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Cell-free DNA discoveries in human reproductive medicine: providing a new tool for biomarker and genetic assays in ART

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Abstract

Cell-free DNAs (cfDNAs) are fragmented forms of DNA that are released into extracellular environments. Analyzing them, regarding either concentration or genetic/epigenetic status can provide helpful information about disorders, response to treatments, estimation of success rates, etc. Moreover, since they are presented in body fluids, evaluation of the aforementioned items would be achieved by less/non-invasive methods. In human reproduction field, it is required to have biomarkers for prediction of assisted reproduction techniques (ART) outcome, as well as some non-invasive procedures for genetic/epigenetic assessments. cfDNA is an appropriate candidate for providing the both approaches in ART. Recently, scientists attempted to investigate its application in distinct fields of reproductive medicine that resulted in discovering its applicability for biomarker and genetic/epigenetic analyses. However, due to some limitations, it has not reached to clinical administration yet. In this article, we have reviewed the current reported data with respect to advantages and limitations of cfDNA utilization in three fields of ART, reproduction of male and female, as well as in vitro developed embryos.

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References

  1. Mandel, P. and P. Metais, Les acides nucleiques du plasma sanguine chez l’homme. 1948.

    Google Scholar 

  2. Meddeb R, et al. Quantifying circulating cell-free DNA in humans. Sci Rep. 2019;9(1):1–16.

    Article  CAS  Google Scholar 

  3. Sun Y, An K, Yang C. Circulating cell-free DNA, in Liquid biopsy: IntechOpen; 2019.

  4. Kustanovich A, Schwartz R, Peretz T, Grinshpun A. Life and death of circulating cell-free DNA. Cancer Biol Ther. 2019;20(8):1057–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Johann DJ Jr, Steliga M, Shin IJ, Yoon D, Arnaoutakis K, Hutchins L, et al. Liquid biopsy and its role in an advanced clinical trial for lung cancer. Exp Biol Med. 2018;243(3):262–71.

    Article  CAS  Google Scholar 

  6. Thierry A, et al. Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev. 2016;35(3):347–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Klump J, et al. Extracellular vesicles or free circulating DNA: where to search for BRAF and cKIT mutations? Nanomedicine: Nanotechnol, Biol Med. 2018;14(3):875–82.

    Article  CAS  Google Scholar 

  8. Barrett AN, Thadani HA, Laureano-Asibal C, Ponnusamy S, Choolani M. Stability of cell-free DNA from maternal plasma isolated following a single centrifugation step. Prenat Diagn. 2014;34(13):1283–8.

    Article  CAS  PubMed  Google Scholar 

  9. Kim K, Shin DG, Park MK, Baik SH, Kim TH, Kim S, et al. Circulating cell-free DNA as a promising biomarker in patients with gastric cancer: diagnostic validity and significant reduction of cfDNA after surgical resection. Ann Surg Treatment Res. 2014;86(3):136–42.

    Article  Google Scholar 

  10. Spindler KLG, et al. Circulating free DNA as biomarker and source for mutation detection in metastatic colorectal cancer. PLoS One. 2015:10(4).

  11. Olsen JA, Kenna LA, Tipon RC, Spelios MG, Stecker MM, Akirav EM. A minimally-invasive blood-derived biomarker of oligodendrocyte cell-loss in multiple sclerosis. EBioMedicine. 2016;10:227–35.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lo YD, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet. 1998;62(4):768–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lo YD. Fetal DNA in maternal plasma: biology and diagnostic applications. Clin Chem. 2000;46(12):1903–6.

    Article  CAS  PubMed  Google Scholar 

  14. Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015;372(17):1589–97.

    Article  CAS  PubMed  Google Scholar 

  15. Stigliani S, Anserini P, Venturini PL, Scaruffi P. Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation. Hum Reprod. 2013;28(10):2652–60.

    Article  CAS  PubMed  Google Scholar 

  16. Chen Y, Liao T, Zhu L, Lin X, Wu R, Jin L. Seminal plasma cell-free mitochondrial DNA copy number is associated with human semen quality. Eur J Obstet Gynecol Reprod Biol. 2018;231:164–8.

    Article  CAS  PubMed  Google Scholar 

  17. Pourmasumi S, Sabeti P, Rahiminia T, Mangoli E, Tabibnejad N, Talebi AR. The etiologies of DNA abnormalities in male infertility: an assessment and review. Int J Reprod BioMed. 2017;15(6):331–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Papachristou F, Simopoulou M, Touloupidis S, Tsalikidis C, Sofikitis N, Lialiaris T. DNA damage and chromosomal aberrations in various types of male factor infertility. Fertil Steril. 2008;90(5):1774–81.

