Recurrent Pregnancy Loss

Immunologic and Nonimmunologic Aspects
  • Henry N. Claman

Abstract

No aspect of the immunology of pregnancy is more controversial than the subject of recurrent pregnancy loss, or, as it will be called here, recurrent spontaneous abortion (RSAb). Nor is there any subject in this book more laden with emotion because the immunologic facts, as perceived, have a very strong influence on therapy decisions for RSAb and thus, potentially, on the ability of the childless to have children. Indeed, it is the question of the relevance of immunology to RSAb that prompted the writing of this book. Because of these two factors—the controversial nature of the data and the emotional implications of the interpretation of the data—there will be few general statements in this chapter that will not be questioned by someone.

Keywords

Placebo Migration Hepatitis Histamine Stratification 

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References

  1. 1.
    Stirrat GM: Recurrent Miscarriage. I. Definition and epidemiology. Lancet 1990; 336: 673–675.PubMedCrossRefGoogle Scholar
  2. 2.
    Mclntyre JA, Coulam CB, Faulk WP: Recurrent spontaneous abortion. Am J Reprod Immunol 1989; 21: 100–104.Google Scholar
  3. 3.
    Lauritsen JG: Genetic aspects of spontaneous abortion. Dan Med Bull 1977; 24: 169–188.PubMedGoogle Scholar
  4. 4.
    Little AB: There’s many a slip’ twixt implantation and the crib. N Engl J Med 1988; 319: 241–242.PubMedCrossRefGoogle Scholar
  5. 5.
    Wilcox AJ, Weinbert GR, O’Connor JF, et al.: Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189–194.PubMedCrossRefGoogle Scholar
  6. 6.
    Clark DA, Chaout G: What do we know about spontaneous abortion mechanisms? Am J Reprod Immunol Microbiol 1989; 19: 28–38.Google Scholar
  7. 7.
    Coulam CB, Moore SB, OTallon WM: Association between major histocompatibility antigen and reproductive performance. Am J Reprod Immunol Microbiol 1987; 14: 54–58.PubMedGoogle Scholar
  8. 8.
    Mclntyre JA, McConnachie PR, Taylor CG, et al.: Clinical, immunologic, and genetic definitions of primary and secondary recurrent spontaneous abortions. Fertil Steril 1984; 42: 849–855.Google Scholar
  9. 9.
    Coulam CB, Mclntyre JA, Faulk WP: Reproductive performance in women with repeated pregnancy losses and multiple partners. Am J Reprod Immunol 1986; 12: 10–12.Google Scholar
  10. 10.
    Reginald PW, Beard RW, Chappie J, et al.: Outcome of pregnancies progressing beyond 28 weeks in gestation in women with a history of recurrent miscarriage. Br J Obstet Gynecol 1987; 94: 643–648.CrossRefGoogle Scholar
  11. 11.
    Stirrat GM: Recurrent miscarriage. II. Clinical associations, causes, and management. Lancet 1990; 336: 728–733.PubMedCrossRefGoogle Scholar
  12. 12.
    Roman E: Fetal loss rates and their relation to pregnancy order. J Epidemiol Community Health 1984; 38: 29–35.PubMedCrossRefGoogle Scholar
  13. 13.
    Houwert-de Jong MH, Termijtelen A, Eskes TKAB, et al.: The natural course of habitual abortion. Eur J Ob Gyn Reprod Biol 1989; 33: 221–228.CrossRefGoogle Scholar
  14. 14.
    Knudsen UB, Hansen V, Juul S, et al.: Prognosis of a new pregnancy following previous spontaneous abortions. Eur J Ob Gyn Reprod Biol 1991; 39: 31–36.CrossRefGoogle Scholar
  15. 15.
    Beard RW, Sharp F: Early pregnancy loss: Mechanisms and treatment. Royal Coll Obstet Gynaecol 1988; 351–354.Google Scholar
  16. 16.
    Beer AE: New horizons in the diagnosis, evaluation and therapy of recurrent spontaneous abortion. Clin Obstet Gynecol 1986; 13: 115–124.Google Scholar
  17. 17.
    Stray-Pedersen B, Stray-Pedersen S: Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol 1984; 148: 140–146.PubMedGoogle Scholar
  18. 18.
