Актуальность. Несмотря на многочисленные исследования, вопросы о выборе наиболее эффективного метода лечения для пациенток с рецидивирующим наружным генитальным эндометриозом (НГЭ), роли и особенностях программ вспомогательных репродуктивных технологий и способах повышения их результативности до сих пор являются не решенными. Цель. Отразить современные представления об этиопатогенезе и тактике ведения пациенток с рецидивирующим НГЭ и бесплодием по данным отечественной и зарубежной литературы. Материалы и методы. Для написания данного обзора был осуществлен поиск отечественных и зарубежных публикаций в российских и международных системах поиска (PubMed, eLIBRARY и пр.) за последние 1–18 лет. В обзор были включены статьи из рецензируемой литературы. Результаты. Представлены факторы риска развития НГЭ, патогенез и клиническая картина заболевания, рассмотрены медикаментозные и оперативные методы терапии эндометриоза. Заключение. Эндометриоз продолжает оставаться загадочным заболеванием для современной науки. Индивидуальный подход с учетом возраста, состояния овариального резерва, хирургического лечения в анамнезе (количество оперативных вмешательств по поводу НГЭ) позволит выработать персональный подход для каждой субфертильной женщины.
Relevance. Despite lots of studies, issues on a choice of the most effective treatment method for patients with recurrent external genital endometriosis (EGE) as well as a role and features of assisted reproductive technology programs and ways to improve their performance are still unresolved. Aim. To provide a current understanding on etiopathogenesis and management strategy for patients with recurrent EGE and infertility according to Russian and foreign literature date. Materials and methods. In order to write this review, domestic and foreign publications were searched in Russian and international search systems (PubMed, eLIBRARY, etc.) for the last 2–15 years. The review includes articles from peer-reviewed literature. Results. The article provides risk factors for EGE development, disease pathogenesis and clinical manifestation as well as drug and surgical methods for a treatment of endometriosis. Conclusion. Endometriosis remains still to be a mysterious disease for modern science. An individual approach given an age, ovarian reserve and a history of surgical treatment (numbers of surgical interventions for EGE) will allow you to elaborate a personal approach for each woman with subfertility.
1. Эндометриоз: диагностика, лечение и реабилитация. Клинические рекомендации по ведению больных. Под ред. Л.В.Адамян. М., 2016.
[Endometrioz: diagnostika, lechenie i reabilitatsiia. Klinicheskie rekomendatsii po vedeniiu bol'nykh. Pod red. L.V.Adamian. Moscow, 2016 (in Russian).]
2. Адамян Л.В., Кулаков В.И., Андреева Е.Н. Эндометриозы. Руководство для врачей М.: Медицина, 2006.
[Adamian L.V., Kulakov V.I., Andreeva E.N. Endometriozy. Rukovodstvo dlia vrachei. Moscow: Meditsina, 2006 (in Russian).]
3. Эндометриоз. Национальные клинические рекомендации. Под ред. Л.В.Адамян. М., 2009.
[Endometrioz. Natsional'nye klinicheskie rekomendatsii. Pod red. L.V.Adamian. Moscow, 2009 (in Russian).]
4. Бесплодие. Клинические рекомендации. М., 2019.
[Besplodie. Klinicheskie rekomendatsii. Moscow, 2019 (in Russian).]
5. Кулаков В.И., Савельева Г.М., Манухин И.Б. Национальное руководство. Гинекология. 2009; с. 338–40.
[Kulakov V.I., Savel'eva G.M., Manukhin I.B. Natsional'noe rukovodstvo. Ginekologiia. 2009; p. 338–40 (in Russian).]
6. Адамян Л.В., Калинина Е.А., Колотовкина А.В., Коган Е.А. Клинико-эмбриологические аспекты эндометриоз-ассоциированного бесплодия. Проблемы репродукции. 2010; 5: 47–51.
