Journal of Reproductive Immunology
Volume 85, Issue 1 , Pages 15-24 , May 2010

Anti-TNFα therapy in immune-mediated subfertility: State of the art

  • David A. Clark

      Affiliations

    • Corresponding Author InformationTel.: +1 905 521 2100x76443; fax: +1 905 521 4971.

Received 21 August 2009 ,Revised 4 December 2009 ,Accepted 14 January 2010.

References 

  1. Allessandri C, Scrivo R, Spinelli FR, Ceccarelli F, Magrini L, et al. Autoantibody production in anti-TNFα-treated patients. Ann. N. Y. Acad. Sci. 2007;1110:319–329
  2. Andalib A, Rezaie A, Oreizy F, Shafiei K, Baluchi S. A study on stress, depression and NK cytotoxic potential in women with recurrent spontaneous abortion. Iranian J. Allergy Asthma Immunol. 2006;5:9–16
  3. Arck PC, Rose M, Hertwig K, Hagen E, Hildebrandt M, Klapp BF. Stress and immune mediators in miscarriage. Hum. Reprod. 2001;16:1505–1551
  4. Arck PC, Rucke M, Rose M, Szekeres-Bartho J, Douglas AJ, Pritsch M, et al. Early risk factors for miscarriage: a prospective cohort study in pregnant women. Reprod. Biomed. Online. 2008;17:101–113
  5. Bayry J, Siberil S, Triebel F, Tough DF, Kaveri SV. Rescuring CD4+CD25+ regulatory T cell functions in rheumatoid arthritis by cytokine-targeted monoclonal antibody therapy. Drug Discov. Today. 2007;12:548–552
  6. Benson K, Hartz AJ. A comparison of observational studies and randomized controlled trials. N. Engl. J. Med. 2000;342:1878–1886
  7. Boomsma CM, Kavelaars A, Eijkemans MJC, Lentjes EG, Fauser BCJM, et al. Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF. Hum. Reprod. 2009;34:1427–1435
  8. Carp HJA. Abstracts of Contributors’ individual data submitted to the worldwide prospective observation study on immunotherapy of treatment of recurrent spontaneous abortion. Am. J. Reprod. Immunol. 1994;32:271–273
  9. Carter J, Ladhani A, Ricca LR, Valeriano J, Vaset FB. A safety assessment of TNF antagonists during pregnancy: a review of the FDA database. J. Rheumatol. 2009;36:635–641
  10. Chaouat G. Should we re-examine the status of lymphocyte alloimmunization therapy for recurrent spontaneous abortion? Am. J. Reprod. Immunol. 2003;50:433–438
  11. Chaouat G, Assal-Meliani A, Martal J, Raghupathy R, Elliot JF, Mosmann T, et al. IL-10 prevents naturally occurring fetal loss in the CBA x DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFNtau. J. Immunol. 1995;154:4261–4268
  12. Clark DA. Is there any evidence for immunologically mediated or immunologically modifiable early pregnancy failure?. J. Assist. Reprod. Genet. 2003;20:63–72
  13. Clark DA. Shall we properly re-examine the status of allogeneic lymphocyte immunotherapy for recurrent early pregnancy failure?. Am. J. Reprod. Immunol. 2004;51:7–15
  14. Clark DA. Is paternal leukocyte immunotherapy indicated?. In:  Carp HJA editors. Recurrent Pregnancy Loss. Oxon, UK: Informa Health Care; 2007;p. 179–184
  15. Clark DA. Immunological factors in pregnancy wastage: fact or fiction. Am. J. Reprod. Immunol. 2008;59:277–300
  16. Clark DA. Should anti-TNFα therapy be offered to patients with infertility and recurrent spontaneous abortion?. Am. J. Reprod. Immunol. 2009;61:107–112
  17. Clark DA, Croitoru K. Th1/Th2/3 imbalance due to cytokine-producing NK, γδT and NK-γδT cells in murine pregnancy decidua in success or failure of pregnancy. Am. J. Reprod. Immunol. 2001;45:257–265
  18. Clark DA, Daya S, Coulam CB, Gunby J, RMIT G. Implications of trophoblast karyotype in the evidence-based approach to the understanding, investigation, and treatment of recurrent spontaneous abortion. Am. J. Reprod. Immunol. 1996;35:495–498
  19. Clark DA, Gunby J, Daya S. The use of allogeneic leukocytes or IV IgG for the treatment of patients with recurrent spontaneous abortions. Transfus. Med. Rev. 1997;11:85–94
