DOI: https://doi.org/10.18370/2309-4117.2013.13.45-55

Possibilities of modern immunotherapy in reproduction

Д. В. Мальцев

Abstract


This article examines the possibilities of modern immunotherapeutic interventions in the pathology of the reproductive sphere, complications of pregnancy and fetal injuries associated with transplacental transfer of autoantibodies from the mother. Article contains the results of the available studies and reports that examine the efficacy and safety of immunoglobulins, growth factors, and different classes of interferons in obstetric practice that form the basis of immunotherapy. Proper implementation of these treatment strategies into clinical practice of medical institutions of Ukraine will increase the quality of medical care for pregnant women and improve the training for planned pregnancy


Keywords


immunotherapy; obstetrics; immunoglobulin; reproduction

References


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Al-Rawi S, Woodward LJ, Knight J Puerperal streptococcal toxic shock syndrome treated with recombinant human activated protein C and intravenous immunoglobulin Int J Obstet Anesth. 2009; 18(2): 169–72.

Bahadur A, Gupta N, Deka D, Mittal S Successful maternal and fetal outcome of Guillain-Barré syndrome complicating pregnancy Indian J Med Sci. 2009; 63(11): 517–8.

Branch DW, Peaceman AM, Druzin M et al. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Am J Obstet Gynecol. 2000; 182(1 Pt 1): 122–7.

Buxmann H, Kamin W, Kriván G et al. An open-label, randomized efficacy and safety trial of subcutaneous and intramuscular BT088 (Fovepta) human hepatitis B immunoglobulin in neonates of HBV-carrier mothers. J Perinat Med. 2012; 40(4): 433–8.

Buxmann H, Stackelberg OM, Schlößer RL et al. Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J Perinat Med. 2012; 40(4): 439–46.

Cho FN, Chen SN, Kan YY et al. Successful management of a pregnant woman with HELLP syndrome, pulmonary edema, postpartum hemorrhage and acute renal failure, using early hemodialysis, intravenous immunoglobulin and noninvasive monitoring: a case report. J Reprod Med. 2007; 52(7): 661–3.

Coulam CB, Acacio B Does immunotherapy for treatment of reproductive failure enhance live births? Am J Reprod Immunol. 2012 Apr; 67(4): 296–304.

De Zwaan SE, Iland HJ, Damian DL Treatment of refractory pyoderma gangrenosum with intravenous immunoglobulin. Australas J Dermatol. 2009; 50(1): 56–9.

Echols KT, Gilles JM, Diro M Mycosis fungoides in pregnancy: remission after treatment with alpha-interferon in a case refractory to conventional therapy: a case report. J Matern Fetal Med. 2001; 10(1): 68–70.

Elliott MA, Tefferi A Interferon-alpha therapy in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 1997; 23(5): 463–72.

Erfurt-Berge C, Herbst C, Schuler G, Bauerschmitz J Successful treatment of pyoderma gangrenosum with intravenous immunoglobulins during pregnancy J Cutan Med Surg. 2012; 16(3): 205–7.

Ferrari VD, Jirillo A, Lonardi F, Pavanato G, Bonciarelli G Pregnancy during alpha-interferon therapy in patients with advanced Hodgkin’s disease. Eur J Cancer. 1995; 31A(12): 2121–2.

Fu B, Li X, Sun R et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A. 2013; 110(3): E231–40.

Gomberg MA Combined treatment of persisting urogenital chlamydia infection with sumamed and interferon alfa] Antibiot Khimioter. 2002; 47(5): 12–5.

Gómez-Puerta JA, Espinosa G, Cervera R Catastrophic antiphospholipid syndrome: diagnosis and management in pregnancy. Clin Lab Med. 2013; 33(2): 391–400.

Gonik B Passive immunization: the forgotten arm of immunologically based strategies for disease containment. Am J Obstet Gynecol. 2011; 205(5): 444.e1–6.

Gonzalez-Granado LI Subcutaneous treatment for common variable immunodeficiency in pregnant women Ceska Gynekol. 2010; 75(2): 159.

Gotić M, Cvetković M, Bozanović T, Cemerikić V Successful treatment of primary myelofibrosis with thrombocytosis during pregnancy with alfa-interferon Srp Arh Celok Lek. 2001;129(11-12):304-8.

Hansen S, Gardulf A, Andersson E et al. Women with primary antibody deficiencies requiring IgG replacement therapy: their perception of prenatal care during pregnancy. J Obstet Gynecol Neonatal Nurs. 2004; 33(5): 604–9.

Heilmann L, Schorsch M, Hahn T CD3-CD56+CD16+ natural killer cells and improvement of pregnancy outcome in IVF/ICSI failure after additional IVIG-treatment. Am J Reprod Immunol. 2010; 63(3): 263–5.

Hellwig K, Beste C, Schimrigk S, Chan A Immunomodulation and postpartum relapses in patients with multiple sclerosis. Ther Adv Neurol Disord. 2009; 2(1): 7–11.

Hot A, Perard L, Coppere B, Simon M, Bouhour F, Ninet J Marked improvement of Churg-Strauss vasculitis with intravenous gamma globulins during pregnancy Clin Rheumatol. 2007; 26(12): 2149–51.

Inocêncio G, Coutinho L, Buchner G, Zulmira R Idiopathic thrombocytopenic purpura during pregnancy. BMJ Case Rep. 2013; 2013.

Isojima S, Hisano M, Suzuki T et al. Early plasmapheresis followed by high-dose γ-globulin treatment saved a severely Rho-incompatible pregnancy J Clin Apher. 2011; 26(4): 216–8.

Izdes S, Altintas ND et al. Intravenous polyclonal IgM-enriched immunoglobulin therapy for resistant Acinetobacter sepsis in a pregnant patient with ARDS due to H1N1 infection. Int J Obstet Anesth. 2011; 20(1): 99–100.

Karabay O, Leblebicioglu H Interferon-beta, prednisolone and lamivudine combination in acute exacerbation of chronic hepatitis b during pregnancy. Hepatol Res. 2013 May 2. [Epub ahead of print].

Kim SY, Linton JM, Kolasinski SL Successful treatment of new onset Wegener’s granulomatosis with IVIG (intravenous immunoglobulin) during pregnancy: a case report Mod Rheumatol. 2008; 18(2): 177–80.

Koh M, Shinohara J, Hongo Y et al. Case treated with triple therapy of lamivudine, interferon-β and prednisolone for acute exacerbation of chronic hepatitis B during pregnancy. Hepatol Res. 2013 Apr; 43(4): 425–9.

Kopeć I, Debski R, Samsel M, Winter W, Maryniak R, Prochorec M, Podstawka U Hairy cell leukemia in pregnancy Ginekol Pol. 2005; 76(11): 898–901.

Labarga P, Pinilla J, Cachorro I, Ruiz Y Infant of 22 months of age with no anomalies born from a HCV- and HIV-infected mother under treatment with pegylated interferon, ribavirin and antiretroviral therapy during the first 16 weeks of pregnancy. Reprod Toxicol. 2007; 24(3-4): 414–6.

Linardaki G, Cherouvim E, Goni G, Boki KA Intravenous immunoglobulin treatment for pregnancy-associated dermatomyositis Rheumatol Int. 2011; 31(1): 113–5.

Lobovská A, Pardon J, Honzáková E The first hyperimmune immunoglobulin against cytomegaloviruses made in the Czech Republic Cas Lek Cesk. 1993; 132(17): 532–4.

Moraru M, Carbone J, Alecsandru D, Castillo-Rama M 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.

Moxley K, Knudtson EJ Resolution of hydrops secondary to cytomegalovirus after maternal and fetal treatment with human cytomegalovirus hyperimmune globulin. Obstet Gynecol. 2008; 111(2 Pt 2): 524–6.

Nicholl MC Successful pregnancy outcome with the use of antenatal high-dose intravenous immunoglobulin following previous neonatal death associated with neonatal haemochromatosis Aust N Z J Obstet Gynaecol. 2010; 50(4): 403–5.

Nigro G, Adler SP, La Torre R, Best AM Congenital Cytomegalovirus Collaborating Group. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med. 2005 Sep 29; 353(13): 1350–62.

