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 .- 41 . (canceled) 
     
     
         42 . A method of inducing ovulation, comprising:
 (A) administering in series at least two pharmaceutical compositions, each of which comprises FSH and hCG in an amount that is selected from the group consisting of:
 i) 50 IU FSH and 1 IU hCG; 
 ii) 50 IU FSH and 5 IU hCG; 
 iii) 50 IU FSH and 10 IU hCG; 
 iv) 50 IU FSH and 25 IU hCG; 
 v) 50 IU FSH and 75 IU hCG; 
 vi) 50 IU FSH and 100 IU hCG; 
 vii) 50 IU FSH and 200 IU hCG; 
 viii) 50 IU FSH and 300 IU hCG; 
 ix) 50 IU FSH and 400 IU hCG; 
 x) 75 IU FSH and 1 IU hCG; 
 xi) 75 IU FSH and 5 IU hCG; 
 xii) 75 IU FSH and 10 IU hCG; 
 xiii) 75 IU FSH and 25 IU hCG; 
 xiv) 75 IU FSH and 50 IU hCG; 
 xv) 75 IU FSH and 75 IU hCG; 
 xvi) 75 IU FSH and 100 IU hCG; 
 xvii) 75 IU FSH and 200 IU hCG; 
 xviii) 75 IU FSH and 300 IU hCG; 
 xix) 75 IU FSH and 400 IU hCG; 
 xx) 100 IU FSH and 1 IU hCG; 
 xxi) 100 IU FSH and 5 IU hCG; 
 xxii) 100 IU FSH and 10 IU hCG; 
 xxiii) 100 IU FSH and 25 IU hCG; 
 xxiv) 100 IU FSH and 50 IU hCG; 
 xxv) 100 IU FSH and 75 IU hCG; 
 xxvi) 100 IU FSH and 100 IU hCG; 
 xxvii) 100 IU FSH and 200 IU hCG; 
 xxviii) 100 IU FSH and 300 IU hCG; 
 xxix) 100 IU FSH and 400 IU hCG; 
 xxx) 150 IU FSH and 1 IU hCG; 
 xxxi) 150 IU FSH and 5 IU hCG; 
 xxxii) 150 IU FSH and 10 IU hCG; 
 xxxiii) 150 IU FSH and 25 IU hCG; 
 xxxiv) 150 IU FSH and 100 IU hCG; 
 xxxv) 150 IU FSH and 200 IU hCG; 
 xxxvi) 150 IU FSH and 300 IU hCG; 
 xxxvii) 150 IU FSH and 400 IU hCG; 
 xxxviii) 200 IU FSH and 1 IU hCG; 
 xxxix) 200 IU FSH and 5 IU hCG; 
 xl) 200 IU FSH and 10 IU hCG; 
 xli) 200 IU FSH and 25 IU hCG; 
 xlii) 200 IU FSH and 50 IU hCG; 
 xliii) 200 IU FSH and 75 IU hCG; 
 xliv) 200 IU FSH and 100 IU hCG; 
 xlv) 200 IU FSH and 200 IU hCG; 
 xlvi) 200 IU FSH and 300 IU hCG; and 
 xlvii) 200 IU FSH and 400 IU hCG; 
   
       wherein the two pharmaceutical compositions differ with respect to the amount of FSH and/or hCG;
 (B) monitoring serum hormone levels, follicle size and follicle number; and then 
 (C) inducing ovulation by administration of an hCG bolus. 
 
     
     
         43 . The method of  claim 42 , wherein each succeeding composition in said series contains hCG that is increased over the preceding composition in said series. 
     
     
         44 . The method of  claim 42 , wherein the period of time between administrations of compositions of the series is selected from the group consisting of 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. 
     
     
         45 . A method of ovulation induction comprising administering FSH and hCG, 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 75 IU hCG;   (v) 75 IU FSH and 100 IU hCG;   (vi) 150 IU FSH and 25 IU hCG;   (vii) 150 IU FSH and 75 IU hCG; and   (viii) 150 IU FSH and 100 IU hCG.   
     