  20. Clark DA, Coulam CB, Stricker RB. Is intravenous immunogloblulins (IVIG) efficacious in early pregnancy failure? A critical review and meta-analysis for patients who fail in vitro fertilization and embryo transfer (IVF). J. Assist. Reprod. Genet. 2006;23:1–13
  21. Clark DA, Yu G, Arck PC, Levy GA, Gorczynski RM. MD-1 is a critical part of the mechanism causing Th-1 cytokine-triggered murine fetal loss syndrome. Am. J. Reprod. Immunol. 2003;49:297–307
  22. Clark DA, Coulam CB, Daya S, Chaouat G. Unexplained sporadic and recurrent miscarriage in the new millennium: a critical analysis of immune mechanisms and treatments. Hum. Reprod. Update. 2001;7:501–511
  23. Collins JA, Wrixon W, Janes LB, Wilson EH. Treatment-independent pregnancy among infertile couples. N. Engl. J. Med. 1983;309:1201–1206
  24. Concato J, Shaw H, Horowitz RE. Randomized controlled trials, observational studies, and hierarchy of research designs. N. Engl. J. Med. 2000;342:1877–1892
  25. Coulam CB, Roussev R. Correlation of NK cell activation and inhibition markers with NK cytotoxicity among women experiencing immunological implantation failure after in vitro fertilization and embryo transfer. J. Assist. Reprod. Genet. 2003;20:58–62
  26. Coulam CB, Roussev RG. Increasing circulating T-cell activation markers are linked to subsequent implantation failure after transfer of in vitro fertilized embryos. Am. J. Reprod. Immunol. 2003;50:340–345
  27. Coulam CB, Stephenson M, Stern JJ, Clark DA. Immunotherapy for recurrent pregnancy loss: analysis of results from clinical trials. Am. J. Reprod. Immunol. 1996;35:352–359
  28. Engel SH, Hullar TE, Adkins DR, Thorstad WL, Sunwoo JB. Temporal relationship between antitumor necrosis factor-α antibody therapy and recrudescence of head and neck squamous cell carcinoma. Laryngoscope. 2008;118:450–452
  29. Fromont A, De Seze J, Fleury MC, Maillefert JF, Moreau T. Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine. 2009;45:55–57
  30. Fukui A, Kwak-Kim J, Ntrivalas R, Gilman-Sachs A, Lee SK, Beaman K. Intracellular cytokine expression of peripheral blood natural killer cell subsets in women with recurrent spontaneous abortions and implantation failure. Fertil. Steril. 2008;89:157–165
  31. Girardi G. Guilty as charged: all available evidence implicates complement's role in fetal demise. Am. J. Reprod. Immunol. 2008;59:183–192
  32. Girardi G, Yarilin D, Thurman JM, Holers VM, Salmon JE. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J. Exp. Med. 2006;203:2165–2175
  33. Greenwold N, Jauniaux E. Collection of villus tissue under ultrasound guidance to improve cytogenetic study of early pregnancy failure. Hum. Reprod. 2002;17:452–456
  34. Guyatt GH, Cook DJ, Jaeshke R, Pauker SG, Schunemann HJ. Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;136(6 (Suppl.)):123S–132S
  35. Horton R. The rhetoric of research. BMJ. 1995;310:985–987
  36. Horton R. The hidden research paper. J. Am. Med. Assoc. 2002;287:2775–2778
  37. Ioannidis JPA, Haidich A-B, Pappa M, Pantazis N, Kokori SI, Tektonidou MG, et al. Comparison of evidence of treatment effects in randomized and nonrandomized studies. JAMA. 2001;286:821–830
  38. Kieszko R, Krawczyk P, Chocholska S, Bojarska-Junak A, Krol A, Rolinski J, et al. Tumor necrosis factor receptors (TNFRs) on T lymphocytes and soluble TNFRs in different clinical courses of sarcoidosis. Respiratory Medicine. 2007;101:645–680
  39. Knackstedt M, Ding JW, Arck PC, Hertwig K, Coulam CB, August C, et al. Activation of the novel prothrombinase, fgl2, as a basis for the pregnancy complications spontaneous abortion and pre-eclampsia. Am. J. Reprod. Immunol. 2001;46:196–210
  40. Kruse C, Varming K, Christiansen OB. Prospective, serial investigations of in-vitro lymphocyte cytokine production, CD62L expression and proliferative response to microbial antigens in women with recurrent miscarriage. Hum. Reprod. 2003;18:2465–2472