Nozaki Y, Ikoma S, Funauchi M, Kinoshita K Respiratory muscle weakness with dermatomyositis during pregnancy: successful treatment with intravenousimmunoglobulin therapy J Rheumatol. 2008; 35(11): 2289.

Okwundu CI, Afolabi BB Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy Cochrane Database Syst Rev. 2013; 1:CD007885.

Onyango-Makumbi C, Omer SB, Mubiru M Safety and efficacy of HIV hyperimmune globulin for prevention of mother-to-child HIV transmission in HIV-1-infected pregnant women and their infants in Kampala, Uganda (HIVIGLOB/NVP STUDY). J Acquir Immune Defic Syndr. 2011; 58(4): 399–407.

Palmeira P, Costa-Carvalho BT, Arslanian C et al. Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin Pediatr Allergy Immunol. 2009 Sep; 20(6): 528–35.

Parez N, Dommergues M, Zupan V, Chambost H Severe congenital dyserythropoietic anaemia type I: prenatal management, transfusion support and alpha-interferon therapy. Br J Haematol. 2000; 110(2): 420–3.

Paupe A, Duclos B, Leroy B, Molho M Prenatal treatment of neonatal hemochromatosis with maternal administration of intravenous immunoglobulins (about four cases). Gynecol Obstet Fertil. 2011; 39(7-8): 418–24.

Perricone R, De Carolis C, Giacomelli R et al. GM-CSF and pregnancy: evidence of significantly reduced blood concentrations in unexplained recurrent abortion efficiently reverted by intravenous immunoglobulin treatment. Am J Reprod Immunol. 2003 Sep; 50(3): 232–7.

Petersen EE, Neumann-Haefelin D, Heussler M Rubella in pregnancy: experimental studies on the value of gamma-globulin after rubella wild virus infection Dtsch Med Wochenschr. 1978; 103(43): 1695–700.

Piper JM, Wen TT, Xenakis EM Interferon therapy in primary care. Prim Care Update Ob Gyns.; 8(4): 163–169.

Polilli E, Parruti G, D’Arcangelo F et al. Preliminary evaluation of the safety and efficacy of standard intravenous immunoglobulins in pregnant women with primary cytomegalovirus infection. Clin Vaccine Immunol. 2012; 19(12): 1991–3.

Pons JC, Lebon P, Frydman R, Delfraissy JF Pharmacokinetics of interferon-alpha in pregnant women and fetoplacental passage. Fetal Diagn Ther. 1995; 10(1): 7–10.

Pourrat O, Ducroz B, Magnin G Intravenous immunoglobulins in postpartum, persistently severe HELLP syndrome: a safe alternative to plasma exchange? Am J Obstet Gynecol. 1992; 166(2): 766.

Rodrigues Cdos S, Filipe P et al. Persistent herpes gestationis treated with high-dose intravenous immunoglobulin. Acta Derm Venereol. 2007; 87(2): 184–6.

Ruffatti A, Marson P, Svaluto-Moreolo G et al. A combination therapy protocol of plasmapheresis, intravenous immunoglobulins and betamethasone to treat anti-

Ro/La-related congenital atrioventricular block. A case series and review of the literature. 2013; 12(7): 768–73.

Ruffatti A, Milanesi O, Chiandetti L, Cerutti A, Gervasi MT, De Silvestro G, Pengo V, Punzi L A combination therapy to treat second-degree anti-Ro/La-related congenital heart block: a strategy to avoid stable third-degree heart block? Lupus. 2012; 21(6): 666–71.

Ruiz-Villaverde R, Sánchez-Cano D, Ramirez-Tortosa CL Pemphigoid gestationis: therapeutic response to pre- and postpartum immunoglobulin therapy Actas Dermosifiliogr. 2011; 102(9): 735–7

Sandberg-Wollheim M, Alteri E, Moraga MS, Kornmann G Pregnancy outcomes in multiple sclerosis following subcutaneous interferon beta-1a therapy. Mult Scler. 2011 Apr; 17(4): 423–30.

Santjohanser C, Knieper C, Franz C et al. Granulocyte-colony stimulating factor as treatment option in patients with recurrent miscarriage. Arch Immunol Ther Exp (Warsz). 2013; 61(2): 159–64.

