Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts

Timofeeva, Angelika V.; Fedorov, Ivan S.; Savostina, Guzel V.; Tarasova, Alla M.; Perminova, Svetlana G.; Nazarenko, Tatyana A.; Sukhikh, Gennady T.

doi:10.3390/ijms262412102

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts

by

Angelika V. Timofeeva

^*

,

Ivan S. Fedorov

,

Guzel V. Savostina

,

Alla M. Tarasova

,

Svetlana G. Perminova

,

Tatyana A. Nazarenko

and

Gennady T. Sukhikh

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician Kulakov V.I., 117997 Moscow, Russia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(24), 12102; https://doi.org/10.3390/ijms262412102

Submission received: 16 November 2025 / Revised: 3 December 2025 / Accepted: 12 December 2025 / Published: 16 December 2025

(This article belongs to the Collection Advances in Cell and Molecular Biology)

Download Versions Notes

Abstract

A predominant etiological factor in implantation failure and early pregnancy loss is embryonic chromosomal abnormalities. The current clinical standard for determining embryonic ploidy is invasive preimplantation genetic testing. This procedure imposes mechanical stress on embryonic cells during trophectoderm biopsy and fails to significantly improve live birth rates per transfer, likely due to its inability to evaluate the embryo’s implantation potential. Consequently, there is a clear need to develop a non-invasive method, suitable for routine clinical practice, that can simultaneously assess both the ploidy and implantation competence of a blastocyst prior to uterine transfer. Our research group was the first to achieve this by quantifying specific piwiRNAs (piR_016677, piR_017716, piR_020497, piR_015462) in spent culture medium. These data served as the foundation for logistic regression models tailored for day 5 blastocysts, day 6 blastocysts, and blastocysts irrespective of their developmental rate. These models demonstrated high diagnostic accuracy, with specificity ranging from 68% to 100% and sensitivity from 71% to 100%. The rationale for employing these molecules as biomarkers lies in their potential biological roles, which encompass maintaining genomic stability through LINE-1 regulation, as well as direct involvement in critical processes such as cell cycle control, spindle assembly, and cellular adhesion—all of which are imperative for successful implantation.

Keywords: blastocyst; euploidy; aneuploidy; implantation potential; piwiRNA; culture medium; real-time PCR; logistic regression model; assisted reproductive technologies

Share and Cite

MDPI and ACS Style

Timofeeva, A.V.; Fedorov, I.S.; Savostina, G.V.; Tarasova, A.M.; Perminova, S.G.; Nazarenko, T.A.; Sukhikh, G.T. Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts. Int. J. Mol. Sci. 2025, 26, 12102. https://doi.org/10.3390/ijms262412102

AMA Style

Timofeeva AV, Fedorov IS, Savostina GV, Tarasova AM, Perminova SG, Nazarenko TA, Sukhikh GT. Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts. International Journal of Molecular Sciences. 2025; 26(24):12102. https://doi.org/10.3390/ijms262412102

Chicago/Turabian Style

Timofeeva, Angelika V., Ivan S. Fedorov, Guzel V. Savostina, Alla M. Tarasova, Svetlana G. Perminova, Tatyana A. Nazarenko, and Gennady T. Sukhikh. 2025. "Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts" International Journal of Molecular Sciences 26, no. 24: 12102. https://doi.org/10.3390/ijms262412102

APA Style

Timofeeva, A. V., Fedorov, I. S., Savostina, G. V., Tarasova, A. M., Perminova, S. G., Nazarenko, T. A., & Sukhikh, G. T. (2025). Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts. International Journal of Molecular Sciences, 26(24), 12102. https://doi.org/10.3390/ijms262412102

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI