Treatment and diagnosis of infertitlity using TGFbeta or activin

Abstract

A method of treating an infertility condition in humans or mammals, by exposure of a prospective mother to TGFβ or derivative or analog of TGFβ. The exposure is advantageously in conjunction with one or more antigens of a prospective father so that a hyporesponsive immune reaction is mounted to the one or more antigens of the prospective father.

1 . A method of treating an infertility condition in a human or mammal by exposure of the prospective mother to TGFβ or an effective derivative or analog thereof before attempted conception to elicit a transient hyporesponsive immune reaction to one or more antigen of a prospective father to thereby alleviate symptoms of the infertility condition.  
     
     
         2 . A method of treating an infertility condition as in  claim 1  by exposure of a prospective mother to said one or more antigens of a prospective father and to TGFβ or an effective derivative or analog thereof before attempted conception to elicit a transient hyporesponsive immune reaction to said one or more antigen to thereby alleviate symptoms of the infertility condition.  
     
     
         3 . A method of treating an infertility condition as in  claim 2  wherein a mucosal surface of the prospective mother is exposed to the one or more antigens.  
     
     
         4 . A method of treating an infertility condition as in  claim 3  wherein the mucosal surface is selected from the group comprising an oral mucosal surface, a respiratory mucosal surface, a gastrointestinal mucosal surface or a genital mucosal surface.  
     
     
         5 . A method of treating an infertility condition as in  claim 3  wherein the mucosal surface is a genital mucosal surface.  
     
     
         6 . A method of treating an infertility condition as in  claim 3  wherein the one or more antigens and TGFβ or derivative or analog thereof is injected for systemic contact.  
     
     
         7 . A method of treating an infertility condition as in  claim 3  wherein the TGFβ or derivative or analog thereof and the one or more antigens are adminstered at one site.  
     
     
         8 . A method of treating an infertility condition as in  claim 3  wherein the TGFβ or derivative or analog thereof and the one or more antigens are each adminstered at a first site and a different site respectively.  
     
     
         9 . A method of treating an infertility condition as in  claim 2  wherein the TGFβ or derivative or analog thereof and the one or more antigen are adminstered temporarily spaced apart.  
     
     
         10 . A method of treating an infertility condition as in  claim 9  wherein the one ore more antigens are adminstered subsequent to administration of the TGFβ or derivative or analog thereof.  
     
     
         11 . A method of treating an infertility condition as in  claim 9  wherein the one or more antigens are administered first followed by administration of TGFβ or derivative or analog thereof.  
     
     
         12 . A method of treating an infertility condition as in  claim 2  wherein the one or more antigens are chosen as a result of being particularly antigenic and prominent either on the sperm, or on the conceptus.  
     
     
         13 . A method of treating an infertility condition as in  claim 2  wherein the one or more antigens are present on cells taken from the prospective lather that contain MHC antigens.  
     
     
         14 . A method of treating an infertility condition as in  claim 13  wherein the antigen is an MHC I antigen of the prospective father.  
     
     
         15 . A method of treating an infertility condition as in  claim 2  wherein the one or more antigens are administered on leukocytes of the prospective father.  
     
     
         16 . A method of treating an infertility condition as in  claim 2  wherein the one or more antigens are administrated on sperm cells of the prospective father.  
     
     
         17 . A method of treating an infertility condition is in  claim 2  wherein the one or more antigens are administrated in the seminal plasma of the prospective father.  
     
     
         18 . A method of treating an infertility condition as in  claim 2  wherein the one or more antigens are presented in purified or semi-purified form.  
     
     
         19 . A method of treating an infertility condition as in  claim 18  wherein the purified or semi purified one or more antigens are presented on inert or adjuvant carriers.  
     
     
         20 . A method of treating an infertility condition as in  claim 2  wherein humans are being treated, and the exposure of TGFβ is to a mucosal surface and the level of TGFβ is greater than 50 ng/ml with a total dose of 150 ng/ml.  
     
     
         21 . A method of treating an infertility condition as in  claim 2  wherein the mucosal surface is exposed to a concentration of TGFβ of between 100 and 400 ng/ml with a total dose of between 100 to 2000 ng.  
     
     
         22 . A method of treating an infertility condition as in  claim 2  wherein the TGFβ or derivative or analog thereof is supplied in a slow release form.  
     
     
         23 . A method of treating an infertility condition as in  claim 2  wherein the exposure of the one or more antigens is to the prospective mother's genital tract in the form of the prospective father's ejaculate, and the level of exposure is determined by the cell count and antigenic density on the surface of such cells.  
     
