Role of natural killer cells in reproductive failure

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Reproductive losses are quite frequent in the modern world. They include: infertility, infertility of unknown etiology, multiple losses when IVF, recurrent implantation failure, miscarriage, recurrent miscarriage, both in the natural cycle and after ART management. It is important to note that the classification of some of these categories are not established yet. The etiology of reproductive losses is extremely diverse. Successful development of pregnancy at early terms is determined by genetic and immunological factors. Among the reproductive failures of unclear etiology, immunological causes are 50-80%. Over the past 20 years there are already known many different immunological factors that play role in the processes of fertilization. In this case, the evidence base on the role of each of them in the pathogenesis of reproductive failures is only being formed. Currently, the immunological relationship between mother and fetus is considered as a two-way communication process: the presentation of fetal antigens on the one hand, and on the other – the recognition and response to these antigens of the maternal immune system. Implantation of the embryo is accompanied by an increase in the production of proinflammatory cytokines followed by a sharp change in the cellular composition in the decidualizing endometrium, and the main population is NK cells. That is why this type of cells have a significant role in the normal development of pregnancy. The properties of NK cells in the uterus and peripheral blood are significantly different. To predict the onset and prolongation of pregnancy, peripheral blood NK (activity and quantity) is used. Evaluation of endometrial NK is often performed for the diagnosis of chronic endometritis. Currently, the definition of NK cells in peripheral blood in many clinics is proposed as a useful diagnostic test to address the issue of further appointment of immunoglobulins and evaluating the effectiveness of this therapy in patients with reproductive losses.

Alana O. Agnaeva

Author for correspondence.
FSBSI “The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott”
Russian Federation, 3, Mendeleevskaya line, Saint Petersburg, 199034

Olesya N. Bespalova
FSBSI “The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott”
Russian Federation, 3, Mendeleevskaya line, Saint Petersburg, 199034

MD, PhD, DMSc, Leading researcher of the 1st obstetric pregnancy pathology department

Dmitriy I. Sokolov
FSBSI “The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott”; I.P. Pavlov First St Petersburg State Medical University; FSBSI “Institute of Experimental Medicine”
Russian Federation, 3, Mendeleevskaya line, Saint Petersburg, 199034; 6/9, Lva Tolstogo street, St. Petersburg, 197089; 12, Academic Pavlov street, Saint-Petersburg, 197376

DBSc, Head of Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

Sergey A. Selkov
FSBSI “The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott”
Russian Federation, 3, Mendeleevskaya line, Saint Petersburg, 199034

MD, professor, Head of the Department of Immunology and Intercellular Interactions

Igor Yu. Kogan
FSBSI “The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott”
Russian Federation, 3, Mendeleevskaya line, Saint Petersburg, 199034

