Compositions and methods for reducing the likelihood of implantation failure or miscarriage in recipients of artificial insemination

Abstract

Methods and kits for preventing or reducing the likelihood of implantation failure or miscarriage in a recipient of artificial insemination are provided. The methods include administering into a recipient of artificial insemination in need of such treatment an effective amount of granulocyte colony stimulating factor (G-CSF).

1 . A method for preventing or reducing the likelihood of implantation failure or miscarriage in a recipient of artificial insemination, comprising administering to the recipient of artificial insemination an effective amount of a composition comprising G-CSF. 
     
     
         2 . The method of  claim 1 , wherein said artificial insemination is intrauterine insemination, intravaginal insemination, intracervical insemination, or intratubal insemination. 
     
     
         3 . The method of  claim 1 , wherein said composition is administered parenterally. 
     
     
         4 . The method of  claim 1 , wherein said composition is administered enterally. 
     
     
         5 . The method of  claim 1 , wherein said composition is administered topically. 
     
     
         6 . The method of  claim 1 , wherein said composition is administered by inhalation. 
     
     
         7 . The method of  claim 1 , wherein said composition is administered prior to said artificial insemination. 
     
     
         8 . The method of  claim 1 , wherein said artificial insemination comprises a controlled ovarian hyperstimulation procedure prior to insemination, and wherein said composition is administered before, during, or after the time of controlled ovarian hyperstimulation. 
     
     
         9 . The method of  claim 1 , wherein said composition is administered daily for one to thirty-five consecutive days. 
     
     
         10 . The method of  claim 1 , wherein said composition is administered daily until the end of first trimester. 
     
     
         11 . The method of  claim 1 , wherein said composition is administered daily until said recipient presents a normal Th1 response or a normal Th2 response or both. 
     
     
         12 . The method of  claim 1 , wherein said G-CSF is administered at a dose of between 0.1 mcg/kg/day to 600 mcg/kg/day. 
     
     
         13 . The method of  claim 12 , wherein said G-CSF is administered at a dose of between 1 mcg/kg/day to 100 mcg/kg/day. 
     
     
         14 . The method of  claim 13 , wherein said G-CSF is administered at a dose of between 1 mcg/kg/day to 50 mcg/kg/day. 
     
     
         15 . The method of  claim 14 , wherein said G-CSF is administered at a dose of between 1 mcg/kg/day to 10 mcg/kg/day. 
     
     
         16 . The method of  claim 15 , wherein said G-CSF is administered at a dose of between 1 mcg/kg/day to 2 mcg/kg/day. 
     
     
         17 . The method of  claim 16 , wherein said G-CSF is administered at a dose of about 1.5 mcg/kg/day to 1.7 mcg/kg/day. 
     
     
         18 . The method of  claim 1 , wherein said G-CSF is administered in the form of a nucleotide sequence encoding G-CSF. 
     
     
         19 . The method of  claim 1 , wherein said composition further comprises an additive. 
     
     
         20 . The method of  claim 19 , wherein said additive is selected from the group consisting of cytokines that suppress Th1 immune response, cytokines that enhance Th2 immune response, cytokines that support successful pregnancy through non-immunologic mechanisms, anti-inflammatory agents, and inhibitors of pro-inflammatory cytokines. 
     
     
         21 . The method of  claim 19 , wherein said additive is selected from the group consisting of interferon alpha, interferon beta, macrophage colony stimulating factor (M-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), transforming growth factor beta (TGF-beta), interleukin-1 (IL-1), IL-3, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-13, IL-14, IL-15, IL-19, IL-20, IL-21, IL-22, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, and IL-35. 
     
     
         22 . The method of  claim 19 , wherein said additive comprises an immunosuppressive agent. 
     
     
         23 . The method of  claim 22 , wherein said immunosuppressive agent comprises vitamin D3 (1,25 dihydroxycholecalciferol), analogs thereof, or corticosteroids. 
     
     
         24 . The method of  claim 23 , wherein said corticosteroid is prednisone or methylprednisolone. 
     
     
         25 . The method of  claim 1 , wherein said composition further comprises a pharmaceutically acceptable carrier. 
     
     
         26 . A kit for preventing or reducing the likelihood of implantation failure and miscarriage in a recipient of artificial insemination, comprising an effective amount of G-CSF; and a label with instructions for using the G-CSF to prevent or reduce the likelihood of implantation failure and miscarriage. 
     
     
         27 . The kit of  claim 26 , wherein said G-CSF is formulated for subcutaneous administration. 
     
     
         28 . The kit of  claim 26 , wherein said G-CSF is formulated for intramuscular administration. 
     
     
         29 . The kit of  claim 26 , wherein said G-CSF is formulated for intravascular administration. 
     
     
         30 . The kit of  claim 26 , further comprising at least one other active compound. 
     
     
         31 . The kit of  claim 30 , wherein said other active compound is another CSF, erythropoietin or stem cell factor. 
     
     
         32 . The kit of  claim 31 , wherein said CSF is G-CSF, GMCSF or macrophage CSF. 
     
     
         33 . The kit of  claim 30 , wherein said other active compound is an anti-inflammatory agent. 
     
     
         34 . The kit of  claim 30 , wherein said one other active compound is an interleukin. 
     
     
         35 . The kit of  claim 26 , wherein said G-CSF is contained in an implantable device for slow release after implantation of the device. 
     
     
         36 . The kit of  claim 26 , wherein said G-CSF is contained in a transdermal patch for slow release after application of the transdermal device. 
     
     
         37 . The kit of  claim 26 , wherein said G-CSF is contained in a vaginal ring. 
     
     
         38 . An implantable device, comprising G-CSF embedded in an inert matrix.