Sixty-five women with unexplained infertility and 65 fertile controls were enrolled in the study. CVD risk markers such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG), insulin resistance (defined by the homeostasis model assessment ratio), and high-sensitivity C-reactive protein (hs-CRP) were assessed. Results: TG, TC, LDL, and hs-CRP levels were higher and HDL levels were lower in patients with unexplained infertility than in fertile controls (p<0.05 for all). Positive associations were found between unexplained infertility and TG, TC, LDL, and hs-CRP levels, and a negative correlation was found for HDL (p<0.05 for all). Multivariate logistic regression analysis showed that TG, HDL, and hs-CRP were independent variables associated with unexplained infertility. Conclusion: Our study showed that women with unexplained infertility had an atherogenic lipid profile and elevated hs-CRP levels, suggesting a higher risk of developing CVD in the future. Further studies with larger groups are needed to investigate the nature of this link.

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References

  1. Smith S, Pfeifer SM, Collins JA. Diagnosis and management of female infertility. JAMA 2003;290:1767-70. https://doi.org/10.1001/jama.290.13.1767
  2. Crosignani PG, Collins J, Cooke ID, Diczfalusy E, Rubin B. Recommendations of the ESHRE workshop on 'Unexplained Infertility': Anacapri, August 28-9, 1992. Hum Reprod 1993;8:977-80. https://doi.org/10.1093/oxfordjournals.humrep.a138177
  3. Siristatidis C, Bhattacharya S. Unexplained infertility: does it really exist? Does it matter? Hum Reprod 2007;22:2084-7. https://doi.org/10.1093/humrep/dem117
  4. Bevc S, Sabic S, Hojs R. Atherosclerosis in hemodialysis patients: the role of microinflammation. Ren Fail 2008;30:1012-6. https://doi.org/10.1080/08860220802406385
  5. Ikonomidis I, Stamatelopoulos K, Lekakis J, Vamvakou GD, Kremastinos DT. Inflammatory and non-invasive vascular markers: the multimarker approach for risk stratification in coronary artery disease. Atherosclerosis 2008;199:3-11. https://doi.org/10.1016/j.atherosclerosis.2008.02.019
  6. Hansson GK. Atherosclerosis-an immune disease: the Anitschkov lecture 2007. Atherosclerosis 2009;202:2-10. https://doi.org/10.1016/j.atherosclerosis.2008.08.039
  7. Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N. Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 2001;86:2453-5. https://doi.org/10.1210/jcem.86.6.7580
  8. Frohlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, et al. Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care 2000;23:1835-9. https://doi.org/10.2337/diacare.23.12.1835
  9. Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996;334:952-7. https://doi.org/10.1056/NEJM199604113341504
  10. Farin HM, Abbasi F, Kim SH, Lamendola C, McLaughlin T, Reaven GM. The relationship between insulin resistance and dyslipidaemia in cigarette smokers. Diabetes Obes Metab 2007;9:65-9. https://doi.org/10.1111/j.1463-1326.2006.00574.x
  11. Kemp DM. Does chronic low-grade endotoxemia define susceptibility of obese humans to insulin resistance via dietary effects on gut microbiota? Adipocyte 2013;2:188-90. https://doi.org/10.4161/adip.24776
  12. Aroor A, McKarns S, Nistala R, Demarco V, Gardner M, Garcia-Touza M, et al. DPP-4 inhibitors as therapeutic modulators of immune cell function and associated cardiovascular and renal insulin resistance in obesity and diabetes. Cardiorenal Med 2013;3:48-56. https://doi.org/10.1159/000348756
  13. Parikh NI, Cnattingius S, Mittleman MA, Ludvigsson JF, Ingelsson E. Subfertility and risk of later life maternal cardiovascular disease. Hum Reprod 2012;27:568-75. https://doi.org/10.1093/humrep/der400
  14. Sotiriadis A, Makrigiannakis A, Stefos T, Paraskevaidis E, Kalantaridou SN. Fibrinolytic defects and recurrent miscarriage: a systematic review and meta-analysis. Obstet Gynecol 2007;109:1146-55. https://doi.org/10.1097/01.AOG.0000260873.94196.d6
  15. Andrews FM, Abbey A, Halman LJ. Stress from infertility, marriage factors, and subjective well-being of wives and husbands. J Health Soc Behav 1991;32:238-53. https://doi.org/10.2307/2136806
  16. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol 2012;10:49. https://doi.org/10.1186/1477-7827-10-49
  17. Prevention of diabetes mellitus: report of a WHO study group. World Health Organ Tech Rep Ser 1994;844:1-100.
