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)

  • David A. ClarkEmail author
  • Carolyn B. Coulam
  • Raphael B. Stricker
Original Paper

Problem : Intravenous Immunoglobulins (IVIG) are widely used off label in the treatment of early reproductive failure. As IVIG is expensive, and may have side-effects, evidence of efficacy is needed. Previous results have suggested that the pre-conception treatment of primary recurrent abortion patients might be effective, but the data set has been too small for adequate statistical power. More recently it has been suggested that IVIG may improve the success rate of in vitro fertilization and embryo transfer (IVF) in patients with prior IVF failures, but clinical trials have given conflicting results that need explanation. Systematic reviews generating inconclusive results have focused on methodological rigor to the exclusion of biological plausibility.

Methods : Review of current basic science of design, measurement, and evaluation of clinical trials and basic science mechanisms providing a rationale for treatment. Meta-analysis of published randomized controlled and cohort-controlled trials (updated with two unpublished data sets) evaluating IVIG treatment in IVF failure patients. Live birth rate was used as the most relevant endpoint. The ability of different sources of IVIG to suppress natural killer (NK) cell activity was determined using a standard 51Cr-release assay in vitro.

Results and conclusions : Meta-analysis of three published randomized controlled trials (RCTs) of IVIG in IVF failure patients shows a significant increase in the live birth rate per woman (p = 0.012; Number Needed to Treat for 1 additional live birth, NNT = 6.0 women). Using live birth rate per embryo transferred, and adding data from two cohort-controlled trials to the meta-analysis further supports this conclusion (overall p = 0.000015, NNT = 3.7 women). Relevant variables appear to include properties and scheduling of the IVIG, and selection of patients with abnormal immune test results. Different IVIG preparations vary significantly in their ability to suppress NK activity in vitro. A rationale for use of IVIG is provided by a review of mechanisms of IVIG action and mechanisms underlying failure of chromosomally normal embryos.


Evidence-based medicine infertility IVIG meta-analysis 


  1. 1.
    Sewell WAC, Jolles S: Immunomodulatory action of intravenous immunoglobulins. Immunology 2002;107:387–393CrossRefPubMedGoogle Scholar
  2. 2.
    Daya S, Gunby J, Clark DA: Intravenous immunoglobulins therapy for recurrent spontaneous abortion: A meta-analysis. Am J Reprod Immunol 1998;39:69–76PubMedGoogle Scholar
  3. 3.
    Daya S, Gunby J, Porter F, Scott J, Clark DA: Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage. Hum Reprod Update 1999;5:475–482CrossRefPubMedGoogle Scholar
  4. 4.
    Stephenson MS, Fluker MR: Treatment of repeated unexplained in vitro fertilization failures with intravenous immunoglobulins: A randomized, placebo-controlled Canadian trial. Fertil Steril 2000;74:1108–1113CrossRefPubMedGoogle Scholar
  5. 5.
    McDonough PG: “In silico experiments”—yes, but the great western cowboy “random chance” is still alive. Fertil Steril 2001;76:639–640CrossRefPubMedGoogle Scholar
  6. 6.
    Sher G, Fisch JD: “In silico experiments”—yes, but the great western cowboy “random chance” is still alive. Fertil Steril 2001;76:636–637CrossRefPubMedGoogle Scholar
  7. 7.
    Stricker RB, Steinleitner A: “In silico experiments”—yes but the great western cowboy “random chance” is still alive. Fertil Steril 2001;76:637–639CrossRefPubMedGoogle Scholar
  8. 8.
    Kleinstein J, Khanga O, Gips H, Kunzel W: Intravenous immunoglobulins increase pregnancy rate in an IVF program. In: Scientific Program and Abstracts of the Society for Gynecological Investigation, Chicago 1994;248 (Abstr #P108)Google Scholar
  9. 9.
    De Placido G, Zullo F, Mollo A, Cappiello F, Nazzaro A, Colacuri N, Palumbo G: Intravenous immunoglobulins (IVIG) in the prevention of implantation failures. Ann NY Acad Sci 1994;734:232–234PubMedCrossRefGoogle Scholar
  10. 10.
    Sher G, Maassarani G, Zouves C, Feinman M, Sohn S, Matzner W, Chong P, Ching W: The use of combined heparin/aspirin and immunoglobulins G therapy in the treatment of in vitro fertilization patients with antithyroid antibodies. Am J Reprod Immunol 1998;39:223–225PubMedGoogle Scholar
  11. 11.
