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Antiphospholipid antibodies by disrupting trophoblast invasion and endometrial angiogenesis might contribute to a defective placentation and, in turn, affect the successful beginning of pregnancy. It is well known and proven that these processes begin with the founding of the utero-placental blood flow. Given the ability of aPLs to affect implantation and placentation, authors have recently suggested the possibility that aPLs may be responsible also for recurrent implantation failure, early pregnancy loss and unexplained sterility. Possible pathogenic mechanisms: the ability of aPLs to exert a direct negative effect on uterine endothelium and preimplantation embryos, increased activity of NK-cells, increased prothrombotic mechanisms and disruption of the processes of fibrinolysis and fibrin formation.

About the Authors

M. I. Krivonos
Institute of Obstetrics Gynecology and Reproductive named after D.O. Ott
Russian Federation

graduate student, 

Mendeleevskaja linija, 3, Sankt-Peterburg, 199034

M. S. Zainulina
The first St. Petersburg State Medical University named after Academician Pavlov; St. Petersburg health care institution "Maternity Hospital №6 them. prof. VF Snegirev"
Russian Federation

MD, Professor of the Department of Obstetrics and Gynecology, ul. L'va Tolstogo, 6-8, Sankt-Peterburg, 197022;

chief physician, ul. Majakovskogo, 5, Sankt-Peterburg, 191014

S. A. Selkov
Institute of Obstetrics Gynecology and Reproductive named after D.O. Ott
Russian Federation

MD, Professor, Honored Worker of Science, Head of the department of immunology and cell-cell interactions,

Mendeleevskaja linija, 3, SanktPeterburg, 199034


1. Makacarija A.D. Thrombotic-hemorrhagic complications in obstetric practice [Trombogemorragicheskie oslozhnenija v akusherskoginekologicheskoj praktike (in Russian)].

2. Moscow. 2011; 496 s.

3. Rojt A., Brjusstoff Dzh., Mejl D. Immunologija. M. 2000.

4. Hizroeva D.H., Mashkova T.Ja. Akusherstvo, ginekologiya i reproduktsiya / Obstetrics, gynecology and reproduction. 2014; 8 (1); 26-30.

5. Chepanov S.V., Sokolov D.I., Shljahtenko T.N., Kapustin R.V., Okorokova L.V., Beljakova K.L., Sel'kov S.A. Akusherstvo i ginekologija. 2016; 5: 82-89.

6. Jarilin A.A. Immunology: textbook [Immunologija: uchebnik (in Russian)]. Moscow. 2010; 752 s.

7. American Society for Reproductive Medicine. A Practice Committee report. Antiphospholipid antibodies do not affect IVF success. 1999. American Society for Reproductive Medicine. Birmingham, AL, USA. 1-3.

8. Alijotas-Reig J. The complement system as a main actor in the pathogenesis of obstetric antiphospholipid syndrome. Med Clin (Barc). 2010; 134 (1): 30-34.

9. Azem F., Geva E., Amit A., Lerner-Geva L., Schwartz T., Ben-Yosef T. et al. High levels of anticardiolipin antibodies in patients with abnormal embryo morphology who attended an in vitro fertilization program. Am J Reprod Immunol. 1998; 39: 161-3.

10. Backos M. Antiphospholipid antibodies and infertility. Hum. Fertil. 2002; 5: 30-4.

11. Bakhtar O., Thajudeen B., Braunhut B.L., Yost S.E., Bracamonte E.R., Sussman A.N., Kaplan B. A case of thrombotic microangiopathy associated with antiphospholipid antibody syndrome successfully treated with eculizumab. Transplantation. 2014; 98: 17-18.

12. Branch D.W., Silver R.M., Porter T.F. Obstetric antiphospholipid syndrome: current uncertainties should guide our way. Lupus. 2010; 19: 446-52.

13. Birdsall M.A., Lockwood G.M., Ledger W.L., Johnson P.M. Antiphospholipid antibodies in women having in-vitro fertilization. Human Reproduction. 1996; 6: 1185-1189.

