akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347.2016.10.4.114-122akusherstvo-378Research ArticleREVIEW ARTICLEНАУЧНЫЙ ОБЗОРANTIPHOSPHOLIPID SYNDROME AND EARLY REPRODUCTIVE FAILUREАНТИФОСФОЛИПИДНЫЙ СИНДРОМ И РАННИЕ РЕПРОДУКТИВНЫЕ ПОТЕРИКривоносМ. И.KrivonosM. I.

аспирант,

Менделеевская линия, д. 3, Санкт-Петербург, 199034

graduate student, 

Mendeleevskaja linija, 3, Sankt-Peterburg, 199034

mmirashvili@yandex.ruЗайнулинаМ. С.ZainulinaM. S.

д.м.н., профессор кафедры акушерства и гинекологии, ул. Льва Толстого, д. 6-8, Санкт-Петербург, 197022;

главный врач, ул. Маяковского д. 5, Санкт-Петербург, 191014

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

Zainulina@yandex.ruСельковС. А.SelkovS. A.

д.м.н., профессор, руководитель отдела иммунологии и межклеточных взаимодействий, заслуженный деятель науки РФ,

Менделеевская линия, д. 3, Санкт-Петербург, 199034

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

Mendeleevskaja linija, 3, SanktPeterburg, 199034

selkovsa@mail.ruФГБНУ «НИИ акушерства гинекологии и репродуктологии имени Д.О. Отта»РоссияInstitute of Obstetrics Gynecology and Reproductive named after D.O. OttRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Минздрава России; Санкт-Петербургское учреждение здравоохранения «Родильный дом №6 им. проф. В.Ф. Снегирева»РоссияThe first St. Petersburg State Medical University named after Academician Pavlov; St. Petersburg health care institution "Maternity Hospital №6 them. prof. VF Snegirev"Russian Federation201610032017104114122Copyright © Krivonos M.I., Zainulina M.S., Selkov S.A., 20172017Кривонос М.И., Зайнулина М.С., Сельков С.А.Krivonos M.I., Zainulina M.S., Selkov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/378

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.

Антифосфолипидные антитела (АФА) многосторонне влияют на процессы формирования и развития трофобласта с момента установления маточно-плацентарного кровотока, когда начинается активный контакт с плазмой матери, содержащей циркулирующие АФА. Открытым и широко обсуждаемым остается вопрос о влиянии АФА на развитие более ранних репродуктивных потерь, то есть на этапе имплантации и инвазии эмбриона, что клинически может проявляться бесплодием неясной этиологии, многократными неудачами экстракорпорального оплодотворения или доклиническими потерями беременности (биохимическими беременностями). Возможными патогенетическими вариантами может быть нарушение процессов ангиогенеза в эндометрии под действием антифосфолипидных антител, повышение активности NK-клеток, усиление протромботических механизмов и десинхронизация процессов фибринолиза и фибринообразования, а также негативное влияние АФА на развитие эмбриона.

