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Part of the book series: Current Clinical Pathology ((CCPATH))

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Abstract

Normal human reproduction is an inefficient process with only 22.8% of conceptive matings resulting in live birth (Fig. 1) (1,2). Miscarriages are the most common complication of pregnancy, affecting 15% of women (3). Loss of pregnancy is a physically and emotionally challenging ordeal. When pregnancy loss is repetitive, these feelings are magnified and the result is a distressing and frustrating problem for both the patients and the physicians. Recurrent pregnancy losses can occur early or late in the pregnancy. Early pregnancy losses are losses of embryos during the first trimester of pregnancy and have been termed abortions or miscarriages. Although most miscarriages are sporadic and not repetitive, there is a subset of couples that suffer recurrent miscarriage. Although the risk of miscarriage increases with maternal age, overall 15% of pregnancies miscarry. Approximately 13% of all recognized first pregnancies are lost. The risk of a second consecutive miscarriage is only slightly increased to 17%. However, the risk of miscarriage after two consecutive pregnancy losses rises to between 35 and 40% and continues to rise with each subsequent miscarriage (4). As many as 5% of all couples conceiving experience two consecutive miscarriages and 2% have three or more consecutive losses. Late pregnancy losses are losses of fetuses after the first trimester of pregnancy. Late pregnancy losses occur far less frequently than early pregnancy losses and comprise only 1% of pregnancies. Late pregnancy losses are usually associated with incompetent cervix, premature rupture of membranes, preterm labor, intrauterine growth retardation, or placental abruption.

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References

  1. Roberts CJ, Lowe CR. Where have all the conceptions gone? Lancet 1975; I: 498 - 499.

    Article  Google Scholar 

  2. Clark DA. Is there any evidence for immunologically mediated or immunologic modifiable early pregnancy failure? J Assist Reprod Genet 2000; 20: 63 - 72.

    Article  Google Scholar 

  3. Daya S. Habitual abortion. In Copeland LJ, Jarrel J, eds. Textbook of Gynecology, 2nd ed. Philadelphia: WB Saunders, 2000, pp. 227 - 271.

    Google Scholar 

  4. Coulam CB. Epidemiology of recurrent spontaneous abortion. Am J Reprod Immunol 1991; 26: 23 - 27.

    PubMed  CAS  Google Scholar 

  5. Munne S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates, and maternal age are correlated with chromosomal abnormalities. Fertil Steril 1995; 64: 382 - 391.

    PubMed  CAS  Google Scholar 

  6. Coulam CB, Stephenson M, Stern JJ, Clark DA. Immunotherapy for recurrent pregnancy loss: analysis of results from clinical trials. Am J Reprod Immunol 1996; 35: 330 - 337.

    Article  Google Scholar 

  7. Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am J Hum Genet 1964; 16: 1 - 25.

    PubMed  CAS  Google Scholar 

  8. Hassold T, Chen N, Funkhouser J, Joss T, Manuel B, Matsuura J. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet Lond 1980; 44: 151 - 178.

    Article  CAS  Google Scholar 

  9. Evenson DP, Jost LK, Zinaman MJ, et al. Utility of the sperm chromatin structure assay (SCSA) as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod 2000; 14: 1039 - 1049.

    Article  Google Scholar 

  10. Peters AJ, Lloyd RP, Coulam CB. Prevalence of out-of-phase endometrial biopsy specimens. Am J Obstet Gynecol 1992; 166: 1738 - 1745.

    PubMed  CAS  Google Scholar 

  11. Coulam CB, Bustillo M, Soenksen DM, Britten S. Ultrasonographic predictors of implantation after assisted reproduction. Fertil Steril 1994; 62: 1004 - 1010.

    PubMed  CAS  Google Scholar 

  12. Battaglia C, Artini PG, Giulini S, et al. Colour Doppler changes and thromboxane production after ovarian stimulation with gonadotropin-releasing hormone agonist. Hum Reprod 1997; 12: 2477 - 2482.

    Article  PubMed  CAS  Google Scholar 

  13. Clark DA, Lea RG, Podor T, Daya S, Banwatt D, Harley C. Cytokines determining the success or failure of pregnancy. Ann N Y Acad Sci 1009; 626: 504 - 534.

