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

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Abstract

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.

About the authors

Yana O. Martirosyan

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

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

Nadezhda S. Pavlova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

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

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

Russian Federation, Moscow

Irina S. Mukosey

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: i_mukosei@oparina4.ru
ORCID iD: 0000-0002-2225-8366

Researcher at the Laboratory of Genomic Data Analysis of the Institute of Reproductive Genetic

Russian Federation, Moscow

Tatiana A. Nazarenko

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

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

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

Russian Federation, Moscow

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