The role of adipokines and gene regulators adipokines in the effectiveness of assisted reproductive technology programs in overweight patients


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Abstract

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/md 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.

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About the authors

Nataliya Vitalievna Dolgushina

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

Email: n_dolgushina@oparina4.ru
M.D., Ph.D., M.P.H., Head of R&D Department

Andrey Evgenievich Donnikov

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

Email: nineks@mail.ru
M.D., Ph.D., Head of Molecular-Genetic Laboratory

Mikhail Yurievich Vyssokikh

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

Email: a_donnikov@oparina4.ru
PhD, Head of mitochondrial medicine research group

Nina Vladimirovna Desiatkova

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

Email: m_vysokikh@oparina4.ru
Post-graduate student, Department of assistive technologies in infertility treatment

Yuliya Alexeevna Suhanova

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

Email: suhanova_julia@hotmail.com
researcher, mitochondrial medicine research group

Oleg Anatolievich Dolgushin

A.A. Vishnevsky Central Military Clinical Hospital

Email: dolgushin70@mail.ru
MD, PhD, Head of 18th Cardiological Department

Alena Alexandrovna Parhomenko

M.V. Lomonosov Moscow State University

Email: parmik243542@yandex.ru
Undergraduate of the Faculty of Fundamental Medicine

References

  1. World Health Organization. Preventing and managing the global epidemic. Report of the World Health Organization on obesity. Geneva: World Health Organization; 1997.
  2. Fedorcsák P., Storeng R., Dale P.O., Tanbo T., Abyholm T. Obesity is associated with early pregnancy loss after IVF or ICSI. Acta Obstet. Gynecol. Scand. 2000; 79(1): 43-8.
  3. Parihar M. Obesity and infertility. Rev. Gynaecol. Pract. 2003; 3(3): 120-6.
  4. Raatikainen K., Heiskanen N., Heinonen S. Transition from overweight to obesity worsens pregnancy outcome in a BMI dependant manner. Obesity (Silver Spring). 2006; 14(1): 165-71.
  5. Maheshwari A., Stofberg L., Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology - a systematic review. Hum. Reprod. Update. 2007;13(5): 433-44.
  6. Brewer C.J., Balen A.H. The adverse effects of obesity on conception and implantation. Reproduction. 2010; 140(3): 347-64.
  7. Luke B., Brown M.B., Stern J.E., Missmer S.A., Fujimoto V.Y., Leach R. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum. Reprod. 2011; 26(1): 245-52.
  8. Jungheim E.S., Travieso J.L., Carson K.R., Moley K.H. Obesity and reproductive functions. Obstet. Gynecol. Clin. North Am. 2012; 39(4): 479-93.
  9. Kumbak B., Oral E., Bukulmez O. Female obesity and assisted reproductive technologies. Semin. Reprod. Med. 2012; 30(6): 507-16.
  10. Dag Z.Ö., Dilbaz B. Impact of obesity on infertility in women. J. Turk. Ger. Gynecol. Assoc. 2015; 16(2): 111-7.
  11. Hassan M.A., Killick S.R. Negative lifestyle is associated with a significant reduction in fecundity. Fertil. Steril. 2004; 81(2): 384-92.
  12. Ghizzoni L., Barreca A., Mastorakos G., Furlini M., Vottero A., Ferrari B. et al. Leptin inhibits steroid biosynthesis by human granulose-lutein cells. Horm. Metab. Res. 2001; 33(6): 323-6.
  13. Mircea C.N., Lujan M.E., Pierson R.A. Metabolic fuel and clinical implications for female reproduction. J. Obstet. Gynaecol. Can. 2007; 29(11): 887-902.
  14. Tong Q., Xu Y. Central leptin regulation of obesity and fertility. Curr. Obes. Rep. 2012; 1(4): 236-44.