    Article  PubMed  Google Scholar 

  19. Gajbhiye R, Fung JN, Montgomery GW. Complex genetics of female fertility. NPJ Genomic Med. 2018;3(1):1–10.

    Article  Google Scholar 

  20. Ménézo YJ. Paternal and maternal factors in preimplantation embryogenesis: interaction with the biochemical environment. Reprod BioMed Online. 2006;12(5):616–21.

    Article  PubMed  Google Scholar 

  21. Kort DH, Chia G, Treff NR, Tanaka AJ, Xing T, Vensand LB, et al. Human embryos commonly form abnormal nuclei during development: a mechanism of DNA damage, embryonic aneuploidy, and developmental arrest. Hum Reprod. 2016;31(2):312–23.

    CAS  PubMed  Google Scholar 

  22. Chou JS, Jacobson JD, Patton WC, King A, Chan PJ. Modified isocratic capillary electrophoresis detection of cell-free DNA in semen. J Assist Reprod Genet. 2004;21(11):397–400.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Li H-G, Huang SY, Zhou H, Liao AH, Xiong CL. Quick recovery and characterization of cell-free DNA in seminal plasma of normozoospermia and azoospermia: implications for non-invasive genetic utilities. Asian J Androl. 2009;11(6):703–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bronkhorst AJ, Ungerer V, Holdenrieder S. The emerging role of cell-free DNA as a molecular marker for cancer management. Biomolecular Detection and Quantification. 2019;17:100087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Costa F, Barbisan F, Assmann CE, Araújo NKF, de Oliveira AR, Signori JP, et al. Seminal cell-free DNA levels measured by PicoGreen fluorochrome are associated with sperm fertility criteria. Zygote. 2017;25(2):111–9.

    Article  CAS  PubMed  Google Scholar 

  26. Bounartzi T, Dafopoulos K, Anifandis G, Messini CI, Koutsonikou C, Kouris S, et al. Pregnancy prediction by free sperm DNA and sperm DNA fragmentation in semen specimens of IVF/ICSI-ET patients. Hum Fertil. 2016;19(1):56–62.

    Article  CAS  Google Scholar 

  27. Wu C, Ding X, Li H, Zhu C, Xiong C. Genome-wide promoter methylation profile of human testis and epididymis: identified from cell-free seminal DNA. BMC Genomics. 2013;14(1):288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wu C, Ding X, Tan H, Li H, Xiong C. Alterations of testis-specific promoter methylation in cell-free seminal deoxyribonucleic acid of idiopathic nonobstructive azoospermic men with different testicular phenotypes. Fertil Steril. 2016;106(6):1331–7.

    Article  CAS  PubMed  Google Scholar 

  29. Gunes S, Arslan MA, Hekim GNT, Asci R. The role of epigenetics in idiopathic male infertility. J Assist Reprod Genet. 2016;33(5):553–69.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shamsi M, Kumar K, Dada R. Genetic and epigenetic factors: role in male infertility. Indian Journal of Urology: IJU: journal of the Urological Society of India. 2011;27(1):110–20.

    Article  CAS  Google Scholar 

  31. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Udesen PB, Sørensen AE, Joglekar MV, Hardikar AA, Wissing MLM, Englund ALM, et al. Levels of circulating insulin cell-free DNA in women with polycystic ovary syndrome–a longitudinal cohort study. Reprod Biol Endocrinol. 2019;17(1):34.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Da Broi MG, et al. Increased concentration of 8-hydroxy-2′-deoxyguanosine in follicular fluid of infertile women with endometriosis. Cell Tissue Res. 2016;366(1):231–42.

    Article  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. 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. Archives of Women’s Mental Health. 2014;17(3):251–3.

    Article  PubMed  Google Scholar 

  36. Busnelli A, Lattuada D, Rossetti R, Paffoni A, Persani L, Fedele L, et al. Mitochondrial DNA copy number in peripheral blood: a potential non-invasive biomarker for female subfertility. J Assist Reprod Genet. 2018;35(11):1987–94.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kenigsberg S, et al. Protocol for exosome isolation from small volume of ovarian follicular fluid: evaluation of ultracentrifugation and commercial kits, in Extracellular vesicles. Berlin: Springer; 2017. p. 321–41.

