Association of follicle-stimulating hormone receptor gene polymorphism with the outcomes of assisted reproductive technology programs


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Abstract

Objective. To analyze the specific features of folliculogenesis, oogenesis, and embryogenesis in patients in relation to follicle-stimulating hormone receptor (FSHR) gene polymorphism (Asn680Ser) [rs6166] in assisted reproductive technology (ART) programs. Subject and methods. One hundred and thirty-five patients referred for IVF were examined during a prospective case-control study. A comparison group consisted of 69 patients with a normal response to ovarian stimulation; Group 1 included 31 patients with a poor ovarian response; Group 2 comprised 35 patients with an excessive ovarian response. FSHR gene polymorphism (Asn680Ser) was determined by polymerase chain reaction anal melting curve analysis. Results. The G allele was statistically significantly more frequently observed in the patients with a hyperresponse (p = 0.019). According to the autosomal recessive model, the presence of the G/G genotype predisposed to a hyperresponse (OR = 2.38 (1.0-5.64); р = 0.046). Aspirated oocytes were found to tend to reduce in number in case of carriage of the G/G genotype in the patients with a poor ovarian response. The chance of obtaining poor-quality embryos (class C and/or D) was statistically significantly higher if the G allele was present in the patient’s genotype ((39.1 versus 20.9%). According to the autosomal dominant model, OR was 2.43 (1.05-5.61) for the G/G and G/A genotypes versus the A/A genotype (p = 0.037). Analysis revealed no statistically significant association between the impact of the Asn680Serpolymorphism and conception rates. Conclusion. The pretreatment determination of FSHR gene polymorphism makes it possible to objectively choose adequate approaches and to improve the quality of therapeutic exposure in the ART programs. Examination of the allelic variants of FSHR may serve as an inexpensive mini-invasive test used before ovarian stimulation. As a result, this will help correct a planned therapy regimen on an individual basis.

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About the authors

I. V Vladimirova

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: i_teterina@oparina4.ru
postgraduate of the Department of assistive reproductive technology in the treatment of infertility

E. A Kalinina

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: e_kalinina@oparina4.ru
M.D., Ph.D., Head of the Department of assistive reproductive technology in the treatment of infertility

A. E Donnikov

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

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

References

  1. Falconer H., Andersson E., Aanesen A., Fried G. Follicle-stimulating hormone receptor polymorphisms in a population of infertile women. Acta Obstet. Gynecol. Scand. 2005; 84(8): 806-11.
  2. Yao Y., Ma C.H., Tang H.L., Hu Y.F. Influence of follicle-stimulating hormone receptor (FSHR) Ser680Asn polymorphism on ovarian function and in-vitro fertilization outcome: a meta-analysis. Mol. Genet. Metab. 2011; 103(4): 388-93.
  3. Huber M., Hadziosmanovic N., Berglund L., Holte J. Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem. Fertil. Steril. 2013; 100(5): 1270-6.
  4. Ferraretti A P., La Marca A., Fauser B.C., Tarlatzis B., Nargund G., Gianaroli L. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum. Reprod. 2011; 26(7): 1616-24.
  5. Polyzos N.P., Devroey P. A systematic review of randomized trials for the treatment of poor ovarian responders: is there any light at the end of the tunnel? Fertil. Steril. 2011; 96(5): 1058-61. e1057.
  6. Назаренко Т.А., Краснопольская К.В. “Бедный ответ”. Тактика ведения пациенток со сниженной реакцией на стимуляцию гонадотропинами в программах ЭКО. 2-е изд. М.: МЕДпресс-информ; 2013. 80 c. [Nazarenko T.A., Krasnopolskaya K.V. “Poor response”. Clinical management of patients with a reduced response to gonadotropin stimulation in IVF programs. 2nd ed. M.: MEDpress Inform; 2013. 80 c.]
  7. American Society of Reproductive Medicine. Ovarian hyperstimulation syndrome. Fertil. Steril. 2008; 90(5, Suppl.): S188-93.
  8. Delvigne A. Symposium: Update on prediction and management of OHSS. Epidemiology of OHSS. Reprod. Biomed. Online. 2009; 19(1): 8-13.
  9. Сухих Г.Т., Назаренко Т.А., ред. Бесплодный брак. Современные подходы к диагностике и лечению. 2-е изд. М.: ГЭОТАР-Медиа; 2010. 784 c. [Sukhikh G.T., Nazarenko T.A., eds. Sterile marriage. Current approaches to diagnosis and treatment. 2nd ed. M.: GEOTAR Media; 2010. 784 c.]
  10. Калинина Е.А., Эбзеева М.В., Кузьмичев Л.Н. Опыт применения “мягких” схем стимуляции суперовуляции у пациенток группы риска развития синдрома гиперстимуляции яичников. Акушерство и гинекология. 2010, 6: 60-4. [Kalinina E.A., Ebzeyeva M.V., Kuzmichev L.N. Experience with mild superovulation regimens used in ovarian hyperstimulation syndrome risk group patients. Obstetrics and Gynecology. 2010, 6: 60-4.]
  11. Altmae S., Hovatta O., Stavreus-Evers A., Salumets A. Genetic predictors of controlled ovarian hyperstimulation: where do we stand today? Hum. Reprod. Update. 2011; 17(6): 813-28.
  12. Desai S.S., Achrekar S.K., Paranjape S.R., Desai S.K., Mangoli V.S., Mahale S.D. Association of allelic combinations of FSHR gene polymorphisms with ovarian response. Reprod. Biomed. Online. 2013; 27(4): 400-6.
  13. Greb R.R., Behre H.M., Simoni M. Pharmacogenetics in ovarian stimulation - current concepts and future options. Reprod. Biomed. Online. 2005; 11(5): 589-600.
  14. Laan M., Grigorova M., Huhtaniemi I.T. Pharmacogenetics of follicle-stimulating hormone action. Curr. Opin. Endocrinol. Diabet. Obes. 2012; 19(3): 220-7.
  15. Perez Mayorga M., Gromoll J., Behre H.M., Gassner C., Nieschlag E., Simoni M. Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. J. Clin. Endocrinol. Metab. 2000; 85(9): 3365-9.
  16. Элдер К., Дэйл Б. Экстракорпоральное оплодотворение: пер. с англ. М.: МЕДпресс-информ; 2008. 276 c.[Elder K., Dale B. In vitro fertilization: trans. from English. M.: MEDpress Inform; 2008. 276 c.]
  17. Moron F.J., Ruiz A. Pharmacogenetics of controlled ovarian hyperstimulation: time to corroborate the clinical utility of FSH receptor genetic markers. Pharmacogenomics. 2010; 11(11): 1613-8.
  18. La Marca A., Sighinolfi G., Argento C., Grisendi V., Casarini L., Volpe A., Simoni M. Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization. Fertil. Steril. 2013; 99(4): 970-8. e971.
  19. Баранов В.С., ред. Генетический паспорт - основа индивидуальной и предиктивной медицины. СПб.: Издательство Н-Л; 2009. 528 с. [Baranov V.S., eds. Genetic passport - the basis of individual and predictive medicine. St. Petersburg: Publisher N-L; 2009. 528 p.]

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