    Google Scholar 

  14. Raghupathy R. Thl type immunity is incompatible with successful pregnancy. Immunol Today 1997; 18: 478 - 482.

    Article  PubMed  CAS  Google Scholar 

  15. Clark DA, Chaouat G, Ding JW, August C, Coulam CB, Levy GA. Fg12 in pregnancy: a novel prothrombinase at the fetomaternal interface may prevent bleeding and cause abortions. Am J Reprod Immunol 1999; 41: 374 - 379.

    Article  Google Scholar 

  16. Roubey RAS, Hoffman M. From antiphospholipid syndrome to antibody mediated thrombosis. Lancet 1997; 350: 1491 - 1492.

    Article  PubMed  CAS  Google Scholar 

  17. Rand JH, Wu XX, Andree HAM, et al. Pregnancy loss in the antiphospholipid syndrome: a possible thrombogenic mechanism. N Enl J Med 1997; 337: 154 - 160.

    Article  CAS  Google Scholar 

  18. Buchholz T, Thaler CJ. Inherited thrombophilia: impact on human reproduction. Am J Reprod Immunol 2003; 50: 20 - 32.

    Article  PubMed  Google Scholar 

  19. Mandel H, Brenner B, Berant M, Rosenberg N, Lanir N, Jakobs C. Coexistence of hereditary homocystinuria and factor V von Leiden: effect on thrombosis. N Engl J Med 1996; 334: 763 - 776.

    Article  PubMed  CAS  Google Scholar 

  20. Levi AJ, Raynault MF, Bergh PA, Drews MR, Miller BT, Scott RT. Reproductive outcome in patients with diminished ovarian reserve. Fertil Steril 2001; 76: 666 - 669.

    Article  PubMed  CAS  Google Scholar 

  21. Smith KE, Buyalos RP. The profound impact of patient age on pregnancy outcome after detection of fetal cardiac activity. Fertil Steril 1996; 5: 35 - 40.

    Google Scholar 

  22. Klein J, Sauer MV. Assessing fertility in women of advanced reproductive age. Am J Obstet Gyn 2001; 185: 758 - 770.

    Article  CAS  Google Scholar 

  23. Seifer DB, Scott RT, Bergh PA, et al. Women with declining ovarian reserve may demonstrate a decrease in day 3 follicle-stimulating hormone. Fertil Steril 1999; 72: 63 - 65.

    Article  PubMed  CAS  Google Scholar 

  24. Seifer DB, Lambert-Messerlian G, Hogan JW, Gardiner AC, Blazar AS, Beck CA. Day 3 serum Inhibin B is predictive of assisted reproductive technologies outcome. Fertil Steril 1997; 67: 110 - 114.

    Article  PubMed  CAS  Google Scholar 

  25. Simpson JL. Fetal wastage. In: Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics: Normal and Problem Pregnancies, 3rd ed. New York: Churhill Livingston, 1996, pp. 717 - 742.

    Google Scholar 

  26. Lockwood GM, Ledger WL, Barlow DH, Groome NP, Muttukrishna S. Measurement of inhibin and activin in early human pregnancy: demonstration of fetoplacental origin and role in prediction of early-pregnancy outcome. Biol Reprod 1997; 57: 1490 - 1494.

    Article  PubMed  CAS  Google Scholar 

  27. Vanderpuye OA, Goodman C, Randall HT, Rooussev RG, Tsao D, Coulam CB. Aneuploidy diagnosis in the first trimester: serum PAPP-A, free beta hCG and Inhibin A. Am J Reprod Immunol 2000; 43: 341

    Google Scholar 

  28. Muttukrishna S, Jauniaux E, Greenwold N, et al. Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages. Hum Reprod 2002; 17: 3072 - 3078.

    Article  PubMed  CAS  Google Scholar 

  29. Phipps MG, Hogan JW, Peipert JE, Lambert-Messerlain GM, Canick JA, Seifer DB. Progesterone, inhibin, and hCG multiple marker strategy to differentiate viable from non-viable pregnancies. Obstet Gynecol 2000; 95: 227 - 231.

    Article  PubMed  CAS  Google Scholar 

  30. Evenson DP, Larson KL, Jost LK. Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Androl 2002; 23: 25 - 42.

    PubMed  Google Scholar 

  31. Kirk EP, Chuong CJ, Coulam CB, Williams TJ. Pregnancy after metroplasty for uterine anomalies. Fertil Steril 1993; 59: 1164 1168.