    Harger JH, Archer DF, Marchesp SG, et al.: Etiology of recurrent pregnancy losses and outcome of subsequent pregnancies. Obstet Gynecol 1983; 62: 574–581.PubMedGoogle Scholar
  19. 19.
    Gill III TJ: Influence of MHC and MHC-linked genes on reproduction. Am J Hum Genet 1992; 50: 1–5.PubMedGoogle Scholar
  20. 20.
    Boue J, Boue A, Lazar P: Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions. Teratology 1975; 12: 11–26.PubMedCrossRefGoogle Scholar
  21. 21.
    Simpson JL, Bombard A: Chromosomal abnormalities in spontaneous abortion: Frequency and genetic counseling, in Bennett MJ, Edmonds DK (eds): Spontaneous and Recurrent Abortion. Oxford, Blackwell Scientific; 1987: 51–76.Google Scholar
  22. 22.
    Kline J, Stein Z: Epidemiology of chromosomal anomalies in spontaneous abortion: Prevalence, manifestation and determinants, in Bennett MJ, Edmonds DK (eds): Spontaneous and Recurrent Abortion. Oxford, Blackwell Scientific; 1987: 29–50.Google Scholar
  23. 23.
    Hassold T, Chen N, Funkhouser J, et al.: A cytogenetic study of 1,000 spontaneous abortions. Ann Hum Genet 1980; 44: 151–178.PubMedCrossRefGoogle Scholar
  24. 24.
    Kajii T, Ferrier A: Cytogenetics of aborters and abortuses. Am J Obstet Gynecol 1978; 131: 33–38.PubMedGoogle Scholar
  25. 25.
    Tharapel AT, Tharapel SA, Bannerman RM: Recurrent pregnancy losses and parental chromosome abnormalities: A review. Br J Obstet Gynaecol 1985; 92: 899–912.PubMedCrossRefGoogle Scholar
  26. 26.
    Sachs ES, Jahoda MGJ, vanHemel JO, et al.: Chromosome studies of 500 couples with two or more abortions. Obstet Gynecol 1985; 65: 375–378.PubMedGoogle Scholar
  27. 27.
    Fryns JP, Kleczkowska A, Kubien E, et al.: Cytogenetic survey in couples with recurrent fetal wastage. Hum Genet 1984; 65: 336–354.PubMedCrossRefGoogle Scholar
  28. 28.
    Campana M, Serra A, Neri G: Role of chromosome aberrations in recurrent abortion: A study of 269 balanced translocations. Am J Med Genet 1986; 24: 341–356.PubMedCrossRefGoogle Scholar
  29. 29.
    Gadow EC, Lippold S, Otano L, et al.: Chromosome rearrangements among couples with pregnancy losses and other adverse reproductive outcomes. Am J Med Genet 1991; 41: 279–281.PubMedCrossRefGoogle Scholar
  30. 30.
    Kleinhout J, Madan K: Repeated abortions and chromosome analysis, in Hafez ESE (ed): Spontaneous Abortion. Boston, MTP Press; 1984: 143–152.CrossRefGoogle Scholar
  31. 31.
    Simpson JL, Meyers CM, Martin AO, et al.: Translocations are infrequent among couples having repeated spontaneous abortions but not other abnormal pregnancies. Fertil Steril 1989; 51: 811–819.PubMedGoogle Scholar
  32. 32.
    Castle D, Bernstein R: Cytogenetic analysis of 688 couples experiencing multiple spontaneous abortions. Am J Med Genet 1988; 29: 549–556.PubMedCrossRefGoogle Scholar
  33. 33.
    Warburton D, Strobino B: Recurrent spontaneous abortion, in Bennett MJ, Edmonds DK (eds): Spontaneous and Recurrent Abortion. Oxford, Blackwell Scientific; 1987: 193–213.Google Scholar
  34. 34.
    Cantin G, Lyonnais J: Anti-PPIPk and early abortions. Transfusion 1983; 23: 350–351.PubMedCrossRefGoogle Scholar
  35. 35.
    Shirey RS, Ness PM, Kickler TS, et al.: The association of antip and early abortion. Transfusion 1987; 27: 189–191.PubMedCrossRefGoogle Scholar
  36. 36.
