Noninvasive diagnosis of embryo chromosomal status in vitro: integration of raman spectrometry and machine learning in assisted reproductive technologies

DOI

https://dx.doi.org/10.18565/aig.2025.251

Valiakhmetovaa E.Z., Rimskaya E.N., Gorevoy A.V., Yakimova A.S., Sysoeva A.P., Ekimov A.N., Makarova N.P., Kalinina E.A., Sukhikh G.T.
1) Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia; 2) Lebedev Physics Institute of the Russian Academy of Sciences, Moscow, Russia

Relevance: This study is relevant due to the relatively low efficiency of in vitro fertilization (IVF), which has an implantation success rate of up to 40%, as well as the invasiveness of current preimplantation genetic testing (PGT-A) used to detect chromosomal abnormalities in embryos. The invasive nature of these procedures poses a risk of embryo damage, highlighting the need for innovative and noninvasive approaches.
Objective: To develop a noninvasive method for assessing the chromosomal status of embryos using spectral analysis of spent culture media and machine learning techniques.
Materials and methods: The study involved 36 couples, from whom 40 samples of spent culture media were obtained (11 from euploid embryos and 29 from aneuploid embryos). Raman scattering (RS) spectra were recorded using a Confotec MR520 microscope-spectrometer with 532 nm laser excitation. Machine learning algorithms, including quadratic discriminant analysis (QDA), combined with stratified fivefold cross-validation, were employed to analyze the spectral characteristics and differentiate between the sample groups.
Results: Significant differences were observed in the mean RS spectra of spent culture media between euploid and aneuploid embryos. The most reliable discriminating features included the intensity ratios of Raman bands at 735 cm-1 (phosphatidylserine, DNA), 1196 cm-1 (nucleic acids), and 1666 cm-1 (C=C stretching, amide I), respectively. The developed predictive model achieved an accuracy, sensitivity, and specificity of 84 %, 80%, and 88%, respectively.
Conclusion: Raman spectra of embryo culture media obtained with 532 nm laser excitation may reveal novel biochemical indicators associated with embryonic developmental abnormalities. These findings provide new perspectives for noninvasive diagnostics in reproductive medicine and have the potential to enhance the effectiveness of assisted reproductive technology programs.

Authors' contributions: Valiakhmetova E.Z., Makarova N.P., Rimskaya E.N., Gorevoy A.V. – conception and design of the study; Sysoeva A.P., Yakimova A.S. – collection and processing of material; Makarova N.P., Valiakhmetova E.Z. – statistical analysis; Valiakhmetova E.Z., Makarova N.P., Rimskaya E.N. – drafting of the manuscript; Kalinina E.A., Sukhikh G.T. – editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was conducted as part of the initiative research project “Study of the influence of extracellular vesicles of biological fluids of reproductive organs and tissues on gametes, the process of fertilization and early human embryogenesis and implantation” (2025–2027, supervisor Makarova N.P.). V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Valiakhmetovaa E.Z., Rimskaya E.N., Gorevoy A.V., Yakimova A.S., Sysoeva A.P., Ekimov A.N., Makarova N.P., Kalinina E.A., Sukhikh G.T. Noninvasive diagnosis of embryo chromosomal status in vitro:
integration of raman spectrometry and machine learning in assisted reproductive technologies.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (1): 78-88 (in Russian)
https://dx.doi.org/10.18565/aig.2025.251

ART

infertility

PGT

RSS

Raman spectroscopy

spent culture medium

IVF

Full text (in Russian)

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Received 15.09.2025

Accepted 29.12.2025

Elvira Z. Valiakhmetova, PhD student at the Prof. B.V. Leonov Department for Assisted Technologies in Infertility Treatment, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, ibraeva1988@list.ru
Elena N. Rimskaya, PhD, Senior Researcher at the Laboratory of Clinical Proteomics, Academician V.I. Kulakov National Medical Research Center for Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4; Researcher at the Laboratory of Laser Nanophysics and Biomedicine,
Center for Laser and Nonlinear Optical Technologies, Department of Quantum Radiophysics named after N.G. Basov, P.N. Lebedev Physics Institute of RAS (FIAN),
119991, Russia, GSP-1 Moscow, Leninsky Ave., 53, rimskaya@lebedev.ru, https://orcid.org/0000-0001-7802-0720
Alexey V. Gorevoy, Researcher at the Laboratory of Laser Nanophysics and Biomedicine, Center for Laser and Nonlinear Optical Technologies, Department of Quantum Radiophysics named after N.G. Basov, P.N. Lebedev Physics Institute of RAS (FIAN), 119991, Russia, GSP-1, Moscow, Leninsky Ave., 53, a.gorevoy@lebedev.ru,
https://orcid.org/0000-0003-4208-0291
Alexandra S. Yakimova, Embryologist at the Prof. B.V. Leonov Department for Assisted Technologies in Infertility Treatment, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, yakimoovaal@gmail.com,
https://orcid.org/0009-0001-5913-2660
Anastasia P. Sysoeva, PhD, Embryologist at the Prof. B.V. Leonov Department for Assisted Technologies in Infertility Treatment, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, a_sysoeva@oparina4.ru,
https://orcid.org/0000-0002-6502-4498
Аlexey N. Ekimov, PhD, Head of the Laboratory of Preimplantation Genetic Testing and Genetic Diagnostics, Academician V.I. Kulakov National Medical Research Center
for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia, a_ekimov@oparina4.ru,
https://orcid.org/0000-0001-5029-0462
Natalya P. Makarova, Dr. Bio. Sci., Leading Researcher at the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4,
np_makarova@oparina4.ru, https://orcid.org/0000-0003-1396-7272
Elena A. Kalinina, Dr. Med. Sci., Professor, Head of the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, e_kalinina@oparina4.ru, https://orcid.org/0000-0002-8922-2878
Gennady T. Sukhikh, Dr. Med. Sci., Professor, Academician of the RAS, Director, Academician V.I. Kulakov National Medical Research Center for Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, g_sukhikh@oparina4.ru, https://orcid.org/0000-0002-7712-1260

Noninvasive diagnosis of embryo chromosomal status in vitro: integration of raman spectrometry and machine learning in assisted reproductive technologies

Valiakhmetovaa E.Z., Rimskaya E.N., Gorevoy A.V., Yakimova A.S., Sysoeva A.P., Ekimov A.N., Makarova N.P., Kalinina E.A., Sukhikh G.T.

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