Methods and systems for assessing infertility and related pathologies

Abstract

Methods for assessing infertility and related pathologies and informing treatment type and timing thereof are provided. According to certain embodiments, methods of the invention include determining levels of one or more transcripts present in a sample obtained from a subject suspected of having endometriosis, identifying transcript levels that correspond to a regulation pattern specific to a time-point in a uterine cycle, and characterizing endometriosis of the subject based upon the identified transcript levels. The invention includes methods for assessing age-associated increase in aneuploidy rates based on FSH levels and IVF success rates based on obesity in PCOS patients.

1 .- 9 . (canceled) 
     
     
         10 . A method for assessing endometriosis, the method comprising:
 a. sequencing nucleic acid obtained from a blood or tissue sample derived from a subject to determine a level of a transcript of one or more endometrial-associated gene(s) present in the blood or tissue sample,   b. analyzing said levels of transcripts against a reference regulation pattern specific to a time-point in a uterine cycle using a computer system having a processor, thereby to generate a patient-specific signature, the reference regulation pattern being generated using gene expression data obtained from the one or more gene(s) across each phase of the uterine cycle from a reference population that includes both normal patients and endometriosis patients; and   c. scoring an endometriosis status of the subject based upon said patient-specific signature.   
     
     
         11 . The method of  claim 10 , wherein the one or more endometrial-associated gene(s) comprise CCL3L1, CCL3, FAM180A, THBS2, PDGFRL, FN1, CLE11A, CCNA2, KIF20A, BUB1B, HSD17B6, HSD11B1, C7, C3, CXCL2, CXCL12, CXCL13, PDGFC, CXCL14, ACTA2, TAGLN, ROBO3, MT1M, or SORBS1. 
     
     
         12 . The method of  claim 10 , wherein the one or more endometrial-associated gene(s) comprise CCNA2, KIF20A, BUB1B, CXCL13, ACTA2, TAGLN, MT1M, SORBS1. 
     
     
         13 . The method of  claim 10 , wherein the one or more endometrial-associated gene(s) comprise SORBS1, TAGLN, or ACTA2. 
     
     
         14 . The method of  claim 10 , wherein the blood or tissue sample endometrial tissue. 
     
     
         15 . The method of  claim 10 , wherein the blood or tissue sample is a blood sample. 
     
     
         16 . The method of  claim 10 , wherein the time-point comprises a phase in the uterine cycle. 
     
     
         17 . A method of treating infertility in a woman, the method comprising:
 subjecting the woman to an in vitro fertility (IVF) treatment, the in vitro fertility (IVF) treatment implanting an embryo into the woman, the woman having a score of likelihood of implantation, clinical pregnancy, and/or live birth outcomes in potential IVF treatment, the score having been generated by:
 i. sequencing nucleic acid obtained from a blood or tissue sample derived from the subject to determine a level of a transcript of one or more infertility-associated gene(s) present in the blood or tissue sample obtained from the subject, 
 ii. analyzing said levels of transcripts against a reference regulation pattern specific to a time-point in a uterine cycle using a computer system having a processor, thereby to generate a patient-specific signature, the reference regulation pattern being generated using gene expression data obtained from the one or more infertility-associated gene(s) across each phase of the uterine cycle from a reference population that includes both normal patients and infertile patients; and 
 iii. scoring the likelihood of implantation, clinical pregnancy, or live birth outcomes in potential IVF treatment of the subject based upon said patient-specific signature. 
   
     
     
         18 . The method of  claim 17 , wherein the one or more infertility-associated gene(s) comprise CCL3L1, CCL3, FAM180A, THBS2, PDGFRL, FN1, CLE11A, CCNA2, KIF20A, BUB1B, HSD17B6, HSD11B1, C7, C3, CXCL2, CXCL12, CXCL13, PDGFC, CXCL14, ACTA2, TAGLN, ROBO3, MT1M, or SORBS1. 
     
     
         19 . The method of  claim 17 , wherein the one or more infertility-associated gene(s) comprise CCNA2, KIF20A, BUB1B, CXCL13, ACTA2, TAGLN, MT1M, SORBS1. 
     
     
         20 . The method of  claim 17 , wherein the one or more infertility-associated gene(s) comprise SORBS1, TAGLN, or ACTA2. 
     
     
         21 . The method of  claim 17 , wherein the blood or tissue sample is a tissue sample. 
     
     
         22 . The method of  claim 21 , wherein the tissue sample comprises endometrial tissue. 
     
     
         23 . The method of  claim 22 , wherein the endometrial tissue is ectopic, eutopic, or both. 
     
     
         24 . The method of  claim 17 , wherein the blood or tissue sample is a blood sample. 
     
     
         25 . The method of  claim 17 , wherein the reference regulation pattern is specific to ectopic tissue, eutopic tissue, or both. 
     
     
         26 . The method of  claim 17 , wherein the time-point comprises a phase in the uterine cycle. 
     
     
         27 . The method of  claim 26 , wherein the phase is selected from the group consisting of the menstruation phase, the proliferative phase, the early secretory phase, the mid-secretory phase, and the late secretory phase. 
     
     
         28 . The method of  claim 17 , wherein the reference regulation pattern comprises one or more transcripts selected from the group consisting of de-regulated transcripts, up-regulated transcripts, and combinations thereof. 
     
     
         29 . The method of  claim 17 , wherein the analyzing step comprises determining the subject's phase in the uterine cycle.