    Race RR, Sanger R: Blood Groups in Man, Oxford, Blackwell Scientific Publishing Co.; 1975: 139.Google Scholar
  37. 37.
    Clarke B, Kirby D: Maintenance of histocompatibility polymorphisms. Nature 1966; 211: 999–1000.PubMedCrossRefGoogle Scholar
  38. 38.
    Scott JR, Rote NS, Branch DW: Immunologic aspects of recurrent abortion and fetal death. Obstet Gynecol 1987; 70: 645–656.PubMedGoogle Scholar
  39. 39.
    Klopper A: Pregnancy proteins and hormones in the immune response of pregnancy, in Stern CMM (ed): Immunology of Pregnancy and its Disorders. Dordrecht, Kluwer Academic Publishers; 1989: 91–113.CrossRefGoogle Scholar
  40. 40.
    Wegmann TG: Placental immunotrophism: The idea and evidence, in Chaouat G (ed): The Immunology of the Fetus. Boca Raton, CRC Press, Inc.; 1990: 180–185.Google Scholar
  41. 41.
    Bobe P, Chaouat G, Stanislawski M, et al.: Immunogenetic studies of spontaneous abortion in mice. II. Antiabortive effects are independent of systemic regulatory mechanisms. Cell Immunol 1986; 98: 477–485.PubMedCrossRefGoogle Scholar
  42. 42.
    Gill III TJ: Immunogenetics of spontaneous abortions in humans. Transplantation 1983; 35: 1–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Awdeh ZL, Raum D, Yunis EJ, et al.: Extended HLA/complement allelic haplotypes: Evidence for a T/Mike complex in man. Proc Natl Acad Sci USA 1983; 80: 259–263.PubMedCrossRefGoogle Scholar
  44. 44.
    Gerencer M, Kastelan A, Drazancic A, et al.: The HLA antigens in women with recurrent abornal pregnancies of unknown etiology. Tissue Antigens 1978; 12: 223–227.PubMedCrossRefGoogle Scholar
  45. 45.
    Takakuwa K, Kanazawa K, Takeuchi S: Production of blocking antibodies by vaccination with husband’s lymphocytes in unexplained recurrent aborters: The role in successful pregnancy. Am J Reprod Immunol Microbiol 1986; 10: 1–9.PubMedGoogle Scholar
  46. 46.
    Beer AE, Quebbeman JF, Ayers JWT, et al.: Major histocompatibility complex antigens, maternal and paternal immune responses and chronic habitual abortions in humans. Am J Obstet Gynecol 1981; 141: 987–999.PubMedGoogle Scholar
  47. 47.
    Mclntyre JA, Faulk WP: Recurrent spontaneous abortion in human pregnancy: Results of immunogenetical, cellular, and humoral studies. Am J Reprod Immunol 1983; 4: 165–170.Google Scholar
  48. 48.
    Thomas ML, Harger JH, Wagener DK, et al.: HLA sharing and spontaneous abortion in humans. Am J Obstet Gynecol 1985; 151: 1053–1057.PubMedGoogle Scholar
  49. 49.
    Unander AM, Lindholm A, Olding LB: Blood transfusions generate/increase previously absent/weak blocking antibody in women with habitual abortion. Fertil Steril 1985; 44: 766–771.PubMedGoogle Scholar
  50. 50.
    Sargent IL, Wilkins T, Redman CWG: Maternal immune responses to the fetus in early pregnancy and recurrent miscarriage. Lancet 1988; 2: 1099–1104.PubMedCrossRefGoogle Scholar
  51. 51.
    Cauchi MN, Tait B, Wilshire MI, et al.: Histocompatibility antigens and habitual abortion. Am J Reprod Immunol Microbiol 1988; 18: 28–31.PubMedGoogle Scholar
  52. 52.
    Caudle MR, Rote NS, Scott JR, et al.: Histocompatibility in couples with recurrent spontaneous abortion and normal fertility. Fertil Steril 1983; 39: 793–798.PubMedGoogle Scholar
  53. 53.
    Lauritsen JG, Kristensen T, Grunnet N: Depressed mixed lymphocyte culture reactivity in mothers with recurrent spontaneous abortion. Am J Obstet Gynecol 1976; 125: 35–39.PubMedGoogle Scholar
  54. 54.