    Google Scholar 

  32. Steer CV, Campbell S, Tan SL, et al. The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer. Fertil Steril 1992; 57: 372 - 376.

    PubMed  CAS  Google Scholar 

  33. Serafini P, Bartzolin J, Nelson J. Uterine power Doppler sonography: a prognosticator of pregnancy in IVF. J Assis Reprod Genet 1997; 14: 525.

    Article  Google Scholar 

  34. Kaider AS, Kaider BD, Janowicz PB, Roussev RG. Immunodiagnostic evaluation in women with reproductive failure. Am J Reprod Immunol 1999; 42: 335 - 346.

    Article  PubMed  CAS  Google Scholar 

  35. Rote NS, Vogt E, De Vere G, Obringer AR, Ng AK. The role of placental trophoblast in pathophysiology of the antiphospholipid antibody syndrome. Am J Reprod Immunol 1998; 39: 125 - 36.

    Article  PubMed  CAS  Google Scholar 

  36. Coulam CB, Roussev RG. Chemical pregnancies: immunologic and ultrasonographic studies. Am J Reprod Immunol 2002; 48: 323 - 328.

    Article  PubMed  Google Scholar 

  37. Keswani S, Chauhan N. Antiphospholipis syndrome. R Soc Med 2002; 95: 336 - 342.

    Article  Google Scholar 

  38. Triplett DA. Antiphospholipid antibodies and recurrent pregnancy loss. Am J Reprod Immunol 1989; 20: 53 - 67.

    Google Scholar 

  39. Shoenfeld Y, Schwartz RS. Genetic and immunologic factors in autoimmune diseases. N Engl J Med 1984; 311: 101 - 108.

    Article  Google Scholar 

  40. Gleicher N, El-Roeiy A. The reproductive autoimmune failure syndrome. Am J Obstet Gynecol 1998; 159: 213 - 217.

    Google Scholar 

  41. Yetman DL, Kutteh WH. Antiphospholipid antibody panels and recurrent pregnancy loss: prevalence of anticardiolipin antibodies compared with other antiphosphlipid antibodies. Fertil Steril 1996; 66: 540 - 546.

    PubMed  CAS  Google Scholar 

  42. Coulam CB, Kaider BD, Kaider AS, Janowicz P, Roussev RG. Antiphospholipid antibodies associated with implantation failure after IVF/ET. J Assist Reprod Genet 1997; 14: 603 - 608.

    Article  PubMed  CAS  Google Scholar 

  43. Kutteh WH. Antiphospholipid antibodies associated with recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynec 1996; 174: 1584 - 1589.

    Article  PubMed  CAS  Google Scholar 

  44. McIntyre JA. Antiphospholipid antibodies in implantation failures. Am J Reprod Immunol 2003; 49: 221 - 229.

    Article  PubMed  CAS  Google Scholar 

  45. McCarty GA, Baddour VT, Giesler L, Wagenknecht DR, McIntyre JA. Antiphospholipid antibody syndrome (APS) patients with antiphosphatidylethanolamine antibodies have APS clinical symptoms. J Autoimmun 2000; 15: A58

    Google Scholar 

  46. McCarty GA, Wagenknecht DR, McIntyre JA. Antiphospholipid antibody syndrome (APS) patients with antiphosphatidylcholine antibodies have APS clinical criteria. J Autoimmun 2000; 15: A59.

    Google Scholar 

  47. Kaider BD, Coulam CB, Roussev RG. Murine embryos as a direct target for some human autoantibodies in vitro. Hum Reprod 1999; 2556 - 2561.

    Google Scholar 

  48. Sugi T, McIntyre JA. Autoantibodies to kininogen-phosphatidylethanolamine complexes augment thrombin-induced platelet aggregation. Thromb Res 1996; 84: 97 - 109.

    Article  PubMed  CAS  Google Scholar 

  49. Pierangeli SS, Gharavi AE, Harris EN. Testing for antiphospholipid antibodies: problems and solutions. Clin Obstet Gyn 2001; 44: 48 - 57.

    Article  CAS  Google Scholar 

  50. Bach JF, Koutouzou S. New clues to systemic lupus. Lancet 1997; 350: 11.

    Article  Google Scholar 

  51. Abramson J, Stagnaro-Green A. In our viewchr(133)thyroid antibodies and fetal loss: an evolving story. Thyroid 2001; 11: 57 - 63.

