Methods and agents to treat infertility in females

Abstract

Described are novel female fertility therapies. A first aspect of the invention is directed to therapies that include FSH lowering methodologies to prevent and/or treat egg infertility. A second aspect of the invention is directed to agents that bind to activin, bind to receptors that bind activin, or that otherwise disrupt activin signaling (collectively referred to herein as “activin pathway modifier agents” or “APM agents”) and methods of utilizing these agents to prevent and/or treat egg infertility. A third aspect of the invention is directed to methods of administering an effective amount of an APM agent to a subject to increase oocyte yield and/or ovarian reserve. All three aspects of the invention may be used in humans and in animals. Additional aspects of the invention include therapeutic drug kits for treatment of humans and animals based on the methodologies described above.

What is claimed is: 
     
         1 . A method of treating and/or reducing the incidence of infertility, miscarriages, trisomic pregnancies, or birth defects in a female subject, wherein said infertility, miscarriages, trisomic pregnancies, or birth defects result from oocyte aneuploidy, embryonic aneuploidy, and/or fetal aneuploidy, said method comprising administering to a female subject at least one FSH lowering agent or activin pathway modifying agent;
 wherein said FSH lowering agent is chosen from LH; an LH derivative; hCG; an hCG derivative; an antibody against FSH; inhibin A; inhibin B; follistatin; follistatin derivatives; ActRIIB:Fc; ActRIIA: Fc; 3α hydroxy-4-pregnen-20-one (3αHP); 3α hydroxy-4-pregnen-20-one-acetate (3αHPA); and anti-Müllerian hormone;   wherein said activin pathway modifying agent is chosen from ActRIIB:Fc; ActRIIA: Fc; follistatin; and follistatin derivatives; and   wherein said at least one FSH lowering agent or activin pathway modifying agent is administered in an amount effective to treat and/or prevent infertility, miscarriages, trisomic pregnancies, or birth defects.   
     
     
         2 . The method of  claim 1  wherein the at least one FSH lowering agent or activin pathway modifying agent is ActRIIB:Fc. 
     
     
         3 . The method of  claim 2  wherein ActRIIB:Fc is given at a dose sufficient to maintain serum levels of ActRIIB:Fc between 4 mg/kg and 10 mg/kg. 
     
     
         4 . A method of increasing oocyte production in a female subject comprising administering to the subject at least one FSH lowering agent or activin pathway modifying agent;
 wherein said FSH lowering agent is chosen from LH; an LH derivative; hCG; an hCG derivative; an antibody against FSH; inhibin A; inhibin B; follistatin; follistatin derivatives; ActRIIB:Fc; ActRIIA: Fc; 3α hydroxy-4-pregnen-20-one (3αHP); 3α hydroxy-4-pregnen-20-one-acetate (3αHPA); and anti-Müllerian hormone;   wherein said activin pathway modifying agent is chosen from ActRIIB:Fc; ActRIIA: Fc; follistatin; and follistatin derivatives; and   wherein the at least one FSH lowering agent or activin pathway modifying agent is administered in an amount effective to increase oocyte production in the subject.   
     
     
         5 . The method of  claim 4  wherein the at least one FSH lowering agent or activin pathway modifying agent is ActRIIB:Fc. 
     
     
         6 . The method of  claim 5  wherein ActRIIB:Fc is given at a dose sufficient to maintain serum levels of ActRIIB:Fc between 4 mg/kg and 10 mg/kg. 
     
     
         7 . The method of  claim 1  further comprising administering the at least one FSH lowering agent or activin pathway modifying agent for at least a portion of one reproductive cycle. 
     
     
         8 . The method of  claim 1  further comprising administering the at least one FSH lowering agent or activin pathway modifying agent for at least a portion of two or more reproductive cycles. 
     
     
         9 . The method of  claim 8  further comprising harvesting and/or attempting fertilization of an oocyte(s) after completion of the second reproductive cycle. 
     
     
         10 . The method of  claim 8  further comprising harvesting and/or attempting fertilization of an oocyte(s) after completion of at least the third reproductive cycle. 
     
     
         11 . The method of  claim 1  wherein the subject is one of a human subject or a non-human animal subject. 
     
     
         12 . A kit for preventing or treating egg infertility in a subject comprising at least one of a FSH lowering agent or an APM agent in an amount effective to prevent or treat the egg fertility. 
     
     
         13 . The kit of  claim 12  further comprising adjunct agents as needed to promote ovulation and/or provide endometrial support. 
     
     
         14 . The kit of  claim 13  wherein the adjunct agents are chosen from human chorionic gonadotropin, progesterone medications and combinations thereof. 
     
     
         15 . A kit for increasing oocyte production in a subject comprising at least one FSH lowering agent or an APM agent in an amount effective to increase oocyte production. 
     
     
         16 . The kit of  claim 15  further comprising adjunct agents as needed to promote ovulation and/or provide endometrial support. 
     
     
         17 . The kit of  claim 16  wherein the adjunct agents are chosen from human chorionic gonadotropin, progesterone medications, and combinations thereof. 
     
     
         18 . The kit of  claim 12  wherein the kit further includes a medical implement for administering the at least one FSH lowering agent or APM agent. 
     
     
         19 . The kit of  claim 15  wherein the kit further includes a medical implement for administering the at least one FSH lowering agent or APM agent.