TEMPLATE LETTER OF PRE-TREATMENT MEDICAL NECESSITY
AND/OR POST-TREATMENT ROUTINE APPEAL

 
 
TO WHOM IT MAY CONCERN:
 
RE:
 
 
            High dose intravenous immunoglobulin (IVIg) therapy is clinically beneficial and not experimental in a variety of immune disorders associated with human reproductive failure and pregnancy.  Examples include: autoimmune diseases, Rh sensitization, hypogammaglobulinemia, recurrent fetal loss and infertility associated with antiphospholipid antibodies, intrauterine growth retardation and idiopathic thrombocytopenia.  The effects of high dose immunoglobulin infusion include:
 

• Feedback inhibition of antibody synthesis
• Down regulation of EDGE Fcg receptor
• Blockage of placental transport of maternal endogenous Edge
• Regulation of idiotype network
• Alteration of T and B lymphocyte functions
• Down regulation of natural killer cell function and tumor necrosis factor secretion.

            The beneficial effects of this medication are documented in the literature involving treatment for autoimmune disorders, organ transplant and bone marrow rejection and autoimmune disorders associated with infertility and pregnancy. Therefore, its use can no longer be labeled as experimental.
 
           

            Women with the autoimmune disorder antiphospholipid antibody syndrome are at risk of infertility and should they conceive, will often experience recurrent pregnancy losses, intrauterine growth retardation, intrauterine fetal death, and maternal complications such as thrombosis (arterial and venous), stroke and transient ischemic episodes.  More than one third of infertile women have circulating antiphospholipid antibodies and antithyroid antibodies that may prevent or impair implantation by compromising syncitalization of the early trophoblast and/or causing local venous and arterial thrombosis. The administration of IVIg in association with infertility treatment and during subsequent pregnancy is often the only method by which reproductive failure can be avoided.
 
Women at risk of pregnancy complications show alterations in their immunophenotype lymphocyte sets particularly in elevations in CD56+ natural killer cells that secrete tumor necrosis factor (TNF).  This factor results in decidual necrosis, death of the placental cells, coagulopathy and eventual death of the infant.  The only medication effective in reducing these natural killer cells and TNF secretion is IVIg.  Other corticosteroids or immunosuppressants are either ineffective or contraindicated during pregnancy.
 
This patient will continue to be at risk of serious complications without IVIg therapy.
 

Sincerely,
 
 
 
 
 
REFERENCES

 
1.       de la C-mara C, Arrieta R, Gonz-lez A, Iglesias E, Ome-aca F.  High dose intravenous immunoglobulin as the sole prenatal treatment for severe Rh immunization.  N Engl J Med  

          1988;318:519-520.
 
2.       Smith CIE, Hammarstrom L.  Intravenous immunoglobulin in pregnancy.  Obstet Gynecol 1985;66:39s.
 
3.       Scott JR, Branch W, Kochenour NK, Ward K.  Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy loss caused by antiphospholipid antibodies

          and Rh immunization.  Am J Obstet Gynecol 1988;159:1055-1056.
 
4.       Parke A, Maier D, Wilson D, Andreoli J, Ballow M.  Intravenous gammaglobulin, antiphospholipid antibodies, and pregnancy.  Ann Int Med 1989;110:495-496.
 
5.       Rose V, Gordon Ll.  Idiopathic thrombocytopenic purpura in pregnancy.  Successful management with immunoglobulin infusion.  JAMA 1985;254:2626-2628.
 
6.       Bussell JB, Pham LC, Aledort L, Nachman R.  Maintenance treatment of adults with refractory immune thrombocytopenic purpura using repeated intravenous infusions of gamma

          globulin.  Blood 1988;72:121-127.
 
7.       Mannhalter JW, Ahmad R, Wolf HM, Eibl MM.  Effect of polymeric Edge on human monocyte functions.  Int Arch Allergy Appl Immunol 1987;82:159-167.
 
8.       Sultan Y, Maisonneuve P, Kazatchkine MD, Nydegger UE.  Anti-idiotypic suppression of autoantibodies to factor VIII b high dose intravenous gammaglobulin.  Lancet 1984;i:765-

          768.
 
9.       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

          (IVF/ET) in antiphospholipid antibody (APA) seropositve women treated with heparin and aspirin.  Human Reproduction  1994;11.
 
10.     Tsubakio T, Kurato Y, Katageri S, et al.  Alteration in T cell subset and immunoglobulin synthesis in vitro during high dose gammaglobulin therapy in patients with idiopathic

          thrombocytopenic purpura.  Clin Exp Immunol  1983;53:697-702.
 
11.     Wapner RJ, Cowchock SF, Shapiro SS.  Successful treatment in two women with antiphospholipid antibodies and refractory pregnancy losses with intravenous immunoglobulin

          infusions.  Am J Obstet Gynecol 1989;161:1271-1272.
 
12.     Kwak JYH, Gilman-Sachs A, Beaman KD, Beer AE.  Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune etiologies; pre vs.

          post conception treatment.  Am J Ostet Gynecol 1992;166:1975-1987.
 
13.     Kwak JYH, Gilman-Sachs A, Beaman KD, Beer AE.  Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology.  J. Reprod Immunol 1992;22:15-

         31.