    Article  PubMed  CAS  Google Scholar 

  52. Stagnaro-Green A, Roman SH, Cabin RH, Harvey E, Alvarez-Marfany M, Davies TF. Detection of at risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 1990; 264: 1422 - 1425.

    Article  PubMed  CAS  Google Scholar 

  53. Lejeune B, Grun JP, DeNayer PH, Servais G, Glinoer D. Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension. Br J Obstet Gynaecol 1993; 100: 669 - 672.

    Article  PubMed  CAS  Google Scholar 

  54. Stewart-Akers AM, Krasnow JS, Brekosky J, Deloia JA. Endometrial leukocytes are altered numerically and functionally in women with implantation defects. Am J Reprod Med 1998; 39: 1 - 11.

    CAS  Google Scholar 

  55. Coulam CB, Goodman C, Roussev RG, Thomason EJ, Beaman KD. Systemic CD56+ cells can predict pregnancy outcome. Am J Reprod Immunol 1995; 33: 40 - 46.

    PubMed  CAS  Google Scholar 

  56. Aoki K, Kajijura S, Matsumoto Y, Okada S, Yaghami Y, Gleicher N. Preconceptual natural killer cell activation as a predictor of miscarriage. Lancet 1995 135: 1340 - 1342.

    Article  Google Scholar 

  57. Kane KL, Ashton FA, Schmitz JL, Folds JD. Determination of natural killer cell function by flow cytometry. Clin Diagn Lab Immunol 1996; 3: 295 - 300.

    PubMed  CAS  Google Scholar 

  58. Kwak JY, Kwak JM, Ainbinder SW, Ruiz AM, Beer AE. Elevated peripheral blood natural killer cells are effectively downregulated by immunoglobulin G infusion in women with recurrent spontaneous abortions. Am J Reprod Immunol 1996; 35: 363 - 369.

    Article  PubMed  CAS  Google Scholar 

  59. Roussev RG, Stern JJ, Thorsell L, Thomason EJ, Coulam CB. Validation of an embryotoxicity assay. Am J Reprod Immunol 1994; 32: 1 - 5.

    Google Scholar 

  60. Verlinsky Y, Cieslak J, Ivakhnenko V, et al. Prevention of age related aneuploidies by polar body testing of oocytes. J Assist Reprod Genet 1999; 16: 165 - 169.

    Article  PubMed  CAS  Google Scholar 

  61. Munne S, Magit C, Cohen J, et al. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod 1999; 14: 2191 - 2199.

    Article  PubMed  CAS  Google Scholar 

  62. Varasteh NN, Neuwirth RS, Levin B, Keltz LB. Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile women. Obstet Gynecol 1999; 94: 168 - 171.

    Article  PubMed  CAS  Google Scholar 

  63. Wada I, Hsu CC, Williams G, Macnamee MC, Brinsden PR. The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assisted conception. Hum Reprod 1994; 7: 1954 - 1957.

    Google Scholar 

  64. Sher G, Fisch JD. Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development. Fertil Steril 2002; 78: 1073 - 1076.

    Article  PubMed  Google Scholar 

  65. Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). Br Med J 1997; 314: 253 - 257.

    Article  CAS  Google Scholar 

  66. Kwak JYH, Gilman-Sachs A, Beaman KD, Beer AE. Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune causes: preconception versus postconception treatment. Am J Obstet Gynecol 1992; 166: 1787 - 1795.

    PubMed  CAS  Google Scholar 

  67. Hasegawa I, Takauwa K, Goto S, et al. Effectiveness of prednisone/aspirin for recurrent aborters with antiphospholipid antibody. Hum Reprod 1992; 7: 203 - 107.

    PubMed  CAS  Google Scholar 

  68. Branch DW, Scoll JR, Kochenour NK, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med 1985; 313: 1322 - 1326.

    Article  PubMed  CAS  Google Scholar 

  69. Alarcon-Segovia D, Deleze M, Oria CV, et al. Antiphospholipid antibodies and the antiphospholipid antibody syndrome in systemic lupus erythematosus. Medicine 1989; 68: 353 - 365.

