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Decreased number of p16-positive senescent cells in human endometrium as a marker of miscarriage

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to evaluate whether the number of p16-positive cells in the functional layer of the endometrium could be a useful biomarker to identify women with recurrent implantation failure (RIF) undergoing in vitro fertilization (IVF) at risk of miscarriage.

Methods

Immunohistochemical staining was performed in 311 endometrial biopsies taken during mid-luteal phase using antibody against p16INK4A. The percentage of p16-positive cells was determined in luminal, glandular and stromal endometrial cells. After embryo transfer, women were divided into the following groups: unsuccessful embryo implantation (n = 151), miscarriage (n = 66) and live birth (n = 94). The percentage of p16-positive cells in all endometrial compartments was compared among these groups.

Results

We found that the percentages of p16-positive glandular and luminal epithelial endometrial cells were significantly higher in patients with live births compared to women with miscarriage (9.3% vs. 2.9%, P < 0.001; and 35.2% vs. 11.7%, P = 0.001, respectively). This tendency was not confirmed in thе stroma. The cut-off values with p16-positive luminal cells lower than 12.5% and p16-positive glandular cells lower than 3.2% could be predictive factors for miscarriage (AUC 0.80 and 0.79; sensitivity 71.3% and 74.5%; specificity 74.2% and 71.2%, respectively).

Conclusion

A decreased number of senescent p16-positive cells could be involved in the implantation failures and aetiology of recurrent miscarriage. Women with history of RIF with reduced populations of p16-positive cells in the endometrial glandular and luminal epithelium may be at greater risk for unsuccessful implantation and miscarriage. The percentage of p16-positive luminal epithelial cells may be clinically useful as a biomarker of miscarriage.

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Acknowledgements

The authors are grateful to Marta Pulido, M.D., for editing the manuscript and editorial assistance.

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Authors and Affiliations

  1. Nadezhda Women’s Health Hospital, 3 “Blaga vest” Street, Sofia, Bulgaria

    Dimitar Parvanov, Rumiana Ganeva, Nina Vidolova & Georgi Stamenov

Authors
  1. Dimitar Parvanov
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  2. Rumiana Ganeva
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  3. Nina Vidolova
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  4. Georgi Stamenov
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Contributions

All authors qualify for authorship by contributing substantially to this article. DP and GS developed the original concept and design of the study. DP, RG and NV collected the data, DP performed the statistical analysis and DP, RG and GS provided input to the interpretation of the data. All authors have contributed to critical discussion and reviewed the final version of the article and approved it for publication.

Corresponding author

Correspondence to Dimitar Parvanov.

Ethics declarations

The protocol of the study and the informed consent forms have been approved by the IRB committee of the Nadezhda Women’s Health Hospital and conform to the ethical principles of the Declaration of Helsinki for medical research involving human subjects.

Conflict of interest

The authors declare no competing interests.

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Parvanov, D., Ganeva, R., Vidolova, N. et al. Decreased number of p16-positive senescent cells in human endometrium as a marker of miscarriage. J Assist Reprod Genet 38, 2087–2095 (2021). https://doi.org/10.1007/s10815-021-02182-5

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  • DOI: https://doi.org/10.1007/s10815-021-02182-5

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