    Coulam CB, Roussev RG: Role of T cell activation and inhibition markers in diagnosing women experiencing immunological implantation failure after in vitro fertilization and embryo transfer. Am J Reprod Immunol 2002;48(Abstr # I12):138CrossRefGoogle Scholar
  12. 12.
    Stricker RB, Steinleitner A, Winger EE: Intravenous immunoglobulins (IVIG) therapy for immunologic abortion. Clin Appl Immunol Rev 2002;2:187–199CrossRefGoogle Scholar
  13. 13.
    Clark DA, Coulam CB, Daya S, Chaouat G: Unexplained sporadic and recurrent miscarriage in the new millennium: A critical analysis of immune mechanisms and treatment. Hum Reprod Update 2001;7:501–511CrossRefPubMedGoogle Scholar
  14. 14.
    Clark DA, Chaouat G: Loss of surface CD200 on stored allogeneic leukocytes may impair anti-abortive effect in vivo. Am J Reprod Immunol 2005;53:13–20CrossRefPubMedGoogle Scholar
  15. 15.
    American Society for Reproductive Medicine, Assisted Reproductive Technology Registry: Assisted reproductive technology in the United States: 1999 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 2002;78:918–931CrossRefGoogle Scholar
  16. 16.
    Early Breast Cancer Trialists’ Collaborative Group: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomized trials. Lancet 2005;365:1687–1717CrossRefGoogle Scholar
  17. 17.
    The 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;32:55–72Google Scholar
  18. 18.
    Clark DA, Gunby J, Daya S: The use of allogeneic leukocytes of IV IgG for the treatment of patients with recurrent spontaneous abortion. Transfus Med Rev 1997;11:85–94CrossRefPubMedGoogle Scholar
  19. 19.
    Concato J, Shah N, Horowitz RI: Randomized, controlled trials, observational studies, and hierarchy of research designs. N Engl J Med 2000;342:1887–1892CrossRefPubMedGoogle Scholar
  20. 20.
    Benson K, Hartz AJ: A comparison of observational studies and randomized, controlled trials. N Engl J Med 2000;342:1878–1886CrossRefPubMedGoogle Scholar
  21. 21.
    Ioannidis JPA, Haidich AB, Pappa M, Pantazia N, Kokori SI, Tektonidou MG, Contopoulos-Ioannidis DG, Lau J: Comparison of evidence of treatment effects in randomized and nonrandomized studies. JAMA 2001;286:821–830CrossRefPubMedGoogle Scholar
  22. 22.
    Coulam CB, Clark DA: Antiphospholipid antibody status and IVF-debate. Fertil Steril 2000;74:848–849CrossRefPubMedGoogle Scholar
  23. 23.
    Sher G, Feinman M, Zouves C, Kuttner G, Maassarani G, Salem R, Matzner W, Ching W, Chong P: High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid seropositive women treated with heparin and aspirin. Hum Reprod 1994;9:2278–2283PubMedGoogle Scholar
  24. 24.
    Sher G, Matzner W, Feinman M, Maassarani G, Zouves C, Ching P, Ching W: The selective use of heparin/aspirin therapy alone of in combination with intravenous immunoglobulin G, in the management of anti-phospholipid antibody-positive women undergoing IVF. Am J Reprod Immunol 1998;40:74–82PubMedGoogle Scholar
  25. 25.
    Kutteh WH, Yetman DL, Chantilis SJ, Crain J: Effect of antiphospholipid antibodies in women undergoing in-vitro fertilization: Role of heparin and aspirin. Hum Reprod 1997;12:1171–1175PubMedCrossRefGoogle Scholar
  26. 26.
    Coulam CB, Roussev RG: 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;20:58–62CrossRefPubMedGoogle Scholar
  27. 27.
    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;50:340–345CrossRefPubMedGoogle Scholar
  28. 28.
    Aoki K, Kajijura S, Matsumoto Y, Okada S, Yagami Y, Gleicher N: Preconceptional natural killer cell activity as a predictor of miscarriage. Lancet 1995;135:1340–1342CrossRefGoogle Scholar
  29. 29.
    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;50:351–354CrossRefPubMedGoogle Scholar
  30. 30.
    Kwak-Kim JY, Chung-Bang HS, Ng SC, Ntrivalas EI, Mangubat CP, Beaman KD, Beer AE, Gillman-Sachs A: 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;18:767–773CrossRefPubMedGoogle Scholar
  31. 31.
    Moffet A, Regan L, Braude P: Natural killer cells, miscarriage, and infertility. Br Med J 2004;329:1283–1285CrossRefGoogle Scholar
  32. 32.
