Methods of assessing the risk of reproductive failure by measuring telomere length

Abstract

The invention features a method of identifying oocytes with a risk of reproductive failure and/or aneuploidy based on a telomere length assay.

1 . A method for determining the risk of reproductive failure in a cell comprising: 
 obtaining at least one chromosome from the cell; 
 measuring telomere length of the chromosome; and  
   comparing the measured length of the telomere to the standardized average length of a control telomere;    to thereby determine the risk of reproductive failure in the cell.    
     
     
         2 . The method of  claim 1 , wherein the cell is an oocyte, an oocyte representative of a population of oocytes, a polar body from a fertilized oocyte, or a polar body from an unfertilized oocyte.  
     
     
         3 . The method of  claim 2 , wherein the cell is an oocyte.  
     
     
         4 . The method of  claim 1 , wherein a labeled telomere-specific probe is hybridized to the chromosome prior to measuring telomere length of the chromosome.  
     
     
         5 . The method of  claim 4 , wherein the probe is hybridized to telomere repeats.  
     
     
         6 . The method of  claim 4 , wherein the probe is peptide nucleic acid (PNA)-labeled.  
     
     
         7 . The method of  claim 1 , wherein the telomere is measured using quantitative fluorescent in situ hybridization (Q-FISH) analysis.  
     
     
         8 . The method of  claim 1  for use in in vitro fertilization (IVF).  
     
     
         9 - 12 . (canceled)  
     
     
         13 . A method for determining the predisposition of an oocyte to reproductive failure comprising: 
 obtaining at least one chromosome from the oocyte:    measuring telomere length of the chromosome; and    comparing the measured length of the telomere to the standardized average length of a control telomere;    to thereby determine the predisposition of the oocyte to reproductive failure.    
     
     
         14 . The method of  claim 13 , wherein a labeled telomere-specific probe is hybridized to the chromosome prior to measuring telomere length of the chromosome.  
     
     
         15 . The method of  claim 14 , wherein the probe is hybridized to telomere repeats.  
     
     
         16 . The method of  claim 14 , wherein the probe is peptide nucleic acid (PNA)-labeled.  
     
     
         17 . The method of  claim 14 , wherein the telomere is measured using quantitative fluorescent in situ hybridization (Q-FISH) analysis.  
     
     
         18 . The method of  claim 13 , wherein the oocyte is representative of a population of oocytes.  
     
     
         19 . A method for selecting a fertilized oocyte with a low risk of reproductive failure for in vitro fertilization, comprising: 
 obtaining at least one chromosome from the polar body of the fertilized oocyte;    measuring telomere length of the chromosome; and    comparing the measured length of the telomere to the standardized average length of a control telomere;    to thereby select a fertilized oocyte with a low risk of reproductive failure for in vitro fertilization.    
     
     
         20 . A method of in vitro fertilization comprising: 
 selecting a fertilized oocyte according to the method of  claim 19;  and    implanting the selected fertilized oocyte in the subject.    
     
     
         21 . The method of  claim 20 , wherein the subject is a human.  
     
     
         22 . A method for optimizing the viability of an embryo comprising: 
 selecting a fertilized oocyte according to the method of  claim 19;  and    implanting the selected fertilized oocyte in a subject.    
     
     
         23 . The method of  claim 22 , wherein the subject is a human.  
     
     
         24 . A method for determining the risk of aneuploidy in a cell comprising: 
 obtaining at least one chromosome from the cell; 
 measuring telomere length of the chromosome; and  
   comparing the measured length of the telomere to the standardized average length of a control telomere;    to thereby determine the risk of aneuploidy in the cell.    
     
     
         25 . The method of  claim 24 , wherein the cell is selected from the group consisting of an oocyte, an oocyte representative of a population of oocytes, a polar body from a fertilized oocyte, and a polar body from an unfertilized oocyte.  
     
     
         26 . The method of  claim 24 , wherein a labeled telomere-specific probe is hybridized to the chromosome prior to measuring telomere length of the chromosome.  
     
     
         27 . The method of  claim 26 , wherein the probe is hybridized to telomere repeats.  
     
     
         28 . The method of  claim 26 , wherein the probe is peptide nucleic acid (PNA)-labeled.  
     
     
         29 . The method of  claim 26 , wherein the telomere is measured using quantitative fluorescent In situ hybridization (Q-FISH) analysis.  
     