Shimada S, Takeda M, Nishihira J et al. A high dose of intravenous immunoglobulin increases CD94 expression on natural killer cells in women with recurrent spontaneous abortion Am J Reprod Immunol. 2009; 62(5): 301–7.

Sieunarine K, Shapiro S, Al Obaidi M, Girling J Intravenous anti-D immunoglobulin in the treatment of resistant immune thrombocytopenic purpura inpregnancy. BJOG. 2007; 114(4): 505–7.

Spivak NIa, Grabchenko NI, Lazarenko LN et al. The antibacterial efficacy of preparations of interferon and its inducers. Mikrobiol Z. 1999; 61(1): 32–45.

Tareeva TG, Malinovskaia VV, Poletaev AB Autoimmune disorders in pregnant women with mixed urogenital infections. Interferon therapy in prophylaxis of obstetric and perinatal complications Antibiot Khimioter. 2000; 45(12): 23–4.

Sun XG, Liu XY, Zhu R et al. Effectiveness of intravenous immunoglobulin therapy in treating unexplained recurrent spontaneous abortion and its effect on the level of serum soluble human leucocyte antigen G Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2010; 32(5): 483–7.

Van den Heuvel Mj, Peralta CG, Hatta K et al. Decline in number of elevated blood CD3(+) CD56(+) NKT cells in response to intravenous immunoglobulin treatment correlates with successful pregnancy Am J Reprod Immunol. 2007; 58(5): 447–59.

Virro MR, Winger EE, Reed JL Intravenous immunoglobulin for repeated IVF failure and unexplained infertility. Am J Reprod Immunol. 2012; 68(3): 218–25.

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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.

Winger EE, Reed JL, Ashoush S et al. Elevated preconception CD56+ 16+ and/or Th1:Th2 levels predict benefit from IVIG therapy in subfertile women undergoing IVF Am J Reprod Immunol. 2011 Nov; 66(5): 394–40

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GOST Style Citations


Мальцев Д.В., Недопако Я.Я. Дефіцит природних кілерів: гетерогенність, клініка, діагностика, лікування, клінічні приклади // Український медичний часопис. – 2013. – № 2(94). – С. 129–142.

Ahmed AR, Gürcan HM Use of intravenous immunoglobulin therapy during pregnancy in patients with pemphigus vulgaris J Eur Acad Dermatol Venereol. 2011;25(9):1073–9.

Al-Rawi S, Woodward LJ, Knight J Puerperal streptococcal toxic shock syndrome treated with recombinant human activated protein C and intravenous immunoglobulin Int J Obstet Anesth. 2009; 18(2): 169–72.

Bahadur A, Gupta N, Deka D, Mittal S Successful maternal and fetal outcome of Guillain-Barré syndrome complicating pregnancy Indian J Med Sci. 2009; 63(11): 517–8.

Branch DW, Peaceman AM, Druzin M et al. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Am J Obstet Gynecol. 2000; 182(1 Pt 1): 122–7.

Buxmann H, Kamin W, Kriván G et al. An open-label, randomized efficacy and safety trial of subcutaneous and intramuscular BT088 (Fovepta) human hepatitis B immunoglobulin in neonates of HBV-carrier mothers. J Perinat Med. 2012; 40(4): 433–8.

Buxmann H, Stackelberg OM, Schlößer RL et al. Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J Perinat Med. 2012; 40(4): 439–46.

Cho FN, Chen SN, Kan YY et al. Successful management of a pregnant woman with HELLP syndrome, pulmonary edema, postpartum hemorrhage and acute renal failure, using early hemodialysis, intravenous immunoglobulin and noninvasive monitoring: a case report. J Reprod Med. 2007; 52(7): 661–3.

Coulam CB, Acacio B Does immunotherapy for treatment of reproductive failure enhance live births? Am J Reprod Immunol. 2012 Apr; 67(4): 296–304.

De Zwaan SE, Iland HJ, Damian DL Treatment of refractory pyoderma gangrenosum with intravenous immunoglobulin. Australas J Dermatol. 2009; 50(1): 56–9.