14. Birkenfeld A., Mukaida T., Minichiello L., Jackson M., Kase N.G., Yemini M. Incidence of autoimmune antibodies in failed embryo transfer cycles. Am J Reprod Immunol. 1994; 31: 65-68.

15. Branch D.W., Khamashta M.A. Antiphospholipid syndrome: obstetric diagnosis, management, and controversies. Obstet Gynecol. 2003; 101 (6): 1333-44.

16. Buckingham K.L., Chamley L.W. A critical assessment of the role of antiphospholipid antibodies in infertility. J Reprod Immunol. 2009; 80 (1-2): 132-45.

17. Caccavo D., Pellegrino N.M., Lorusso F., Capotorto M., Vacca M., Vimercati A., Depalo R. Anticardiolipin antibody levels in women undergoing first in vitro fertilization/embryo transfer. Human Reproduction. 2007; 22 (9): 2494-2500.

18. Chighizola C.B., Ubiali T., Meroni P.L. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management – An Insight into Future Approaches. Journal of Immunology Research. 2015; 2015: 951424.

19. Chilcott I.T., Margara R., Cohen H., Rai R., Skull J., Pickering W., Regan L. Pregnancy outcome is not affected by antiphospholipid antibody status in women referred for in vitro fertilization. Fertil Steril. 2000; 73 (3): 526-30.

20. Cervera R., Khamashta M.A., Shoenfeld Y., Camps M.T., Jacobsen S., Kiss E., et al. Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2009; 68: 1428-32.

21. Costedoat-Chalumeau N., Guettrot-Imbert G., Leguern V., Leroux G., Le ThiHuong D., Wechsler B., et al. Pregnancy and antiphospholipid syndrome. Revue de Medecine Interne. 2012; 33: 209-16.

22. Coulam C., Kaider B., Janowicz P., Roussev R. Antiphospholipid antibodies associated with implantation failure after IVF/ET. J Assist Reprod Genet. 1997; 14: 603-6.

23. Coulam C.B., Roussev R. Chemical pregnancies: immunologic and ultrasonographic studies. Am J Reprod Immunol. 2002; 48 (5): 323-8.

24. Denis A.L., Guido M., Adler R.D., Bergh P.A., Brenner C., Scott R.T. Antiphospholipid antibodies and pregnancy rates and outcome in IVF patients. Fertil Steril. 1997; 67: 1084-90.

25. Devreese K., Hoylaerts M.F. Is there an association between complement activation and antiphospholipid antibody related thrombosis? Thromb Haemost. 2010; 104: 1279-1281.

26. Di Simone N., Castellani R., Caliandro D., Caruso A. Antiphospholid antibodies regulate the expression of trophoblast cell adhesion molecules. Fertil Steril. 2002; 77: 805-11.

27. Di Simone N., Di Nicuolo F., D'Ippolito S., Castellani R., Tersigni C., Caruso A. et al. Antiphospholipid antibodies affect human endometrial angiogenesis. BiolReprod. 2010; 83: 212-9.

28. Di Simone N., Meroni P.L., del Papa N., Raschi E., Caliandro D., De Carolis S. et al. Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta2-glycoprotein I. Arthritis Rheum. 2000; 43: 140-50.

29. Di Simone N., Raschi E., Testoni C., Castellani R., D'AstaM, Shi T. et al. Pathogenic role of antibeta 2-glycoprotein I antibodies in antiphospholipid associated fetal loss: characterization of beta 2-glycoprotein I binding to trophoblast cells and functional effects of anti-beta 2-glycoprotein I antibodies in vitro. Ann Rheum Dis. 2005; 64: 462-7.

30. Di Nisio M., Rutjes A.W., Ferrante N., Tiboni G.M., Cuccurullo F., Porreca E. Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis. Blood. 2011; 118 (10): 2670-8.

31. D'Ippolito S., Meroni P.L., Koike T., Veglia M., Scambia G., Di Simone N. Obstetric antiphospholipid syndrome: A recent classification for an old defined disorder. Autoimmunity Reviews. 2014; 13: 901-8.

