Compositions and methods for enhancing sperm function

Abstract

The disclosure provides, inter alia, methods of improving sperm function and related methods of fertilization, together with preparations of activated or potentiated sperm. The disclosure additionally provides articles of manufacture suitable for performing the methods provided by the invention. The methods provided by the disclosure, in some embodiments entail energy depletion with subsequent staged reintroduction of different energy sources.

What is claimed is: 
     
         1 . A method for preparing a mammalian sperm for use in an assisted reproductive procedure, the method comprising;
 (a) incubating the mammalian sperm under energy depletion conditions for a time suitable to generate a potentiated mammalian sperm; and   (b) providing the potentiated mammalian sperm from step (a) with an effective amount of a first energy source and a second energy source in a serial manner, wherein the effective amount is the amount sufficient to induce improved sperm function, and wherein the mammalian sperm provided by step (b) is suitable for use in the assisted reproductive procedure.   
     
     
         2 . The method of  claim 1 , wherein one or more sperm function is selected from curvilinear velocity, amplitude or lateral head displacement, autophagy, sperm capacitation, percentage of hyperactivated sperm, percentage of intermediate motility sperm and percentage of hyperactivated sperm and intermediate motility sperm, is improved relative to a suitable control sperm. 
     
     
         3 . The method of  claim 1 , further comprising resuspending the mammalian sperm provided by step (b) in a fertilization medium, a preservation medium, or a culture medium. 
     
     
         4 . The method of  claim 3 , wherein the fertilization medium is human tubal fertilization medium. 
     
     
         5 . The method of  claim 1 , further comprising the step of cryopreserving the mammalian sperm provided by step (b) prior to use in the assisted reproductive procedure. 
     
     
         6 . The method of  claim 1 , wherein the assisted reproductive procedure comprises in vitro fertilization of an egg by the mammalian sperm provided by step (b) to generate an embryo. 
     
     
         7 . The method of  claim 1 , wherein the assisted reproductive procedure is selected from the group consisting of frozen embryo transfer (FET), intracytoplasmic sperm injection (ICSI), gamete intrafallopian tube transfer (GIFT), and zygote intrafallopian tube transfer (ZIFT). 
     
     
         8 . The method of  claim 1 , wherein the assisted reproductive procedure is artificial insemination of the mammalian sperm provided by step (b). 
     
     
         9 . The method of  claim 8 , wherein the artificial insemination is intra-uterine insemination or intracervical insemination of the mammalian sperm provided by step (b). 
     
     
         10 . The method of  claim 1 , wherein the mammalian sperm of step (a) is recovered from a cryogenic storage. 
     
     
         11 . The method of  claim 1 , wherein the mammalian sperm of step (a) is recovered from a non-cryogenic storage. 
     
     
         12 . The method of  claim 1 , wherein the mammalian sperm of step (a) is from an oligospermic subject or a subfertile subject. 
     
     
         13 . The method of  claim 1 , wherein the mammalian sperm of step (a) is a human sperm. 
     
     
         14 . The method of  claim 1 , wherein the mammalian sperm of step (a) is provided as a pool of two or more ejaculates. 
     
     
         15 . The method of  claim 1 , wherein the mammalian sperm of step (a) is enriched from semen prior to step (a) by density gradient centrifugation, swim up, or microfluidics. 
     
     
         16 . The method of  claim 1 , wherein the first energy source is a glycolytic energy source and the second energy source is a gluconeogenesis substrate, or the first energy source is the glycolytic energy source and the second energy source is the gluconeogenesis substrate. 
     
     
         17 . The method of  claim 16 , wherein the glycolytic energy source is glucose. 
     
     
         18 . The method of  claim 16 , wherein the gluconeogenesis substrate is pyruvate. 
     
     
         19 . The method of  claim 1 , wherein the method is performed at an osmolality ranging from 200-280 mOsm/kg. 
     
     
         20 . The method of  claim 1 , wherein the incubating under energy depletion conditions of step (a) is for at least 10 min.