Chimerism pp 19-31 | Cite as

Pregnancy and Multiple Gestations

  • Linda Marie Randolph
  • Ramen H. ChmaitEmail author


Chimerism in medicine refers to harboring cells or DNA that are genetically disparate, having arisen from two separate entities, such as two zygotes or two fetuses. When the amount of at least one cell line is small, it is called microchimerism, or Mc. Microchimerism in pregnancy is common between fetus and mother and between twins, and the chimerism can be long-lasting. When assisted reproductive technology is employed, chimerism appears to be more common than otherwise in dizygotic twins. This chapter reviews postulated mechanisms and health effects of chimerism that can result. It is important to recognize chimerism as a potential confounding factor in checking zygosity during and after pregnancy, as this chapter illustrates.


Chimerism Placenta Microchimerism Assisted reproductive technology Twin-twin transfusion Multiple gestation Twins Monochorionic Dizygotic 


  1. 1.
    Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci U S A. 1996;93(2):705–8.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Yan Z, Lambert NC, Guthrie KA, Porter AJ, Loubiere LS, Madeleine MM, Stevens AM, Hermes HM, Nelson JL. Male microchimerism in women without sons: quantitative assessment and correlation with pregnancy history. Am J Med. 2005;118(8):899–906.CrossRefPubMedGoogle Scholar
  3. 3.
    Gammill HS, Nelson JL. Naturally acquired microchimerism. Int J Dev Biol. 2010;54(2–3):531–43.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lo YM, Lau TK, Chan LY, Leung TN, Chang AM. Quantitative analysis of the bidirectional fetomaternal transfer of nucleated cells and plasma DNA. Clin Chem. 2000;46:1301–9.PubMedGoogle Scholar
  5. 5.
    Maloney S, Smith A, Furst DE, Myerson D, Rupert K, Evans PC, Nelson JL. Microchimerism of maternal origin persists into adult life. J Clin Invest. 1999;104(1):41–7.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bryan JN. Fetal microchimerism in cancer protection and promotion: current understanding in dogs and the implications for human health. AAPS J. 2015;17(3):506–12.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lillie FR. The theory of the free-martin. Science. 1916;43(1113):611–3.CrossRefPubMedGoogle Scholar
  8. 8.
    Vigier B, Watrin F, Magre S, Tran D, Garrigou O, Forest MG, Josso N. Anti-müllerian hormone and freemartinism: inhibition of germ cell development and induction of seminiferous cord-like structures in rat fetal ovaries exposed in vitro to purified bovine AMH. Reprod Nutr Dev. 1988;28(4B):1113–28. Erratum in: Reprod Nutr Dev 1988;28 Suppl 1:199.CrossRefPubMedGoogle Scholar
  9. 9.
    Padula AM. The freemartin syndrome: an update. Anim Reprod Sci. 2005;87(1–2):93–109. Scholar
  10. 10.
    Nylander P, Osunkoya B. Unusual monochorionic placentation with heterosexual twins. Obstet Gynecol. 1970;36:621–5.PubMedGoogle Scholar
  11. 11.
    Van Gemert MJ, Sterenborg HJ. Haemodynamic model of twin–twin transfusion syndrome in monochorionic twin pregnancies. Placenta. 1998;19:195–208.CrossRefPubMedGoogle Scholar
  12. 12.
    Souter VL, Kapur RP, Nyholt DR, Skogerboe K, Myerson D, Ton C, Opheim K, Easterling TR, Shields LE, Montgomery GW, Glass IA. A report of dizygous monochorionic twins. N Engl J Med. 2003;349(2):154–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Ginsberg NA, Ginsberg S, Rechitsky S, Verlinsky Y. 2005. Fusion as the etiology of chimerism in monochorionic dizygotic twins. Fetal Diagn Ther. 2005;20(1):20–2.CrossRefPubMedGoogle Scholar
  14. 14.
    Van den Wijngaard JP, Lopriore E, van der Salm SM, Schaap AH, Vandenbussche FP, DeRuiter MC, van Gemert MJ. Deep-hidden anastomoses in monochorionic twin placentae are harmless. Prenat Diagn. 2007;27:233–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Viëtor H, Hamel B, van Bree S, van der Meer E, Smeets D, Otten B, Holl R, Claas F. Immunological tolerance in an HLA non-identical chimeric twin. Hum Immunol. 2000;61:190–2.CrossRefPubMedGoogle Scholar