    Clark DA, Yu G, Levy GA, Gorczynski RM: Procoagulants in fetus rejection: The role of the OX-2 (CD200) tolerance signal. Semin Immunol 2001;13:255–263CrossRefPubMedGoogle Scholar
  33. 33.
    Lachapelle MH, Miron P, Hemmings R, Roy DA: Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. J Immunol 1996;158:4886–4891Google Scholar
  34. 34.
    Coulam CB, Stephenson M, Stern JJ, Clark DA: Immunotherapy for recurrent pregnancy loss: Analysis of results from clinical trials. Am J Reprod Immunol 1996;35:352–359PubMedGoogle Scholar
  35. 35.
    Clark DA, Daya S, Coulam CB, Gunby J, and The Recurrent Miscarriage Immunotherapy Trialists Group: Implications of abnormal human trophoblast karyotype for the evidence-based approach to the understanding, investigation, and treatment of recurrent spontaneous abortion. Am J Reprod Immunol 1996;35:495–498PubMedGoogle Scholar
  36. 36.
    Laudenslager ML, Aasal R, Adler L, Berger CL, Montgomery PT, Sandberg E, Wahlberg LJ, Wilkins RT, Zweig L, Reit ML: Elevated cytotoxicity in combat-veterans with long-term post-traumatic stress disorder: Preliminary observations. Brain Behav Immun 1998;12:74–79CrossRefPubMedGoogle Scholar
  37. 37.
    Clark DA, Croitoru K: TH1/TH2,3 imbalance due to cytokine-producing NK, γδT, and NKγδT cells in murine deciduas in success or failure of pregnancy. Am J Reprod Immunol 2001;45:108–115CrossRefPubMedGoogle Scholar
  38. 38.
    Mincheva-Nilsson L, Kling M, Hammarstrom S, Nagaeva O, Sundqvist KG, Hammarstrom ML, Baranov V: γδ T cells of human early pregnancy decidua: Evidence for local proliferation, phenotypic heterogeneity, and extrathymic differentiation. J Immunol 1997;159:3266–3277PubMedGoogle Scholar
  39. 39.
    Nagaeva O, Bondestam K, Olofsson J, Damber MG, Mincheva-Nilsson L: An optimized technique for separation of human decidual leukocytes for cellular and molecular analyses. Am J Reprod Immunol 2002;47:203–212CrossRefPubMedGoogle Scholar
  40. 40.
    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;48:9–17CrossRefPubMedGoogle Scholar
  41. 41.
    Szekeres-Bartho J, Barakonyi A, Miko E, Polgar B, Palkovics T: The role of γ/δ T cells in the feto-maternal relationship. Semin Immunol 2001;13:229–233CrossRefPubMedGoogle Scholar
  42. 42.
    Hill JA, Polgar K, Anderson DJ: T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion. JAMA 1995;273:1933–1936CrossRefPubMedGoogle Scholar
  43. 43.
    Hamai Y, Fujii T, Yamashita T, Miki A, Kozuma S, Geraghty DE, Taketani Y: Peripheral blood mononuclear cells from women with recurrent abortion exhibit an aberrant reaction to release cytokines upon the direct contact of human leukocyte antigen-G-expressing cells. Am J Reprod Immunol 1998;40:408–413PubMedGoogle Scholar
  44. 44.
    Ruiz JE, Kwak JY, Baum L, Gilman-Sachs A, Beaman KD, Kim YB, Beer AE: Intravenous immunoglobulins inhibits natural killer activity in vivo in women with recurrent spontaneous abortion. Am J Reprod Immunol 1996;35:370–375PubMedGoogle Scholar
  45. 45.
    Kwak JY, Kwak FM, Ainbinder SW, Ruiz AM, Beer AE: Elevated peripheral blood natural killer cells are effectively downregulated by immunoglobulin G infusion in women with recurrent spontaneous abortions. Am J Reprod Immunol 1996;35:363–369PubMedGoogle Scholar
  46. 46.
    Ruiz JE, Kwak JY, Baum L, Gilman-Sachs A, Beaman KD, Kim YB, Beer AE: Effects of intravenous immunoglobulin G on natural killer cell cytotoxicity in vitro in women with recurrent spontaneous abortion. J Reprod Immunol 1996;31:125–141CrossRefPubMedGoogle Scholar
  47. 47.
    Graphou O, Chioti A, Pantazi A, Tsukoura C, Kontopoulou V, Guorgiadou E, Balafoutas C, Koussoulakos S, Margaritis LH, Varla-Leftherioti M: Effect of intravenous immunoglobulins treatment on the Th1/Th2 balance in women with recurrent spontaneous abortions. Am J Reprod Immunol 2003;49:21–29CrossRefPubMedGoogle Scholar
  48. 48.
