Inhibitors of phosphodiesterases in infertility

Abstract

The present invention is directed to methods of increasing oocyte production in a mammal. More specifically, the specification describes methods and compositions for inducing follicular maturation using a PDE inhibitor. The inhibitor may be used alone at high doses. Alternatively, the follicular maturation is achieved by combining a low dose of FSH with the PDE inhibitor treatment.

1 . A method of increasing oocyte maturation comprising treating an oocyte in vitro with at least one gonadotropin hormone selected from the group consisting of follicle stimulating hormone (FSH), luteinizing hormone (LH), and chorionic gonadotropin (CH) and a composition comprising a phosphodiesterase (PDE) inhibitor in a collective amount effective to cause oocyte maturation. 
     
     
         2 . The method of  claim 1 , wherein the composition comprises at least one PDE 4 inhibitor. 
     
     
         3 . The method of  claim 1 , wherein the composition comprises at least one PDE 4 inhibitor selected from the group consisting of: Piclamilast, Roflumilast, Cilomilast, Filaminast, Mesopram, D4418, Arofylline and CL1044. 
     
     
         4 . The method of  claim 1 , wherein the composition comprises at least one PDE 4 inhibitor and one other PDE inhibitor selected from the group consisting of a PDE 1 inhibitor, a PDE 7 inhibitor, a PDE 9 inhibitor, a PDE 10 inhibitor, and a PDE 11 inhibitor. 
     
     
         5 . The method of  claim 1 , wherein the gonadotropin hormone is FSH. 
     
     
         6 . The method of  claim 1 , wherein the gonadotropin hormone is LH. 
     
     
         7 . The method of  claim 1 , wherein the gonadotropin hormone is CG. 
     
     
         8 . The method of  claim 1 , wherein the method comprises administering a stimulator, agonist or adjuvant of FSH in combination with a PDE 4 inhibitor. 
     
     
         9 . The method of  claim 1 , wherein the PDE inhibitor is an inhibitor of at least one PDE type selected form 1, 5 and 6. 
     
     
         10 . The method of  claim 1 , wherein the PDE inhibitor is a selective inhibitor of PDE 1 and PDE 5. 
     
     
         11 . The method of  claim 1 , wherein the PDE inhibitor is a selective PDE 1 inhibitor. 
     
     
         12 . The method of  claim 1 , wherein the PDE inhibitor is a selective PDE 5 inhibitor. 
     
     
         13 . The method of  claim 1 , wherein the composition is administered simultaneously, separately or sequentially with said at least one gonadotropin hormone. 
     
     
         14 . The method of  claim 13 , wherein the composition is administered simultaneously with said at least one gonadotropin hormone. 
     
     
         15 . The method of  claim 1 , wherein the dose of gonadotropin hormone is less than the dose required in the absence of the PDE inhibitor, in order to achieve the same result in terms of follicular growth.