The spectrum of genetic causes of female infertility: modern molecular mechanisms and clinical significance

DOI

https://dx.doi.org/10.18565/aig.2025.254

Martirosyan Ya.O., Pavlova N.S., Mukosey I.S., Nazarenko T.A.
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia

Objective: To summarize the current data on the role of genetic factors in female infertility, including disorders of oocyte maturation, fertilization, embryonic developmental arrest, and to consider the possibilities of molecular genetic diagnosis.
Materials and methods: The article presents a review of recent Russian and foreign publications on the molecular and chromosomal etiology of female infertility with focus on phenotypes associated with pathogenic gene variants, as well as modern methods of molecular analysis (WES, WGS, GWAS).
Results: Female infertility affects 10-15% of reproductive-aged couples, while up to 30% of cases remain idiopathic. Genetic factors play a leading role in the pathogenesis of infertility, especially with repeated ART failures. Chromosomal and monogenic mechanisms have been identified in both syndromic and non-syndromic forms. More than 90 genes associated with premature ovarian insufficiency have been found; TUBB8, PATL2, TRIP13, TBPL2, ZP1-3, WEE2, CDC20, BTG4, PADI6, and other genes determine the phenotypes of disorders of oogenesis, fertilization and early embryogenesis. Key molecular complexes have been identified, including the subcortical maternal complex (SCMC), which is critically important for early embryo development. The use of NGS technologies made it possible to better understand the genetic basis of infertility and to identify new clinical variants.
Conclusion: The genetic etiology of female infertility is more complex than previously believed; therefore, it is necessary to integrate molecular genetic methods into the practice of obstetricians, gynecologists and reproductive medicine specialists. Precision diagnosis and genetic counseling can increase the effectiveness of ART programs and help personalize the choice of treatment options.

Authors’ contributions: Nazarenko T.A. – developing the design of the study; Martirosyan Ya.O., Pavlova N.S., Mukosey I.S. – review of publications on the subject of the study; Martirosyan Ya.O., Pavlova N.S. – analysis of the obtained data, writing the text of the manuscript.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: Agreement with the Russian Science Foundation No. 25-65-00040 dated May 22, 2025, on the subject “Development of genetically based approaches to realizing the reproductive potential of patients and their families with disorders of the formation and functioning of the reproductive system”.
For citation: Martirosyan Ya.O., Pavlova N.S., Mukosey I.S., Nazarenko T.A. The spectrum of
genetic causes of female infertility: modern molecular mechanisms and clinical significance.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (11): 38-46 (in Russian)
https://dx.doi.org/10.18565/aig.2025.254

female infertility

assisted reproductive technologies

genetic etiology

oocyte maturation

embryogenesis

genetic counseling

Full text (in Russian)

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Received 17.09.2025

Accepted 05.10.2025

Yana O. Martirosyan, PhD, obstetrician-gynecologist, Researcher at the F. Paulsen Research and Educational Center for ART with the Clinical Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, marti-yana@yandex.ru, https://orcid.org/0000-0002-9304-4410
Nadezhda S. Pavlova, Junior Researcher at the Department of Clinical Genetic of the Institute of Reproductive Genetic, V.I. Kulakov NMRC for OG&P, Ministry of Health
of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(916)080-82-35, pav.nad.ser@gmail.com, https://orcid.org/0000-0001-5619-2695
Irina S. Mukosey, Researcher at the Laboratory of Genomic Data Analysis of the Institute of Reproductive Genetic, V.I. Kulakov NMRC for OG&P, Ministry of Health
of Russia, 4, Ac. Oparin str., Moscow, Russia, 117997, +7(495)438-13-41, i_mukosei@oparina4.ru, https://orcid.org/0000-0002-2225-8366
Tatiana A. Nazarenko, Dr. Med. Sci., Professor, Head of the Institute of Reproductive Medicine, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)438-13-41, t.nazarenko@mail.ru, https://orcid.org/0000-0002-5823-1667

The spectrum of genetic causes of female infertility: modern molecular mechanisms and clinical significance

Martirosyan Ya.O., Pavlova N.S., Mukosey I.S., Nazarenko T.A.

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