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УДК: 618.177-089.888.11-07
ББК: Р716.11с13

Яковлев П.П.

Активность овариальной ароматазы в патогенезе нормогонадотропной ановуляции при синдроме поликистозных яичников и ее влияние на протоколы ЭКО

Ключевые слова: овариальная ароматаза, синдром поликистозных яичников, экстракорпоральное оплодотворение (ЭКО)

Определение факторов, влияющих на эффективность программ вспомогательных репродуктивных технологий, является актуальной и важной задачей. В статье рассмотрены современные представления об участии активности овариальной ароматазы в патогенезе нормогонадотропной ановуляции и ее влиянии на протоколы экстракорпорального оплодотворения. Изменение активности овариальной ароматазы играет важную роль в патогенезе развития нормогонадотропной ановуляции. Полиморфизм гена CYP 19 может приводить к изменению активности овариальной ароматазы и влиять на показатели протокола экстракорпорального оплодотворения. Разработка неинвазивных методик определения активности овариальной ароматазы позволит прогнозировать результативность протоколов экстракорпорального оплодотворения во врачебной практике.

Yakovlev P.

Ovarian aromatase activity in the pathogenesis of normogonadotropic anovulation in polycystic ovarian syndrome and its effect on IVF protocols

Keywords: ovarian aromatase, polycystic ovarian syndrome, in vitro fertilization (IVF)

Identification of factors influencing the effectiveness of assisted reproductive technologies is an urgent and important objective. The article examines contemporary views on participation of ovarian aromatase activity in the pathogenesis of normogonadotropic anovulation and its effect on IVF protocols. A change in the activity of ovarian aromatase plays an important role in the pathogenesis of the normogonadotropic anovulation development. Polymorphism of CYP 19 gene results in changing the activity of ovarian aromatase and affects an IVF protocol parameters. Development of non-invasive techniques for determining ovarian aromatase activity will make it possible to predict the effectiveness of extracorporal fertilization protocols in medical practice.

Литература

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  13. Berstein L.M., Imyanitov E.N., Kovalevskij A.J. et al. CYP17 and CYP19 genetic polymorphisms in endometrial cancer: association with intratumoral aromatase activity. Cancer Lett. 2004; 207: 191–6. doi: 10.1016/j.canlet.2004.01.001.
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  15. Carlsson I.B., Scott J.E., Visser J.A., Ritvos O., Themmen A.P., Hovatta O. Anti-Mullerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro. Hum Reprod. 2006; 21: 2223–7.
  16. Catteau-Jonard S., Dewailly D. Pathophysiology of polycystic ovary syndrome: the role of hyperandrogenism. Front Horm Res. 2013; 40: 22–7.
  17. Chen J., Shen S., Tan Y. et al. The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome. Journal of Ovarian Research. 2015; 8(1, article 11): 1–6. doi: 10.1186/s13048-015-0139-1.
  18. Das M., Gillott D.J., Saridogan E., Djahanbakhch O. Anti-Mullerian hormone is increased in follicular fluid from unstimulated ovaries in women with polycystic ovary syndrome. Hum Reprod. 2008; 23: 2122–6.
  19. Desforges-Bullet V., Gallo C., Lefebvre C., Pigny P., Dewailly D., Catteau-Jonard S. Increased anti-Mullerian hormone and decreased FSH levels in follicular fluid obtained in women with polycystic ovaries at the time of follicle puncture for in vitro fertilization. Fertil Steril. 2010; 94: 198–204.
  20. Fatemi H.M., Garcia-Velasco J. Avoiding ovarian hyperstimulation syndrome with the use of gonadotropin-releasing hormone agonist trigger. Fertil Steril. 2015; 103: 870–3.
  21. Gabrilove J.L. The pathogenesis of the polycystic ovary syndrome: a hypothesis. Endocr Pract. 2002; 8: 127–32.
  22. Heijnen E.M., Eijkemans M.J., Hughes E.G. et al. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update. 2006; 12: 13–21.
  23. Jakimiuk A.J., Weitsman S.R., Brzechffa P.R., Magoffin D.A. Aromatase mRNA expression in individual follicles from polycystic ovaries. Mol Hum Reprod. 1998; 4: 1–8.
  24. Kirilovas D., Chaika A., Bergström M., Bergstrom-Petterman E., Carlström K., Nosenko J. et al. Granulosa cell aromatase enzyme activity: effects of follicular fluid from patients with polycystic ovary syndrome, using aromatase conversion and [11C]vorozole-binding assays. Gynecol Endocrinol. 2006; 22: 685–91. doi: 10.1080/09513590601037535.
  25. Lazaros L., Hatzi E., Xita N. et al. Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation.  Assist Reprod Genet. 2012; 29: 203–209. doi: 10.1007/s10815-011-9673-y.
  26. Leandros L., Nectaria X., Elissavet H., Atsushi T., Apostolos K., Georgios M. et al. CYP19 gene variants affect the assisted reproduction outcome of women with polycystic ovary syndrome. Gynecol Endocrinol. 2013; 29: 478–82. doi: 10.3109/09513590.2013.774359.
  27. Lee H.S., Kim K.H., Hwang J.S. Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls. Endocrinol (Oxf). 2014; 81(3): 395-400. doi: 10.1111/ cen.12439.
  28. Li H.W., Lee V.C., Lau E.Y., Yeung W.S., Ho P.C., Ng E.H. Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilisation treatment. J Assist Reprod Genet. 2014; 31: 205–11.
  29. Lin L., Ercan O., Raza J. et al. Variable phenotypes associated with aromatase (CYP19) insufficiency in humans. Clin. Endocrinol. Metabol. 2007; 92: 982–90.
  30. McCormick B., Thomas M., Maxwell R., Williams D., Aubuchon M. Effects of polycystic ovarian syndrome on in vitro fertilizationembryo transfer outcomes are influenced by body mass index. Fertil Steril. 2008; 90: 2304–9.
  31. National Collaborating Centre for Women’s and Children’s Health / National Institue for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. RCOG Press, 2004.
  32. National Institute for Health and Care Excellence. Fertility: assessment and treatment for people with fertility problems. NICE guidance, 2013.
  33. Nejad E.S., Saedi T., Saedi S., Rashidi B.H., Nekoo Z.A., Jahangiri N. Comparison of in vitro fertilisation success in patients with polycystic ovary syndrome and tubal factor. Gynecol Endocrinol. 2011; 27: 117–20.
  34. Rowe P.J., Comhaire F.H., Hargreave T.B., Mellows H.J.WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple. Cambridge, Cambridge University Press, 1997.
  35. Sahu B., Ozturk O., Ranierri M., Serhal P. Comparison of oocyte quality and intracytoplasmic sperm injection outcome in women with isolated polycystic ovaries or polycystic ovarian syndrome. Arch Gynecol Obstet. 2008; 277: 239–44.
  36. Söderlund D., Canto P., Carranza-Lira S., Méndez J.P. No evidence of mutations in the P450 aromatase gene in patients with polycystic ovary syndrome. Hum Reprod. 2005; 20: 965–9.
  37. Stratakis C.A., Vottero A., Brodie A. et al. The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. J Clin Endocrinol Metabol. 1998; 83: 1348–57.
  38. Weghofer A., Munne S., Chen S., Barad D., Gleicher N. Lack of association between polycystic ovary syndrome and embryonic aneuploidy. Fertil Steril. 2007; 88: 900–5.
  39. Yang F., Ruan Y.C., Yang Y.J. et al. Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women. Reproduction. 2015; 150: 289–96. doi: 10.1530/REP-15-0044.

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  11. Balen A.H., Morley L.C., Misso M., Franks S., Legro R.S., Wijeyaratne C.N., Stener-Victorin E., Fauser B., Norman R.J., Teede H. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016; 10: 1–22.
  12. Belgorosky A., Pepe C., Marino R. et al. Hypothalamic-pituitaryovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the CYP19 gene. J Clin Endocrinol Metabol. 2003; 88: 5127–31.
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  14. Broekmans F.J., Knauff E.A., Valkenburg O., Laven J.S., Eijkemans M.J., Fauser B.C. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG. 2006; 113: 1210–17.
  15. Carlsson I.B., Scott J.E., Visser J.A., Ritvos O., Themmen A.P., Hovatta O. Anti-Mullerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro. Hum Reprod. 2006; 21: 2223–7.
  16. Catteau-Jonard S., Dewailly D. Pathophysiology of polycystic ovary syndrome: the role of hyperandrogenism. Front Horm Res. 2013; 40: 22–7.
  17. Chen J., Shen S., Tan Y. et al. The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome. Journal of Ovarian Research. 2015; 8(1, article 11): 1–6. doi: 10.1186/s13048-015-0139-1.
  18. Das M., Gillott D.J., Saridogan E., Djahanbakhch O. Anti-Mullerian hormone is increased in follicular fluid from unstimulated ovaries in women with polycystic ovary syndrome. Hum Reprod. 2008; 23: 2122–6.
  19. Desforges-Bullet V., Gallo C., Lefebvre C., Pigny P., Dewailly D., Catteau-Jonard S. Increased anti-Mullerian hormone and decreased FSH levels in follicular fluid obtained in women with polycystic ovaries at the time of follicle puncture for in vitro fertilization. Fertil Steril. 2010; 94: 198–204.
  20. Fatemi H.M., Garcia-Velasco J. Avoiding ovarian hyperstimulation syndrome with the use of gonadotropin-releasing hormone agonist trigger. Fertil Steril. 2015; 103: 870–3.
  21. Gabrilove J.L. The pathogenesis of the polycystic ovary syndrome: a hypothesis. Endocr Pract. 2002; 8: 127–32.
  22. Heijnen E.M., Eijkemans M.J., Hughes E.G. et al. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update. 2006; 12: 13–21.
  23. Jakimiuk A.J., Weitsman S.R., Brzechffa P.R., Magoffin D.A. Aromatase mRNA expression in individual follicles from polycystic ovaries. Mol Hum Reprod. 1998; 4: 1–8.
  24. Kirilovas D., Chaika A., Bergström M., Bergstrom-Petterman E., Carlström K., Nosenko J. et al. Granulosa cell aromatase enzyme activity: effects of follicular fluid from patients with polycystic ovary syndrome, using aromatase conversion and [11C]vorozole-binding assays. Gynecol Endocrinol. 2006; 22: 685–91. doi: 10.1080/09513590601037535.
  25. Lazaros L., Hatzi E., Xita N. et al. Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation.  Assist Reprod Genet. 2012; 29: 203–209. doi: 10.1007/s10815-011-9673-y.
  26. Leandros L., Nectaria X., Elissavet H., Atsushi T., Apostolos K., Georgios M. et al. CYP19 gene variants affect the assisted reproduction outcome of women with polycystic ovary syndrome. Gynecol Endocrinol. 2013; 29: 478–82. doi: 10.3109/09513590.2013.774359.
  27. Lee H.S., Kim K.H., Hwang J.S. Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls. Endocrinol (Oxf). 2014; 81(3): 395-400. doi: 10.1111/ cen.12439.
  28. Li H.W., Lee V.C., Lau E.Y., Yeung W.S., Ho P.C., Ng E.H. Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilisation treatment. J Assist Reprod Genet. 2014; 31: 205–11.
  29. Lin L., Ercan O., Raza J. et al. Variable phenotypes associated with aromatase (CYP19) insufficiency in humans. Clin. Endocrinol. Metabol. 2007; 92: 982–90.
  30. McCormick B., Thomas M., Maxwell R., Williams D., Aubuchon M. Effects of polycystic ovarian syndrome on in vitro fertilizationembryo transfer outcomes are influenced by body mass index. Fertil Steril. 2008; 90: 2304–9.
  31. National Collaborating Centre for Women’s and Children’s Health / National Institue for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. RCOG Press, 2004.
  32. National Institute for Health and Care Excellence. Fertility: assessment and treatment for people with fertility problems. NICE guidance, 2013.
  33. Nejad E.S., Saedi T., Saedi S., Rashidi B.H., Nekoo Z.A., Jahangiri N. Comparison of in vitro fertilisation success in patients with polycystic ovary syndrome and tubal factor. Gynecol Endocrinol. 2011; 27: 117–20.
  34. Rowe P.J., Comhaire F.H., Hargreave T.B., Mellows H.J.WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple. Cambridge, Cambridge University Press, 1997.
  35. Sahu B., Ozturk O., Ranierri M., Serhal P. Comparison of oocyte quality and intracytoplasmic sperm injection outcome in women with isolated polycystic ovaries or polycystic ovarian syndrome. Arch Gynecol Obstet. 2008; 277: 239–44.
  36. Söderlund D., Canto P., Carranza-Lira S., Méndez J.P. No evidence of mutations in the P450 aromatase gene in patients with polycystic ovary syndrome. Hum Reprod. 2005; 20: 965–9.
  37. Stratakis C.A., Vottero A., Brodie A. et al. The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. J Clin Endocrinol Metabol. 1998; 83: 1348–57.
  38. Weghofer A., Munne S., Chen S., Barad D., Gleicher N. Lack of association between polycystic ovary syndrome and embryonic aneuploidy. Fertil Steril. 2007; 88: 900–5.
  39. Yang F., Ruan Y.C., Yang Y.J. et al. Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women. Reproduction. 2015; 150: 289–96. doi: 10.1530/REP-15-0044.

 

Сведения об авторах

Яковлев Павел Павлович
аспирант отделения вспомогательных репродуктивных технологий, Научно-исследовательский институт акушерства, гинекологии и репродуктологии, Россия, Москва (iakovlevpp@gmail.com; )

Ссылка на статью

Яковлев П.П. Активность овариальной ароматазы в патогенезе нормогонадотропной ановуляции при синдроме поликистозных яичников и ее влияние на протоколы ЭКО [Электронный ресурс] // Acta medica Eurasica. – 2018. – №2. – С. 42-49. – URL: https://acta-medica-eurasica.ru/single/2018/2/7/.

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