Identification of Viable Human Embryos
Disclosed herein is a method for assessing the probability of embryo implantation success during the in vitro fertilization process. A method of the disclosure can predict embryo implantation success based on, for example, the amount of specific metabolites present in embryo conditioned culture media.
1 . A method comprising:
a) obtaining a sample of culture media in which one or more embryos has been cultured in vitro;
b) measuring from the sample an amount of one or more metabolites in the sample, wherein at least one of the metabolites is selected from the group consisting of caprolactam, N-cyclohexylformamide, threo-3-hydroxy-2-methylbutyric acid, sulfoacetic acid, (2,7-dimethyloctahydro-1H-cyclopenta[c]pyridin-4-yl)methanol, trans-3-indoleacrylic acid, pantothenic acid, diaveridine, (5-benzyl-3,6-dioxo-2-piperazinyl)acetic acid, dasytrichone, indole, leucoline, skatole, 6-hydroxycaproic acid, 1,2,6-hexanetriol, naphthalen-2-amine, 8-hydroxyquinoline, 2,2,6,6-tetramethyl-4-piperidinol, 1,5-naphthalenediamine, 1H-indole-2-carboxylic acid, (E)-dacarbazine, dinitrosopentamethylenetetramine, 5-hydroxyindole-3-acetic acid, 3-amino-5,7-dimethyl-1-adamantanol, 11-aminoundecanoic acid, kynurenine, N-hydroxy-L-tryptophan, 2-(methylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, 5-hydroxy-N formylkynurenine, and N-lauroylglycine; and
c) comparing the amount of the one or more metabolites in the sample to a reference of known clinical outcomes; and
d) transferring one or more embryos with a high probability of implantation success based on step c) into a subject's uterus.
2 . The method of claim 1 , wherein the metabolite is caprolactam.
3 . The method of claim 1 , wherein the metabolite is N-cyclohexylformamide.
4 . The method of claim 1 , wherein the metabolite is threo-3-hydroxy-2-methylbutyric acid.
5 . The method of claim 1 , wherein the metabolite is sulfoacetic acid.
6 . The method of claim 1 , wherein the metabolite is (2,7-dimethyloctahydro-1H cyclopenta[c]pyridin-4-yl)methanol.
7 . The method of claim 1 , wherein the metabolite is trans-3-indoleacrylic acid.
8 . The method of claim 1 , wherein the metabolite is pantothenic acid.
9 . The method of claim 1 , wherein the metabolite is diaveridine.
10 . The method of claim 1 , wherein the metabolite is (5-benzyl-3,6-dioxo-2-piperazinyl)acetic acid.
11 . The method of claim 1 , wherein the metabolite is dasytrichone.
12 . The method of claim 1 , wherein the metabolite is indole.
13 . The method of claim 1 , wherein the metabolite is leucoline.
14 . The method of claim 1 , wherein the metabolite is skatole.
15 . The method of claim 1 , wherein the metabolite is 6-hydroxycaproic acid.
16 . The method of claim 1 , wherein the metabolite is 1,2,6-hexanetriol.
17 . The method of claim 1 , wherein the metabolite is naphthalen-2-amine.
18 . The method of claim 1 , wherein the metabolite is 8-hydroxyquinoline.
19 . The method of claim 1 , wherein the metabolite is 2,2,6,6-tetramethyl-4-piperidinol.
20 . The method of claim 1 , wherein the metabolite is 1,5-naphthalenediamine.
21 . The method of claim 1 , wherein the metabolite is 1H-indole-2-carboxylic acid.
22 . The method of claim 1 , wherein the metabolite is (E)-dacarbazine.
23 . The method of claim 1 , wherein the metabolite is dinitrosopentamethylenetetramine.
24 . The method of claim 1 , wherein the metabolite is 5-hydroxyindole-3-acetic acid.
25 . The method of claim 1 , wherein the metabolite is 3-amino-5,7-dimethyl-1-adamantanol.
26 . The method of claim 1 , wherein the metabolite is 11-aminoundecanoic acid.
27 . The method of claim 1 , wherein the metabolite is kynurenine.
28 . The method of claim 1 , wherein the metabolite is N-hydroxy-L-tryptophan.
29 . The method of claim 1 , wherein the metabolite is 2-(methylamino)-1H benzo[de]isoquinoline-1,3(2H)-dione.
30 . The method of claim 1 , wherein the metabolite is 5-hydroxy-N-formylkynurenine.
31 . The method of claim 1 , wherein the metabolite is N-lauroylglycine.
32 . A method comprising:
a) obtaining a sample of culture media in which one or more embryos has been cultured in vitro;
b) measuring from the sample an amount of at least four metabolites selected from the group consisting of: caprolactam, N-cyclohexylformamide, threo-3-hydroxy-2-methylbutyric acid, sulfoacetic acid, phenylalanine, (2,7-dimethyloctahydro-1H-cyclopenta[c]pyridin-4-yl)methanol, trans-3-indoleacrylic acid, DL-tryptophan, pantothenic acid, diaveridine, (5-benzyl-3,6-dioxo-2-piperazinyl)acetic acid, dasytrichone, indole, leucoline, skatole, 6-hydroxycaproic acid, 1,2,6-hexanetriol, naphthalen-2-amine, 8-hydroxyquinoline, 2,2,6,6-tetramethyl-4-piperidinol, 1,5-naphthalenediamine, 1H-indole-2-carboxylic acid, (E)-dacarbazine, dinitrosopentamethylenetetramine, 5-hydroxyindole-3-acetic acid, 3-amino-5,7-dimethyl-1-adamantanol, 11-aminoundecanoic acid, kynurenine, N-hydroxy-L-tryptophan, 2-(methylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, 5-hydroxy-N-formylkynurenine, and N-lauroylglycine; and
c) comparing the amount of each measured metabolite in the sample to a reference of known clinical outcomes; and
d) transferring one or more embryos with a high probability of implantation success based on step c) into a subject's uterus.
33 . A kit comprising an aliquot of each of 3 metabolites selected from the group consisting of: caprolactam, N-cyclohexylformamide, threo-3-hydroxy-2-methylbutyric acid, sulfoacetic acid, (2,7-dimethyloctahydro-1H-cyclopenta[c]pyridin-4-yl)methanol, trans-3-indoleacrylic acid, pantothenic acid, diaveridine, (5-benzyl-3,6-dioxo-2-piperazinyl)acetic acid, dasytrichone, indole, leucoline, skatole, 6-hydroxycaproic acid, 1,2,6-hexanetriol, naphthalen-2-amine, 8-hydroxyquinoline, 2,2,6,6-tetramethyl-4-piperidinol, 1,5-naphthalenediamine, 1H-indole-2-carboxylic acid, (E)-dacarbazine, dinitrosopentamethylenetetramine, 5-hydroxyindole-3-acetic acid, 3-amino-5,7-dimethyl-1-adamantanol, 11-aminoundecanoic acid, kynurenine, N-hydroxy-L-tryptophan, 2-(methylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, 5-hydroxy-N-formylkynurenine, DL-tryptophan, phenylalanine, and N-lauroylglycine.