Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential

Amy E. Iager, Arif M. Kocabas, Hasan H. Otu, Patricia Ruppel, Anna Langerveld, Patricia Schnarr, Mariluz Suarez, John C. Jarrett, Joe Conaghan, Guilherme J.M. Rosa, Emilio Fernández, Richard G. Rawlins, Jose B. Cibelli, Javier A. Crosby

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Objective: To identify a gene expression signature in human cumulus cells (CCs) predictive of pregnancy outcome across multiple clinics, taking into account the clinic and patient variations inherent in IVF practice. Design: Retrospective analysis of single human cumulus-oocyte complexes with the use of a combined microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) approach. Setting: Multiple private IVF clinics. Patient(s): Fifty-eight patients. Samples from 55 patients underwent qRT-PCR analysis, and samples from 27 patients resulted in live birth. Intervention(s): Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately after oocyte retrieval. Pregnancy prediction analysis used leave-one-out cross-validation with weighted voting. Main Outcome Measure(s): Combinatorial expression of 12 genes in 101 samples from 58 patients. Result(s): We found a set of 12 genes predictive of pregnancy outcome based on their expression levels in CCs. This pregnancy prediction model had an accuracy of 78%, a sensitivity of 72%, a specificity of 84%, a positive predictive value of 81%, and a negative predictive value of 76%. Receiver operating characteristic analysis found an area under the curve of 0.763 ± 0.079, significantly greater than 0.5 (random chance prediction). Conclusion(s): Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET.

Original languageEnglish (US)
Pages (from-to)745-752.e6
JournalFertility and Sterility
Volume99
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

Cumulus Cells
Oocytes
Pregnancy
Pregnancy Outcome
Genes
Gene Expression
Reverse Transcription
Oocyte Retrieval
Polymerase Chain Reaction
Live Birth
Politics
Transcriptome
ROC Curve
Area Under Curve
Outcome Assessment (Health Care)

Keywords

  • Human cumulus cells
  • gene expression
  • human embryo
  • human oocyte
  • pregnancy outcome

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential. / Iager, Amy E.; Kocabas, Arif M.; Otu, Hasan H.; Ruppel, Patricia; Langerveld, Anna; Schnarr, Patricia; Suarez, Mariluz; Jarrett, John C.; Conaghan, Joe; Rosa, Guilherme J.M.; Fernández, Emilio; Rawlins, Richard G.; Cibelli, Jose B.; Crosby, Javier A.

In: Fertility and Sterility, Vol. 99, No. 3, 01.03.2013, p. 745-752.e6.

Research output: Contribution to journalArticle

Iager, AE, Kocabas, AM, Otu, HH, Ruppel, P, Langerveld, A, Schnarr, P, Suarez, M, Jarrett, JC, Conaghan, J, Rosa, GJM, Fernández, E, Rawlins, RG, Cibelli, JB & Crosby, JA 2013, 'Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential', Fertility and Sterility, vol. 99, no. 3, pp. 745-752.e6. https://doi.org/10.1016/j.fertnstert.2012.10.041
Iager, Amy E. ; Kocabas, Arif M. ; Otu, Hasan H. ; Ruppel, Patricia ; Langerveld, Anna ; Schnarr, Patricia ; Suarez, Mariluz ; Jarrett, John C. ; Conaghan, Joe ; Rosa, Guilherme J.M. ; Fernández, Emilio ; Rawlins, Richard G. ; Cibelli, Jose B. ; Crosby, Javier A. / Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential. In: Fertility and Sterility. 2013 ; Vol. 99, No. 3. pp. 745-752.e6.
@article{e56b094497eb41d4ae3295703d813f3e,
title = "Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential",
abstract = "Objective: To identify a gene expression signature in human cumulus cells (CCs) predictive of pregnancy outcome across multiple clinics, taking into account the clinic and patient variations inherent in IVF practice. Design: Retrospective analysis of single human cumulus-oocyte complexes with the use of a combined microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) approach. Setting: Multiple private IVF clinics. Patient(s): Fifty-eight patients. Samples from 55 patients underwent qRT-PCR analysis, and samples from 27 patients resulted in live birth. Intervention(s): Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately after oocyte retrieval. Pregnancy prediction analysis used leave-one-out cross-validation with weighted voting. Main Outcome Measure(s): Combinatorial expression of 12 genes in 101 samples from 58 patients. Result(s): We found a set of 12 genes predictive of pregnancy outcome based on their expression levels in CCs. This pregnancy prediction model had an accuracy of 78{\%}, a sensitivity of 72{\%}, a specificity of 84{\%}, a positive predictive value of 81{\%}, and a negative predictive value of 76{\%}. Receiver operating characteristic analysis found an area under the curve of 0.763 ± 0.079, significantly greater than 0.5 (random chance prediction). Conclusion(s): Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET.",
keywords = "Human cumulus cells, gene expression, human embryo, human oocyte, pregnancy outcome",
author = "Iager, {Amy E.} and Kocabas, {Arif M.} and Otu, {Hasan H.} and Patricia Ruppel and Anna Langerveld and Patricia Schnarr and Mariluz Suarez and Jarrett, {John C.} and Joe Conaghan and Rosa, {Guilherme J.M.} and Emilio Fern{\'a}ndez and Rawlins, {Richard G.} and Cibelli, {Jose B.} and Crosby, {Javier A.}",
year = "2013",
month = "3",
day = "1",
doi = "10.1016/j.fertnstert.2012.10.041",
language = "English (US)",
volume = "99",
pages = "745--752.e6",
journal = "Fertility and Sterility",
issn = "0015-0282",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential

AU - Iager, Amy E.

AU - Kocabas, Arif M.

AU - Otu, Hasan H.

AU - Ruppel, Patricia

AU - Langerveld, Anna

AU - Schnarr, Patricia

AU - Suarez, Mariluz

AU - Jarrett, John C.

AU - Conaghan, Joe

AU - Rosa, Guilherme J.M.

AU - Fernández, Emilio

AU - Rawlins, Richard G.

AU - Cibelli, Jose B.

AU - Crosby, Javier A.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Objective: To identify a gene expression signature in human cumulus cells (CCs) predictive of pregnancy outcome across multiple clinics, taking into account the clinic and patient variations inherent in IVF practice. Design: Retrospective analysis of single human cumulus-oocyte complexes with the use of a combined microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) approach. Setting: Multiple private IVF clinics. Patient(s): Fifty-eight patients. Samples from 55 patients underwent qRT-PCR analysis, and samples from 27 patients resulted in live birth. Intervention(s): Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately after oocyte retrieval. Pregnancy prediction analysis used leave-one-out cross-validation with weighted voting. Main Outcome Measure(s): Combinatorial expression of 12 genes in 101 samples from 58 patients. Result(s): We found a set of 12 genes predictive of pregnancy outcome based on their expression levels in CCs. This pregnancy prediction model had an accuracy of 78%, a sensitivity of 72%, a specificity of 84%, a positive predictive value of 81%, and a negative predictive value of 76%. Receiver operating characteristic analysis found an area under the curve of 0.763 ± 0.079, significantly greater than 0.5 (random chance prediction). Conclusion(s): Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET.

AB - Objective: To identify a gene expression signature in human cumulus cells (CCs) predictive of pregnancy outcome across multiple clinics, taking into account the clinic and patient variations inherent in IVF practice. Design: Retrospective analysis of single human cumulus-oocyte complexes with the use of a combined microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) approach. Setting: Multiple private IVF clinics. Patient(s): Fifty-eight patients. Samples from 55 patients underwent qRT-PCR analysis, and samples from 27 patients resulted in live birth. Intervention(s): Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately after oocyte retrieval. Pregnancy prediction analysis used leave-one-out cross-validation with weighted voting. Main Outcome Measure(s): Combinatorial expression of 12 genes in 101 samples from 58 patients. Result(s): We found a set of 12 genes predictive of pregnancy outcome based on their expression levels in CCs. This pregnancy prediction model had an accuracy of 78%, a sensitivity of 72%, a specificity of 84%, a positive predictive value of 81%, and a negative predictive value of 76%. Receiver operating characteristic analysis found an area under the curve of 0.763 ± 0.079, significantly greater than 0.5 (random chance prediction). Conclusion(s): Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET.

KW - Human cumulus cells

KW - gene expression

KW - human embryo

KW - human oocyte

KW - pregnancy outcome

UR - http://www.scopus.com/inward/record.url?scp=84875230255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875230255&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2012.10.041

DO - 10.1016/j.fertnstert.2012.10.041

M3 - Article

C2 - 23200692

AN - SCOPUS:84875230255

VL - 99

SP - 745-752.e6

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

IS - 3

ER -