32. Erkan D., Salmon J.E. The Role of Complement Inhibition in Thrombotic Angiopathies and

33. Antiphospholipid Syndrome. Turk J. Haematol. 2016; 33 (1); 1-7.

34. Ernest J.M., Marshburn P.B., Kutteh W.H. Obstetric antiphospholipid syndrome: an update on pathophysiology and management. SeminReprod Med. 2011; 29: 522-39.

35. Fisch B., Rikover Y., Shohat L., Zurgil N., Tadir Y., Ovadia J., Witz I.P., Yron I. The relationship between in vitro fertilization and naturally occurring antibodies: evidence for increased production of antiphospholipid autoantibodies. Fertility Sterility. 1991; 56 (4): 718-24.

36. Geva E., Yaron Y., Lessing J.B., Yovel I., Vardinon N., Burke M. et al. Circulating autoimmune antibodies may be responsible for implantation failure in in-vitro-fertilization. Fertil Steril. 1994; 62: 802-6.

37. Girardi G., Berman J., Redecha P., Spruce L., Thurman J.M., Kraus D., Hollmann T.J., Casali P., Caroll M.C., Wetsel R.A., Lambris J.D., Holers V.M., Salmon J.E. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003; 112 (11): 1644-54.

38. Girling J.E., Rogers P.A. Recent advances in endometrial angiogenesis research. Angiogenesis. 2005; 8: 89-99.

39. Gleicher N., Liu H., Dudkiewicz A., Rosenwaks Z., Kaberlein G., Pratt D., et al. Autoantibody profiles and immunoglobulin levels as predictors of IVF success. Am J Obstet Gynecol. 1994; 170: 1145-9.

40. Hammadeh M.E., Ertan A.K., Zeppezauer M., Baltes S., Georg T., Rosenbaum P., Schmidt W. Immunoglobulins and cytokines level in follicular fluid in relation to etiology of infertility and their relevance to IVF outcome. Am J ReprodImmunol. 2002; 47 (2): 82-90.

41. Hill J., Scott R. Immunological tests and IVF: “please, enough already.” Fertil Steril. 2000; 74: 439-42.

42. Holers V.M., Girardi G., Mo L., Guthridge J.M., Molina H., Pierangeli S.S., Espinola R., Xiaowei L.E., Mao D., Vialpando C.G., Salmon J.E. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med. 2002; 195 (2): 211-20.

43. Hornstein M., Davis O., Massey J., Paulson R., Collins J. Antiphospholipid antibodies and invitro fertilization success: a meta-analysis. Fertil Steril. 2000; 73: 330-3.

44. Kaider B.D., Coulam C.B. and Roussev R.G. Murine embryos as a direct target for some human autoantibodies in vitro. Human Reproduction. 1999; 14: 2556-61.

45. Kowalik A., Vichnin M., Liu H., Branch W., Berkeley A. Midfollicular anticardiolipin and antiphosphatidylserine antibody titres do not correlate with in vitro fertilization outcome. Fertil Steril. 1997; 68: 298-304.

46. Lonze B.E., Zachary A.A., Magro C.M., Desai N.M., Orandi B.J., Dagher N.N., Singer A.L., Carter-Monroe N., Nazarian S.M., Segev D.L., Streiff M.B., Montgomery R.A. Eculizumab prevents recurrent antiphospholipid antibody syndrome and enables successful renal transplantation. Am J Transplant. 2014; 14: 459-465.

47. Matsubayashi H., Sugi T., Arai T., Shida M., Kondo A., Suzuki T., Izumi S., McIntyre J.A. IgG-antiphospholipid antibodies in follicular fluid of IVF-ET patients are related to low fertilization rate of their oocytes. Am J Reprod Immunol. 2006; 55 (5): 341-8.

48. Mariee N.G., Tuckerman E., Laird S., Li T.C. The correlation of autoantibodies and uNK cells in women with reproductive failure. J ReprodImmunol. 2012; 95 (1-2): 59-66.

49. Miyakis S., Lockshin M.D., Atsumi T. et al. International consensus statement on an update of the classification criteriafor definite antiphospholipid syndrome (APS). Journal of Thrombosis and Haemostasis. 2006; 4 (2): 295-306.

50. Oku K., Amengual O., Atsumi T. Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome. Eur J ClinInvest. 2012; 42: 1126-1135.

51. Parr M.B., Parr E.L. Immunohistochemical localization of immunoglobulins A, G and M

52. in the mouse female genital tract. J. Reprod. Fert. 1985; 74: 361-70.

53. Pierangeli S.S., Girardi G., Vega-Ostertag M., Liu X., Espinola R.G., Salmon J. Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthritis Rheum. 2005; 52: 2120-2124.

54. Porter T.F. Antiphospholipid Antibodies and Infertility. Clinical Obstetrics and Gynecology. 2001; 44 (1): 29-35.

55. Rachman F., Casimiri V., Psychoyos A. and Bernard O. Immunoglobulins in the mouse uterus during the oestrous cycle. J. Reprod. Fert. 1983; 69: 17-21.

56. Redecha P., Franzke C.W., Ruf W., Mackman N., Girardi G. Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome. J Clin Invest. 2008; 118: 3453-61.

57. Salmon J.E., Girardi G., Holers V.M. Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis. Ann Rheum Dis. 2002; 61 (2): 46-50.

58. Sanmarco M., Bardin N., Camoin L., Beziane A., Dignat-George F., Gamerre F., Porcu G. Antigenic Profile, Prevalence, and Clinical Significance of Antiphospholipid Antibodies in Women Referred for in Vitro Fertilization. Ann. N.Y. Acad. Sci. 2007; 1108: 457-465.

59. Sauer R., Roussev R., Jeyendran R.S., Coulam C.B. Prevalence of antiphospholipid antibodies among women experiencing unexplained infertility and recurrent implantation failure. Fertil Steril. 2010; 93 (7); 2441-3.

60. Sher G., Fisch J.D., Maassarani G., Matzner W., Ching W., Chong P. Antibodies to phosphatidylethanolamine and phosphatidylserine are associated with increased natural killer cell activity in non-male factor infertility patients. Hum Reprod. 2000; 15: 1932-6.

61. Smith S.K. Angiogenesis and reproduction. BJOG. 2001; 108: 777-83.

62. Staub H.L., Dal Ben E.R., Bauer M.E. The antiphospholipid syndrome and Tregs. Autoimmun Rev. 2014; 13 (6): 697-8.

63. Stern C., Chamley L., Hale L., Kloss M., Speirs A., Baker HWG., et al. Antibodies to β_2 glycoprotein I are associated with in vitro fertilization implantation failure as well as recurrent miscarriage: results of a prevalence study. Fertil Steril. 1998; 70: 938-44.

64. Sthoeger Z.M., Mozes E. and Tartakovsky B. Anti-cardiolipin antibodies induce pregnancy failure by impairing embryonic implantation. Proceedings National Academy of Sciences USA. 1993; 90: 6464-7.

65. Strakhan M., Hurtado-Sbordoni M., Galeas N., Bakirhan K., Alexis K., Elrafei T. 36-yearold female with catastrophic antiphospholipid syndrome treated with eculizumab: a case report and review of literature. Case Rep Hematol. 2014; 2014: 704371.

66. Tartakovsky B., Bermas B.L., Sthoeger Z., Shearer G.M. and Mozes E. Defective maternalfetal interaction in a murine autoimmune model. Human Reproduction. 1996; 11: 2408-11.

67. Viall C.A., Chamley L.W. Histopathology in the placentae of women with antiphospholipid antibodies: A systematic review of the literature. Autoimmun Rev. 2015; 14 (5): 446-71.

For citation:

Krivonos M.I., Zainulina M.S., Selkov S.A. ANTIPHOSPHOLIPID SYNDROME AND EARLY REPRODUCTIVE FAILURE. Obstetrics, Gynecology and Reproduction. 2016;10(4):114-122. (In Russ.)

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ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)