    Oksenberg JR, Pesitz E, Amar A, et al.: Mixed lymphocyte reactivity non-responsiveness in couples with multiple spontaneous abortions. Fertil Steril 1983; 39: 525–529.PubMedGoogle Scholar
  55. 55.
    Ho H-N, Gill III TJ, Hsieh R-P, et al.: Sharing of human leukocyte antigens (HLA) in primary and secondary recurrent spontaneous abortions. Am J Obstet Gynecol 1990; 163: 178–188.PubMedGoogle Scholar
  56. 56.
    Ober CL, Martin AO, Simpson JL, et al.: Shared HLA antigens and reproductive performance among Hutterites. Am JHum Genet 1983; 35: 994–1004.PubMedGoogle Scholar
  57. 57.
    Ober CL, Hauck WW, Kostyu DD, et al.: Adverse effects of human leukocyte DR sharing on fertility: A cohort study in a human isolate. Fertil Steril 1985; 44: 221–232Google Scholar
  58. 58.
    Ober C, Elias S, O’Brien E, et al.: HLA sharing and fertility in Hutterite couples: Evidence for prenatal selection against compatible fetuses. Am J Reprod Immunol Microbiol 1988; 18: 111–115.PubMedGoogle Scholar
  59. 59.
    Ober C, Elias S, Kostyu DD, et al.: Decreased fecundability in Hutterite couples sharing HLA-DR. Am J Hum Genet 1992; 50: 6–14.PubMedGoogle Scholar
  60. 60.
    Jazwinska EC, Kilpatrick DC, Smart GE, et al.: Fetomaternal HLA compatibility does not have a major influence on human pregnancy except for lymphocytotoxin production. Clin Exp Immunol 1987; 69: 116–122.PubMedGoogle Scholar
  61. 61.
    Christiansen OB, Riisom K, Lauritsen G, et al.: Association of maternal HLA haplotypes with recurrent spontaneous abortions. Tissue Antigens 1989; 34: 190–199.PubMedCrossRefGoogle Scholar
  62. 62.
    Unander AM, Olding LB: Habitual abortion: Parental sharing of HLA antigens, absence of maternal blocking antibody, and suppression of maternal lymphocytes. Am J Reprod Immunol 1983; 4: 171–178.PubMedGoogle Scholar
  63. 63.
    Power DA, Catto GRD, Mason RJ, et al.: Evidence for protective antibodies to HLA-linked paternal antigens. Lancet 1983; ii: 701–704.CrossRefGoogle Scholar
  64. 64.
    Johnson PM, Barnes RMR, Harti CA, et al.: Determinants of immunological responsiveness in recurrent spontaneous abortion. Transplantation 1984; 38: 280–284.PubMedCrossRefGoogle Scholar
  65. 65.
    Rocklin RE, Kitzmiller JL, Carpenter CB, et al.: Maternal-fetal relation: Absence of an immunologic blocking factor from the serum of women with chronic abortions. N Engl J Med 1976; 295:1209–1213.Google Scholar
  66. 66.
    Rocklin RE, Kitzmiller JL, Kaye MD: Immunobiology of the maternal-fetal relationship. Ann Rev Med 1979; 30: 375–404.PubMedCrossRefGoogle Scholar
  67. 67.
    Stimson WH, Strachan AF, Shepherd A: Studies on the maternal immune response to placental antigens: Absence of a blocking factor from the blood of abortion-prone women. Br J Obstet Gynecol 1979; 86: 41–45.CrossRefGoogle Scholar
  68. 68.
    Unander AM, Cindholm A: Transfusions of leukocyte rich erythrocyte concentrates: A successful treatment in selected cases of habitual abortion. Am J Obstet Gynecol 1984; 154: 516–520.Google Scholar
  69. 69.
    van Rood JJ: Pretransplant blood transfusion: Sure! But how and why? Transplant Proc 1983; 15: 915–916.Google Scholar
  70. 70.
    Singal DP, Butler L, Liao S-K, et al.: The fetus as an allograft: Evidence for antiidiotypic antibodies induced by pregnancy. Am J Reprod Immunol 1984; 6: 145–151.PubMedGoogle Scholar
  71. 71.
    Regan L, Braude PR: Is paternal cytotoxic antibody a valid marker in the management of recurrent abortion? Lancet 1987; ii: 1280.Google Scholar
  72. 72.
