Skip to main content
SpringerLink
Log in

Antiphospholipid Antibodies Associated with Implantation Failure After IVF/ET

  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose: Our purpose was to determine the specific anti-phospholipid antibodies (APAs) that should be evaluated to identify individuals at risk for implantation failure associated with reproductive autoimmune failure syndrome (RAFS).

Methods: The prevalence of APAs among 312 women with implantation failure was compared with that of 100 fertile control women. To be included in the implantation failure group, each woman had to have had at least 12 embryos transferred without subsequent positive pregnancy test. Enzyme-linked immunoabsorbant assay was used to measure IgG, IgM, and IgA anticardiolipin, antiphosphatidyl ethanol-amine, antiphosphatidyl inositol, antiphospatidic acid, antiphosphatidyl glycerol, antiphosphatidyl choline, and antiphosphatidyl serine.

Results: When the values for each of the seven APAs in three isotypes were compared between women with implantation failure and the control population, all of the APAs tested had a significantly higher frequency among women with implantation failure. Positive APAs were detected in 69 (22%) of the 312 women with implantation failure compared with 5 (5%) of the 100 control women (P < 0.0001). Anticardiolipin antibodies were found in 13 (4%) of the 312 women with implantation failure and none of the controls. Fifty-six (18%) of the 312 with implantation failure were negative for anticardiolipin antibodies but had positive values of other APAs.

Conclusions: A complete APA panel using seven isotypes is necessary for diagnosing implantation failure associated with RAFS. If only anticardiolipin antibody is measured, 4% (13/312) of the positive APAs are detected, and 81% (56/69) of women with implantation failure associated with RAFS will have the diagnosis missed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Cowchock S, Smith JB, Gocial B: Antibodies to phospholipids and nuclear antigens in patients with repeated abortions. Am J Obstet Gynecol 1986;155:1002–1010

    Google Scholar 

  2. Petri M, Golbus M, Anderson R, Whiting-O'Keefe Q, Corash L, Hellmann D: Antinuclear antibody, lupus anticoagulant, and anticardiolipin antibody in women with idiopathic habitual abortion: A controlled prospective study of 44 women. Arth Rheum 1987;30:601–606

    Google Scholar 

  3. Triplett DA: Antiphospholipid antibodies and recurrent pregnancy loss. Am J Reprod Immunol 1989;20:52–67

    Google Scholar 

  4. Rote NA, Dostal-Johnson DA, Branch DW: Antiphospholipid antibodies and recurrent pregnancy loss: correlation between the activated partial thromboplastin time and antibodies against phosphatidyl-serine and cardiolipin. Am J Obstet Gynecol 1990;163:575–584

    Google Scholar 

  5. Roussev RG, Kaider BD, Price DE, Coulam CB: Laboratory evaluation of women experiencing reproductive failure. Am J Reprod Immunol 1996;35:415–420

    Google Scholar 

  6. Yetman DL, Kutteh WH: Antiphospholipid antibody panels and recurrent pregnancy loss: Prevalence of anticardiolipin antibodies compared with other antiphospholipid antibodies. Fertil Steril 1996;66:540–546

    Google Scholar 

  7. Matzner W, Chong P, Xu G, Ching W: Characterization of antiphospholipid antibodies in women with recurrent spontaneous abortions. J Reprod Med 1994;39:27–30

    Google Scholar 

  8. Gilman-Sachs A, Lubinski J, Beer AE, Brend S, Beaman KD: Patterns of antiphospholipid antibody specificities. J Clin Lab Immunol 1991;35:83–88

    Google Scholar 

  9. Branch DW, Silver R, Pierangeli S, Van Leeuwen I, Harris EN: Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls and antiphospholipid syndrome. Obstet Gynecol 1997;89:549–555

    Google Scholar 

  10. Hughes GR, Harrison EN, Gharavi AE: The anticardiolipin syndrome. J Rheumatol 1986;13:486–489

    Google Scholar 

  11. Bringly PJ, Hoffbrand BI: Antiphospholipid antibody syndrome: A review. J Roy Soc Med 1987;80:445–448

    Google Scholar 

  12. Gleicher N, El-Roeiy A, Confino E, Friberg J: Reproductive failure because of autoantibodies: Unexplained infertility and pregnancy wastage. Am J Obstet Gynecol 1989;160:1376–1385

    Google Scholar 

  13. Nilsson IM, Astedt B, Hedner U, Berezin D: Intrauterine death and circulating anticoagulant (“antithromboplastin”). Acta Med Scand 1975;197:153–159

    Google Scholar 

  14. Gleicher N, El-Roeiy A: The reproductive autoimmune failure syndrome. Am J Obstet Gynecol 1988;159:223–117

    Google Scholar 

  15. El Roeiy A, Gleicher N, Confino E, Friberg J, Dudkiewicz AB: Correlation between peripheral blood and follicular fluid: Autoantibodies and impact on in vitro fertilization. Obstet Gynecol 1987;70:163–170

    Google Scholar 

  16. Fisch B, Rikover Y, Shohat L, Zurgil N, Tadir Y, Ovadia J, Witz IP, Yron I: The relationship between in vitro fertilization and naturally occurring antibodies: Evidence for increased production of antiphospholipid autoantibodies. Fertil Steril 1991;56:718–724

    Google Scholar 

  17. Birkenfield A, Mukaida T, Minichiello L, Jackson M, Kase NG, Yemini M: Incidence of autoimmune antibodies in failed embryo transfer cycles. Am J Reprod Immunol 1994;31:65–68

    Google Scholar 

  18. Geva E, Yaron Y, Lessing JB, Yovel I, Vardinon N, Burke M, Amit A: Circulating autoimmune antibodies may be responsible for implantation failure in in vitro fertilization. Fertil Steril 1994;62:802–806

    Google Scholar 

  19. Sher G, Feinman M, Zouves C, Kuttner G, Maassarani G, Salem R, Matzner W, Ching W, Chong P: High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin. Hum Reprod 1994;9:2278–2283

    Google Scholar 

  20. Gleicher N, Liu HC, Dudkiewicz A, Rosenwaks Z, Kaberlein G, Pratt D, Karande V: Autoantibody profiles and immunoglobulin levels as predictors of in vitro fertilization success. Am J Obstet Gynecol 1994;170:1145–1149

    Google Scholar 

  21. Nipp MM, Taylor PV, Rutherford AJ, Hancock KW: Autoantibodies and follicular fluids of infertile patients: Relation to reproductive outcome after in vitro fertilization. Hum Reprod 1995;10:2564–2569

    Google Scholar 

  22. Fisch B, Fried S, Manor Y, Ovadia J, Witz IP, Yron I: Increased antiphospholipid antibody activity in in vitro fertilization patients is not treatment dependent but rather an inherent characteristic of infertile state. Am J Reprod Immunol 1995;34:370–374

    Google Scholar 

  23. Kaider BD, Price BE, Roussev RG, Coulam CB: Antiphospholipid antibody prevalence in patients with IVF failure. Am J Reprod Immunol 1996;35:388–393

    Google Scholar 

  24. Birdsall M, Lockwood GM, Ledger WL, Johnson PM, Chamley LW: Antiphospholipid antibodies in women having in vitro fertilization. Hum Reprod 1996;11:1185–1189

    Google Scholar 

  25. Schenk LM, Butler, L, Morris JP, et al.: Heparin and aspirin treatment yields higher implantation rates in IVFF patients with antiphospholipid antibody seropositivity compared to untreated seronegative patients. American Society of Reproductive Medicine Meeting, Boston, MA, November 1996, abstract 0-076

  26. Kutteh WH, Yetman DL, Chantiles SJ, Cr1ain J: Effect of antiphospholipid antibodies in women undergoing in vitro fertilization: Role of heparin and aspirin. Hum Reprod 1997;12:1171–1175

    Google Scholar 

  27. Denis AL, Guido M, Adler RD, Bergh PA, Brenner C, Scott RT: Antiphospholipid antibodies and pregnancy rates and outcome in in vitro fertilization patients. Fertil Steril 1997;67:1084–1090

    Google Scholar 

  28. Kowalik A, Vichin M, Lui HC, Branch W, Berkeley AS: Midfollicular anticardiolipin and antiphosphatidyl serine antibody titers do not correlate with in vitro fertilization outcome. Fertil Steril 1997;68:298–304

    Google Scholar 

  29. Theofilopolous AN: Autoimmunity in basic and clinical immunology. In Basic and Clinical Immunology, DE Stites, ID Stobo, HH Fudenberg, JV Wells (eds). Los Altos, CA: Lange Medical, 1985, pp 153–156

    Google Scholar 

  30. Coulam CB, Krysa LLW, Bustillo M: Intravenous immunoglobulin for in vitro fertilization failure. Hum Reprod 1995;9:2265–2269

    Google Scholar 

  31. Lockwood CJ, Romero R, Feinberg RF, Clyne LP, Coster B, Hobbins JC: The prevalence and biological significance of lupus anticoagulant and cardiolipin antibodies in general obstetric population. Am J Obstet Gynecol 1989;161:369–373

