Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 32, Issue 11, pp 1697–1703 | Cite as

Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment

  • J. Czamanski-CohenEmail author
  • O. Sarid
  • J. Cwikel
  • A. Douvdevani
  • E. Levitas
  • E. Lunenfeld
  • I. Har-Vardi
Technological Innovations

Abstract

Purpose

The current research is aimed at finding potential non-invasive bio-markers that will help us learn more about the mechanisms at play in failed assisted reproduction treatment. This exploratory pilot study examined the relationship between cell-free DNA (CFD) in plasma and telomere length in lymphocytes among women undergoing in vitro fertilization (IVF) and compared telomere length and CFD levels to a healthy control group.

Methods

Blood of 20 women undergoing IVF was collected at three time points during the IVF cycle. We assessed the relationship between CFD and telomere length as well as controlling for morning cortisol levels. We also collected blood of 10 healthy controls at two time points (luteal and follicular phases of the menstrual cycle) and compared mean telomere length, CFD, and cortisol levels between the IVF patients and healthy controls.

Results

The results revealed an inverse relationship between CFD levels and telomere lengths at several time points that remained significant even after controlling for cortisol levels. Women undergoing IVF had statistically significant higher levels of CFD and shorter telomeres compared to healthy controls.

Conclusions

The relationship between telomere length and CFD should be further explored in larger studies in order to uncover potential mechanisms that cause both shortened telomere length and elevated CFD in women undergoing IVF.

Keywords

In vitro fertilization Cell-free DNA Telomere length Cortisol 

Notes

Acknowledgments

This study was completed with the generous help of the Warshawsky family, in memory of their daughter, Dr. Lora Warshawsky-Livne, z’l. While submitting this paper, Johanna Czamanski-Cohen was supported by a NIH R25T Cancer Prevention and Control Translational Research postdoctoral fellowship, grant number: R25 (CA078447-14), Alberts (PI).

Compliance with ethical standards

The protocol was approved by the hospital’s ethics review board.

