Identifying status of male fertility by determining sperm capacitation

Abstract

This disclosure provides a method for determining male fertility status. The method comprises determining GM1 distribution patterns following induced sperm capacitation, identifying the frequency of distribution of various patterns, and determining if the frequency distribution of certain GM1 patterns in response to induced capacitation is altered. Based on the change in the frequency distribution patterns of certain patterns in response to induced capacitation, alone or in combination with other sperm attributes, male fertility status can be identified.

What is claimed is: 
     
         1 . A method for identifying fertility status of a human male individual as infertile, sub-fertile, or fertile, comprising:
 exposing a sperm sample from the individual to capacitating conditions to obtain capacitated sperm;   fixing the capacitated sperm with a fixative;   staining the capacitated sperm to identify G M1  patterns;   determining a frequency of selected G M1  patterns in the capacitated sperm; and   comparing the frequency of one or more G M1  patterns to a reference to determine fertility status of the individual.   
     
     
         2 . The method of  claim 1 , wherein the one or more G M1  patterns are INTER, AA, and/or APM. 
     
     
         3 . The method of  claims 1 - 2 , wherein the reference is a fertility threshold, and wherein a frequency less than the fertility threshold is indicative of a fertility status of infertile or sub-fertile. 
     
     
         4 . The method of  claim 3 , wherein the fertility threshold is a percentage of AA+APM patterns one standard deviation below a mean percentage of AA+APM patterns in capacitated sperm for a population of known fertile individuals. 
     
     
         5 . The method of  claim 3 , wherein the fertility threshold is the AA+APM pattern frequency at which the fertility of a population ceases to substantially increase. 
     
     
         6 . The method of  claim 3 , wherein the fertility threshold is a level of AA+APM at which more than 50% of the population are fertile. 
     
     
         7 . The method of  claim 3 , wherein the fertility threshold is a level of AA+APM at which more than 60-85% of a population is fertile. 
     
     
         8 . The method of  claim 3 , wherein the fertility threshold is a level of AA+APM in the range of 35-40% of the total G M1  patterns, inclusive. 
     
     
         9 . The method of  claim 3 , wherein the fertility threshold is a level of AA+APM of 38, 38.5, 39, or 39.5% of the total G M1  patterns. 
     
     
         10 . The method of  claims 1 - 2 , wherein the reference is an infertility threshold, and wherein a frequency less than the fertility threshold is indicative of a fertility status of infertile. 
     
     
         11 . The method of  claim 10 , wherein the infertility threshold is a percentage of AA+APM patterns two standard deviations below a mean percentage of AA+APM patterns in capacitated sperm for a population of known fertile individuals. 
     
     
         12 . The method of  claim 10 , wherein the infertility threshold is the AA+APM pattern frequency at which the fertility of a population begins to substantially increase. 
     
     
         13 . The method of  claim 10 , wherein the infertility threshold is a level of AA+APM at which less than 50% of the population are fertile. 
     
     
         14 . The method of  claim 10 , wherein the fertility threshold is a level of AA+APM at which more than 60-85% of a population is fertile. 
     
     
         15 . The method of  claim 10 , wherein the infertility threshold is a level of AA+APM in the range of 14-18% of the total G M1  patterns, inclusive. 
     
     
         16 . The method of  claim 10 , wherein the infertility threshold is a level of AA+APM of 14, 14.5, 15, or 15.5% of the total G M1  patterns. 
     
     
         17 . The method of  claims 1 - 2 , wherein the capacitating conditions include exposure to one or more of bicarbonate ions, calcium ions, and a mediator of sterol efflux. 
     
     
         18 . The method of  claim 17 , wherein the mediator of sterol efflux is 2-hydroxy-propyl β cyclodextrin, methyl-β-cyclodextrin, serum albumin, high density lipoprotein, phospholipid vesicles, fetal cord serum ultrafiltrate, fatty acid binding proteins, or liposomes. 
     
     
         19 . The method of  claim 1 , wherein the fixative comprises paraformaldehyde, glutaraldehyde or combinations thereof. 
     
     
         20 . A method for identifying fertility status of a male individual comprising:
 obtaining a sperm sample, wherein the sperm sample is from the individual, and wherein the sperm sample has been exposed to capacitating conditions, has been fixed, and has been stained for G M1  patterns;   determining a frequency of G M1  patterns in the sperm sample; and   comparing the frequency of one or more G M1  patterns to a reference to determine fertility status of the individual.