    PubMed  CAS  Google Scholar 

  70. Lubbe WF, Liggins CG. Lupus anticoagulant and pregnancy. Am J Obstet Gynecol 1985; 153: 322 - 327.

    PubMed  CAS  Google Scholar 

  71. Carreras KO, Perez GN, Vega HR, Maclouf J. Lupus anticoagulant and recurrent fetal loss: successful treatment with gammaglobulin. Lancet 1988; 2: 393.

    Article  PubMed  CAS  Google Scholar 

  72. Francois A, Freund M, Reym P. Repeated fetal losses and the lupus anticoagulant. Ann Int Med 1988; 109: 933 - 934.

    Google Scholar 

  73. Scott JR, Branch DW, Knochenour NK, Ward K. Intravenous treatment of pregnant patients with recurrent pregnancy loss caused by antiphospholipid antibodies and Rh immunization. Am J Obstet Gynecol 1988; 159: 1055 - 1056.

    PubMed  CAS  Google Scholar 

  74. Parke A, Maier D, Wilson D, Andreole J, Ballow M. Intravenous immunoglobulin, antiphospholipid antibodies, and pregnancy. Ann Int Med 1989; 110: 495 - 496.

    PubMed  CAS  Google Scholar 

  75. MacLachlan NA, Letsky E, De Sweit M. The use of intravenous immunoglobulin therapy in the management of antiphospholipid antibody associated pregnancies. Clin Exp Rheumatol 1990; 8: 221 - 224.

    Google Scholar 

  76. Cowchock FS, Resse EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative trial comparing treatment with prednisone to low dose heparin. Am J Obstet Gynecol 1992; 166: 1318 - 1323.

    PubMed  CAS  Google Scholar 

  77. Ramsdon CF, Faquharson RG. A woman with twelve first trimester losses in whom lupus anticoagulant was detected and treated with steroids, sandoglobulin and heparin. Clin Exp Rheumat 1990; 8: 221.

    Google Scholar 

  78. Lachapelle MH, Miron P, Hemmings R, Roy DA. Endometrial T, B and NK cells in patients with recurrent abortion: altered profile and pregnancy outcome. J Immunol 1996; 156: 4227 - 4234.

    Google Scholar 

  79. Coulam CB, Goodman C. Increased pregnancy rates after IVF/ET with intravenous immunoglobulin treatment in women with elevated circulating CD56+ cells. Early Pregnancy 2000; 4: 90 - 98.

    PubMed  CAS  Google Scholar 

  80. Mueller-Eckhart G, Malimann P, Neppert J, et al. for the German RSA/IVIG Trialist Group. Immunogenetic and serological investigations of nonpregnancy and pregnant women with a history of recurrent spontaneous abortion. J Reprod Immunol 1994; 27: 95 - 109.

    Article  Google Scholar 

  81. Coulam CB, Krysa LW, Stem JJ, Bustillo M. Intravenous immunoglobulin for treatment of recurrent pregnancy loss. Am J Reprod Immunol 1995; 34: 333 - 337.

    PubMed  CAS  Google Scholar 

  82. Christiansen OB, Pedersen B, Rosgaard A, Husth M. A randomized, double-blind, placebo controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage. Hum Reprod 2002; 17: 809 - 816.

    Article  PubMed  CAS  Google Scholar 

  83. Stephenson MD, Dreher K, Houlihan E, Wu V. Prevention of unexplained recurrent spontaneous abortion using intravenous immunoglobulin: a prospective, randomized, double-blinded, placebo-controlled trial. Am J Reprod Immunol 1998; 39: 82 - 88.

    Article  PubMed  CAS  Google Scholar 

  84. Recurrent Miscarriage Immunotherapy Trialists Group (RMITG). Worldwide prospective observational study and meta-analysis on allogeneic leukocyte immunotherapy for recurrent spontaneous abortion. Am J Reprod Immunol 1994; 32: 55 - 72.

    Google Scholar 

  85. Chaouat G, Assai-Meliani A, Martal J, et al. IL-10 prevents naturally occurring fetal loss in the CBA X DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of INF-tau. J Immunol 1995; 154: 4261 - 4268.

    PubMed  CAS  Google Scholar 

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Coulam, C.B. (2004). Recurrent Pregnancy Loss. In: Gronowski, A.M. (eds) Handbook of Clinical Laboratory Testing During Pregnancy. Current Clinical Pathology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-787-1_15

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  • DOI: https://doi.org/10.1007/978-1-59259-787-1_15

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