professor, scientific secretery

  • Choudhury S. Human reproductive failure I: Immunological factors. Human Reproduction Update. 2001;7(2):113-34. doi: 10.1093/humupd/7.2.113.
  • Edmonds DK, Lindsay KS, Miller JF, et al. Early embryonic mortality in women. Fertil Steril. 1982;38(4):447-53. doi: 10.1016/S0015-0282(16)46579-9.
  • Sermondade N, Delarouzière V, Ravel C, et al. Characterization of a recurrent poor-quality embryo morphology phenotype and zygote transfer as a rescue strategy. Reprod Biomed Online. 2012;24(4):403-9. doi: 10.1016/j.rbmo.2012.01.004. Epub 2012 Jan 24.
  • Tan B, Vandekerckhove P, Kennedy R, Keay S. Investigation and current management of recurrent IVF treatment failure in the UK. BJOG: An International Journal of Obstetrics and Gynaecology. 2005;112(6):773-780. doi: 10.1111/j.1471-0528.2005.00523.x.
  • Debrock S, Melotte C, Spiessens C, Peeraer K. Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial. Fertil Steril. 2010;93(2):364-73. doi: 10.1016/j.fertnstert.2008.10.072. Epub 2009 Feb 26.
  • Margalioth E, Ben-Chetrit A, Gal M, Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF-ET. Human Reproduction. 2006;21(12):3036-3043. doi: 10.1093/humrep/del305.
  • Firouzabadi RD, Ahmadi S, Oskouian H, Davar R. Comparing GnRH agonist long protocol and GnRH antagonist protocol in outcome the first cycle of ART. Arch Gynecol Obstet. 2010;281(1):81-5. doi: 10.1007/s00404-009-1073-5. Epub 2009 Apr 9.
  • Polanski L, Baumgarten M, Quenby S. What exactly do we mean by ‘recurrent implantation failure’? A systematic review and opinion. Reproductive BioMedicine Online. 2014;28(4):409-423. doi: 10.1016/j.rbmo.2013.12.006.
  • Кошелева Н.Г., Плужникова Т.А. Невынашивание беременности // Мир медицины. – 1998. – № 11–12. – С. 43. [Kosheleva NG, Pluzhnikova TA. Nevynashivanie beremennosti. Mir mediciny. 1998;(11-12):43. (In Russ.)]
  • Сидельникова В.М., Сухих Г.Т. Невынашивание беременности: руководство для практикующих врачей. – М., 2011. [Sidel’nikova VM, Suhih GT. Nevynashivanie beremennosti: rukovodstvo dlja praktikujushhih vrachej. Moscow, 2011. (In Russ.)]
  • Сидельникова В.М. Привычная потеря беременности. – M.: Триада-Х, 2002. [Sidel’nikova VM. Privychnaja poterja beremennosti. Moscow, Triada-X; 2002. (In Russ.)]
  • Bashiri A, Harlev A, Agarwal A. Recurrent Pregnancy Loss. 1st ed. Cham: Springer International Publishing; 2016.
  • Беспалова О.Н. Генетические факторы риска невынашивания беременности: автореф. дис. … д-ра мед. наук. – СПб., 2009. [Bespalova ON. Geneticheskie faktory riska nevynashivanija beremennosti [dissertation]. Saint Petersburg; 2009. (In Russ.)]
  • Тетруашвили Н.К. Ранние потери беременности (иммунологические аспекты, пути профилактики и терапии): автореф. дис. … д-ра мед. наук. – М., 2008 [Tetruashvili NK. Rannie poteri beremennosti (immunologicheskie aspekty, puti profilaktiki i terapii). [dissertation] Moscow, 2008. (In Russ.)]
  • Сельков С.А. Иммунологические аспекты невы нашивания беременности: автореф. дис. … д-ра мед. наук. – СПб., 1996. [Sel’kov SA. Immunologicheskie aspekty nevynashivanija beremennosti. [dissertation] Saint Petersburg; 1996. (In Russ.)]
  • Газиева И.А. Иммунопатогенетические механизмы формирования плацентарной недостаточности и ранних репродуктивных потерь: автореф. дис. … канд. мед. наук. – Екатеринбург, 2014. [Gazieva IA. Immunopatogeneticheskie mehanizmy formirovanija placentarnoj nedostatochnosti i rannih reproduktivnyh poter’. [dissertation] Ekaterinburg; 2014. (In Russ.)]
  • Сотникова Н.Ю. Иммунные механизмы регуляции инвазии трофобласта // Российский иммунологический журнал. – 2010. – № 4. – С. 9–13. [Sotnikova NJu. Immunnye mehanizmy reguljacii invazii trofoblasta. Rossijskij immunologicheskij zhurnal. 2010;(4):9-13. (In Russ.)]