    Google Scholar 

  38. Dimopoulou M, Anifandis G, Messini CI, Dafopoulos K, Kouris S, Sotiriou S, et al. Follicular fluid oocyte/cumulus-free DNA concentrations as a potential biomolecular marker of embryo quality and IVF outcome. Biomed Res Int. 2014;2014:1–5.

    Article  Google Scholar 

  39. Traver S, et al. Cell-free DNA in human follicular microenvironment: new prognostic biomarker to predict in vitro fertilization outcomes. PLoS One. 2015:10(8).

  40. Konstantinos S, Petroula T, Evangelos M, Polina G, Argyro G, Sokratis G, et al. Assessing the practice of LuPOR for poor responders: a prospective study evaluating follicular fluid cfDNA levels during natural IVF cycles. J Assist Reprod Genet. 2020;37:1183–94.

    Article  PubMed  Google Scholar 

  41. Liu Y, Shen Q, Zhao X, Zou M, Shao S, Li J, et al. Cell-free mitochondrial DNA in human follicular fluid: a promising bio-marker of blastocyst developmental potential in women undergoing assisted reproductive technology. Reprod Biol Endocrinol. 2019;17(1):54.

    Article  PubMed  PubMed Central  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. Kassim, H.R., H.L. AL-Omary, S.J. Ahmed, Evaluation of cell free DNA in follicular fluid and embryo quality in poly cystic ovarian syndrome of Iraqi women.

  44. Khan HL, et al. Cell-free nucleic acids and melatonin levels in human follicular fluid predict embryo quality in patients undergoing in-vitro fertilization treatment. Journal of Gynecology Obstetrics and Human Reproduction. 2020;49(1):101624.

    Article  Google Scholar 

  45. Guan Y, Zhang W, Wang X, Cai P, Jia Q, Zhao W. Cell-free DNA induced apoptosis of granulosa cells by oxidative stress. Clin Chim Acta. 2017;473:213–7.

    Article  CAS  PubMed  Google Scholar 

  46. Regan SL, et al. Granulosa cell apoptosis in the ovarian follicle—a changing view. Front Endocrinol. 2018;9:61.

    Article  Google Scholar 

  47. Regan SL, et al. The effect of ovarian reserve and receptor signalling on granulosa cell apoptosis during human follicle development. Mol Cell Endocrinol. 2018;470:219–27.

    Article  CAS  PubMed  Google Scholar 

  48. Ichikawa K, Shibahara H, Shirasuna K, Kuwayama T, Iwata H. Cell-free DNA content in follicular fluid: a marker for the developmental ability of porcine oocytes. Reproductive Medicine and Biology. 2020;19(1):95–103.

    Article  CAS  PubMed  Google Scholar 

  49. Kansaku K, et al. Mitochondrial dysfunction in cumulus-oocyte complexes increases cell-free mitochondrial DNA. J Reprod Dev. 2018;64(3):261–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gianaroli L, et al. Blastocentesis: a source of DNA for preimplantation genetic testing. Results from a pilot study. Fertility and sterility. 2014;102(6):1692–1699. e6.

    Article  Google Scholar 

  51. Tobler KJ, Zhao Y, Ross R, Benner AT, Xu X, du L, et al. Blastocoel fluid from differentiated blastocysts harbors embryonic genomic material capable of a whole-genome deoxyribonucleic acid amplification and comprehensive chromosome microarray analysis. Fertil Steril. 2015;104(2):418–25.

    Article  CAS  PubMed  Google Scholar 

  52. Hammond ER, et al. Characterizing nuclear and mitochondrial DNA in spent embryo culture media: genetic contamination identified. Fertility and Sterility. 2017;107(1):220–228. e5.

    Article  PubMed  Google Scholar 

  53. Kuznyetsov V, et al. Minimally invasive cell-free human embryo aneuploidy testing (miPGT-A) utilizing combined spent embryo culture medium and blastocoel fluid–towards development of a clinical assay. Sci Rep. 2020;10(1):1–12.

    Article  Google Scholar 

  54. Stigliani S, Persico L, Lagazio C, Anserini P, Venturini PL, Scaruffi P. Mitochondrial DNA in day 3 embryo culture medium is a novel, non-invasive biomarker of blastocyst potential and implantation outcome. Mol Hum Reprod. 2014;20(12):1238–46.

