Clinical and anamnestic characteristics of couples referred for whole-exome sequencing in the context of assisted reproductive technology programs

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Abstract

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.

About the authors

Yana O. Martirosyan

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Author for correspondence.
Email: marti-yana@yandex.ru
ORCID iD: 0000-0002-9304-4410

PhD, Obstetrician-Gynecologist, Researcher at the F. Paulsen Research and Educational Center for ART with the Clinical Department

Russian Federation, Moscow

Tatiana A. Nazarenko

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: t.nazarenko@mail.ru
ORCID iD: 0000-0002-5823-1667

Professor, Dr. Med. Sci., Director of the Institute of Reproductive Medicine

Russian Federation, Moscow

Polina N. Tsabai

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: polinatsabai@gmail.com
ORCID iD: 0000-0001-5110-0827

Geneticist at the Department of Clinical Genetics

Russian Federation, Moscow

Nadezhda S. Pavlova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: pav.nad.ser@gmail.com
ORCID iD: 0000-0001-5619-2695

Junior Researcher at the Department of Clinical Genetics at the Institute of Reproductive Genetics

Russian Federation, Moscow

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