     
         46 . A method according to  claim 45  wherein the amount of FSH and hCG is selected from the group consisting of: (i) 75 IU FSH and 100 IU hCG, and (ii) 150 IU FSH and 100 IU hCG. 
     
     
         47 . A method according to  claim 45 , wherein the FSH and hCG are administered as a single pharmaceutical composition consisting essentially of FSH and hCG in a pharmaceutically acceptable carrier. 
     
     
         48 . A method according to  claim 45  wherein the FSH and hCG are administered separately. 
     
     
         49 . A method of treatment of infertility comprising administering FSH and hCG, wherein the FSH and hCG are administered as a single pharmaceutical composition consisting essentially of FSH and hCG in a pharmaceutically acceptable carrier, wherein the amount of FSH and hCG in the composition 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 75 IU hCG;   (v) 75 IU FSH and 100 IU hCG;   (vi) 150 IU FSH and 25 IU hCG;   (vii) 150 IU FSH and 75 IU hCG; and   (viii) 150 IU FSH and 100 IU hCG.   
     
     
         50 . A method according to  claim 49 , wherein the treatment of infertility is selected from the group consisting of treatment of anovulatory infertility, in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), cryopreserved embryo transfer, intrauterine insemination (IUD, donor oocyte transfer, cryopreserved embryo transfer from donor oocytes, and ART cycles for host uterus transfer. 
     
     
         51 . A method according to  claim 49 , for the treatment of anovulatory patients or patients with hypogonadotropic hypogonadism or polycystic ovary syndrome. 
     
     
         52 . A method according to  claim 49 , wherein the amount of FSH and hCG is selected from the group consisting of: (i) 75 IU FSH and 100 IU hCG, and (ii) 150 IU FSH and 100 IU hCG. 
     
     
         53 . A single 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 75 IU hCG;   (v) 75 IU FSH and 100 IU hCG;   (vi) 150 IU FSH and 25 IU hCG;   (vii) 150 IU FSH and 75 IU hCG; and   (viii) 150 IU FSH and 100 IU hCG.   
     
     
         54 . A method of inducing ovulation, comprising:
 (A) administering at least one single 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 75 IU hCG; 
 (v) 75 IU FSH and 100 IU hCG; 
 (vi) 150 IU FSH and 25 IU hCG; 
 (vii) 150 IU FSH and 75 IU hCG; and 
 (viii) 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.   
     
     
         55 . The method of  claim 54 , 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. 
     
     
         56 . The method of  claim 54 , wherein the amount of FSH and hCG is selected from the group consisting of (i) 75 IU FSH and 25 IU hCG; and (ii) 75 IU FSH and 75 IU hCG. 
     
     
         57 . The method of  claim 54 , wherein the amount of FSH and hCG is 150 IU FSH and 25 IU hCG. 
     
     
         58 . The method of  claim 54 , wherein step (A) comprises administering in series a first single pharmaceutical composition and at least one second single pharmaceutical compositions wherein
 (A) said first single 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 75 IU hCG; 
 (v) 75 IU FSH and 100 IU hCG; 
 (vi) 150 IU FSH and 25 IU hCG; 
 (vii) 150 IU FSH and 75 IU hCG; and 
 (viii) 150 IU FSH and 100 IU hCG; 
   (B) said second single 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.   
     
     
         59 . The method of  claim 58 , 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. 
     
     
         60 . The method of  claim 58 , wherein the period of time between administrations of said compositions of the series is selected from the group consisting of 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. 
     
     
         61 . The method of  claim 58 , wherein the method further comprises administering a pharmaceutical composition comprising pure FSH. 
     
     
         62 . The method of  claim 58 , wherein the method further comprises administering a pharmaceutical composition comprising pure hCG.