антифосфолипидные антителаантифосфолипидный синдромимплантациянеудачи ЭКОранние репродуктивные потерибесплодие неясной этиологииantiphospholipid antibodiesantiphospholipid syndromeimplantationin vitro fertilization failureearly reproductive failureunexplained infertilityReferencesМакацария А.Д. Тромбогеморрагические осложнения в акушерско-гинекологической практике. М. 2011; 496 с.Makacarija A.D. Thrombotic-hemorrhagic complications in obstetric practice [Trombogemorragicheskie oslozhnenija v akusherskoginekologicheskoj praktike (in Russian)].Ройт А., Брюсстофф Дж., Мейл Д. Иммунология. М. 2000.Moscow. 2011; 496 s.Хизроева Д.Х., Машкова Т.Я. Вспомогательные репродуктивные технологии и антифософлипидный синдром. Акушерство, гинекология и репродукция. 2014; 8 (1); 26-30.Rojt A., Brjusstoff Dzh., Mejl D. Immunologija. M. 2000.Чепанов С.В., Соколов Д.И., Шляхтенко Т.Н., Капустин Р.В., Окорокова Л.В., Белякова К.Л., Сельков С.А. Экспериментальное обоснование эндотелиопротективного эффекта иммуноглобулинов для внутривенного введения при акушерской патологии. Акушерство и гинекология. 2016; 5: 82-89.Hizroeva D.H., Mashkova T.Ja. Akusherstvo, ginekologiya i reproduktsiya / Obstetrics, gynecology and reproduction. 2014; 8 (1); 26-30.Ярилин А.А. Иммунология: учебник. М. 2010; 752 с.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.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.Jarilin A.A. Immunology: textbook [Immunologija: uchebnik (in Russian)]. Moscow. 2010; 752 s.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.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.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.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.Backos M. Antiphospholipid antibodies and infertility. Hum. Fertil. 2002; 5: 30-4.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.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.Backos M. Antiphospholipid antibodies and infertility. Hum. Fertil. 2002; 5: 30-4.Branch D.W., Silver R.M., Porter T.F. Obstetric antiphospholipid syndrome: current uncertainties should guide our way. Lupus. 2010; 19: 446-52.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.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.Branch D.W., Silver R.M., Porter T.F. Obstetric antiphospholipid syndrome: current uncertainties should guide our way. Lupus. 2010; 19: 446-52.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.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.Branch D.W., Khamashta M.A. Antiphospholipid syndrome: obstetric diagnosis, management, and controversies. Obstet Gynecol. 2003; 101 (6): 1333-44.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.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.Branch D.W., Khamashta M.A. Antiphospholipid syndrome: obstetric diagnosis, management, and controversies. Obstet Gynecol. 2003; 101 (6): 1333-44.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.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.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.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.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 vitroChighizola 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.fertilization. Fertil. Steril. 2000; 73 (3): 526-30.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.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.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.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.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.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.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.Coulam C.B., Roussev R. Chemical pregnancies: immunologic and ultrasonographic studies. Am J Reprod Immunol. 2002; 48 (5): 323-8.Coulam C.B., Roussev R. Chemical pregnancies: immunologic and ultrasonographic studies. Am J Reprod Immunol. 2002; 48 (5): 323-8.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.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.Devreese K., Hoylaerts M.F. Is there an association between complement activation and antiphospholipid antibody related thrombosis? Thromb Haemost. 2010; 104: 1279-1281.Devreese K., Hoylaerts M.F. Is there an association between complement activation and antiphospholipid antibody related thrombosis? Thromb Haemost. 2010; 104: 1279-1281.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.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.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.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.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.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.Di Simone N., Raschi E., Testoni C., Castellani R., D'AstaM, Shi T. et al. Pathogenic role of anti-beta 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.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.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.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.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.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.Erkan D., Salmon J.E. The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid Syndrome. Turk J. Haematol. 2016; 33 (1); 1-7.Erkan D., Salmon J.E. The Role of Complement Inhibition in Thrombotic Angiopathies andErnest J.M., Marshburn P.B., Kutteh W.H. Obstetric antiphospholipid syndrome: an update on pathophysiology and management. SeminReprod Med. 2011; 29: 522-39.Antiphospholipid Syndrome. Turk J. Haematol. 2016; 33 (1); 1-7.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.Ernest J.M., Marshburn P.B., Kutteh W.H. Obstetric antiphospholipid syndrome: an update on pathophysiology and management. SeminReprod Med. 2011; 29: 522-39.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.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.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.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.Girling J.E., Rogers P.A. Recent advances in endometrial angiogenesis research. Angiogenesis. 2005; 8: 89-99.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.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.Girling J.E., Rogers P.A. Recent advances in endometrial angiogenesis research. Angiogenesis. 2005; 8: 89-99.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.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.Hill J., Scott R. Immunological tests and IVF: “please, enough already.” Fertil Steril. 2000; 74: 439-42.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.Holers V.M., Girardi G., Mo L., Guthridge J.M., Molina H., Pierangeli S.S., Espinola R.,Hill J., Scott R. Immunological tests and IVF: “please, enough already.” Fertil Steril. 2000; 74: 439-42.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.Oku K., Amengual O., Atsumi T. Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome. Eur J ClinInvest. 2012; 42: 1126-1135.Oku K., Amengual O., Atsumi T. Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome. Eur J ClinInvest. 2012; 42: 1126-1135.Parr M.B., Parr E.L. Immunohistochemical localization of immunoglobulins A, G and M in the mouse female genital tract. J. Reprod. Fert. 1985; 74: 361-70.Parr M.B., Parr E.L. Immunohistochemical localization of immunoglobulins A, G and MPierangeli 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.in the mouse female genital tract. J. Reprod. Fert. 1985; 74: 361-70.Porter T.F. Antiphospholipid Antibodies and Infertility. 2001; 44 (1): 29-35.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.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.Porter T.F. Antiphospholipid Antibodies and Infertility. Clinical Obstetrics and Gynecology. 2001; 44 (1): 29-35.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.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.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.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.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.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.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.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.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.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.Smith S.K. Angiogenesis and reproduction. BJOG. 2001; 108: 777-83.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.Staub H.L., Dal Ben E.R., Bauer M.E. The antiphospholipid syndrome and Tregs. Autoimmun Rev. 2014; 13 (6): 697-8.Smith S.K. Angiogenesis and reproduction. BJOG. 2001; 108: 777-83.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.Staub H.L., Dal Ben E.R., Bauer M.E. The antiphospholipid syndrome and Tregs. Autoimmun Rev. 2014; 13 (6): 697-8.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.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.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.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.Tartakovsky B., Bermas B.L., Sthoeger Z., Shearer G.M. and Mozes E. Defective maternal-fetal interaction in a murine autoimmune model. Human Reproduction. 1996; 11: 2408-11.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.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.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.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.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.

The authors declare that there are no conflicts of interest present.