Unitary Combinations of FSH and hCG

Abstract

A novel ovulatory induction paradigm entails administration of hCG in combination with FSH during all stages of treatment, where the ratio of FSH to hCG is adjusted to optimize ovulatory stimulation and minimize complications. The use of compositions characterized by various FSH:hCG ratios enables the practitioner readily to tailor the treatment regimen and accommodate different therapeutic goals as well as individual patient responses to gonadotropin administration.

1 . A pharmaceutical composition consisting essentially of FSH and hCG in a pharmaceutically acceptable carrier, wherein the amount of FSH and hCG is selected from the group consisting of:
 (i) 50 IU FSH and 100 IU hCG;   (ii) 50 IU FSH and 200 IU hCG;   (iii) 75 IU FSH and 25 IU hCG;   (iv) 75 IU FSH and 50 IU hCG;   (v)75 IU FSH and 75 IU hCG;   (vi) 75 IU FSH and 100 IU hCG;   (vii) 150 IU FSH and 25 IU hCG;   (viii) 150 IU FSH and 50 IU hCG,   (ix) 150 IU FSH and 75 IU hCG; and   (x) 150 IU FSH and 100 IU hCG.   
     
     
         2 . The pharmaceutical composition of  claim 1  free from any other proteins of mammal origin. 
     
     
         3 . The pharmaceutical composition of  claim 1  wherein the amount of FSH and hCG is selected from the group consisting of (i) 50 IU FSH and 100 IU hCG and (ii) 50 IU FSH and 200 IU hCG. 
     
     
         4 . The pharmaceutical composition of  claim 1  wherein the amount of FSH and hCG is selected from the group consisting of (i) 75 IU FSH and 25 IU hCG; (ii) 75 IU FSH and 50 IU hCG; and (iii) 75 IU FSH and 75 IU hCG. 
     
     
         5 . The pharmaceutical composition of  claim 1  wherein the amount of FSH and hCG is 150 IU FSH and 25 IU hCG. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein said FSH is human-derived FSH. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , in lyophilized form. 
     
     
         8 . The pharmaceutical composition according to  claim 1 , in unit dosage form. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , in solid dosage form. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the solid dosage form is selected from the group consisting of capsules, tablets, suppositories, pills, powders, and granules. 
     
     
         11 . The pharmaceutical composition according to  claim 1  in liquid form. 
     
     
         12 . The pharmaceutical composition according to  claim 11  wherein the liquid form is supplied in a vial. 
     
     
         13 . The pharmaceutical composition according to  claim 11  wherein the liquid form is supplied in a pre-filled syringe or cartridge. 
     
     
         14 . The composition of  claim 1 , wherein said FSH is recombinant and wherein said hCG is recombinant. 
     
     
         15 . An assemblage comprising a first vial and a second vial, each of said vials containing a pharmaceutical composition according to  claim 1 , wherein a ratio of FSH to hCG differs between the first vial and the second vial. 
     
     
         16 . The assemblage according to  claim 15  further comprising written instructions on the timing for administering the compositions contained in the first and second vials. 
     
     
         17 . A method of inducing ovulation, comprising:
 (A) administering at least one pharmaceutical composition comprising an amount of FSH and hCG selected from the group consisting of:
 (i) 50 IU FSH and 100 IU hCG; 
 (ii) 50 IU FSH and 200 IU hCG; 
 (iii) 75 IU FSH and 25 IU hCG; 
 (iv) 75 IU FSH and 50 IU hCG; 
 (v) 75 IU FSH and 75 IU hCG; 
 (vi) 75 IU FSH and 100 IU hCG; 
 (vii) 150 IU FSH and 25 IU hCG; 
 (viii) 150 IU FSH and 50 IU hCG; 
 (ix) 150 IU FSH and 75 IU hCG; and 
 (x) 150 IU FSH and 100 IU hCG; 
   (B) monitoring serum hormone levels, follicle size and follicle number; and then   (C) administering an hCG bolus, thereby inducing ovulation.   
     
     
         18 . The method of  claim 17 , wherein the amount of FSH and hCG is selected from the group consisting of (i) 50 IU FSH and 100 IU hCG and (ii) 50 IU FSH and 200 IU hCG. 
     
     
         19 . The method of  claim 17 , wherein the amount of FSH and hCG is selected from the group consisting of (i) 75 IU FSH and 25 IU hCG; (ii) 75 IU FSH and 50 IU hCG; and (iii) 75 IU FSH and 75 IU hCG. 
     
     
         20 . The method of  claim 17 , wherein the amount of FSH and hCG is 150 IU FSH and 25 IU hCG. 
     
     
         21 . The method of  claim 17 , wherein step (A) comprises administering in series a first pharmaceutical composition and at least one second pharmaceutical compositions wherein
 (A) said first pharmaceutical composition comprises an amount of FSH and hCG selected from the group consisting of:
 (i) 50 IU FSH and 100 IU hCG; 
 (ii) 50 IU FSH and 200 IU hCG; 
 (iii) 75 IU FSH and 25 IU hCG; 
 (iv) 75 IU FSH and 50 IU hCG; 
 (v) 75 IU FSH and 75 IU hCG; 
 (vi) 75 IU FSH and 100 IU hCG; 
 (vii) 150 IU FSH and 25 IU hCG; 
 (viii) 150 IU FSH and 50 IU hCG; 
 (ix) 150 IU FSH and 75 IU hCG; and 
 (x) 150 IU FSH and 100 IU hCG; 
   (B) said second pharmaceutical composition comprises FSH and hCG,   wherein the amount of FSH and hCG in said second pharmaceutical composition is the same as or different from the amount of FSH and hCG in said first pharmaceutical composition.   
     
     
         22 . The method of  claim 21 , wherein each of said at least one second pharmaceutical compositions comprises an amount of hCG that is increased over the preceding pharmaceutical composition in said series. 
     
     
         23 . The method of  claim 21 , wherein the period of time between administrations of said compositions of the series is selected from the group consisting of from 1 hour, 5 hours, 10 hours, 12 hours, 24 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, and 15 days. 
     
     
         24 . The method of  claim 17 , wherein the method further comprises administering a pharmaceutical composition comprising pure FSH. 
     
     
         25 . The method of  claim 17 , wherein the method further comprises administering a pharmaceutical composition comprising pure hCG.