    Article  CAS  PubMed  Google Scholar 

  55. Stigliani S, Orlando G, Massarotti C, Casciano I, Bovis F, Anserini P, et al. Non-invasive mitochondrial DNA quantification on day 3 predicts blastocyst development: a prospective, blinded, multi-centric study. Mol Hum Reprod. 2019;25(9):527–37.

    Article  CAS  PubMed  Google Scholar 

  56. Desquiret-Dumas V, et al. The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. Hum Reprod. 2017;32(3):607–14.

    CAS  PubMed  Google Scholar 

  57. Chappel S. The role of mitochondria from mature oocyte to viable blastocyst. Obstet Gynecol Int. 2013;2013:1–10.

    Article  Google Scholar 

  58. Rule K, Chosed RJ, Arthur Chang T, David Wininger J, Roudebush WE. Relationship between blastocoel cell-free DNA and day-5 blastocyst morphology. J Assist Reprod Genet. 2018;35(8):1497–501.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Assou S, Aït-Ahmed O, el Messaoudi S, Thierry AR, Hamamah S. Non-invasive pre-implantation genetic diagnosis of X-linked disorders. Med Hypotheses. 2014;83(4):506–8.

    Article  CAS  PubMed  Google Scholar 

  60. Wu H, et al. Medium-based noninvasive preimplantation genetic diagnosis for human α-thalassemias-SEA. Medicine. 2015:94(12).

  61. Liu W, Liu JQ, du HZ, Ling JW, Sun XF, Chen DJ. Non-invasive pre-implantation aneuploidy screening and diagnosis of beta thalassemia IVSII654 mutation using spent embryo culture medium. Ann Med. 2017;49(4):319–28.

    Article  CAS  PubMed  Google Scholar 

  62. Galluzzi L, et al. Extracellular embryo genomic DNA and its potential for genotyping applications. Future Science OA. 2015;1(4).

  63. Rubio C, Rienzi L, Navarro-Sánchez L, Cimadomo D, García-Pascual CM, Albricci L, et al. Embryonic cell-free DNA versus trophectoderm biopsy for aneuploidy testing: concordance rate and clinical implications. Fertil Steril. 2019;112(3):510–9.

    Article  CAS  PubMed  Google Scholar 

  64. Vera-Rodriguez M, Diez-Juan A, Jimenez-Almazan J, Martinez S, Navarro R, Peinado V, et al. Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development. Hum Reprod. 2018;33(4):745–56.

    Article  CAS  PubMed  Google Scholar 

  65. Feichtinger M, Vaccari E, Carli L, Wallner E, Mädel U, Figl K, et al. Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study. Reprod BioMed Online. 2017;34(6):583–9.

    Article  PubMed  Google Scholar 

  66. Huang L, Bogale B, Tang Y, Lu S, Xie XS, Racowsky C. Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy. Proc Natl Acad Sci. 2019;116(28):14105–12.

    Article  CAS  PubMed  Google Scholar 

  67. Ho JR, et al. Pushing the limits of detection: investigation of cell-free DNA for aneuploidy screening in embryos. Fertil Steril. 2018;110(3):467–475. e2.

    Article  PubMed  Google Scholar 

  68. Lane M, Zander-Fox DL, Hamilton H, Jasper MJ, Hodgson BL, Fraser M, et al. Ability to detect aneuploidy from cell free DNA collected from media is dependent on the stage of development of the embryo. Fertil Steril. 2017;108(3):e61.

    Article  Google Scholar 

  69. Rubio C, Navarro-Sánchez L, García-Pascual CM, Ocali O, Cimadomo D, Venier W, et al. Multicenter prospective study of concordance between embryo cell-free DNA and trophectoderm biopsies from 1,301 human blastocysts. Am J Obstet Gynecol. 2020;223:751.e1–751.e13.

    Article  CAS  Google Scholar 

  70. Sophie, B., et al., Is cell-free DNA in spent embryo culture medium an alternative to embryo biopsy for preimplantation genetic testing? A systematic review. Reproductive BioMedicine Online, 2020.

  71. Kahraman S, Cetinkaya M, Yuksel B, Yesil M, Pirkevi Cetinkaya C. The birth of a baby with mosaicism resulting from a known mosaic embryo transfer: a case report. Hum Reprod. 2020;35(3):727–33.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Sachdev NM, Maxwell SM, Besser AG, Grifo JA. Diagnosis and clinical management of embryonic mosaicism. Fertil Steril. 2017;107(1):6–11.

