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Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability

  • General Gynecology: Original Article
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Abstract

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high-throughput technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered “case” and non-ectopic considered “control.” For pregnancy viability, viable intrauterine pregnancy was considered “case” and early pregnancy loss + ectopic pregnancy were considered “control.” Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker’s discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥0.80: lutropin subunit beta and serpin B8. While some of the markers had previously been implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high-throughput platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

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Funding

This work was supported by the NICHD R01 HD076279.

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Authors and Affiliations

  1. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, 3701 Market St, 8th Floor, Philadelphia, PA, 19104, USA

    Iris T. Lee, Suneeta Senapati, Nathanael Koelper & Kurt T. Barnhart

  2. Division of Complex Family Planning, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA

    Courtney Schreiber

  3. Division of Female Pelvic Medicine and Reconstructive Surgery (Urogynecology), Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA

    Peter Takacs

Authors
  1. Iris T. Lee
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  2. Suneeta Senapati
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  3. Courtney Schreiber
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  4. Nathanael Koelper
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  5. Peter Takacs
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  6. Kurt T. Barnhart
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Contributions

Conceptualization: Kurt Barnhart, Courtney Schreiber, Suneeta Senapati. Methodology: Kurt Barnhart, Nathanael Koelper. Formal analysis and investigation: Nathanael Koelper. Writing—original draft preparation: Iris Lee. Writing—review and editing: Kurt Barnhart, Courtney Schreiber, Suneeta Senapati, Peter Takacs. Funding acquisition: Kurt Barnhart. Resources: Kurt Barnhart, Courtney Schreiber. Supervision: Kurt Barnhart

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Correspondence to Iris T. Lee.

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Ethics Approval

This study was approved by the University of Pennsylvania Institutional Review Board. Informed consent for participation and publication was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Supplementary Information

Supplementary file 1

Supplemental Table 1. Quality control results by pregnancy outcome (DOCX 12 kb)

Supplementary file 2

Supplemental Table 2. Function of 20 highly predictive biomarkers (DOCX 29 kb)

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Lee, I.T., Senapati, S., Schreiber, C. et al. Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability. Reprod. Sci. 30, 3641–3647 (2023). https://doi.org/10.1007/s43032-023-01325-6

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  • DOI: https://doi.org/10.1007/s43032-023-01325-6

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