ESR1 and VEGFA gene polymorphisms as a predictor for the course of ovarian hyperstimulation syndrome in an in vitro fertilization program

Strelchenko D.A., Perminova S.G., Donnikov A.E.

1Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow 117997, Ac. Oparina str. 4, Russia 2OOO «DNA Technology Research-and-Production Firm»; Moscow, Russia
Objective. To search for molecular genetic markers associated with different types of the clinical course of ovarian hyperstimulation syndrome (OHSS) in an IVF program.
Subjects and methods. The clinical course of OHSS in the IVF program used in 59 patients admitted to hospital for therapy aimed at relieving the symptoms of this complication. According to the onset of OHSS manifestations, the patients were divided into two groups: 1) 42 patients with early OHSS; 2) 17 patients with late OHSS.
A wide panel of genetic markers also potentially involved in the development of clinical manifestations of OHSS was examined. The frequency of different alleles of each gene candidate was analyzed in two patient groups (with early and late OHSS).
Results. The analysis of a relationship of candidate genes to the onset of OHSS manifestations revealed a statistically significant association of the VEGFA -2578(-2595) A>C [rs699947], VEGFA -634 G>C [rs2010963], ESR1 -351 A>G [XbaI] [rs9340799], and ESR1 -397 T> [PvuII] [rs2234693] polymorphisms with the onset of clinical manifestations of OHSS. According to an autosomal recessive model, the VEGFA -634G/G genotype and VEGFA -2578А/A genotype were associated with late OHSS (p = 0.016; OR = 5.87 (95% CI 1.22-28.19) and p = 0.035; OR = 2.38 (95% CI 1.05-5,38), respectively). Examination of ESR1 gene polymorphisms established that according to the autosomal recessive model, the -397C/C and -351G/G genotypes increased the risk of late OHSS (OR = 2.32 (95% CI 1.03-5.23); p = 0.039 and OR = 3.17 (95% CI 1.38-7.28), p = 0.005, respectively). Analyzing the linkage of the examined VEGFA gene loci revealed a pronounced non-equilibrium coupling between the -2578 A>C and -634 G>C loci and that of the -397C>T (PvuII) and -351G>A (XbaI) polymorphism loci in the ESR1 gene.
Conclusion. The findings suggest that there is a possible difference in the early and late forms of OHSS in the molecular mechanisms of development determining the pathogenetic features of the course of this complication.


single nucleotide polymorphism
in vitro fertilization
ovarian hyperstimulation syndrome (OHSS)
early OHSS
late OHSS
molecular genetic predictors
human chorionic gonadotropin
follicle-stimulating hormone
luteinizing hormone/human chorionic gonadotropin
vascular endothelial growth factor
estrogen receptor 1
gene polymorphism


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Received 31.08.2016

Accepted 02.09.2016

About the Authors

Strelchenko Daria Andreevna, graduate student of Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79099832944. E-mail:
Perminova Svetlana Grigorievna, MD, Leading Researcher of the 1st gynecological department, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79162021687. E-mail:
Donnikov Andrey Evgenyevich, PhD, senior staff scientist of laboratory of molecular genetic methods, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381341. E-mail:

For citations: Strelchenko D.A., Perminova S.G., Donnikov A.E. ESR1
and VEGFA gene polymorphisms as a predictor for the course of ovarian
hyperstimulation syndrome in an in vitro fertilization program.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (5): 90-7. (in Russian)

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