References

  1. 1.
    Scalici E, Traver S, Molinari N, Mullet T, Monforte M, Vintejoux E, et al. Cell-free DNA in human follicular fluid as a biomarker of embryo quality. Hum Reprod. 2014;29(12):2661–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Czamanski-Cohen J, Sarid O, Cwikel J, Lunenfeld E, Douvdevani A, Levitas E, et al. Increased plasma cell-free DNA is associated with low pregnancy rates among women undergoing IVF-embryo transfer. Reprod Biomed Online. 2013;26(1):36–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Kalmbach KH, Antunes DMF, Dracxler RC, Knier TW, Seth-Smith ML, Wang F, et al. Telomeres and human reproduction. Fertil Steril. 2013;99(1):23–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Destouni A, Vrettou C, Antonatos D, Chouliaras G, Traeger-Synodinos J, Patsilinakos S, et al. Cell-free DNA levels in acute myocardial infarction patients during hospitalization. Acta Cardiol. 2009;64(1):51–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Shimony A, Zahger D, Gilutz H, Goldstein H, Orlov G, Merkin M, et al. Cell free DNA detected by a novel method in acute ST-elevation myocardial infarction patients. Acute Card Care. 2010;12(3):109–11.CrossRefPubMedGoogle Scholar
  6. 6.
    Iida M, Iizuka N, Sakaida I, Moribe T, Fujita N, Miura T, et al. Relation between serum levels of cell-free DNA and inflammation status in hepatitis C virus-related hepatocellular carcinoma. Oncol Rep. 2008;20(4):761–5.PubMedGoogle Scholar
  7. 7.
    Zhang R, Shao F, Wu X, Ying K. Value of quantitative analysis of circulating cell free DNA as a screening tool for lung cancer: a meta-analysis. Lung Cancer. 2010;69(2):225–31.CrossRefPubMedGoogle Scholar
  8. 8.
    García Moreira V, Prieto García B, Baltar Martín JM, Ortega Suárez F, Alvarez FV. Cell-free DNA as a noninvasive acute rejection marker in renal transplantation. Clin Chem. 2009;55(11):1958–66.CrossRefPubMedGoogle Scholar
  9. 9.
    Hahn S, Zhong XY, Bürk MR, Troeger C, Kang A, Holzgreve W. Both maternal and fetal cell-free DNA in plasma fluctuate. Ann N Y Acad Sci. 2001;945:141–4.CrossRefPubMedGoogle Scholar
  10. 10.
    Hahn S, Zimmermann BG. Cell-free DNA in maternal plasma: has the size-distribution puzzle been solved? Clin Chem. 2010;56(8):1210–1.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhong X, Holzgreve W, Hahn S. The Levels of circulatory fetal DNA in maternal plasma are elevated prior to the onset of preeclampsia. Hypertens Pregnancy. 2002;21(1):1.CrossRefGoogle Scholar
  12. 12.
    Traver S, Assou S, Scalici E, Haouzi D, Al-Edani T, Belloc S, et al. Cell-free nucleic acids as non-invasive biomarkers of gynecological cancers, ovarian, endometrial and obstetric disorders and fetal aneuploidy. Hum Reprod Update. 2014;20(6):905–23.CrossRefPubMedGoogle Scholar
  13. 13.
    Atamaniuk J, Kopecky C, Skoupy S, Säemann MD, Weichhart T. Apoptotic cell-free DNA promotes inflammation in haemodialysis patients. Nephrol Dial Transplant. 2012;27(3):902–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Carp HJ, Selmi C, Shoenfeld Y. The autoimmune bases of infertility and pregnancy loss. J Autoimmun. 2012;38(2):J266–J74.CrossRefPubMedGoogle Scholar
  15. 15.
    Hart EA, Patton WC, Jacobson JD, King A, Corselli J, Chan PJ. Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology. J Assist Reprod Genet. 2005;22(5):213–7.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Czamanski-Cohen J, Sarid O, Cwikel J, Levitas E, Lunenfeld E, Douvdevani A, et al. Decrease in cell free DNA levels following participation in stress reduction techniques among women undergoing infertility treatment. Arch Womens Ment Health. 2014;17(3):251–3.CrossRefPubMedGoogle Scholar
  17. 17.
    Hayflick L, Moorhead P. The human fibroblast and a new model for cellular senescence. Exp Cell Res. 1961;25:585–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458–60.CrossRefPubMedGoogle Scholar
  19. 19.
    O’Donovan A, Pantell MS, Puterman E, Dhabhar FS, Blackburn EH, Yaffe K, et al. Cumulative inflammatory load is associated with short leukocyte telomere length in the Health, Aging and Body Composition Study. PLoS One. 2011;6(5), e19687.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    McCarthy A. Taking stock of telomere length at telome health. Chemistry & biology. 2011;18(8):937–8.CrossRefGoogle Scholar
  21. 21.
    Wikgren M, Maripuu M, Karlsson T, Nordfjäll K, Bergdahl J, Hultdin J, et al. Short telomeres in depression and the general population are associated with a hypocortisolemic state. Biol Psychiatry. 2012;71(4):294–300.CrossRefPubMedGoogle Scholar
  22. 22.
    Tomiyama AJ, O’Donovan A, Lin J, Puterman E, Lazaro A, Chan J, et al. Does cellular aging relate to patterns of allostasis? An examination of basal and stress reactive HPA axis activity and telomere length. Physiol Behav. 2012;106(1):40–5.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    O’Donovan A, Tomiyama AJ, Lin J, Puterman E, Adler NE, Kemeny M, et al. Stress appraisals and cellular aging: a key role for anticipatory threat in the relationship between psychological stress and telomere length. Brain Behav Immun. 2012;26(4):573–9.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Price LH, Kao H-T, Burgers DE, Carpenter LL, Tyrka AR. Telomeres and early-life stress: an overview. Biol Psychiatry. 2013;73(1):15–23.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Smeenk JM, Verhaak CM, Vingerhoets AJ, Sweep CG, Merkus JM, Willemsen SJ, et al. Stress and outcome success in IVF: the role of self-reports and endocrine variables. Hum Reprod. 2005;20(4):991–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Verhaak CM, Smeenk JM, Evers AW, Kremer JA, Kraaimaat FW, Braat DD. Women’s emotional adjustment to IVF: a systematic review of 25 years of research. Hum Reprod Update. 2007;13(1):27–36.CrossRefPubMedGoogle Scholar
  27. 27.
    Kudielka BM, Wüst S. Human models in acute and chronic stress: assessing determinants of individual hypothalamus–pituitary–adrenal axis activity and reactivity. Stress. 2010;13(1):1–14.CrossRefPubMedGoogle Scholar
  28. 28.
    McEwen BS, Seeman T. Protective and damaging effects of mediators of stress: elaborating and testing the concepts of allostasis and allostatic load. Ann N Y Acad Sci. 1999;896(1):30–47.CrossRefPubMedGoogle Scholar
  29. 29.
    Turnbull AV, Rivier CL. Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev. 1999;79(1):1–71.PubMedGoogle Scholar
  30. 30.
    Ramírez R, Carracedo J, Jiménez R, Canela A, Herrera E, Aljama P, et al. Massive telomere loss is an early event of DNA damage-induced apoptosis. J Biol Chem. 2003;278(2):836–42.CrossRefPubMedGoogle Scholar
  31. 31.
    Mondello C, Scovassi AI. Telomeres, telomerase, and apoptosis. Biochem Cell Biol. 2004;82(4):498–507.CrossRefPubMedGoogle Scholar
  32. 32.
    Phillippe M. Cell-Free Fetal DNA, Telomeres, and the Spontaneous Onset of Parturition. Reproductive Sciences; 2015:1933719115592714.Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • J. Czamanski-Cohen
    • 1
    Email author
  • O. Sarid
    • 2
  • J. Cwikel
    • 2
  • A. Douvdevani
    • 3
    • 4
  • E. Levitas
    • 4
    • 5
  • E. Lunenfeld
    • 4
    • 5
  • I. Har-Vardi
    • 4
    • 5
  1. 1.University of Arizona Cancer CenterTucsonUSA
  2. 2.The Spitzer Department of Social Work and the Center for Women’s Health Studies and PromotionBen-Gurion University of the NegevBeer-ShevaIsrael
  3. 3.Department of Clinical Biochemistry and PharmacologySoroka University Medical CenterBeer ShevaIsrael
  4. 4.Faculty of Health SciencesBen Gurion University of the NegevBeer ShevaIsrael
  5. 5.Fertility and IVF Unit, Department of Ob/GynSoroka University Medical CenterBeer ShevaIsrael

Personalised recommendations