    Google Scholar 

  32. El-Roeiy A, Gleicher N: Definition of normal autoantibody levels in an apparently healthy population. Obstet Gynecol 1996;174:1584–1589

    Google Scholar 

  33. Kutteh WH: Antiphospholipid antibody-associated recurrent pregnancy loss: Treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol 1996;174:1584–1589

    Google Scholar 

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

    Google Scholar 

  35. Chamely LW, McKay EJ, Rattison NS: Inhibition of heparin/antithrombin III cofactor activity by anticardiolipin antibodies: A mechanism for thrombosis. Thromb Res 1993;71:103–111

    Google Scholar 

  36. Rote NS: Antiphospholipid antibodies and recurrent pregnancy loss. Am J Reprod Immunol 1996;35:394–401

    Google Scholar 

  37. Gleicher N, Harlow L, Zilberstein M: Regulatory effect of antiphospholipid antibodies on signal transduction: A possible model for antibody induced reproductive failure. Am J Obstet Gynecol 1992;167:637–642

    Google Scholar 

  38. Rote NS, Vogt E, Se Vere G, Obringer AR, Ng AK: The role of placental trophoblast in the pathophysiology of the antiphospholipid antibody syndrome. Am J Reprod Immunol 1997 (in press)

  39. Tartakovsky B, Bermas BL, Sthoeger Z, Shearer GM, Mozes E: Defective maternal-fetal interaction in a murine autoimmune model. Hum Reprod 1996;11:2408–2411

    Google Scholar 

  40. Schick PK, Kurica KB, Chacko GK: Localization of phosphatidyl ethanolamine and phosphatidyl serine in the human platelet plasma membrane. J Clin Invest 1976;57:1221–1226

    Google Scholar 

  41. Op den Kamp JAF: Lipid asymmetry in membranes. Annu Rev Biochem 1979;48:47–71

    Google Scholar 

  42. Nakashima S, Suganuma A, Matsui A, Nozawa Y: Thormobin induces a biphasic 1,2-diacyl glycerol production in human platelets. Biochem J 275:355–361

  43. Dale MP, Robinson NC: Synthesis of cardiolipin derivatives with protection of the free hydroxyl: Its application to the study of cardiolipin stimulation of cytochrome c oxidase. Biochemistry 1988;27:8270–8275

    Google Scholar 

  44. Rand JH, WU XX, Guller S, Gil J, Guha A, Scher J, Lockwood CJ: Reduction of annexin V (placental anticoagulant protein-I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneous abortion. Am J Obstet Gynecol 1994;171:1566–1572

    Google Scholar 

  45. Kirkun G, Lockwood CJ, Wu XX, Zhou XD, Guller S, Calandri C, Guha A, Nemerson Y, Rand JH: The expression of the placental anticoagulant protein, annexin V, by villous trophoblasts: Immunolocalization and in vitro regulation. Placenta 1994;15:601–612

    Google Scholar 

  46. Romisch J, Schorlemmer V, Fickenscher K, Paques EP, Heimburger N: Anticoagulant properties of placental protein 4 (annexin V). Thromb Res 1990;60:355–366

    Google Scholar 

  47. Rimarchin JA, Zaninovic N, Vuck LL, Posenwaks Z: Programmed cell death (apoptosis) in human gametes and preembryos in vitro. Hum Reprod 1997;12:39

    Google Scholar 

  48. Kaider BD, Purvis MT, Kovacs L, Coulam CB, Roussev RG: In vitro effect of antiphospholipid, antinuclear and antithyroid antibodies upon murine cultured embryos. Am J Reprod Immunol 1996;35:459

    Google Scholar 

  49. Coulam CB: Implantation failure and immunotherapy. Hum Reprod 1995;10:1338–1340

    Google Scholar 

  50. Tan EM, Cohen AS, Fries JE, et al.: The 1982 revised criteria for classification of systemic lupus erythematosis. Arth Rheum 1982;25:127–132

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Center for Human Reproduction, 750 North Orleans Street, Chicago, Illinois, 60610

    Carolyn B. Coulam, Brian D. Kaider, Azadeth S. Kaider, Patrick Janowicz & Roumen G. Roussev

Authors
  1. Carolyn B. Coulam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian D. Kaider
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Azadeth S. Kaider
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrick Janowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roumen G. Roussev
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coulam, C.B., Kaider, B.D., Kaider, A.S. et al. Antiphospholipid Antibodies Associated with Implantation Failure After IVF/ET. J Assist Reprod Genet 14, 603–608 (1997). https://doi.org/10.1023/A:1022588903620

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022588903620

Search

Navigation