Pharmacogenetic approach to managing women with an unpredictable poor response to ovarian stimulation in the in vitro fertilization program

Perminova S.G., Belova I.S., Donnikov A.E.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia
Female poor responders to ovarian stimulation (OS) are a large portion (9–24%) of patients in the in vitro fertilization (IVF) programs. In accordance with the POSEIDON classification, the patients with a poor response to OS are stratified into 4 groups by age, the number of antral follicles (AF), and the level of anti-Müllerian hormone (AMH). Particular emphasis is placed on patients with an unexpected poor response to gonadotropic stimulation with the normal parameters of the ovarian reserve (POSEIDON Group 1) that is associated with reduced ovarian sensitivity to gonadotropins due to individual genetic variability. The review considers the contribution of single nucleotide polymorphisms (SNPs) of the genes of gonadotropins, steroid hormones and their receptors, AMH, P450 aromatase, and growth differentiation factor 9 (GDF9) to the genesis of an unpredictable poor and suboptimal response to OS. It discusses whether it is expedient to apply a pharmacogenetic approach to OS in this group of patients in order to select the optimal gonadotropins and to adjust their doses to increase the effectiveness of the IVF program.
Conclusion: A priori understanding of individual genetic variability in a patient population with an unpredictable poor ovarian response and preserved ovarian reserve parameters along with known clinical and laboratory markers will assist in developing personalized OS protocols in the IVF program.


in vitro fertilization
ovarian stimulation
POSEIDON classification
single nucleotide polymorphism
unpredictable poor response


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Received 31.10.2022

Accepted 28.11.2022

About the Authors

Svetlana G. Perminova, Dr. Med. Sci., Associate Professor, Leading Researcher at Reproductology Department, Academician V.I. Kulakov NMRC for OG&P,
Ministry of Health of Russia,, 117997, Russia, Moscow, Ac. Oparin str., 4.
Irina S. Belova, graduate student, Academician V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,,
117997, Russia, Moscow, Ac. Oparin str., 4.
Andrey E. Donnikov, PhD, Head of the Laboratory of Molecular Genetic Methods, Academician V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
+7(495)438-13-41,, 117997, Russia, Moscow, Ac. Oparin str., 4.

Authors’ contributions: Perminova S.G., Donnikov A.E. – editing and final approval of the manuscript; Belova I.S. – literature search and analysis, processing the source material, writing the text of the manuscript.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article has been prepared without financial support.
For citation: Perminova S.G., Belova I.S., Donnikov A.E. Pharmacogenetic approach to managing women with an unpredictable poor response to ovarian stimulation
in the in vitro fertilization program.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 12: 66-74 (in Russian)

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