  16. 16.
    Hackmon R, Jormark S, Cheng V, O’Reilly Green C, Divon MY. Monochorionic dizygotic twins in a spontaneous pregnancy: a rare case report. J Matern Fetal Neonatal Med. 2009;22(8):708–10.CrossRefPubMedGoogle Scholar
  17. 17.
    Miura K, Niikawa N. Do monochorionic dizygotic twins increase after pregnancy by assisted reproductive technology. J Hum Genet. 2005;50(1):1–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Peters HE, König TE, Verhoeven MO, Schats R, Mijatovic V, Ket JC, Lambalk CB. Unusual twinning resulting in chimerism: a systematic review on monochorionic dizygotic twins. Twin Res Hum Genet. 2017;20(2):161–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Dziegiel MH, Hansen MH, Haedersdal S, Barrett AN, Rieneck K, Main KM, Hansen AT, Clausen FB. Blood chimerism in dizygotic monochorionic twins during 5 years observation. Am J Transplant. 2017;17(10):2728–32.CrossRefPubMedGoogle Scholar
  20. 20.
    Johannsen TH, Lundsteen C, Visfeldt J, Schwartz M, Petersen BL, Byskov AG, Müller J. Erroneous genetic sex determination of a newborn twin girl due to chimerism caused by foetal blood transfusion: a case report. Horm Res. 2003;60:148–51.PubMedGoogle Scholar
  21. 21.
    Quintero RA, Mueller OT, Martinez JM, Arroyo J, Gilbert Barness E, Hilbelink D, et al. Twin–twin transfusion syndrome in a dizygotic monochorionic-diamniotic twin pregnancy. J Matern Fetal Neonatal Med. 2003;14(4):279–81.PubMedGoogle Scholar
  22. 22.
    Williams CA, Wallace MR, Drury KC, Kipersztok S, Edwards RK, Williams RS, et al. Blood lymphocyte chimerism associated with IVF and monochorionic dizygous twinning: case report. Hum Reprod. 2004;19:2816–21.CrossRefPubMedGoogle Scholar
  23. 23.
    Yoon G, Beischel LS, Johnson JP, Jones MC. Dizygotic twin pregnancy conceived with assisted reproductive technology associated with chromosomal anomaly, imprinting disorder, and monochorionic placentation. J Pediatr. 2005;146:565–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Nishio K, Yokota T, Sugiura H, Oguri I, Ueda M, Hamashima T, et al. Monochorionic diamniotic twins discordant for gender (in Japanese; abstract from the 48th Annual Meeting of Japan Society for Premature and Newborn Medicine). J Jpn Soc Perinat Neonatal Med. 2003;15:534.Google Scholar
  25. 25.
    Tsuruta S, Kida Y, Hasegawa H, Itai M, Yoshida K, Kitani Y, Saito Y. Monochorionic diamniotic twins discordant for external genitalia (in Japanese; abstract from the 48th Annual Meeting of Japan Society for Premature and Newborn Medicine). J Jpn Soc Perinat Neonatal Med. 2003;15:534.Google Scholar
  26. 26.
    Yamaguchi T, Seki M, Sato K. A case of dizygotic twins discordant for gender, showing TTTS and monochorionic placentation (in Japanese; abstract from the 48th Annual Meeting of Japan Society for Premature and Newborn Medicine). J Jpn Soc Perinat Neonatal Med. 2003;15:534.Google Scholar
  27. 27.
    Niikawa N. Clinical significance of monochorionic dizygotic twins. Paper presented at the Fourth Conference of the Pacific Rim Society for Fertility and Sterility, Isehara, Japan. 2004.Google Scholar
  28. 28.
    Aoki R, Honma Y, Yada Y, Momoi MY, Iwamoto S. Blood chimerism in monochorionic twins conceived by induced ovulation: case report. Hum Reprod. 2006;21:735–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Shalev SA, Shalev E, Pras E, Shneor Y, Gazit E, Yaron Y, Loewenthal R. Evidence for blood chimerism in dizygotic spontaneous twin pregnancy discordant for Down syndrome. Prenat Diagn. 2006;26:782–4.CrossRefPubMedGoogle Scholar
  30. 30.
    Walker SP, Meagher S, White SM. Confined blood chimerism in monochorionic dizygous (MCDZ) twins. Prenat Diagn. 2007;27:369–72.CrossRefPubMedGoogle Scholar
  31. 31.
    Ekelund CK, Skibsted L, Søgaard K, Main KM, Dziegiel MH, Schwartz M, et al. Dizygotic monochorionic twin pregnancy conceived following intracytoplasmic sperm injection treatment and complicated by twin–twin transfusion syndrome and blood chimerism. Ultrasound Obstet Gynecol. 2008;32(6):832–4.CrossRefPubMedGoogle Scholar