    Fizet D, Bousquet J, Piquet Y, et al.: Identification of a factor blocking a cellular cytotoxicity reaction in pregnant serum. Clin Exp Immunol 1983; 52: 648–654.PubMedGoogle Scholar
  73. 73.
    Fizet D, Bousquet J: Absence of a factor blocking a cellular cytotoxicity reaction in the serum of women with recurrent abortions. Br J Obstet Gynaecol 1983; 90: 453–56.PubMedCrossRefGoogle Scholar
  74. 74.
    Fiddes TM, O’Reilly DB, Centrulo C, et al.: Phenotypic and functional evaluation of suppressor cells in normal pregnancy and in chronic aborters. Cell Immunol 1986; 97: 407–418.PubMedCrossRefGoogle Scholar
  75. 75.
    Faulk WP, Temple A, Lovins RE, et al.: Antigens of human trophoblasts: A working hypothesis for their role in normal and abnormal pregnancies. Proc Natl Acad Sci USA 1978; 75:1947–1951.PubMedCrossRefGoogle Scholar
  76. 76.
    Mclntyre JA: In search of trophoblast-lymphocyte crossreactive (TLX) antigens. Am J Reprod Immunol Microbiol 1988; 17:100–110.Google Scholar
  77. 77.
    Michel M, Underwood J, Clark DA, et al.: Histologic and immunologie study of uterine biopsy tissue of women in incipient abortion. Am J Obstet Gynecol 1989; 161: 409–414.PubMedGoogle Scholar
  78. 78.
    Taylor C, Faulk WP: Prevention of recurrent abortion with leukocyte transftision. Lancet 1981; ii: 68–70.Google Scholar
  79. 79.
    Taylor C, Faulk WP, Mclntyre JA: Prevention of recurrent spontaneous abortions by leukocyte transfusion. J Royal Soc Med 1985; 78: 623–627.Google Scholar
  80. 80.
    Fedele L, Acaia B, Parazzini F, et al.: Ectopic pregnancy and recurrent spontaneous abortion: Two associated reproductive failures. Obstet Gynecol 1989; 73: 206–208.PubMedGoogle Scholar
  81. 81.
    Clark DA, Daya S: Trials and tribulation in the treatment of recurrent spontaneous abortion. Am J Reprod Immunol 1991; 25: 18–24.PubMedGoogle Scholar
  82. 82.
    Hill JA: Immunological mechanisms of pregnancy maintenance and failure: a critique of theories and therapy. Am J Reprod Immunol 1990; 22: 33–42.PubMedGoogle Scholar
  83. 83.
    Mowbray JF, Gibbings C, Liddell H, et al.: Controlled trial of treatment of recurrent spontaneous abortion by immunisation with paternal cells. Lancet 1985; 4/27/85 issue: 941–943.Google Scholar
  84. 84.
    Ho H-N, Gill TJ, Hsieh H-J, et al.: Immunotherapy for recurrent spontaneous abortions in a Chinese population. Am J Reprod Immunol 1991; 25: 10–15.PubMedGoogle Scholar
  85. 85.
    Cauchi MN, Lim D, Young DE, et al.: Treatment of recurrent aborters by immunization with paternal cells—controlled trial. Am J Reprod Immunol 1991; 25: 16–17.PubMedGoogle Scholar
  86. 86.
    Coulam C, Peters A, Mclntyre J, et al.: The use of IVIG for the greatment of recurrent spontaneous abortion, in Imbach P (ed): Immunotherapy with Intravenous Immunoglobulins. London, Academic Press; 1991:395–400.Google Scholar
  87. 87.
    Dwyer JM: Manipulating the immune system with immune globulin. N Engl J Med 1992; 326: 107–116.PubMedCrossRefGoogle Scholar
  88. 88.
    Wapner RJ, Cowchuck FS, Shapiro SS: Successful treatment in two women with antiphospholipid antibodies and refractory pregnancy losses with intravenous immunoglobulin. Am J Obstet Gynecol 1989; 161: 1271–1272.PubMedGoogle Scholar
  89. 89.
    Buckley RH, Schiff RI: The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med 1991; 325: 110–117.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Henry N. Claman
    • 1
  1. 1.University of Colorado Health Sciences CenterDenver

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