  15. Gil-Campos M., Canete R.R., Gil A. Adiponectin, the missing link in insulin resistance and obesity. Clin. Nutr. 2004; 23(5): 963-74.
  16. Gambino Y.P., Maymo J.L., Pérez Peréz A., Calvoa J.C., Sánchez-Margalet V., Varone C.L. Elsevier Trophoblast Research Award Lecture: Molecular mechanisms underlying estrogen functions in trophoblastics cells - focus on leptin expression. Placenta. 2012; 33(Suppl.): S63-70.
  17. Moschos S., Chan J.L., Mantzoros C.S. Leptin and reproduction: a review. Fertil. Steril. 2002; 77(3): 433-44.
  18. Kadowaki T., Yamauchi T. Adiponectin and adiponectin receptors. Endocr. Rev. 2005; 26(3): 439-51.
  19. Lee B., Shao J. Adiponectin and energy homeostasis. Rev. Endocr. Metab. Disord. 2014; 15(2): 149-56.
  20. Hoffstedt J., Eriksson P., Mottagui-Tabar S., Arner P. A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin. Horm. Metab. Res. 2002; 34(7): 355-9.
  21. Ukkola O., Tremblay A., Després J.P., Chagnon Y.C., Campfield L.A., Bouchard C. Leptin receptor Gln223Arg variant is associated with a cluster of metabolic abnormalities in response to long-term overfeeding. J. Intern. Med. 2000; 248(5): 435-9.
  22. Nieters A., Becker N., Linseisen J. Polymorphisms in candidate obesity genes and their interaction with dietary intake of n-6 polyunsaturated fatty acids affect obesity risk in a sub-sample of the EPIC-Heidelberg cohort. Eur. J. Nutr. 2002; 41(5): 210-21.
  23. Mammès O., Betoulle D., Aubert R., Herbeth B., Siest G., Fumeron F. Association of the G-2548A polymorphism in the 5’ region of the LEP gene with overweight. Ann. Hum. Genet. 2000; 64(Pt 5): 391-4.
  24. Beate K., Joseph N., Nicolas de R., Wolfram K. Genetics of isolated hypogonadotropic hypogonadism: role of GnRH receptor and other genes. Int. J. Endocrinol. 2012; 2012: 147893.
  25. Vasku J.A., Vasku A., Dostálová Z., Bienert P. Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus. Genes Nutr. 2006; 1(2): 117-23.
  26. Rigo J., Szendei G., Rosta K., Fekete A., Bögi K., Molvarec A. et al. Leptin receptor gene polymorphisms in severely pre-eclamptic women. Gynecol. Endocrinol. 2006; 22(9): 521-5.
  27. Приказ МЗ РФ №107н от 30 августа 2012 г. „О порядке использования вспомогательных репродуктивных технологий, противопоказаниях и ограничениях к их применению” (с изменениями и дополнениями). [Order of the RF Ministry of Health №107n on August 30, 2012 „On the procedure for the use of assisted reproductive technologies, contraindications and limitations to their use” (as amended). (in Russian)]
  28. Горшинова В.К., Десяткова Н.В., Беляева Н.А., Смольникова В.Ю., Калинина Е.А. Влияние ожирения на исходы лечения в программе ЭКО, ретроспективное исследование за 2013 г. Акушерство и гинекология. 2015; 6: 79-83. [Gorshinova V.K., Desyatkova N.V., Belyaeva N.A., Smolnikova V.Yu., Kalinina E.A. Impact of obesity on treatment outcomes in an in vitro fertilization program: Retrospective study in 2013. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; (6): 79-83. (in Russian)]
  29. Передереева Е.В., Лушникова А.А., Фрыкин А.Д., Пароконная А.А. Гормон лептин и проблемы репродукции. Злокачественные опухоли. 2012; 2(1): 35-9. [Peredereeva E.V., Lushnikova A.A., Fryikin A.D., Parokonnaya A.A. The hormone leptin and reproduction problems. Zlokachestvennyie opuholi. 2012; 2(1): 35-9. (in Russian)]
  30. Парфенова Н.С., Танявский Д.А. Адипонектин: благоприятное воздействие на метаболические и сердечно-сосудистые нарушения. Артериальная гипертензия. 2013; 19(1): 84-96. [Parfenova N.S., Tanyavskiy D.A. Adiponectin: a beneficial effect on metabolic and cardiovascular disorders. Arterialnaya gipertenziya. 2013; 19(1): 84-96. (in Russian)]

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