The role of adipokines and gene regulators adipokines in the effectiveness of assisted reproductive technology programs in overweight patients
Objective. To assess the role of adipokines and their regulatory genes in the effectiveness of ART programs in overweight patients. Subject and methods. A prospective cohort study enrolled 106 patients with a body mass index (BMI) of ≥23 kg/m2 and 41 patients with a BMI of <23 kg/m2. Plasma leptin and adiponectin levels were measured using a Luminex multiplex 200 analyzer. The polymorphism of the genes regulating the level of adipokines (LEP: -2548 (2453) G>A, LEPR: 818(853) A>G (Gln223Arg), and LEPR: 476 (511) A>G (Lys109Arg)) was analyzed by allele-specific polymerase chain reaction. The primary endpoint was an adjusted odds ratio (ORadj) for the occurrence of clinical pregnancy and live births in relation to the patients’ BMI. Results. The patients with a BMI≥23 kg/m2 were observed to have statistically significantly fewer clinical pregnancies (ORadj = 3.1 (95% CI 1.4; 6.6)) and live births (ORadj = 2.8 (95% CI, 1.2; 6.4)) than those with a BMI of <23 kg/m2. When the patients had a BMI of ≥23 kg/m2, they had significantly higher blood levels of leptin (21.9±10.5 ng/ml and 7.1±5.6 ng/ml) with the lower level of adiponectin (9.7±5.3 µg/ml vs. 14.3±6.6 µg/ml). The leptin levels were also higher in patients in whom pregnancy did not occur with IVF. The GG genotype of LEPR c.476 (511) A>G was associated with the lower level of leptin and with the high one of adiponectin, as well as with a greater probability of live births in the ART programs. Conclusion. The GG genotype of LEPR c.476 (511) A>G plays a protective role in the metabolism of adipokines and is associated with the positive outcomes of ART programs. When this genotype is present, the probability of live births increases two-fold with decreases in BMI and leptin level.Dolgushina N.V., Donnikov A.E., Vyssokikh M.Yu., Desiatkova N.V., Suhanova Yu.A., Dolgushin O.A., Parhomenko A.A.
Keywords
in vitro fertilization
assisted reproductive technologies
leptin
adiponectin
obesity
overweight
Supplementary Materials
- Fig. 1. IVF outcomes in patients with different BMI
- Fig. 2. Box plot of average leptin (ng/mL) and adiponectin (mcg/mL) levels due to BMI (А) and IVF outcomes (Б)
- Fig. 3. LEP c.-2548 (2453) G>A (genotype АА) (А) и LEPR c.476 (511) A>G (genotype АА and GG) (B) association with live birth in IVF programs
- Table 1. Characteristics of patients included in the study
- Table 2. Leptin and adiponectin levels due to adipokine gene SNP
- Table 3. Results of multifactor regression analysis of combined effect of BMI (kg/m2), leptin level (ng/mL), adiponectin level (mcg/mL) and GG genotype of LEPR c.476 (511) A>G gene on live birth probability in IVF programs
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Received 01.11.2016
Accepted 11.11.2016
About the Authors
Dolgushina Nataliya Vitalievna, M.D., Ph.D., M.P.H., Head of R&D Department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: n_dolgushina@oparina4.ruDonnikov Andrey Evgenievich, M.D., Ph.D., Head of Molecular-Genetic Laboratory, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: a_donnikov@oparina4.ru
Vyssokikh Mikhail Yurievich, PhD, Head of mitochondrial medicine research group, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: m_vysokikh@oparina4.ru
Desiatkova Nina Vladimirovna, Post-graduate student, Department of assistive technologies in infertility treatment, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: nineks@mail.ru
Suhanova Yuliya Alexeevna, researcher, mitochondrial medicine research group, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: suhanova_julia@hotmail.com
Dolgushin Oleg Anatolievich, MD, PhD, Head of 18th Cardiological Department, A.A. Vishnevsky Central Military Clinical Hospital. 143421, Russia, Moskovskaya Oblast', Krasnogorsk region, Archangelskoe, settlement Noviy. E-mail: dolgushin70@mail.ru
Parhomenko Alena Alexandrovna, Undergraduate of the Faculty of Fundamental Medicine of Lomonosov Moscow State University.
117192, Russia, Moscow, Lomonosovsky Prospekt 31-5. E-mail: parmik243542@yandex.ru
For citations: Dolgushina N.V., Donnikov A.E., Vyssokikh M.Yu., Desiatkova N.V., Suhanova Yu.A., Dolgushin O.A., Parhomenko A.A. The role of adipokines and their regulatory genes in the effectiveness of ART programs in overweight patients. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (2): 71-8. (in Russian)
http://dx.doi.org/10.18565/aig.2017.2.71-8
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