  41. Kwak-Kim JY, Chung-Bang HS, Ng SC, Ntrivales EI, Mangubat CP, Beaman KD, et al. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum. Reprod. 2003;18:767–773
  42. Koren G, Inoue M. Do tumor necrosis factor inhibitors cause malformations in humans?. J. Rheumatol. 2009;36:465–466
  43. Kuriya, B., 2008. Safety of anti-TNFα agents during pregnancy. http://www.rheumatology.utoronto.ca/Assets/Rounds/ICC+April+8th$!2c+2008.pdf.
  44. Laudenslager ML, Aasal R, Adler L, Berger CL, Montgomery PT, et al. Elevated cytotoxicity in combat veterans with long-term post-traumatic stress disorder: preliminary observations. Brain Behav. Immun. 1998;12:74–79
  45. Lidz CW, Appelbaum PS, Joffe S, Albert J, Rosenbaum J, Simon L. Competing commitments in clinical trials. IRB: Ethics Hum. Res. 2009;31:1–6
  46. Lozeron P, Denier C, Lacroix C, Adams D. Long-term course of demyelinating neuropathies occurring during tumor necrosis factor-α blockade. Arch. Neurol. 2009;66:490–497
  47. Mangubat CP, Thaker PP, Cavalcante M, Kwak-Kim JYH, Beer AE. Etanercept and immune treatment in multiple IVF failures. Am. J. Reprod. Immunol. 2001;45:345–346
  48. Medawar PB. Advice to a Young Scientist. New York, NY, USA: Harper & Row; 1979;
  49. Montori VM, Jaeschke R, Schunemann HJ, Bhandari M, Brozek JL, Devereaux PJ, et al. Users’ guide to detecting misleading claims in clinical research reports. BMJ. 2004;329:1093–1096
  50. Mueller-Eckhardt G, Mallmann P, Neppert J, Lattermann A, Melk A, Heine O, et al. Immunogenetic and serological investigations in nonpregnant and in pregnant women with a history of recurrent spontaneous abortions. J. Reprod. Immunol. 1994;27:95–109
  51. Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA. Interferon gamma in successful pregnancies. Biol. Reprod. 2009;80:848–859
  52. Nadkarni S, Mauri C, Ehrenstein MR. Anti-TNFα therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-β. N. Engl. J. Med. 2007;204:33–39
  53. Nagaeva O, Jonsson L, Mincheva-Nilsson L. Dominant IL-10 and TGF-β mRNA expression in γδT cells of human early pregnancy decidua suggests immunoregulatory potential. Am. J. Reprod. Immunol. 2002;48:9–17
  54. Nisashima A, Shiozaki A, Myojo S, Ito M, Tatematsu M, Sakai M, et al. Granulysin produced by uterine natural killer cells induces apoptosis of extravillous trophoblasts during spontaneous abortion. Am. J. Pathol. 2008;173:653–664
  55. Ottenbacher K. Impact of random assignment on study outcome: an empirical examination. Control. Clin. Trials. 1992;13:50–61
  56. Piccinni MP. T cells in pregnancy. Chem. Immunol. Allergy. 2005;89:3–9
  57. Redecha P, Tilley R, Tencati M, Salmon JE, Kirchhofer D, Mackman N, et al. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood. 2007;110:2423–2431
  58. Redecha P, Franzke CW, 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;118:3453–3461
  59. Redecha P, van Rooijen N, Torry D, Girardi G. Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury. Blood. 2009;113:4101–4109
  60. RMITG (Recurrent Miscarriage Immunotherapy Trialists Group) . Worldwide collaborative observational study and meta-analysis on allogeneic leukocyte immunotherapy for recurrent spontaneous abortion. Am. J. Reprod. Immunol. 1994;32:55–72
  61. Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Biomed. Cent. 2009;11(Suppl. 1):1–12
  62. Saad AA, Symmons DPM, Noyce PR, Ashcroft DM. Risks and benefits of tumor necrosis factor-α inhibitors in the management of psoriatic arthritis: systematic review and metaanalysis of randomized controlled trials. J. Rheumatol. 2008;35:883–890
  63. Scarpellini R, Sbracia M. Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomized controlled trial. Hum. Reprod. 2009;24:2703–2708
  64. Scarpellini R, Sbracia M, Patella A. G=CSF pharmacologic supplementation in the ART (assisted reproductive technologies) treatment cycles of low responder women. J. Reprod. Immunol. 2009;81:158–159
