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Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

  • Physiology
  • Published:
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Abstract

Purpose: DNA-damaging factors have been reported in patients that failed to achieve pregnancy after assisted reproductive technologies (ART). The hypothesis was that increased circulating cell-free DNA released by damaged cells could predict unfavorable conditions leading to failed ART treatment. The objective was to compare the relative concentrations of cell-free DNA in the luteal phase sera of nonpregnant versus pregnant patients.

Methods: Frozen-thawed sera (30 IVF cases) were obtained 1 week after embryo transfer. There were 16 pregnant and 14 nonpregnant cases and controls consisting of male sera (n = 8 cases). Modified isocratic capillary electrophoresis was performed and the images analyzed for cell-free DNA.

Results: Circulating cell-free DNA were identified in the sera of all patients. The serum concentrations of high (12 kb) and low (1 kb) molecular weight cell-free DNA were similar for both nonpregnant and pregnant patients. Male control sera had higher cell-free DNA concentrations compared with females. Evaluation of sera from a control case showed no fluctuations in cell-free DNA concentrations throughout specific days of the menstrual cycle.

Conclusions: The results do not support the use of the luteal phase cell-free DNA concentration as a marker for failed pregnancies. The equal concentrations of high and low molecular weight cell-free DNA and ladder band-like gel patterns suggested cell apoptosis as the source of DNA.

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References

  1. Chavez DJ, McIntyre JA: Sera from women with histories of repeated pregnancy losses cause abnormalities in peri-implantation blastocysts. J Reprod Immunol 1984;6:273–281

    Article  CAS  PubMed  Google Scholar 

  2. Oksenberg JR, Brautbar C: In vitro suppression of murine blastocysts growth by sera from women with reproductive disorders. Am J Reprod Immunol Microbiol 1986;11:118–124

    CAS  PubMed  Google Scholar 

  3. Porter AJ, Singh SM, Jung JH: Evaluation of serum-associated embryotoxicity/mutagenicity in females with reproductive dysfunction using preimplantation mouse embryos in vitro. Mutagenesis 1988;3:403–408

    CAS  PubMed  Google Scholar 

  4. Abir R, Zisman I, Ben Hur H, Yaffe P, Ornoy A: The effects of serum from women with miscarriages on the in vitro development of mouse preimplantation embryos. Acta Obstet Gynecol Scand 1990;69:27–33

    CAS  PubMed  Google Scholar 

  5. Hill JA, Polgar K, Harlow BL, Anderson DJ: Evidence of embryo- and trophoblast-toxic cellular immune response(s) in women with recurrent spontaneous abortion. Am J Obstet Gynecol 1992;166:1044–1052

    CAS  PubMed  Google Scholar 

  6. Dokras A, Sargent IL, Redman CWG, Barlow DH: Sera from women with unexplained infertility inhibit both mouse and human embryo growth in vitro. Fertil Steril 1993;60:285–292

    CAS  PubMed  Google Scholar 

  7. Simon C, Frances A, Piquette GN, el Danasouri I, Zurawski G, Dang W, Polan ML: Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist (IL-1ra). Endocrinology 1994;134:521–528

    Article  CAS  PubMed  Google Scholar 

  8. Thomason EJ, Roussev RG, Stern JJ, Coulam CB: Prevalence of embryotoxic factor in sera from women with unexplained recurrent abortion. Am J Reprod Immunol 1995;34:338–341

    CAS  PubMed  Google Scholar 

  9. Fein A, Yacobovich R, Torchinsky A, Ben-Rafael Z, Carp H, Toder V: Evaluation of serum-associated embryotoxicity in women with reproductive disorders. J Assist Reprod Genetics 1995:12;305–311

    CAS  Google Scholar 

  10. Cameo M, Fontana V, Cameo P, Vauthay LG, Kaplan J, Tesone M: Similar embryotoxic effects of sera from infertile patients and exogenous interferon-γ on long-term in-vitro development of mouse embryos. Hum Reprod 1999;14:959–963

    Article  CAS  PubMed  Google Scholar 

  11. Jebelli B, Chan PJ, Corselli J, Patton WC, King A: Oocyte comet assay of luteal phase sera from non-pregnant patients after assisted reproductive procedures. J. Assist. Reprod. Genetics 2001;18:421–425