    Perricone R, De Carolis C, Giacomelli R, Guarino MD, De Sanctis G, Fontana L: GM-CSF and pregnancy: Evidence of significantly reduced blood concentrations in unexplained recurrent abortion efficiently reversed by intravenous immunoglobulin treatment. Am J Reprod Immunol 2003;50:232–237CrossRefPubMedGoogle Scholar
  49. 49.
    Sjoblom C, Wikland M, Robertson SA: Granulocyte-macrophage colony stimulating factor (GM-CSF) acts independently of the beta common subunit of the GM-CSF receptor to prevent inner cell mass apoptosis in human embryos. Biol Reprod 2002;67:1817–1823CrossRefPubMedGoogle Scholar
  50. 50.
    Regan L, Backos MJ, Rai R: Immunological testing and interventions for reproductive failure. RCOG (UK) Scientific Advisory Committee Opinion Paper #5, 2003. Retreived from
  51. 51.
    Coulam CB, Krysa L, Stern JJ, Bustillo M: Intravenous immunoglobulin for treatment of recurrent pregnancy loss. Am J Reprod Immunol 1995;34:333–337PubMedGoogle Scholar
  52. 52.
    Kiprov DD, Nachtigall RD, Weaver RC, Jacaobson A, Main EK, Garvoy MR: The use of intravenous immunoglobulin in recurrent pregnancy loss associated with combined alloimmune and autoimmune abnormalities. Am J Reprod Immunol 1996;36:228–234PubMedGoogle Scholar
  53. 53.
    Stricker RB, Steinleitner A, Bookoff CN, Weckstein LN, Winger EE: Successful treatment of immunological abortion with low-dose intravenous immunoglobulin. Fertil Steril 2000;73:536–540CrossRefPubMedGoogle Scholar
  54. 54.
    Stephenson MD, Dreher K, Houlihan E, Wu V: Prevention of unexplained recurrent spontaneous abortion using intravenous immunoglobulin: A prospective, randomized, double-blind, placebo-controlled trial. Am J Reprod Immunol 1998;39:82–88PubMedGoogle Scholar
  55. 55.
    Anonymous: Intravenous immunoglobulin in the prevention of recurrent miscarriage. The German RSA/IVIG Group. Br J Obstet Gynaecol 1994;101:1072–1077Google Scholar
  56. 56.
    Christiansen OB, Mathiesen O, Husth M, Rasmussen KL, Ingerslev HJ, Lauritsen JG, Grunnet N: Placebo-controlled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i.v. immunoglobulin. Hum Reprod 1995;10:2690–2695PubMedGoogle Scholar
  57. 57.
    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;17:809–816CrossRefPubMedGoogle Scholar
  58. 58.
    Perino A, Vassiliadis A, Vucetich A, Colacurci N, Menato G, Cignitti M, Semprini AE: Short-term therapy for recurrent abortion using intravenous immunoglobulins: Results of a double-blind placebo-controlled Italian study. Hum Reprod 1997;12:2388–2392CrossRefPubMedGoogle Scholar
  59. 59.
    Jablonowska B, Selbing A, Palfi M, Ernerudh J, Kjelberg S, Lindton B: Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: A double-blind placebo-controlled study. Hum Reprod 1999;14:838–841CrossRefPubMedGoogle Scholar
  60. 60.
    Ratko TA, Burnett DA, Foulke GE, Matszewski KA, Sacher RA, and the University Hospital Consortium Expert Panel for Off-Label use of Polyvalent Intravenously Administered Immunoglobulin Preparations: Recommendations for off-label use of intravenously administered immunoglobulin preparations. JAMA 1995;273:1865–1870CrossRefPubMedGoogle Scholar
  61. 61.
    Clark DA: Is there any evidence for immunologically-mediated or immunologically-modifiable early pregnancy failure? J Assist Reprod Genet 2003;20:62–71CrossRefGoogle Scholar
  62. 62.
    Munne S, Sultan KM, Weler HU, Grifo JA, Cohen J, Rosenwaks Z: Assessment of numeric abnormalities of X, Y, 18 and 16 chromosomes in preimplantation human embryos before transfer. Am J Obstet Gynecol 1995;172:1191–1199CrossRefPubMedGoogle Scholar
  63. 63.
    Clark DA, Ding J, Yu G, Levy GA, Gorczynski RM: Fgl2 prothrombinase expression in mouse trophoblast and deciduas triggers abortion but may be countered by OX-2. Mol Hum Reprod 2001;7:185–194CrossRefPubMedGoogle Scholar
  64. 64.