  32. 32.
    Shaikh S, Kaufman RM, Jardim GM, Hwang DG, Hirsch MS, Milford EL, et al. Blood chimerism in monochorionic twins: an unusual cause of ABO discrepancy. Transfusion. 2009;49:114A.Google Scholar
  33. 33.
    Bogdanova, N., Siebers, U., Kelsch, R., Markoff, A., Röpke, A., Exeler, R., . . . Wieacker, P. (2010). Blood chimerism in a girl with Down syndrome and possible freemartin effect leading to aplasia of the Mullerian derivatives.Hum Reprod, 25, 1339–1343.CrossRefPubMedGoogle Scholar
  34. 34.
    Assaf SA, Randolph LM, Benirschke K, Wu S, Samadi R, Chmait RH. Discordant blood chimerism in dizygotic monochorionic laser-treated twin-twin transfusion syndrome. Obstet Gynecol. 2010;116(Suppl 2):483–5.CrossRefPubMedGoogle Scholar
  35. 35.
    Chen K, Chmait RH, Vanderbilt D, Wu S, Randolph L. Chimerismin in monochorionic dizygotic twins: case study and review. Am J Med Genet A. 2013;161A(7):1817–24.CrossRefPubMedGoogle Scholar
  36. 36.
    Hawcutt D, Hammond B, Sibbring J, Gokhale D, Ellis I, Bricker L, Subhedar N. Twin-twin confusion syndrome: blood chimerism in opposite sex dizygotic twins. J Obstet Gynaecol. 2011;31:446–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Loriaux A, Boulet S, Delorme V, Althuser M, Giroud LC, Grego S, et al. Tetragametic chimerism: case report. J Gynecol Obstet Biol Reprod. 2011;40:77–80.CrossRefGoogle Scholar
  38. 38.
    Umstad MP, Short RV, Wilson M, Craig JM. Chimaeric twins: why monochorionicity does not guarantee monozygosity. Aust N Z J Obstet Gynaecol. 2012;52:305–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Choi DH, Kwon H, Lee SD, Moon MJ, Yoo EG, Lee KH, et al. Testicular hypoplasia in monochorionic dizygous twin with confined blood chimerism. J Assist Reprod Genet. 2013;30:1487–91.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kanda T, Ogawa M, Sato K. Confined blood chimerism in monochorionic dizygotic twins conceived spontaneously. AJP Rep. 2013;3:33–6.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Smeets D, van Vugt JM, Gomes I, van den Heuvel S, van Heijst A, Reuss A, Claahsen-van der Grinten HL. Monochorionic dizygous twins presenting with blood chimerism and discordant sex. Twin Res Hum Genet. 2013;16(4):799–801.CrossRefPubMedGoogle Scholar
  42. 42.
    Lee HJ, Yoon SC, Ko JM, Seong MW, Park SS, Choi JS, Oh SK. Monochorionic dizygotic twins with discordant sex and confined blood chimerism. Eur J Pediatr. 2014;173:1249–52.CrossRefPubMedGoogle Scholar
  43. 43.
    Fumoto S, Hosoi K, Ohnishi H, Hoshina H, Yan K, Saji H, Oka A. Chimerism of buccal membrane cells in a monochorionic dizygotic twin. Pediatrics. 2014;133(4):e1097–100.CrossRefPubMedGoogle Scholar
  44. 44.
    Lee OJ, Cho D, Shin MG, Kim SO, Park JT, Kim HK, Ryang DW. The first known case of blood group chimerism in monochorionic dizygotic twins in Korea. Ann Lab Med. 2014;34(3):259–62.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Rodriguez-Buritica D, Rojnueangnit K, Messiaen LM, Mikhail FM, Robin NH. Sex-discordant monochorionic twins with blood and tissue chimerism. Am J Med Genet A. 2015;167:872–7.CrossRefGoogle Scholar
  46. 46.
    Mayeur Le Bras A, Petit F, Benachi A, Bedel B, Oucherif S, Martinovic J, et al. Confined blood chimerism in a monochorionic dizygotic sex discordant twin pregnancy conceived after induced ovulation. Birth Defects Res A Clin Mol Teratol. 2016;106:298–303.CrossRefPubMedGoogle Scholar
  47. 47.
    Macatangga M, De la Calle M, Torres ML, Bartha JL. Monozygotic monochorionic twins discordant for trisomy 21: a reason to evaluate both fetuses: a case report. J Reprod Med. 2016;61(3–4):167–70.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Medical GeneticsChildren’s Hospital Los Angeles, University of Southern California, Keck School of MedicineLos AngelesUSA
  2. 2.Los Angeles Fetal SurgeryPasadenaUSA
  3. 3.Obstetrics and Gynecology, Pediatrics, and SurgeryUniversity of Southern California, Keck School of MedicinePasadenaUSA

Personalised recommendations