    Article  CAS  Google Scholar 

  12. Dokras A, Sargent IL, Redman CWG, Barlow DH: Sera from women with unexplained infertility inhibit both mouse and human embryo growth in vitro. Fertil Steril 1993;60:285–292

    CAS  PubMed  Google Scholar 

  13. Mandel P, Métais P: Les acides nucléiques du plasma sanguin chez l’homme. C.R. Acad Sci Paris 1948;142:241–243

    CAS  Google Scholar 

  14. Tan EM, Schur PH, Carr RI, Kunkel HG: Deoxyribonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest 1966;45:1732–1740

    CAS  PubMed  Google Scholar 

  15. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ: Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977;37:646–650

    CAS  PubMed  Google Scholar 

  16. Fournie GJ, Courtin JP, Laval F, Chale JJ, Pourrat JP, Pujazon MC, Lauque D, Carles P: Plasma DNA as a marker of cancerous cell death. Investigations in patients suffering from lung cancer and in nude mice bearing human tumours. Cancer Lett. 1995;91:221–227

    CAS  Google Scholar 

  17. Rogers JC, Boldt D, Kornfeld S, Skinner A, Valeri CR: Excretion of deoxyribonucleic acid by lymphocytes stimulated with phytohemagglutinin or antigen. Proc Natl Acad Sci USA. 1972;69:1685–1689

    CAS  PubMed  Google Scholar 

  18. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS: Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;16:485–487

    Article  Google Scholar 

  19. Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM: Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998;62:768–775

    Google Scholar 

  20. Tsuda T, Nakagawa G, Sato M, Yagi K: Separation of nucleotides by high-voltage capillary electrophoresis. J Appl Biochem. 1983 AugOct;5(45):330–336

    CAS  Google Scholar 

  21. Kasper TJ, Melera M, Gozel P, Brownlee RG: Separation and detection of DNA by capillary electrophoresis. J Chromatogr. 1988 Dec 23;458:303–312

    Article  Google Scholar 

  22. Cohen AS, Najarian DR, Paulus A, Guttman A, Smith JA, Karger BL: Rapid separation and purification of oligonucleotides by high-performance capillary gel electrophoresis. Proc Natl Acad Sci USA. 1988 Dec;85(24):9660–9663

    CAS  Google Scholar 

  23. Purdy JM: Methods for fertilization and embryo culture in vitro, in: Human Conception In Vitro (eds. RG Edwards and JM Purdy), Academic Press, London, 1982, pp 135–148

    Google Scholar 

  24. Wu TL, Zhang D, Chia JH, Tsao KH, Sun CF, Wu JT: Cell-free DNA: measurement in various carcinomas and establishment of normal reference range. Clin Chim Acta 2002;321:77–87

    Article  CAS  PubMed  Google Scholar 

  25. Kopreski MS, Benko FA, Kwee C, Leitzel KE, Eskander E, Lipton A, Gocke CD: Detection of mutant K-ras DNA in plasma or serum of patients with colorectal cancer. Br J Cancer 1997;76:1293–1299

    CAS  PubMed  Google Scholar 

  26. Anker P, Lefort F, Vasioukhin V, Lyautey J, Lederrey C, Chen XQ, Stroun M, Mulcahy HE, Farthing MJ: K-ras mutations are found in DNA extracted from the plasma of patients with colorectal cancer. Gastroenterology 1997;112:1114–1120

    CAS  PubMed  Google Scholar 

  27. Lee TH, Montalvo L, Chrebtow V, Busch MP: Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma. Transfusion 2001;41:276–282

    Article  CAS  PubMed  Google Scholar 

  28. Holmgren L, Szeles A, Rajnavolgyi E, Folkman J, Klein G, Ernberg I, Falk KI: Horizontal transfer of DNA by the uptake of apoptotic bodies. Blood 1999;93:3956–3963

    CAS  PubMed  Google Scholar 

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Correspondence to Philip J. Chan.

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Hart, E.A., Patton, W.C., Jacobson, J.D. et al. Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology. J Assist Reprod Genet 22, 213–217 (2005). https://doi.org/10.1007/s10815-005-4924-4

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  • DOI: https://doi.org/10.1007/s10815-005-4924-4

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