Echols KT, Gilles JM, Diro M Mycosis fungoides in pregnancy: remission after treatment with alpha-interferon in a case refractory to conventional therapy: a case report. J Matern Fetal Med. 2001; 10(1): 68–70.

Elliott MA, Tefferi A Interferon-alpha therapy in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 1997; 23(5): 463–72.

Erfurt-Berge C, Herbst C, Schuler G, Bauerschmitz J Successful treatment of pyoderma gangrenosum with intravenous immunoglobulins during pregnancy J Cutan Med Surg. 2012; 16(3): 205–7.

Ferrari VD, Jirillo A, Lonardi F, Pavanato G, Bonciarelli G Pregnancy during alpha-interferon therapy in patients with advanced Hodgkin’s disease. Eur J Cancer. 1995; 31A(12): 2121–2.

Fu B, Li X, Sun R et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A. 2013; 110(3): E231–40.

Gomberg MA Combined treatment of persisting urogenital chlamydia infection with sumamed and interferon alfa] Antibiot Khimioter. 2002; 47(5): 12–5.

Gómez-Puerta JA, Espinosa G, Cervera R Catastrophic antiphospholipid syndrome: diagnosis and management in pregnancy. Clin Lab Med. 2013; 33(2): 391–400.

Gonik B Passive immunization: the forgotten arm of immunologically based strategies for disease containment. Am J Obstet Gynecol. 2011; 205(5): 444.e1–6.

Gonzalez-Granado LI Subcutaneous treatment for common variable immunodeficiency in pregnant women Ceska Gynekol. 2010; 75(2): 159.

Gotić M, Cvetković M, Bozanović T, Cemerikić V Successful treatment of primary myelofibrosis with thrombocytosis during pregnancy with alfa-interferon Srp Arh Celok Lek. 2001;129(11-12):304-8.

Hansen S, Gardulf A, Andersson E et al. Women with primary antibody deficiencies requiring IgG replacement therapy: their perception of prenatal care during pregnancy. J Obstet Gynecol Neonatal Nurs. 2004; 33(5): 604–9.

Heilmann L, Schorsch M, Hahn T CD3-CD56+CD16+ natural killer cells and improvement of pregnancy outcome in IVF/ICSI failure after additional IVIG-treatment. Am J Reprod Immunol. 2010; 63(3): 263–5.

Hellwig K, Beste C, Schimrigk S, Chan A Immunomodulation and postpartum relapses in patients with multiple sclerosis. Ther Adv Neurol Disord. 2009; 2(1): 7–11.

Hot A, Perard L, Coppere B, Simon M, Bouhour F, Ninet J Marked improvement of Churg-Strauss vasculitis with intravenous gamma globulins during pregnancy Clin Rheumatol. 2007; 26(12): 2149–51.

Inocêncio G, Coutinho L, Buchner G, Zulmira R Idiopathic thrombocytopenic purpura during pregnancy. BMJ Case Rep. 2013; 2013.

Isojima S, Hisano M, Suzuki T et al. Early plasmapheresis followed by high-dose γ-globulin treatment saved a severely Rho-incompatible pregnancy J Clin Apher. 2011; 26(4): 216–8.

Izdes S, Altintas ND et al. Intravenous polyclonal IgM-enriched immunoglobulin therapy for resistant Acinetobacter sepsis in a pregnant patient with ARDS due to H1N1 infection. Int J Obstet Anesth. 2011; 20(1): 99–100.

Karabay O, Leblebicioglu H Interferon-beta, prednisolone and lamivudine combination in acute exacerbation of chronic hepatitis b during pregnancy. Hepatol Res. 2013 May 2. [Epub ahead of print].

Kim SY, Linton JM, Kolasinski SL Successful treatment of new onset Wegener’s granulomatosis with IVIG (intravenous immunoglobulin) during pregnancy: a case report Mod Rheumatol. 2008; 18(2): 177–80.

Koh M, Shinohara J, Hongo Y et al. Case treated with triple therapy of lamivudine, interferon-β and prednisolone for acute exacerbation of chronic hepatitis B during pregnancy. Hepatol Res. 2013 Apr; 43(4): 425–9.