  • Айламазян Э.К., Павлов О.В., Сельков С.А. Роль иммунной системы фетоплацентарного комплекса в механизмах преждевременного прерывания беременности // Акушерство и гинекология. – 2004. – № 2. – С. 9–15. [Ajlamazjan JeK, Pavlov OV, Sel’kov SA. Rol’ immunnoj sistemy fetoplacentarnogo kompleksa v mehanizmah prezhdevremennogo preryvanija beremennosti. Akusherstvo i ginekologija. 2004;(2):9-15. (In Russ.)]
  • Mikhailova V, Belyakova K, Selkov S, Sokolov D. Peculiarities of NK cells differentiation: CD56dim and CD56bright NK cells at pregnancy and in non-pregnant state. Medical Immunology (Russia). 2017;19(1):19-26. doi: 10.15789/1563-0625-2017-1-19-26.
  • Михайлова В.А., Сельков С.А., Соколов Д.И. Фенотипические и функциональные харак теристики NK-клеток при беременности // Акушерство и гинекология. – 2011. – № 5. – С. 4–9.[Mihajlova VA, Sel’kov SA, Sokolov DI. Fenotipicheskie i funkcional’nye harakteristiki NK-kletok pri beremennosti. Akusherstvo i ginekologija. 2011;(5):4-9. (In Russ.)]
  • Bulmer JN, Morrison L, Longfellow M, et al. Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. Hum Reprod. 1991Jul;6(6):791-8. doi: 10.1093/oxfordjournals.humrep.a137430.
  • Starkey PM, Clover LM, Rees MC. Variation during the menstrual cycle of immune cell populations in human endometrium. Eur J Obstet Gynecol Reprod Biol. 1991;39(3):203-7. doi: 10.1016/0028-2243(91)90058-S.
  • Northern AL, Rutter SM, Peterson CM. Cyclic changes in the concentrations of peripheral blood immune cells during the normal menstrual cycle. Proc Soc Exp Biol Med. 1994;207(1):81-8. doi: 10.3181/00379727-207-43795.
  • Yovel G, Shakhar K, Ben-Eliyahu S. The effects of sex, menstrual cycle, and oral contraceptives on the number and activity of natural killer cells. Gynecol Oncol. 2001;81(2):254-62. doi: 10.1006/gyno.2001.6153.
  • Souza SS, Castro FA, Mendonça HC, et al. Influence of menstrual cycle on NK activity. J Reprod Immunol. 2001;50(2):151-9. doi: 10.1016/S0165-0378(00)00091-7.
  • Григорьева В.В., Сельков С.А., Шапахова О.В., Малыгин А.М. Активность естественных киллеров при различных формах невынашивания беременности // Aкушерство и гинекология. – 1991. – № 4. – С. 26–28. [Grigor’eva VV, Sel’kov SA, Shapahova OV, Malygin AM. Aktivnost’ estestvennyh killerov pri razlichnyh formah nevynashivanija beremennosti. Akusherstvo i ginekologija. 1991;(4):26-8. (In Russ.)]
  • Gregory CD, Shah LP, Lee H, et al. Cytotoxic reactivity of human natural killer (NK) cells during normal pregnancy: a longitudinal study. J Clin Lab Immunol. 1985;18(4):175-81.
  • Gregory CD, Lee H, Scott IV, Golding PR. Phenotypic heterogeneity and recycling capacity of natural killer cells in normal human pregnancy. J Reprod Immunol. 1987;11(2):135-45. doi: 10.1016/0165-0378(87)90017-9.
  • Ponte M, Cantoni C, Biassoni R. Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor. Proc Natl Acad Sci USA. 1999;96(10):5674-9. doi: 10.1073/pnas.96.10.5674.
  • Dosiou C, Giudice L. Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives. Endocrine Reviews. 2005;26(1):44-62. doi: 10.1210/er.2003-0021.
  • Ширшев С.В., Некрасова И.В., Орлова Е.Г. Регуляция фенотипического созревания NK и NKT клеток гормонами репродукции // Вестник Пермского университета. – 2008. – Вып. 9(25). – С. 100–103. [Shirshev SV, Nekrasova IV, Orlova EG. Reguljacija fenotipicheskogo sozrevanija NK i NKT kletok gormonami reprodukcii. Vestnik Permskogo universiteta. 2008;9(25):100-3. (In Russ.)]
  • Laskarin G, Strbo N, Sotosek V, Rukavina D, et al. Progesterone directly and indirectly affects perforin expression in cytolytic cells. Am J Reprod Immunol. 1999;42(5): 312-20. doi: 10.1111/j.1600-0897.1999.tb00107.x.