     
         30 . The method of  claim 26  for use in vitro fertilization (IVF).  
     
     
         31 . The method of  claim 24  wherein said cell is in a population of cells representative of said cell.  
     
     
         32 . The method of  claim 31  wherein the cell is an.  
     
     
         33 . The method of  claim 33  further comprising: 
 hybridizing telomere-specific probes to said chromosome; and  
 performing quantitative fluorescent in situ hybridization (Q-FISH) analysis.  
 
     
     
         34 . A method for selecting a fertilized oocyte with a low risk of aneuploidy for in vitro fertilization, comprising: 
 obtaining at least one chromosome from the polar body of the fertilized oocyte;    hybridizing telomere-specific probes to said chromosome;    performing quantitative fluorescent in situ hybridization (Q-FISH) analysis;    measuring telomere length of the chromosome; and    comparing the measured length of the telomere to the standardized average length of a control telomere;    to thereby select a cell with a low risk of aneuploidy.    
     
     
         35 . A method for determining the predisposition of an oocyte to anouploidy comprising: 
 obtaining at least one chromosome from the oocyte;    measuring telomere length of the chromosome; and    comparing the measured length of the telomere to the standardized average length of a control telomere;    to thereby optimize the viability of the embryo.    
     
     
         36 . The method of  claim 35 , wherein a labeled telomere-specific probe is hybridized to the chromosome prior to measuring telomere length of the chromosome.  
     
     
         37 . The method of  claim 36 , wherein the probe is hybridized to telomere repeats.  
     
     
         38 . The method of  claim 36 , wherein the probe is peptide nucleic acid (PNA)-labeled.  
     
     
         39 . The method of  claim 35 , wherein the telomere is measured using quantitative fluorescent in situ hybridization (Q-FISH) analysis.  
     
     
         41 . The method of  claim 35 , for use in vitro fertilization.  
     
     
         42 . The method of  claim 35 , wherein the oocyte is representative of a population of oocytes.  
     
     
         43 . A method of pre-implantation genetic testing to identify an oocyte with a predisposition to aneuploidy comprising: 
 obtaining at least one chromosome from the oocyte;    measuring telomere length of the chromosome; and    comparing the measured length of the telomere to the standardized average length of a control telomere.    
     
     
         44 . The method of  claim 43 , wherein a labeled telomere-specific probe is hybridized to the chromosome prior to measuring telomere length of the chromosome.  
     
     
         45 . The method of  claim 43 , wherein the telomere is measured using quantitative fluorescent in situ hybridization (Q-FISH) analysis.  
     
     
         46 . The method of  claim 43  for use in vitro fertilization (IVF).  
     
     
         47 . The method according to  claim 1 , further comprising obtaining a probe for hybridizing to the chromosome.  
     
     
         48 . The method according of  claim 47 , wherein said probe is a labeled telomere-specific probe.  
     
     
         49 . The method according to  claim 48 , wherein the telomere specific probe comprises a nucleic acid sequence identified by any one of SEQ ID NOS: 1 through 10.  
     
     
         50 . The method according to  claim 48 , wherein the telomere specific probe comprises a nucleic acid sequence having at least about 80 percent sequence identity to any one of SEQ ID. NOS. 1 through 10.  
     
     
         51 . The method according to  claim 48 , wherein the telomere specific probe comprises a nucleic acid sequence having at least about 90 percent sequence identity to any one of SEQ ID. NOS. 1 through 10.  
     
     
         52 . A kit for determining the risk of reproductive failure and/or aneuploidy in a cell comprising 
 reagents for preparing a chromosomal spread from the cell or at least one cell in a population of cells representative of said cell; labeled telomere-specific repeat probes; reagents for performing quantitative fluorescent in situ hybridization (Q-FISH) analysis on the chromosomal spread; and instructions for measuring the length of a telomere obtained from the chromosomal spread, or obtained from a chromosome of said cell, and comparing the measured length of the telomere to the standardized average length of a control.    
     
     
         53 . The kit of  claim 52 , wherein the chromosome is obtained from a cell selected from the group consisting of an oocyte, an oocyte representative of a population of oocytes, or the polar body from a fertilized or unfertilized oocyte.  
     
     
         54 . The kit of  claim 52 , wherein the probes are peptide nucleic acid (PNA)-labeled.