[Adamian L.V., Kalinina E.A., Kolotovkina A.V., Kogan E.A. Kliniko-embriologicheskie aspekty endometrioz-assotsiirovannogo besplodiia. Problemy reproduktsii. 2010; 5: 47–51 (in Russian).]
7. Краснопольская К.В. Лечение бесплодия при эндометриозе: Взгляд репродуктолога. М., 2019; с. 28–80.
[Krasnopol'skaia K.V. Lechenie besplodiia pri endometrioze: Vzgliad reproduktologa. Moscow, 2019; p. 28–80 (in Russian).]
8. Калинина Е.А., Смольникова В.Ю. Эндометриоз и бесплодие. Проблемы репродукции. 2012; 3: 341–3.
[Kalinina E.A., Smol'nikova V.Iu. Endometrioz i besplodie. Problemy reproduktsii. 2012; 3: 341–3 (in Russian).]
9. Общая заболеваемость взрослого населения России в 2011 и 2012 гг. Департамент анализа, прогноза, развития здравоохранения и медицинской науки Минздрава России. ФГБУ «Центральный научно-исследовательский институт организации и информатизации здравоохранения». М., 2013.
[Obshchaia zabolevaemost' vzroslogo naseleniia Rossii v 2011 i 2012 gg. Departament analiza, prognoza, razvitiia zdravookhraneniia i meditsinskoi nauki Minzdrava Rossii. FGBU "Tsentral'nyi nauchno-issledovatel'skii institut organizatsii i informatizatsii zdravookhraneniia". Moscow, 2013 (in Russian).]
10. Хамошина М.Б., Леваков С.А. Эндометриоз: мировой прорыв в медикаментозном лечении. М.: Status Praesens, 2012.
[Khamoshina M.B., Levakov S.A. Endometrioz: mirovoi proryv v medikamentoznom lechenii. Moscow: Status Praesens, 2012 (in Russian).]
11. Оразов М.Р. и др. Факторы риска наружного генитального эндометриоза у женщин в мегаполисе на примере г. Москвы. В сб.: Национальный конгресс «Онкология репродуктивных органов: от профилактики и раннего выявления к эффективному лечению». 19–21 мая 2016 г. М., 2016.
[Orazov M.R. et al. Faktory riska naruzhnogo genital'nogo endometrioza u zhenshchin v megapolise na primere g. Moskvy. V sb.: Natsional'nyi kongress "Onkologiia reproduktivnykh organov: ot profilaktiki i rannego vyiavleniia k effektivnomu lecheniiu". 19–21 maia 2016 g. Moscow, 2016 (in Russian).]
12. Колотовкина А.В., Калинина Е.А., Коган Е.А. Морфофункциональные особенности эндометрия у больных эндометриозассоциированным бесплодием (обзор литературы). Гинекология. 2012; 14 (4): 74–9.
[Kolotovkina A.V., Kalinina E.A., Kogan E.A. Morfo-functional features of endometrium in patients with endometriosis-associated infertility (literary review). Gynecology. 2012; 14 (4): 74–9 (in Russian).]
13. Баскаков В.П. Клиника и лечение эндометриоза. Л.: Медицина, 1990; с. 230–6.
[Baskakov V.P. Klinika i lechenie endometrioza. Leningrad: Meditsina, 1990; p. 230–6 (in Russian).]
14. Консенсус по ведению эндометриоза. Клинические рекомендации. Human Reproduction. 2013; 4: 1–17.
[Konsensus po vedeniiu endometrioza. Klinicheskie rekomendatsii. Human Reproduction. 2013; 4: 1–17 (in Russian).]
15. Логинова О.Н., Сонова М.М. Эндометриоз и бесплодие: патофизиология и тактика ведения. Рос. вестн. акушера-гинеколога. 2011; 6: 47–53.
[Loginova O.N., Sonova M.M. Endometrioz i besplodie: patofiziologiia i taktika vedeniia. Ros. vestn. akushera-ginekologa. 2011; 6: 47–53 (in Russian).]
16. Aflatoonian A, Rahmani E, Rahsepar M. Assessing the efficacy of aspiration and ethanol injection in recurrent endometrioma before IVF cycle: A randomized clinical trial. Iran J Reprod Med 2013; 11 (3): 179–84.
17. Vercellini P, Somigliana E, Viganò P et al. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review. Acta Obstet Gynecol Scand 2009; 88: 1074–82.
18. Guo SW Recurrence of endometriosis and its control. Hum Reprod Update 2009; 15: 441–61.
19. Santos-Ribeiro S, Tournaye H, Polyzos NP. Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies. Hum Reprod 2016; 31 (2): 393–402.
20. Cheng LY, Lin PY, Huang FJ et al. Ectopic pregnancy following in vitro fertilization with embryo transfer: A single-center experience during 15 years. Taiwanese J Obstet Gynecol 2015; 54 (5): 541–5.
21. Taylor MM. Endometriosis – a missed malady. AORN J 2003; 77: 298–313.
22. Hummelshoj L et al. Update on endometriosis. Women's Health 2006; 2: 53–6.
23. Child TJ, Tan SL. Endometriosis: aetiology, pathogenesis and treatment. Drugs 2001; 61: 1735–50.
24. Cramer DW, Missmer SA. The epidemiology of endometriosis. Ann NY Acad Sci 2002; 955: 11–22.
25. Bischoff F, Simpson JL. Genetic basis of endometriosis. Ann NY Acad Sci 2004; 1034; 284–99.
26. Lessey DA. Assessment of endometrial receptivity. Fertil Steril 2011; 96: 522–9.
27. Koninckx PR, Ussia A, Donnez J et al. The title is misleading: An opinion paper is not a consensus paper. Hum Reprod 2013; 28 (11): 3161.
28. Van Langendonct A, Casanas-Roux F, Donnes J. Oxidative stress and peritoneal endometriosis. Fertil Steril 2002; 77 (7): 861–70.
29. Rombauts L, McMaster R, Motteram C, Fernando S. Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles. Hum Reprod 2015; 30 (12): 2846–52.
30. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014; 29 (3): 400–12.
31. May KE, Conduit-Hulbert SA, Villar J et al. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update 2010; 16: 651–74.
32. Clinical Practice Guideline SOGC. The materials of 2nd Asian Conference of Endometriosis 2012, Istanbul; The materials of 2nd European Conference of Endometriosis 2012, Italy. J Obstet Gynecol Canada 2010; 6.
33. Danselman GA, Vermeulen N, Becker S et al. European Society Human Reproduction and Embryology. Gul Repro 2014; 29 (3): 400–12.
34. Wimberger P, Grübling N, Riehn A et al. Endometriosis A Chameleon Patients’ Perception of Clinical Symptoms, Treatment Strategies and Their Impact on Symptoms. Geburdshilfe Frauenheilkd 2014; 74 (10): 940–6.
35. Nasu K, Yuge A, Tsuno A et al. Involvement of resistance to apoptosis in the pathogenesis of endometriosis. Histopathol 2009; 24: 1181–92.
36. Exacoustos C, Zupi E, Amadio A et al. Recurrence of endometriomas after laparoscopic removal: sonographic and clinical follow-up and indication for second surgery. J Minim Invasive Gynecol 2006; 13: 281–8.
37. Vignali M, Bianchi S, Candiani M et al. Surgical treatment of deep endometriosis and risk of recurrence. J Minim Invasive Gynecol 2005; 12: 508–13.
38. Vercellini P, Barbara G, Abbiati A et al. Repetitive surgery for recurrent symptomatic endometriosis: what to do? Eur J Obstet Gynecol Reprod Biol 2009; 146: 15–21.
39. Bulletti C, DeZiegler D, Stefanetti M et al. Endometriosis: absence of recurrence in patients after endometrial ablation. Hum Reprod 2001; 16: 2676–9.
40. Blumenfeld Z. Hormonal suppressive therapy for endometriosis may not improve patient health. Fertil Steril 2004; 81 (3): 487–92.
41. Tummon I, Asher L, Martin J, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril 1997; 68: 8–12.
42. Costello MF Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination. Aust N Z J Obstet Gynaecol 2004; 44: 93–102.
43. Kemmann E, Ghazi D, Corsan G, Bohrer MK. Does ovulation stimulation improve fertility in women with minimal/mild endometriosis after laser laparoscopy? Int J Fertil Menopausal Stud 1993; 38 (1): 16–21.
44. Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev 2006; 1: D004635.
45. Bedaiwy MA, Allaire C, Alfaraj S. Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy. Fertil Steril 2017; 107 (3): 537–48. DOI: 10.1016/j.fertnstert.2016.12.024
46. Xing W, Lin H, Wu Z et al. Effect of pelvic endometriosis, endometriomas and recurrent endometriomas on ivf-et/icsi outcomes. Mater Sociomed 2016; 28 (2): 91–4.
47. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril 2002; 77: 1148–55.
48. Taylor RN, Yu J, Torres PB et al. Mechanistic and therapeutic implications of angiogenesis in endometriosis. Reprod Sci 2009; 16 (2): 140–6.
49. Borrelli GM, Carvalho KI, Kallas EG et al. Chemokines in the pathogenesis of endometriosis and infertility. J Reprod Immunol. 2013; 98: 1–9.
50. Bulun SE, Cheng YH, Yin P et al. Progesterone resistance in ndometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol 2006; 248: 94–103.
51. Hauzman EE, Garcia-Velasco JA, Pellicer A. Oocyte donation and endometriosis: what are the lessons? Semin Reprod Med 2013; 31: 173–7.
52. Sarapik A, Haller-Kikkatalo K, Utt M et al. Serum anti-endometrial antibodies in infertile women – potential risk factor for implantation failure. Am J Reprod Immunol 2010; 63: 349–57.
________________________________________________
1. Endometrioz: diagnostika, lechenie i reabilitatsiia. Klinicheskie rekomendatsii po vedeniiu bol'nykh. Pod red. L.V.Adamian. Moscow, 2016 (in Russian).
2. Adamian L.V., Kulakov V.I., Andreeva E.N. Endometriozy. Rukovodstvo dlia vrachei. Moscow: Meditsina, 2006 (in Russian).
3. Endometrioz. Natsional'nye klinicheskie rekomendatsii. Pod red. L.V.Adamian. Moscow, 2009 (in Russian).
4. Besplodie. Klinicheskie rekomendatsii. Moscow, 2019 (in Russian).
5. Kulakov V.I., Savel'eva G.M., Manukhin I.B. Natsional'noe rukovodstvo. Ginekologiia. 2009; p. 338–40 (in Russian).
6. Adamian L.V., Kalinina E.A., Kolotovkina A.V., Kogan E.A. Kliniko-embriologicheskie aspekty endometrioz-assotsiirovannogo besplodiia. Problemy reproduktsii. 2010; 5: 47–51 (in Russian).
7. Krasnopol'skaia K.V. Lechenie besplodiia pri endometrioze: Vzgliad reproduktologa. Moscow, 2019; p. 28–80 (in Russian).
8. Kalinina E.A., Smol'nikova V.Iu. Endometrioz i besplodie. Problemy reproduktsii. 2012; 3: 341–3 (in Russian).
9. Obshchaia zabolevaemost' vzroslogo naseleniia Rossii v 2011 i 2012 gg. Departament analiza, prognoza, razvitiia zdravookhraneniia i meditsinskoi nauki Minzdrava Rossii. FGBU "Tsentral'nyi nauchno-issledovatel'skii institut organizatsii i informatizatsii zdravookhraneniia". Moscow, 2013 (in Russian).
10. Khamoshina M.B., Levakov S.A. Endometrioz: mirovoi proryv v medikamentoznom lechenii. Moscow: Status Praesens, 2012 (in Russian).
11. Orazov M.R. et al. Faktory riska naruzhnogo genital'nogo endometrioza u zhenshchin v megapolise na primere g. Moskvy. V sb.: Natsional'nyi kongress "Onkologiia reproduktivnykh organov: ot profilaktiki i rannego vyiavleniia k effektivnomu lecheniiu". 19–21 maia 2016 g. Moscow, 2016 (in Russian).
12. Kolotovkina A.V., Kalinina E.A., Kogan E.A. Morfo-functional features of endometrium in patients with endometriosis-associated infertility (literary review). Gynecology. 2012; 14 (4): 74–9 (in Russian).
13. Baskakov V.P. Klinika i lechenie endometrioza. Leningrad: Meditsina, 1990; p. 230–6 (in Russian).
14. Konsensus po vedeniiu endometrioza. Klinicheskie rekomendatsii. Human Reproduction. 2013; 4: 1–17 (in Russian).
15. Loginova O.N., Sonova M.M. Endometrioz i besplodie: patofiziologiia i taktika vedeniia. Ros. vestn. akushera-ginekologa. 2011; 6: 47–53 (in Russian).
16. Aflatoonian A, Rahmani E, Rahsepar M. Assessing the efficacy of aspiration and ethanol injection in recurrent endometrioma before IVF cycle: A randomized clinical trial. Iran J Reprod Med 2013; 11 (3): 179–84.
17. Vercellini P, Somigliana E, Viganò P et al. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review. Acta Obstet Gynecol Scand 2009; 88: 1074–82.
18. Guo SW Recurrence of endometriosis and its control. Hum Reprod Update 2009; 15: 441–61.
19. Santos-Ribeiro S, Tournaye H, Polyzos NP. Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies. Hum Reprod 2016; 31 (2): 393–402.
20. Cheng LY, Lin PY, Huang FJ et al. Ectopic pregnancy following in vitro fertilization with embryo transfer: A single-center experience during 15 years. Taiwanese J Obstet Gynecol 2015; 54 (5): 541–5.
21. Taylor MM. Endometriosis – a missed malady. AORN J 2003; 77: 298–313.
22. Hummelshoj L et al. Update on endometriosis. Women's Health 2006; 2: 53–6.
23. Child TJ, Tan SL. Endometriosis: aetiology, pathogenesis and treatment. Drugs 2001; 61: 1735–50.
24. Cramer DW, Missmer SA. The epidemiology of endometriosis. Ann NY Acad Sci 2002; 955: 11–22.
25. Bischoff F, Simpson JL. Genetic basis of endometriosis. Ann NY Acad Sci 2004; 1034; 284–99.
26. Lessey DA. Assessment of endometrial receptivity. Fertil Steril 2011; 96: 522–9.
27. Koninckx PR, Ussia A, Donnez J et al. The title is misleading: An opinion paper is not a consensus paper. Hum Reprod 2013; 28 (11): 3161.
28. Van Langendonct A, Casanas-Roux F, Donnes J. Oxidative stress and peritoneal endometriosis. Fertil Steril 2002; 77 (7): 861–70.
29. Rombauts L, McMaster R, Motteram C, Fernando S. Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles. Hum Reprod 2015; 30 (12): 2846–52.
30. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014; 29 (3): 400–12.
31. May KE, Conduit-Hulbert SA, Villar J et al. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update 2010; 16: 651–74.
32. Clinical Practice Guideline SOGC. The materials of 2nd Asian Conference of Endometriosis 2012, Istanbul; The materials of 2nd European Conference of Endometriosis 2012, Italy. J Obstet Gynecol Canada 2010; 6.
33. Danselman GA, Vermeulen N, Becker S et al. European Society Human Reproduction and Embryology. Gul Repro 2014; 29 (3): 400–12.
34. Wimberger P, Grübling N, Riehn A et al. Endometriosis A Chameleon Patients’ Perception of Clinical Symptoms, Treatment Strategies and Their Impact on Symptoms. Geburdshilfe Frauenheilkd 2014; 74 (10): 940–6.
35. Nasu K, Yuge A, Tsuno A et al. Involvement of resistance to apoptosis in the pathogenesis of endometriosis. Histopathol 2009; 24: 1181–92.
36. Exacoustos C, Zupi E, Amadio A et al. Recurrence of endometriomas after laparoscopic removal: sonographic and clinical follow-up and indication for second surgery. J Minim Invasive Gynecol 2006; 13: 281–8.
37. Vignali M, Bianchi S, Candiani M et al. Surgical treatment of deep endometriosis and risk of recurrence. J Minim Invasive Gynecol 2005; 12: 508–13.
38. Vercellini P, Barbara G, Abbiati A et al. Repetitive surgery for recurrent symptomatic endometriosis: what to do? Eur J Obstet Gynecol Reprod Biol 2009; 146: 15–21.
39. Bulletti C, DeZiegler D, Stefanetti M et al. Endometriosis: absence of recurrence in patients after endometrial ablation. Hum Reprod 2001; 16: 2676–9.
40. Blumenfeld Z. Hormonal suppressive therapy for endometriosis may not improve patient health. Fertil Steril 2004; 81 (3): 487–92.
41. Tummon I, Asher L, Martin J, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril 1997; 68: 8–12.
42. Costello MF Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination. Aust N Z J Obstet Gynaecol 2004; 44: 93–102.
43. Kemmann E, Ghazi D, Corsan G, Bohrer MK. Does ovulation stimulation improve fertility in women with minimal/mild endometriosis after laser laparoscopy? Int J Fertil Menopausal Stud 1993; 38 (1): 16–21.
44. Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev 2006; 1: D004635.
45. Bedaiwy MA, Allaire C, Alfaraj S. Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy. Fertil Steril 2017; 107 (3): 537–48. DOI: 10.1016/j.fertnstert.2016.12.024
46. Xing W, Lin H, Wu Z et al. Effect of pelvic endometriosis, endometriomas and recurrent endometriomas on ivf-et/icsi outcomes. Mater Sociomed 2016; 28 (2): 91–4.
47. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril 2002; 77: 1148–55.
48. Taylor RN, Yu J, Torres PB et al. Mechanistic and therapeutic implications of angiogenesis in endometriosis. Reprod Sci 2009; 16 (2): 140–6.
49. Borrelli GM, Carvalho KI, Kallas EG et al. Chemokines in the pathogenesis of endometriosis and infertility. J Reprod Immunol. 2013; 98: 1–9.
50. Bulun SE, Cheng YH, Yin P et al. Progesterone resistance in ndometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol 2006; 248: 94–103.
51. Hauzman EE, Garcia-Velasco JA, Pellicer A. Oocyte donation and endometriosis: what are the lessons? Semin Reprod Med 2013; 31: 173–7.
52. Sarapik A, Haller-Kikkatalo K, Utt M et al. Serum anti-endometrial antibodies in infertile women – potential risk factor for implantation failure. Am J Reprod Immunol 2010; 63: 349–57.
1. ФГАОУ ВО «Российский университет дружбы народов». 117198, Россия, Москва, ул. Миклухо-Маклая, д. 6;
2. ООО «МедИнСервис» – Центр репродукции и генетики «Nova Clinic». 129090, Россия, Москва, ул. Щепкина, д. 25/20
*omekan@mail.ru
________________________________________________
Mekan R. Orazov*1, Viktor E. Radzinskiy1, Marina B. Khamoshina1, Elena V. Kavteladze2, Irina F. Pukhalskaya2, Viktoriya B. Shustova2, Yurii S. Сhitanava1
1. People’s Friendship University of Russia. 6, Miklukho-Maklaya st., Moscow, 117198, Russian Federation;
2. MedInServis – Center for Reproduction and Genetics “Nova Clinic”. 25/20, Shchepkina st., Moscow, 129090, Russian Federation.
*omekan@mail.ru