Studies on Immune Problems

Early studies on immunological problems:

  1. Dr. Alan Beer and his associates, in an award winning 1995 study presented to the 6th International Congress of Reproductive Immunology, reported that 86.6% of women with elevated Natural Killer Cells had a successful pregnancy outcome when treated with preconception IVIg, aspirin and heparin.
  2. Dr. Carolyn Coulam finished a double blind study on IVIg therapy for immune problems resulting in infertility. Her results were published in the December 1995 issue of The American Journal of Reproductive Immunology. Her study showed a 3:1 ratio of increased births to women receiving IVIg vs. a placebo. These results are now being presented to the FDA to support the approval and the use of this drug for reproductive immunology purposes.
  3. In 1994, an article was published by Coulam, C.B., Krysa, L.W., and Bustillo, M. in Human Reproduction 9, 2265 – 2269, entitled “Intravenous Immunoglobulin for In-Vitro Fertilization Failure”.
  4. DePlacido, G., Zullo, Mallo, A. Capieio, F., Nazarro, A., Colarcurci, N., Palumbo, G. published in 1994 in the Annals of the New York Academy of Science, 734, 1 – 3 an article entitled, ” Intravenous Immunoglobulin (IVIg) in Prevention of Implantation Failures”.
  5. Kleinstein, J., Khanaga, O., Gips, H. and Kunzel, W. published the article entitled, “Intravenous Immunoglobulin Increase Clinical Pregnancy Rates in IVF Program in 1994 in the Society Gynecological Invest, 41st Annual Meeting, Abstract #P108.
  6. In a 1994 article in the American Journal of Reproductive Immunology, the Recurrent Miscarriage Immunologist Trialist Group published the results of a Meta-Analysis of White Blood Cell Immunizations that was organized by the American Society of Reproductive Immunology Ethics Committee. Two different analyses showed an increase in live births (a ratio of 1.16 in one analysis and a ratio of 1.21 in the second). When the analysis was limited to women with primary miscarriages it increased to a ratio of 1.46. These results were significant at the p=.006 level. The studies that used subcutaneous immunization vs. intravenous with white blood cell (LIT) immunizations showed better results. Also, those studies included in the Meta-Analysis that screened out the women with other immune problems showed better results (example APA and Natural Killer Cells). The presence of these additional problems seemed to cause pregnancy losses even when LIT was given.
  7. A good portion of infertility may be very early miscarriage. This theory was reported in the American College of Gynecology (ACOG) September 1995 Bulletin. “Approximately 50-70% of pregnancies end in spontaneous abortion. Most of these pregnancy losses are unrecognized because they occur before, or at the time of, the expected menses”. When these patients are studied carefully, 15% show an unexpected pregnancy per menstrual cycle that did not take.
  8. A study by Geoffrey Sher was published in Human Reproduction, vol. 9, no. 12 PP 2279-2283, 1994, “High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid seropositive women treated with heparin and aspirin”. This study showed a 49% viable pregnancy rate for women positive for antiphospholipid antibodies and treated with heparin and aspirin vs. 16% of seropositive women not treated with heparin and aspirin.

Recent research on immunological problems:

1. Winger EE, Reed JL, Ashoush S, El-Toukhy T, Taranissi M. Die-Off Ratio Correlates with Increased TNF-á:IL-10 Ratio and Decreased IVF Success Rates Correctable with Humira. Am J Reprod Immunol. 2012 Jul 30. doi: 10.1111/j.1600-0897.2012.01179.x. 
2. Virro M, Winger EE, Reed JL. Intravenous Immunoglobulin for Repeated IVF Failure and Unexplained Infertility. Am J Reprod Immunol. 2012 Jul 17. doi: 10.1111/j.1600-0897.2012.01169.x. 

3. Winger EE, Reed JL, Ashoush S, El-Toukhy T, Ahuja S, Taranissi M. Elevated Preconception CD56(+) 16(+) and/or Th1:Th2 Levels Predict Benefit from IVIG Therapy in Subfertile Women Undergoing IVF. Am J Reprod Immunol. 2011 May 30. doi: 10.1111/j.1600-0897.2011.01018.x.

4. Winger EE, Reed JL, Ashoush S, El-Toukhy T, Ahuja S, Taranissi M. Birth Defect Rates in Women Using Adalimumab (Humira(®) ) to Treat Immunologic-Based Infertility in IVF Patients. Am J Reprod Immunol. 2011 Apr 19. doi: 10.1111/j.1600-0897.2011.00994.x. 

5. Winger EE, Reed JL. Low Circulating CD4(+)CD25(+)Foxp3(+) T Regulatory Cell Levels Predict Miscarriage Risk in Newly Pregnant Women with a History of Failure. Am J Reprod Immunol. 2011 Feb 14. doi: 10.1111/j.1600-0897.2011.00992.x.

6. Winger EE , Reed JL, Ashoush S, Ahuja S , El-Toukhy T, Taranissi M: Degree of TNF-a/IL-10 Cytokine Elevation Correlates With IVF Success Rates in Women Undergoing Treatment With Adalimumab (Humira) and IVIG. Am J Reprod Immunol. 2011
7. Winger EE, Reed JL:A retrospective analysis of fondaparinux versus enoxaparin treatment in women with infertility or pregnancy loss. Am J Reprod Immunol 2009 Oct;62(4):253-60. Epub 2009 Aug 24.

8. Winger EE, Reed JL, Ashoush S, Sapna A, El-Toukhy T, Taranissi M: “Treatment with adalimumab (Humira) and intravenous immunoglobulin (IVIG) improves pregnancy rates in women undergoing IVF. American Journal of Reproductive Immunology, 2009; 61:113-120.

9. 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. Free full text article: Click here .
10. Winger EE, Reed JL, Stricker RB: Los Gatos, USA Lymphocyte Immunization Therapy (LIT) Combined with Intravenous Immunoglobulin (IVIG) Improves Live Birth Rates in Women with Primary Recurrent Spontaneous Abortion (RSA) European Conference for Reproductive Immunology, Berlin, Germany, Sept 2 2007.

11. Winger EE: CD57+ cells and recurrent spontaneous abortion. Am J Reprod Immunol 2007 Oct;58(4):311-4.

12. Stricker RB, Winger EE. Update on treatment of immunologic abortion with low-dose intravenous immunoglobulin. Am J Reprod Immunol. 2005 Dec;54(6):390-6.

13. Stricker RB, Steinleitner A, Winger EE: Intravenous immunoglogulin (IVIG) therapy for immunologic abortion. Clinical and Applied Immunology Reviews 2 (2002) 187-199. Free full text article: Click here.

14. Stricker RB, Steinleitner A, Bookoff CN, Weckstein LN, Winger EE. Successful treatment of immunologic abortion with low-dose intravenous immunoglobulin. Fertil Steril. 2000 Mar;73(3):536-40.