  65. Shakhar K, Rosenne E, Loenwentahl R, Rosenne E, Shakhar G, Carp H, et al. High NK activity in recurrent miscarriage: what are we really measuring?. Hum. Reprod. 2006;21:2421–2425
  66. Sheridan C. Small molecule challenges dominance of TNFα inhibitors. Nat. Biotechnol. 2008;26:143–144
  67. Silverman SL. From randomized trials to observational studies. Am. J. Med. 2009;122:114–120
  68. Straus S, Haynes S, Glasziou P, Dickerson K, Guyatt G. Misunderstandings, misperceptions, and mistakes. Evidence Based Med. 2007;12:2–3
  69. Stephenson MD, Kutteh W, Purkiss S, Librach C, Houlihan E, Schulz P. Intravenous immunoglobulin (IVIG) for treatment of idiopathic secondary recurrent miscarriage (ISRM): a prospective, randomized, double-blinded, placebo-controlled, multi-centered study. Fertil. Steril. 2009;92(Suppl.):S67–S68
  70. Tilburgs T, Roelen DL, ven der Mast BJ, de Groot-Swungs GM, Kleijburg C, Scherjon SA, et al. Evidence for selective migration of fetus-specific CD4+ CD25bright regulatory T cells from the peripheral blood to the decidua in human pregnancy. J. Immunol. 2008;180:5737–5745
  71. Torchinsky A, Shepshelovich J, Orenstein H, Zaslavsky Z, Savion S, Carp H, et al. TNFα protects embryos exposed to developmental toxicants. Am. J. Reprod. Immunol. 2003;49:159–168
  72. Tsiodras S, Samonis G, Boumpas DT, Kontoyiannis DP. Fungal infections complicating tumor necrosis factor alpha blockade therapy. Mayo Clin. Proc. 2008;83:181–194
  73. Vigna-Perez M, Abdul-Mendoza C, Portillo-Salazar H, Alvarado-Sanchez B, Cuevas-Orta E, Moreno-Valdes R, et al. Immune effects of therapy with adalimumab in patients with rheumatoid arthritis. Clin. Exp. Immunol. 2005;141:372–380
  74. Vist, G.E., Bryant, D., Somerville, L., Birmingham, T, Oxman, A.D., 2008. Outcome of patients who participate in randomized controlled trials compared to similar patients receiving similar interventions who do not participate. Cochrane Database Syst. Rev (3), MR000009 (update of Cochrane Database Syst. Rev. 2007;(2):MR000009, PMID: 17443630).
  75. Wegmann TG, Lin H, Guilbert L, Mossmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a Th2 phenomenon. Immunol. Today. 1993;14:353–356
  76. Williams GM. Antitumor necrosis factor-α therapy and potential cancer inhibition. Eur. J. Cancer Prev. 2008;17:169–177
  77. 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;60:8–16
  78. Winger EE, Reed J. Does “A safety assessment of TNF antagonists during pregnancy: a review of the Food and Drug Administration Database by Carter et al. properly asses risk?. J. Rheumatol. 2009;36:2112
  79. Winger EE, Reed J, Ashoush S, Sapna A, El-Roukhy T, Teranissi M. Treatment with adalimumab (Humira) and intravenous immunoglobulin (IVIG) improves pregnancy rates in women undergoing IVF. Am. J. Reprod. Immunol. 2009;61:113–120
  80. Winger EE, Rooed JL, Ashoush S, Jadhav J, Taranissi M. Degree of Th1/Th2 cytokine elevation predicts IVF success rates in women undergoing treatment with adalimumab (Humira) and intravenous immunoglobulin for immunological infertility. J. Reprod. Immunol. 2009;81:150
  81. Winger EE, Reed JL, Ashoush S, Jadhav J, Taranissi M. Birth defect rates in women using adalimumab (Humira) and intravenous immunoglobulin to treat immunologic-based infertility in IVF. J. Reprod. Immunol. 2009;81:169–170
  82. Yamada H, Morikawa M, Kato EH, Shimada S, Kobashi G, Minakami H. Preconceptional natural killer cell activity and percentage as predictors of biochemical pregnancy and spontaneous abortion with a normal karyotype. Am. J. Reprod. Immunol. 2003;50:351–354

☆ From an invited state-of-the art presentation at the European Society for Reproductive Immunology, Marathon, Greece, September 2009.

PII: S0165-0378(10)00043-4

doi: 10.1016/j.jri.2010.01.007

Journal of Reproductive Immunology
Volume 85, Issue 1 , Pages 15-24 , May 2010

Article Tools

* Image Usage & Resolution