    Knackstedt M, Ding JW, Arck PC, Hertwig K, Coulam CB, August C, Lea R, Dudenhausen JW, Gorczynski RM, Levy GA, Clark DA: Activation of the novel prothrombinase fgl2 as a basis for the pregnancy complications spontaneous abortion and preeclampsia. Am J Reprod Immunol 2001;46:196–210CrossRefPubMedGoogle Scholar
  65. 65.
    Clark DA, Foerster K, Fung L, He W, Lee L, Mendicino M, Markert U, Gorczynski RM, Marsden P, Levy GA: The fgl2 prothrombinase/fibroleukin gene is required for LPS-triggered abortions and for normal hemostasis during murine reproduction. Mol Hum Reprod 2004;10:99–108CrossRefPubMedGoogle Scholar
  66. 66.
    Mellor AL, Sivakumar J, Chandler P, Smith K, Molina H, Mao D, Munn DH: Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2001;2:64–68CrossRefPubMedGoogle Scholar
  67. 67.
    Clark DA, Manuel J, Lee L, Chaouat G, Gorczynski RM, Levy GA: Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA x DBA/2 model. I. Synergistic effect of LPS and (TNF-α + IFN-γ) on pregnancy loss. Am J Reprod Immunol 2004;52:370–378CrossRefPubMedGoogle Scholar
  68. 68.
    Clark DA, Yu G, Arck PC, Levy GA, Gorczynski RM: MD-1 is a critical part of the mechanism causing Th-1 cytokine-triggered fetal loss syndrome. Am J Reprod Immunol 2003;49:297–307CrossRefPubMedGoogle Scholar
  69. 69.
    Chaouat G, Ledee-Bataille N, Zourbas S, Ostojic S, Dubanchet S, Martal J, Frydman R: Cytokines, implantation and early abortion: Re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept. Am J Reprod Immunol 2003;50:177–186CrossRefPubMedGoogle Scholar
  70. 70.
    De Carolis C, Greco E, Guarino MD, Perricone C, Dal Lango A, Giacomelli R, Fontana L, Perricone R: Anti-thyroid antibodies and anti-phospholipid syndrome: Evidence of reduced fecundity and of poor pregnancy outcome in recurrent spontaneous aborters. Am J Reprod Immunol 2004;52:263–266CrossRefPubMedGoogle Scholar
  71. 71.
    Clark DA, Banwatt D, Chaouat G: Stress-triggered abortion in mice is prevented by alloimmunization. Am J Reprod Immunol 1993;29:141–147PubMedGoogle Scholar
  72. 72.
    Clark DA, Blois S, Kandil J, Handjiski B, Manuel J, Arck PC: Reduced indoleamine 2,3-dioxygenase versus increased Th1/Th2 cytokine ratios as a basis for occult and clinical pregnancy failure in mice and humans. Am J Reprod Immunol 2005;54:203–216CrossRefPubMedGoogle Scholar
  73. 73.
    Simon HU, Sapth PJ: IVIG-mechanisms of action. Allergy 2003;58:543–552CrossRefPubMedGoogle Scholar
  74. 74.
    Wright GJ, Cherwinski H, Foster-Cuevas M, Brooke G, Puklavec MJ, Bigler M, Song Y, Jenmalm M, Gorman D, McClanahan T, Lin M-R, Brown MH, Sedgwick JD, Phillips JH, Barclay AN: Characterization of the CD200 receptor family in mice and humans and their interaction with CD200. J Immunol 2003;171:3034–3046PubMedGoogle Scholar
  75. 75.
    Gorczynski RM, Lee L, Boudakov I: Augmented induction of CD4+CD25+ Treg using monoclonal antibodies to CD200R. Transplantation 2005;79:488–491CrossRefPubMedGoogle Scholar
  76. 76.
    Aluvihare VR, Kallikourdis M, Betz AG: Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 2004;5:266–271CrossRefPubMedGoogle Scholar
  77. 77.
    Zenclussen AC, Gerlof K, Zenclussen ML, Sollwedel A, Bertoja AZ, Ritter T, Kotsch K, Leber J, Volk HD: Abnormal T cell reactivity against paternal antigens in spontaneous abortion. Adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model. Am J Pathol 2005;166:811–822PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • David A. Clark
    • 1
    Email author
  • Carolyn B. Coulam
    • 2
  • Raphael B. Stricker
    • 3
  1. 1.Department of MedicineMcMaster UniversityHamiltonCanada
  2. 2.Millenova LaboratoriesChicagoUS
  3. 3.California Pacific Medical CenterSan FranciscoUS

Personalised recommendations