  18. Lawlor DA, Emberson JR, Ebrahim S, Whincup PH, Wannamethee SG, Walker M, et al. Is the association between parity and coronary heart disease due to biological effects of pregnancy or adverse lifestyle risk factors associated with child-rearing? Findings from the British Women's Heart and Health Study and the British Regional Heart Study. Circulation 2003;107:1260-4. https://doi.org/10.1161/01.CIR.0000053441.43495.1A
  19. Parikh NI, Cnattingius S, Dickman PW, Mittleman MA, Ludvigsson JF, Ingelsson E. Parity and risk of later-life maternal cardiovascular disease. Am Heart J 2010;159:215-21.e6. https://doi.org/10.1016/j.ahj.2009.11.017
  20. Solomon CG, Hu FB, Dunaif A, Rich-Edwards JE, Stampfer MJ, Willett WC, et al. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab 2002;87:2013-7. https://doi.org/10.1210/jcem.87.5.8471
  21. Gregg EW, Cheng YJ, Cadwell BL, Imperatore G, Williams DE, Flegal KM, et al. Secular trends in cardiovascular disease risk factors according to body mass index in US adults. JAMA 2005;293:1868-74. https://doi.org/10.1001/jama.293.15.1868
  22. Flynn RW, Macdonald TM, Jung RT, Morris AD, Leese GP. Mortality and vascular outcomes in patients treated for thyroid dysfunction. J Clin Endocrinol Metab 2006;91:2159-64. https://doi.org/10.1210/jc.2005-1833
  23. Kurabayashi T, Mizunuma H, Kubota T, Hayashi K. Ovarian infertility is associated with cardiovascular disease risk factors in later life: a Japanese cross-sectional study. Maturitas 2016;83:33-9. https://doi.org/10.1016/j.maturitas.2015.08.015
  24. Reindollar RH. Contemporary issues for spontaneous abortion. Does recurrent abortion exist? Obstet Gynecol Clin North Am 2000;27:541-54. https://doi.org/10.1016/S0889-8545(05)70154-6
  25. Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 2001;323:1213-7. https://doi.org/10.1136/bmj.323.7323.1213
  26. Della-Morte D, Beecham A, Dong C, Wang L, McClendon MS, Gardener H, et al. Association between variations in coagulation system genes and carotid plaque. J Neurol Sci 2012;323:93-8. https://doi.org/10.1016/j.jns.2012.08.020
  27. Verit FF, Erel O, Celik N. Serum paraoxonase-1 activity in women with endometriosis and its relationship with the stage of the disease. Hum Reprod 2008;23:100-4.
  28. Kinugasa S, Shinohara K, Wakatsuki A. Increased asymmetric dimethylarginine and enhanced inflammation are associated with impaired vascular reactivity in women with endometriosis. Atherosclerosis 2011;219:784-8. https://doi.org/10.1016/j.atherosclerosis.2011.08.005
  29. Santoro L, D'Onofrio F, Campo S, Ferraro PM, Tondi P, Campo V, et al. Endothelial dysfunction but not increased carotid intima-media thickness in young European women with endometriosis. Hum Reprod 2012;27:1320-6. https://doi.org/10.1093/humrep/des062
  30. Wellons M. Cardiovascular disease and primary ovarian insufficiency. Semin Reprod Med 2011;29:328-41. https://doi.org/10.1055/s-0031-1280918
  31. Verit FF, Keskin S, Omer B, Yalcinkaya S, Sakar N. Is there any relationship between cardiovascular risk markers and young women with diminished ovarian reserve? Gynecol Endocrinol 2014; 30:697-700. https://doi.org/10.3109/09513590.2014.922948
  32. Purcell SH, Moley KH. The impact of obesity on egg quality. J Assist Reprod Genet 2011;28:517-24. https://doi.org/10.1007/s10815-011-9592-y
  33. Michalakis K, Coppack SW. Primary ovarian insufficiency: relation to changes in body composition and adiposity. Maturitas 2012;71:320-5. https://doi.org/10.1016/j.maturitas.2011.12.023
  34. Pacchiarotti A, Mohamed MA, Micara G, Linari A, Tranquilli D, Espinola SB, et al. The possible role of hyperhomocysteinemia on IVF outcome. J Assist Reprod Genet 2007;24:459-62. https://doi.org/10.1007/s10815-007-9165-2
  35. Gaikwad S, Garrido N, Cobo A, Pellicer A, Remohi J. Bed rest after embryo transfer negatively affects in vitro fertilization: a randomized controlled clinical trial. Fertil Steril 2013;100:729-35. https://doi.org/10.1016/j.fertnstert.2013.05.011
  36. Loftis JM, Huckans M, Morasco BJ. Neuroimmune mechanisms of cytokine-induced depression: current theories and novel treatment strategies. Neurobiol Dis 2010;37:519-33. https://doi.org/10.1016/j.nbd.2009.11.015
  37. Khovidhunkit W, Kim MS, Memon RA, Shigenaga JK, Moser AH, Feingold KR, et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 2004;45:1169-96. https://doi.org/10.1194/jlr.R300019-JLR200
  38. Rizzo M, Rizvi AA, Rini GB, Berneis K. The therapeutic modulation of atherogenic dyslipidemia and inflammatory markers in the metabolic syndrome: what is the clinical relevance? Acta Diabetol 2009;46:1-11. https://doi.org/10.1007/s00592-008-0057-4

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