The risk of epigenetic changes in children born after assisted reproductive technologies

DOI

https://dx.doi.org/10.18565/aig.2025.357

Pitskhelauri E.G., Ignatko I.V., Timokhina E.V., Kuzmina T.E., Bogomazova I.M., Belousova V.S., Gorbunova V.A., Totchiev G.F., Churganova A.A., Pashkov V.M., Lebedev V.A., Kardanova M.A., Fedyunina I.A.
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia

Assisted reproductive technologies (ART) involve chemical and physical manipulations of gametes, the induction of non-physiological levels of gonadotropins, in vitro fertilization, cultivation, freezing and transfer of embryos under artificial conditions. Some studies suggest that children conceived by ART are at a higher risk of hypotrophy, neonatal complications and congenital malformations compared with naturally conceived children. One of the most relevant and controversial issues is epigenetic changes in children born after ART. According to some authors, epigenetic disorders such as Beckwith–Wiedemann syndrome, Angelman syndrome, Prader–Willi syndrome and Silver–Russell syndrome are associated with assisted reproduction. Epigenetics is basically a set of mechanisms that regulate gene expression in various cells of the body, thereby determining their functions. Epigenetic mechanisms are realized through DNA methylation, histone modifications or RNA-mediated (transcriptional) mechanisms. One special mechanism of epigenetics involves imprinted genes, the expression of which is determined by whether the chromosome is of maternal or paternal origin. These genes largely determine the processes of embryonic and intrauterine development and placentation, as well as the distribution of resources for fetal growth. Why is it so important to consider the potential impact of ART on epigenetics? Precisely because, during the formation of the primordial germ cell line and subsequently during implantation, global demethylation occurs (that is, the removal of all these methyl marks, both in imprinted and other genes) and new marks are established. In vitro cultivation, freezing and embryo transfer under artificial conditions occur during the period when the epigenome is most vulnerable to errors. This raises a number of questions: is the use of ART the underlying cause of epigenetic changes, or are there factors that may mediate the effect of these methods on the epigenome?
Conclusion. Assisted reproduction is associated with epigenetic changes, but the effects of these technologies are mediated by many other factors. Epigenetic changes may be stochastic and mosaic in nature. The age of patients and conditions leading to infertility increase these risks. It is necessary to continue closely monitoring children born after ART in order to identify any potential consequences of this method of treating infertility.

Authors’ contribution. Ignatko I.V., Lebedev V.A., Pashkov V.M., Pitskhelauri E.G., Timokhina E.V. – developing the concept behind the review topic; Pitskhelauri E.G., Gorbunova V.A., Kuzmina T.E., Fedyunina I.A., Churganova A.A. – collecting and processing information; Pitskhelauri E.G., Gorbunova V.A., Kardanova M.A., Bogomazova I.M. – writing the text; Ignatko I.V., Timokhina E.V., Belousova V.S., Gorbunova V.A., Totchiev G.F., Pitskhelauri E.G. – editing the article.
Conflicts of interest. The authors declare that there are no conflicts of interest.
Funding. The study was conducted without sponsorship.
Generative Artificial Intelligence. Generative AI technologies were not used in preparing this article.
For citation: Pitskhelauri E.G., Ignatko I.V., Timokhina E.V., Kuzmina T.E., Bogomazova I.M., Belousova V.S., Gorbunova V.A., Totchiev G.F., Churganova A.A., Pashkov V.M., Lebedev V.A., Kardanova M.A., Fedyunina I.A.
The risk of epigenetic changes in children born after assisted reproductive technologies.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (7): 48-56 (in Russian)
https://dx.doi.org/10.18565/aig.2025.357

assisted reproductive technologies

epigenetic changes

neonatal complications

DNA methylation

in vitro fertilization

children’s health

Full text (in Russian)

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Received 05.12.2025

Accepted 25.06.2026

Elena G. Pitskhelauri, PhD, Associate Professor, Associate Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2,
+7(916)334-00-89, pitskhelauri_e_g@staff.sechenov.ru, https://orcid.org/0000-0002-9634-1541
Irina V. Ignatko, Dr. Med. Sci., Corresponding Member of the Russian Academy of Sciences, Professor of the Russian Academy of Sciences, Professor, Head of the Department of Obstetrics, Gynecology, and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, ignatko_i_v@staff.sechenov.ru, https://orcid.org/0000-0002-9945-3848
Elena V. Timokhina, Dr. Med. Sci., Associate Professor, Professor at the Department of Obstetrics, Gynecology, and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, timokhina_e_v@staff.sechenov.ru, https://orcid.org/0000-0001-6628-0023
Tatiana E. Kuzmina, PhD, Associate Professor, Associate Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2,
kuzmina_t_e@staff.sechenov.ru, https://orcid.org/0000-0001-9649-5383
Irina M. Bogomozova, PhD, Associate Professor, Associate Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, +7(926)305-04-03, bogomazova_i_m@staff.sechenov.ru, https://orcid.org/0000-0003-1156-7726
Vera S. Belousova, Dr. Med. Sci., Associate Professor, Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine,
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, belousova_v_s@staff.sechenov.ru, https://orcid.org/0000-0001-8332-7073
Violetta A. Gogbunova, student at Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia
(Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, violagorbunova.03@mail.ru, https://orcid.org/0009-0001-6105-9060
Georgi F. Totchiev, Dr. Med. Sci., Associate Professor, Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine,
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2,
totchiev_g_f@staff.sechenov.ru, https://orcid.org/0000-0001-6830-2548
Anastasia A. Churganova, PhD, Associate Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine,
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2,
churganova_a_a@staff.sechenov.ru, https://orcid.org/0000-0001-9398-9900
Vladimir M. Pashkov, Dr. Med. Sci., Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, pashkov_v_m@staff.sechenov.ru, https://orcid.org/0000-0003-3768-7822
Vladimir A. Lebedev, Dr. Med. Sci., Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, lebedev_v_a@staff.sechenov.ru, https://orcid.org/0000-0002-3302-5533
Madina A. Kardanova, PhD, Associate Professor at the Department of Obstetrics, Gynecology and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, kardanova_m_a@staff.sechenov.ru, https://orcid.org/ 0000-0002-4315-0717
Irina A. Fedyunina, PhD, Associate Professor at the Department of Obstetrics, Gynecology, and Perinatology, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russian Federation, 119991, Russia, Moscow, Trubetskaya str., 8, bldg. 2, fedyunina_i_a@staff.sechenov.ru, https://orcid.org/0000-0002-9661-5338

The risk of epigenetic changes in children born after assisted reproductive technologies

Pitskhelauri E.G., Ignatko I.V., Timokhina E.V., Kuzmina T.E., Bogomazova I.M., Belousova V.S., Gorbunova V.A., Totchiev G.F., Churganova A.A., Pashkov V.M., Lebedev V.A., Kardanova M.A., Fedyunina I.A.

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