Kopeć I, Debski R, Samsel M, Winter W, Maryniak R, Prochorec M, Podstawka U Hairy cell leukemia in pregnancy Ginekol Pol. 2005; 76(11): 898–901.

Labarga P, Pinilla J, Cachorro I, Ruiz Y Infant of 22 months of age with no anomalies born from a HCV- and HIV-infected mother under treatment with pegylated interferon, ribavirin and antiretroviral therapy during the first 16 weeks of pregnancy. Reprod Toxicol. 2007; 24(3-4): 414–6.

Linardaki G, Cherouvim E, Goni G, Boki KA Intravenous immunoglobulin treatment for pregnancy-associated dermatomyositis Rheumatol Int. 2011; 31(1): 113–5.

Lobovská A, Pardon J, Honzáková E The first hyperimmune immunoglobulin against cytomegaloviruses made in the Czech Republic Cas Lek Cesk. 1993; 132(17): 532–4.

Moraru M, Carbone J, Alecsandru D, Castillo-Rama M 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.

Moxley K, Knudtson EJ Resolution of hydrops secondary to cytomegalovirus after maternal and fetal treatment with human cytomegalovirus hyperimmune globulin. Obstet Gynecol. 2008; 111(2 Pt 2): 524–6.

Nicholl MC Successful pregnancy outcome with the use of antenatal high-dose intravenous immunoglobulin following previous neonatal death associated with neonatal haemochromatosis Aust N Z J Obstet Gynaecol. 2010; 50(4): 403–5.

Nigro G, Adler SP, La Torre R, Best AM Congenital Cytomegalovirus Collaborating Group. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med. 2005 Sep 29; 353(13): 1350–62.

Nozaki Y, Ikoma S, Funauchi M, Kinoshita K Respiratory muscle weakness with dermatomyositis during pregnancy: successful treatment with intravenousimmunoglobulin therapy J Rheumatol. 2008; 35(11): 2289.

Okwundu CI, Afolabi BB Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy Cochrane Database Syst Rev. 2013; 1:CD007885.

Onyango-Makumbi C, Omer SB, Mubiru M Safety and efficacy of HIV hyperimmune globulin for prevention of mother-to-child HIV transmission in HIV-1-infected pregnant women and their infants in Kampala, Uganda (HIVIGLOB/NVP STUDY). J Acquir Immune Defic Syndr. 2011; 58(4): 399–407.

Palmeira P, Costa-Carvalho BT, Arslanian C et al. Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin Pediatr Allergy Immunol. 2009 Sep; 20(6): 528–35.

Parez N, Dommergues M, Zupan V, Chambost H Severe congenital dyserythropoietic anaemia type I: prenatal management, transfusion support and alpha-interferon therapy. Br J Haematol. 2000; 110(2): 420–3.

Paupe A, Duclos B, Leroy B, Molho M Prenatal treatment of neonatal hemochromatosis with maternal administration of intravenous immunoglobulins (about four cases). Gynecol Obstet Fertil. 2011; 39(7-8): 418–24.

Perricone R, De Carolis C, Giacomelli R et al. GM-CSF and pregnancy: evidence of significantly reduced blood concentrations in unexplained recurrent abortion efficiently reverted by intravenous immunoglobulin treatment. Am J Reprod Immunol. 2003 Sep; 50(3): 232–7.

Petersen EE, Neumann-Haefelin D, Heussler M Rubella in pregnancy: experimental studies on the value of gamma-globulin after rubella wild virus infection Dtsch Med Wochenschr. 1978; 103(43): 1695–700.

Piper JM, Wen TT, Xenakis EM Interferon therapy in primary care. Prim Care Update Ob Gyns.; 8(4): 163–169.

Polilli E, Parruti G, D’Arcangelo F et al. Preliminary evaluation of the safety and efficacy of standard intravenous immunoglobulins in pregnant women with primary cytomegalovirus infection. Clin Vaccine Immunol. 2012; 19(12): 1991–3.

Pons JC, Lebon P, Frydman R, Delfraissy JF Pharmacokinetics of interferon-alpha in pregnant women and fetoplacental passage. Fetal Diagn Ther. 1995; 10(1): 7–10.