     
         24 . A method of treating an infertility condition as in  claim 3  wherein humans are being treated and the one or more antigens are present on leukocytes, whereby between 10 7  and 10 9  leukocytes are adminstered to a mucosal surface.  
     
     
         25 . A method of treating an infertility condition as in  claim 2  wherein the TGFβ is selected from the group of TGFβ 1 , TGFβ 2  and TGFβ 3 .  
     
     
         26 . A method of treating an infertility condition as in  claim 2  wherein the TGFβ is TGFβ 1 .  
     
     
         27 . A method of treating an infertility condition as in  claim 2  wherein the TGFβ is modified.  
     
     
         28 . A method of treating an infertility condition as in  claim 27  wherein the modification is selected from the group comprising substitution, deletion or addition mutants, peptide fragments of TGFβ or derivative or analog thereof, and peptide fragments of TGFβ or derivative or analog thereof which have been incorporated into another protein.  
     
     
         29 . A method of treating an infertility condition as in  claim 2  wherein the TGFβ or derivative or analog thereof is a member of the TGFβ superfamily.  
     
     
         30 . A method of treating an infertility condition as in  claim 29  wherein the member of the TGFβ superfamily is activin.  
     
     
         31 . A method of treating an infertility condition as in  claim 2  wherein TGFβ is administered in its active form.  
     
     
         32 . A method of treating an infertility condition as in  claim 2  wherein TGFβ is administered in precursor form.  
     
     
         33 . A method of treating an infertility condition as in  claim 2  wherein the prospective mother is incapable of converting sufficient of the inactive form of TGFβ to active TGFβ, and the method of treating includes administration of active TGFβ.  
     
     
         34 . A method of treating an infertility condition as in  claim 2  wherein the prospective mother is incapable of converting the inactive form of TGFβ to active TGFβ, and the method of treating includes administration of a compound capable of activating TGFβ.  
     
     
         35 . A method of treating an infertility condition as in  claim 2  wherein the prospective mother is incapable of converting the inactive form of TGFβ to active TGFβ, and the method of treating includes administration of plasmin, so as to increase the level of active TGFβ.  
     
     
         36 . A method of treating an infertility condition as in  claim 2  wherein TGFβ is administered in an unpurified form using a biological source rich in TGFβ.  
     
     
         37 . A method of treating an infertility condition as in  claim 36  wherein the TGFβ is administered in the form of platelets.  
     
     
         38 . A method of treating an infertility condition as in  claim 3  wherein humans are being treated and the exposure to TGFβ and male antigen is a multiple exposure.  
     
     
         39 . A method of treating an infertility condition as in  claim 38  wherein the multiple exposure is preferably performed over a period spanning at least three months prior to attempted conception.  
     
     
         40 . A method of treating an infertility condition as in  claim 2  wherein humans are being treated and exposure is at least one week before conception is attempted.  
     
     
         41 . A method of treating an infertility condition as in  claim 2  wherein the exposure is before attempted conception.  
     
     
         42 . A method of treating an infertility condition as in  claim 2  wherein administration of TGFβ or derivative or analog thereof and the one ore more antigen occurs at least once after the prospective date of conception.  
     
     
         43 . A method of treating an infertility condition as in  claim 42  wherein the exposure continues over a period of the first 12 weeks of pregnancy.  
     
     
         44 . A method of treating an infertility condition as in  claim 2  first including the step of diagnosing or testing whether the male has adequate levels of TGFβ or the female has the capacity to activate TGFβ, or alternatively whether anti-sperm antibodies exist.  
     
     
         45 . A method of treating an infertility condition as in  claim 2  used in conjunction with IVF treatment, whereby the transient hyporeactive immune response is elicited before transfer of the conceptus or genetics is attempted.  
     
     
         46 . A method of diagnosing an infertility condition in males by testing the level of TGFβ in seminal fluid.  
     
     
         47 . A method of diagnosing an infertility condition in a female by testing for the capacity of the female to convert the inactive form of TGFβ to the active form.  
     
     
         48 . A composition for use in treating an infertility condition, comprising TGFβ or derivative or analog thereof and one or more paternal antigens, and a pharmaceutically acceptable carrier, suitable for administration to a mucosal surface.  
     
     
         49 . A composition for use in treating an infertility condition as in  claim 48  wherein the composition comprises a vaginal gel.