    Article  PubMed  Google Scholar 

  73. Fang R, Yang W, Zhao X, Xiong F, Guo C, Xiao J, et al. Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study. J Transl Med. 2019;17(1):73.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Xu J, Fang R, Chen L, Chen D, Xiao JP, Yang W, et al. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. Proc Natl Acad Sci. 2016;113(42):11907–12.

    Article  CAS  PubMed  Google Scholar 

  75. Shamonki MI, Jin H, Haimowitz Z, Liu L. Proof of concept: preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media. Fertil Steril. 2016;106(6):1312–8.

    Article  CAS  PubMed  Google Scholar 

  76. Yeung QS, et al. A prospective study of non-invasive preimplantation genetic testing for aneuploidies (NiPGT-A) using next-generation sequencing (NGS) on spent culture media (SCM). J Assist Reprod Genet. 2019;36(8):1609–21.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Perloe M, Welch C, Morton P, Venier W, Wells D, Palini S. Validation of blastocoele fluid aspiration for preimplantation genetic screening using array comparative genomic hybridization (aCGH). Fertil Steril. 2013;100(3):S208.

    Article  Google Scholar 

  78. Zhang Y, Li N, Wang L, Sun H, Ma M, Wang H, et al. Molecular analysis of DNA in blastocoele fluid using next-generation sequencing. J Assist Reprod Genet. 2016;33(5):637–45.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Magli MC, et al. Preimplantation genetic testing: polar bodies, blastomeres, trophectoderm cells, or blastocoelic fluid? Fertility and Sterility. 2016;105(3):676–683. e5.

    Article  PubMed  Google Scholar 

  80. Palini S, Galluzzi L, de Stefani S, Bianchi M, Wells D, Magnani M, et al. Genomic DNA in human blastocoele fluid. Reprod BioMed Online. 2013;26(6):603–10.

    Article  CAS  PubMed  Google Scholar 

  81. Capalbo A, et al. Diagnostic efficacy of blastocoel fluid and spent media as sources of DNA for preimplantation genetic testing in standard clinical conditions. Fertility and Sterility. 2018;110(5):870–879. e5.

    Article  PubMed  Google Scholar 

  82. Li P, et al. Preimplantation genetic screening with spent culture medium/blastocoel fluid for in vitro fertilization. Sci Rep. 2018;8(1):1–10.

    Google Scholar 

  83. Kuznyetsov V, Madjunkova S, Antes R, Abramov R, Motamedi G, Ibarrientos Z, et al. Evaluation of a novel non-invasive preimplantation genetic screening approach. PLoS One. 2018;13(5):e0197262.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yang L, Lv Q, Chen W, Sun J, Wu Y, Wang Y, et al. Presence of embryonic DNA in culture medium. Oncotarget. 2017;8(40):67805–9.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Jiao J, Shi B, Sagnelli M, Yang D, Yao Y, Li W, et al. Minimally invasive preimplantation genetic testing using blastocyst culture medium. Hum Reprod. 2019;34(7):1369–79.

    Article  CAS  PubMed  Google Scholar 

  86. Wan Y, Liu B, Lei H, Zhang B, Wang Y, Huang H, et al. Nanoscale extracellular vesicle-derived DNA is superior to circulating cell-free DNA for mutation detection in early-stage non-small-cell lung cancer. Ann Oncol. 2018;29(12):2379–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Hur JY, Kim HJ, Lee JS, Choi CM, Lee JC, Jung MK, et al. Extracellular vesicle-derived DNA for performing EGFR genotyping of NSCLC patients. Mol Cancer. 2018;17(1):15.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Ben-Nagi J, et al. The first ongoing pregnancy following comprehensive aneuploidy assessment using a combined blastocenetesis, cell free DNA and trophectoderm biopsy strategy. J Reprod Infertil. 2019;20(1):57.

    PubMed  PubMed Central  Google Scholar 

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  1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Qasemi & Fardin Amidi

  2. Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran

    Reza Mahdian

  3. Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Fardin Amidi

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  1. Maryam Qasemi
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Qasemi, M., Mahdian, R. & Amidi, F. Cell-free DNA discoveries in human reproductive medicine: providing a new tool for biomarker and genetic assays in ART. J Assist Reprod Genet 38, 277–288 (2021). https://doi.org/10.1007/s10815-020-02038-4

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