Clinical and anamnestic characteristics of couples referred for whole-exome sequencing in the context of assisted reproductive technology programs
Martirosyan Ya.O., Nazarenko T.A., Tsabai P.N., Pavlova N.S.
Objective. To evaluate the diagnostic accuracy of whole-exome sequencing in identifying genetic causes of recurrent embryonic developmental arrest in IVF/ICSI cycles and assess its potential to guide treatment strategies.
Materials and methods. This retrospective, single-center study was conducted between January 2021 and May 2025. Among 3,779 couples who underwent 6,674 ART cycles, a subgroup with ≥3 IVF/ICSI attempts was identified (n = 1,750). The phenotype of recurrent early embryonic arrest, defined as the absence of embryos available for transfer or cryopreservation by day 5, was observed in 782 couples. A target subgroup of women younger than 36 years with total arrest across all cycles was selected for in-depth genetic analysis (n = 125). All participants underwent standardized clinical assessments, embryological evaluations, and whole-exome sequencing.
Results. Early embryonic arrest was present in 44.7% (782/1,750) of couples with ≥3 ART attempts, representing 20.7% of the entire initial cohort. In the target subgroup (n=125), the mean age was 32.1 (2.8) years, the mean duration of infertility was 5.2 (1.4) years, and primary infertility was documented in 85.4% of the cases. Ovarian reserve parameters were preserved (AMH 2.31 ng/mL; AFC 14.2 (4.0), and the mean fertilization rate was 92.7 (4.4)%; however, embryonic development was uniformly arrested in all cycles.
Conclusion. Recurrent early embryonic arrest, in the presence of preserved ovarian reserve and normal fertilization, is a clinically significant problem affecting approximately one in five couples undergoing multiple ART attempts. Among women < 36 years of age presenting with this phenotype (who accounted for 16% of the arrest subgroup), a genetic etiology is highly probable. This supports the use of whole-exome sequencing as a tool for etiological stratification and individualized treatment planning.
Authors' contributions. Martirosyan Y.O., Nazarenko T.A. – conception and design of the study, data collection and analysis, review of the relevant literature, drafting of the manuscript; Tsabai P.N. – conducting and supervising the embryological phase of the research, interpreting embryological data; Pavlova N.S. – organizing and conducting genetic studies, bioinformatic analysis of whole-exome sequencing data, interpreting molecular genetic results.
Conflicts of interest. The authors have no conflicts of interest to declare.
Funding. Agreement No. 25-65-00040 with the Russian Science Foundation, dated May 22, 2025, on the topic: “Development of genetically informed approaches to realizing the reproductive potential of patients and their families in cases of abnormalities in the development and functioning of the reproductive system”.
Ethical Approval. The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Generative Artificial Intelligence. No artificial intelligence tools were used in the preparation of this manuscript.
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: Martirosyan Ya.O., Nazarenko T.A., Tsabai P.N., Pavlova N.S. Clinical and anamnestic characteristics of couples referred for whole-exome sequencing in the context of assisted reproductive technology programs.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (6): 153-162 (in Russian)
https://dx.doi.org/10.18565/aig.2025.354
Keywords
unexplained infertility
genetics
genetic testing
assisted reproductive technologies
exome sequencing
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Received 04.12.2025
Accepted 30.04.2026
About the Authors
Yana O. Martirosyan, PhD, Obstetrician-Gynecologist, Researcher at the F. Paulsen Research and Educational Center for ART with the Clinical Department,Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Moscow, Russia,
Ac. Oparina str., 4, marti-yana@yandex.ru, https://orcid.org/0000-0002-9304-4410
Tatiana. A. Nazarenko, Professor, Dr. Med. Sci., Director of the Institute of Reproductive Medicine, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Moscow, Russia, Ac. Oparina str., 4, t.nazarenko@mail.ru,
https://orcid.org/0000-0002-5823-1667
Polina N. Tsabai, Geneticist at the Department of Clinical Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Moscow, Russia, Ac. Oparina str., 4, polinatsabai@gmail.com, https://orcid.org/0000-0001-5110-0827
Nadezhda S. Pavlova, Junior Researcher at the Department of Clinical Genetics at the Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Moscow, Russia, Ac. Oparina str., 4, pav.nad.ser@gmail.com,
https://orcid.org/0000-0001-5619-2695
Corresponding author: Yana O. Martirosyan, marti-yana@yandex.ru
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