  • Roussev R, Ng S, Coulam C. Natural Killer Cell Functional Activity Suppression By Intravenous Immunoglobulin, Intralipid and Soluble Human Leukocyte Antigen-G. American Journal of Reproductive Immunology. 2007;57(4):262-269. doi: 10.1111/j.1600-0897.2007.00473.x.
  • Choudhury S. Human reproductive failure II: Immunogenetic and interacting factors. Human Reproduction Update. 2001;7(2):135-160. doi: 10.1093/humupd/7.2.135.
  • Beer A, Kwak J, Ruiz J. Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent pregnancy losses and in infertile women with multiple failed in vitro fertilization cycles. American Journal of Reproductive Immunology. 1996;35(4):376-382. doi: 10.1111/j.1600-0897.1996.tb00497.x.
  • Michou VI, Kanavaros P, Athanassiou V. Fraction of the peripheral blood concentration of CD56+/CD16–/CD3-cells in total natural killer cells as an indication of fertility and infertility. Fertil Steril. 2003;80(Suppl 2):691-7.
  • Thum MY, Bhaskaran S, Abdalla HI, et al. An increase in the absolute count of CD56dimCD16+CD69+ NK cells in the peripheral blood is associated with a poorer IVF treatment and pregnancy outcome. Hum Reprod. 2004;19(10):2395-400. Epub 2004 Aug 19
  • The Role of Natural Killer Cells in Human Fertility. Scientific Impact Paper No. 53, 2016. URL: (дата обращения: 13.04.2017).
  • Чугунова А.А., Зайнулина М.С., Селютин А.В. Содержание основных субпопуляций иммунокомпетентных клеток у беременных с невынашивание и антифосфолипидным синдромом при лечении препаратами иммуноглобулинов // Акушерство и гинекология. – 2012. – № 2. – С. 30–35.[Chugunova AA, Zajnulina MS, Seljutin AV. The content of main subpopulations of immunocompetent cells in pregnant women with miscarriage and antiphospholipid syndrome during intravenous immunoglobulin treatment. Obstetrics and Gynecology. 2012;(2):30-5. (In Russ.)]
  • Clark D, Coulam C, Stricker R. Is intravenous immunoglobulins (IVIG) efficacious in early pregnancy failure? A critical review and meta-analysis for patients who fail in vitro fertilization and embryo transfer (IVF). Journal of Assisted Reproduction and Genetics. 2006;23(9-10):383. doi: 10.1007/s10815-006-9057-x.
  • Cohn EJ, Strong LE, et al. Preparation and properties of serum and plasma proteins; a system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids. J Am Chem Soc. 1946;68:459-75. doi: 10.1021/ja01207a034.
  • Агаджанова A.A., Сидельникова В.М. Опыт применения препарата Гамимун-Н у больных с антифосфолипидным синдромом и привычным невынашиванием беременности // Материалы VII Российского форума «Мать и дитя». – М., 2005. – С. 28 [Agadzhanova AA, Sidel’nikova VM. Opyt primenenija preparata Gamimun-N u bol’nyh s antifosfolipidnym sindromom i privychnym nevynashivaniem beremennosti. Materialy VII Rossijs kogo foruma “Mat’ i ditja”. (conference proceedings) Moscow; 2005:28. (In Russ.)]
  • Егорян Л.С. Иммуноглобулины в профилактике внутриутробных инфекций: автореф. дис. … канд.мед. наук. – Ростов на/Д, 2006. [Egorjan LS. Immunoglobuliny v profilaktike vnutriutrobnyh infekcij. [dissertation]. Rostov-on-Don; 2006 (In Russ.)]
  • Сельков С.А., Соколов Д.И., Чепанов С.В. Иммунорегуляторные эффекты иммуноглобулинов для внутривенного ведения // Медицинская иммунология. – 2013. – Т. 15. – № 1. – С. 5–12. [Sel’kov SA, Sokolov DI, Chepanov SV. Immunoreguljatornye jeffekty immunoglobulinov dlja vnutrivennogo vedenija. Medicinskaja immunologija. 2013;15(1):5-12. (In Russ.)]
  • Формуляр по использованию препаратов иммуноглобулинов для внутривенного введения в неонатологии // Н.Н. Володин, ред. Протоколы диагностики, лечения и профилактики внутриутробных инфекций у новорожденных детей . – М., 2001. – С. 72–90. [Formuljar po ispol’zovaniju preparatov immunoglobuli nov dlja vnutrivennogo vvedenija v neonatologii. N.N. Volodin, ed. Protokoly diagnostiki, lechenija i profilaktiki vnutriutrobnyh infekcij u novorozhdjonnyh detej. Moscow; 2001: P. 72-90. (In Russ.)]
  • Carp H. Recurrent Pregnancy Loss. 2nd ed. Tel Aviv: CRS Press; 255-261.
  • Чепанов С.В., Соколов Д.И., Шляхтенко Т.Н. Экспериментальное обоснование эндотелиопротекторного эффекта иммуноглобулинов для внутривенного ведения при акушерской патологии // Акушерство и гинекология. – 2016. – № 5. – С. 82–89. [Chepanov SV, Sokolov DI, Shlachtenko TN, et al. Experimental rationale for the endothelial protective effect of intravenous immunoglobulins in obstetric disease. Obstetrics and Gynecology. 2016;(5):82-9. (In Russ.)]
  • Ушкалова Е.А., Шифман Е.М. Проблема нерегламентированного применения иммуно глобулина для внутривенного введения в акушерстве // Акушерство и гинекология. – 2011. – № 3. – C. 74–80. [Ushkalova EA, Shifman EM. Problema nereglamentirovannogo primenenija immunoglobulina dlja vnutrivennogo vvedenija v akusherstve. Akusherstvo i ginekologija. 2011;(3):74-80 (In Russ.)]
  • Seshadri S, Sunkara S. Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Human Reproduction Update. 2013;20(3):429-438. doi: 10.1093/humupd/dmt056.
  • Moraru M, Carbone J, Alecsandru D, et al. Intravenous immunoglobulin treatment increased live birth rate in a Spanish cohort of women with recurrent reproductive failure and expanded CD56(+) cells. Am J Reprod Immunol. 2012;68(1):75-84. doi: 10.1111/j.1600-0897.2012.01135.x. Epub 2012 Apr 18.
  • Кривонос М.И., Зайнулина М.С., Чепанов С.В., и др. Клинико-иммунологические аспекты ведения женщин с неудачами ВРТ // Журнал акушерства и женских болезней. – 2014. – № 5. – C. 89–94. [Krivonos MI, Zaynulina MS, Chepanov SV, et al. Clinical and immunological aspects of treatment women with repeated in-vitro fertilization failure. Journal of Obstetrics and Women’s Diseases. 2014;(5):89-94. (In Russ.)]
  • Hutton B, Sharma R, Fergusson D, et al. Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review. BJOG. 2007;114(2): 134-42. Epub 2006 Dec 12.
  • Li J, Chen Y, Liu C, et al. Intravenous immunoglobulin treatment for repeated IVF/ICSI failure and unexplained infertility: a systematic review and a meta-analysis. Am J Reprod Immunol. 2013;70(6):434-47. doi: 10.1111/aji.12170.
  • Kwak JY, Beaman KD, Gilman-Sachs A, et al. Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses. Am J Reprod Immunol. 1995;34(2):93-9. doi: 10.1111/j.1600-0897.1995.tb00924.x.
  • Higuchi K, Aoki K, Kimbara T, Hosoi N. Suppression of natural killer cell activity by monocytes following immunotherapy for recurrent spontaneous aborters. Am J Reprod Immunol. 1995;33(3):221-7. doi: 10.1111/j.1600-0897.1995.tb00888.x.
  • Emmer PM, Nelen WL, Steegers EA, et al. Peripheral natural killer cytotoxicity and CD56(pos)CD16(pos) cells increase during early pregnancy in women with a history of recurrent spontaneous abortion. Hum Reprod. 2000;15(5):1163-9. doi: 10.1093/humrep/15.5.1163.
  • Ntrivalas EI, Kwak-Kim JY, Gilman-Sachs A, et al. Status of peripheral blood natural killer cells in women with recurrent spontaneous abortions and infertility of unknown aetiology. Hum Reprod. 2001;16(5):855-61. doi: 10.1093/humrep/16.5.855.
  • Souza SS, Ferriani RA, Santos CM, Voltarelli JC. Immunological evaluation of patients with recurrent abortion. J Reprod Immunol. 2002;56(1-2):111-21. doi: 10.1016/S0165-0378(01)00145-0.
  • Yamada H, Morikawa M, Kato EH, et al. Pre-conceptional natural killer cell activity and percentage as predictors of biochemical pregnancy and spontaneous abortion with normal chromosome karyotype. Am J Reprod Immunol. 2003;50(4):351-4. doi: 10.1034/j.1600-0897.2003.00095.x.
  • Roussev R, Ng S, Coulam C. Natural Killer Cell Functional Activity Suppression By Intravenous Immunoglobulin, Intralipid and Soluble Human Leukocyte Antigen-G. American Journal of Reproductive Immunology. 2007;57(4): 262-269. doi: 10.1111/j.1600-0897.2007.00473.x.
  • Perricone C, De Carolis C, Giacomelli R, et al. High levels of NK cells in the peripheral blood of patients affected with anti-phospholipid syndrome and recurrent spontaneous abortion: a potential new hypothesis. Rheumatology. 2007;46(10):1574-8. doi: 10.1093/rheumatology/kem197.
  • Sacks G, Yang Y, Gowen E, et al. Detailed analysis of peripheral blood natural killer cells in women with repeated IVF failure. Am J Reprod Immunol. 2012;67(5):434-42. doi: 10.1111/j.1600–0897.2012.01105.x.
  • Lachapelle MH, Miron P, Hemmings R, Roy DC. Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered profile and pregnancy outcome. J Immunol. 1996 15;156(10):4027-34.
  • Quenby S, Bates M, Doig T. Pre-implantation endometrial leukocytes in women with recurrent miscarriage. Hum Reprod. 1999;14(9):2386-91. doi: 10.1093/humrep/14.9.2386.
  • Clifford K, Flanagan AM, Regan L. Endometrial CD56+ natural killer cells in women with recurrent miscarriage: a histomorphometric study. Hum Reprod. 1999;14(11):2727-30. doi: 10.1093/humrep/14.11.2727.
  • Emmer PM, Steegers EA, Kerstens HM. Altered phenotype of HLA-G expressing trophoblast and decidual natural killer cells in pathological pregnancies. Hum Reprod. 2002;17(4):1072-80. doi: 10.1093/humrep/17.4.1072.
  • Shimada S, Kato EH, Morikawa M, Iwabuchi K, et al. No difference in natural killer or natural killer T-cell population, but aberrant T-helper cell population in the endometrium of women with repeated miscarriage. Hum Reprod. 2004;19(4):1018-24. doi: 10.1093/humrep/deh159.
  • Michimata T, Ogasawara MS, Tsuda H, et al. Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion. Am J Reprod Immunol. 2002;47(4):196-202. doi: 10.1034/j.1600-0897.2002.01048.x.
  • Intravenous immunoglobulin in the prevention of recurrent miscarriage. The German RSA/IVIG Group. Br J Obstet Gynaecol. 1994;101(12):1072-7. doi: 10.1111/j.1471-0528.1994.tb13584.x.
  • Christiansen OB, Mathiesen O, Husth M, et al. Placebo-controlled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i. v. immunoglobulin. Hum Reprod. 1995;10(10):2690-5. doi: 10.1093/oxfordjournals.humrep.a135769.
  • Coulam CB, Krysa L, Stern JJ, Bustillo M. Intravenous immunoglobulin for treatment of recurrent pregnancy loss. Am J Reprod Immunol. 1995;34(6):333-7. doi: 10.1111/j.1600-0897.1995.tb00960.x.
  • 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(2):82-8. doi: 10.1111/j.1600-0897.1998.tb00339.x.
  • Jablonowska B, Selbing A, Palfi M, Ernerudh J. Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study. Hum Reprod. 1999;14(3):838-41. doi: 10.1093/humrep/14.3.838.
  • 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(3):809-16. doi: 10.1093/humrep/17.3.809.
  • Triolo G, Ferrante A, Ciccia F, Accardo-Palumbo A. Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis Rheum. 2003;48(3):728-31. doi: 10.1002/art.10957.
  • Winger EE, Reed JL.Treatment with tumor necrosis factor inhibitors and intravenous immunoglobulin improves live birth rates in women with recurrent spontaneous abortion. Am J Reprod Immunol. 2008;60(1):8-16. doi: 10.1111/j.1600–0897.2008.00585.x.

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