Pourrat O, Ducroz B, Magnin G Intravenous immunoglobulins in postpartum, persistently severe HELLP syndrome: a safe alternative to plasma exchange? Am J Obstet Gynecol. 1992; 166(2): 766.

Rodrigues Cdos S, Filipe P et al. Persistent herpes gestationis treated with high-dose intravenous immunoglobulin. Acta Derm Venereol. 2007; 87(2): 184–6.

Ruffatti A, Marson P, Svaluto-Moreolo G et al. A combination therapy protocol of plasmapheresis, intravenous immunoglobulins and betamethasone to treat anti-

Ro/La-related congenital atrioventricular block. A case series and review of the literature. 2013; 12(7): 768–73.

Ruffatti A, Milanesi O, Chiandetti L, Cerutti A, Gervasi MT, De Silvestro G, Pengo V, Punzi L A combination therapy to treat second-degree anti-Ro/La-related congenital heart block: a strategy to avoid stable third-degree heart block? Lupus. 2012; 21(6): 666–71.

Ruiz-Villaverde R, Sánchez-Cano D, Ramirez-Tortosa CL Pemphigoid gestationis: therapeutic response to pre- and postpartum immunoglobulin therapy Actas Dermosifiliogr. 2011; 102(9): 735–7

Sandberg-Wollheim M, Alteri E, Moraga MS, Kornmann G Pregnancy outcomes in multiple sclerosis following subcutaneous interferon beta-1a therapy. Mult Scler. 2011 Apr; 17(4): 423–30.

Santjohanser C, Knieper C, Franz C et al. Granulocyte-colony stimulating factor as treatment option in patients with recurrent miscarriage. Arch Immunol Ther Exp (Warsz). 2013; 61(2): 159–64.

Shimada S, Takeda M, Nishihira J et al. A high dose of intravenous immunoglobulin increases CD94 expression on natural killer cells in women with recurrent spontaneous abortion Am J Reprod Immunol. 2009; 62(5): 301–7.

Sieunarine K, Shapiro S, Al Obaidi M, Girling J Intravenous anti-D immunoglobulin in the treatment of resistant immune thrombocytopenic purpura inpregnancy. BJOG. 2007; 114(4): 505–7.

Spivak NIa, Grabchenko NI, Lazarenko LN et al. The antibacterial efficacy of preparations of interferon and its inducers. Mikrobiol Z. 1999; 61(1): 32–45.

Tareeva TG, Malinovskaia VV, Poletaev AB Autoimmune disorders in pregnant women with mixed urogenital infections. Interferon therapy in prophylaxis of obstetric and perinatal complications Antibiot Khimioter. 2000; 45(12): 23–4.

Sun XG, Liu XY, Zhu R et al. Effectiveness of intravenous immunoglobulin therapy in treating unexplained recurrent spontaneous abortion and its effect on the level of serum soluble human leucocyte antigen G Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2010; 32(5): 483–7.

Van den Heuvel Mj, Peralta CG, Hatta K et al. Decline in number of elevated blood CD3(+) CD56(+) NKT cells in response to intravenous immunoglobulin treatment correlates with successful pregnancy Am J Reprod Immunol. 2007; 58(5): 447–59.

Virro MR, Winger EE, Reed JL Intravenous immunoglobulin for repeated IVF failure and unexplained infertility. Am J Reprod Immunol. 2012; 68(3): 218–25.

Wang FY, Lin P, Zhang HZ A randomized controlled trial on effect of hepatitis B immune globulin in preventing hepatitis B virus transmission from mothers to infants Zhonghua Er Ke Za Zhi. 2008; 46(1): 61–3.

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.

Winger EE, Reed JL, Ashoush S et al. Elevated preconception CD56+ 16+ and/or Th1:Th2 levels predict benefit from IVIG therapy in subfertile women undergoing IVF Am J Reprod Immunol. 2011 Nov; 66(5): 394–40

Winger EE, Reed JL, Ashoush S et al. Treatment with adalimumab (Humira) and intravenous immunoglobulin improves pregnancy rates in women undergoing IVF. Am J Reprod Immunol. 2009; 61(2): 113–20.

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