Molecular genetic predictors for the development of ovarian hyperstimulation syndrome in an IVF program


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Abstract

Objective. To estimate the contribution of molecular genetic markers as predictors for ovarian hyperstimulation syndrome (OHSS) in an IVF program. Subject and methods. At Step 1, clinical anamnestic data and the anatomical and functional status of the reproductive system were assessed in 152 patients who had asked for an IVF program. A study group comprised 30 patients with developed OHSS; a control group consisted of 122 patients who had not developed OHSS. To analyze the prognostic value of the generally accepted clinical and functional parameters, 152 patients included in this investigation were divided into two groups: 1) 36 patients with a normal ovarian response to stimulation; 2) 116 patients with a hyper-response. At Step 2, a wide panel of genetic markers potentially involved in the development and clinical manifestations of OHSS was examined. The frequency of various alleles of each candidate gene was analyzed in the two baseline groups (patients with developed OHSS and a control group). Results. 86.7% of the 30 patients with developed clinically significant OHSS were in a risk group at baseline, in this connection they underwent preventive measures whereas 13.3% of the patients had normal baseline ovarian reserve indicators (by anti-Müllerian hormone, the number of antral growing follicles); therefore OHSS was not prevented for lack of any risk for this complication. The performed analysis of a relationship of candidate genes to the development of clinically significant OHSS revealed a statistically significant association of VEGFA:936 C>T [rs3025039] and TSHR.2181 C>G (Asp727Glu) [rs1991517] polymorphisms with the development of OHSS. The presence of the TSHR:2181 C/C genotype according to the autosomal recessive model (р = 0.012; OR = 4.18 (95% CI, 1.25-13.96)) or that of the VEGFA:936T allele according to the autosomal dominant model (р = 0.022; OR = 2.26 (95% CI, 1.11-4.60)) predisposes to a risk for OHSS. Conclusion. The general accepted clinical markers for the risk of OHSS are not specific, which necessitates a search for predictors that are able to supplement the available panel of clinical and functional parameters. The TSHR and VEGFA genes may be a complement to a number of prognostic markers used in routine practice in the ART programs as a reliable test before ovarian stimulation in the IVF program.

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About the authors

Daria Andreevna Strelchenko

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: da_strelchenko@mail.ru
graduate student

Svetlana Grigorievna Perminova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: perisvet@list.ru
MD, Leading Researcher of the 1st gynecological department

Andrey Evgenyevich Donnikov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; OOO "DNA Technology Research-and-Production Firm"

Email: a_donnikov@oparina4.ru
PhD, senior staff scientist of laboratory of molecular genetic methods

V. V Kadochnikova

OOO "DNA Technology Research-and-Production Firm"

Email: kadochnikova@dna-technology.ru

Dmitry Dmitrievich Abramov

National Research Center "Institute of Immunology", Federal Biomedical Agency of Russia; OOO "DNA Technology Research-and-Production Firm"

Email: d.d.abramov@mail.ru
PhD, senior staff scientist of laboratory of molecular immunogenetic

Irina Evgenyevna Korneeva

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: irina.korneeva@inbox.ru
MD, Leading Researcher of the 1st gynecological department

Tatevik Tigrani Saroyan

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: tata-l976@mail.ru
PhD, staff scientist of the 1st gynecological department

Idar Nazimovich Abubakirov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: nondoc555@yahoo.ru
PhD, head of the 1st gynecological department

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