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Рождение здорового ребенка в программе вспомогательных репродуктивных технологий после аутологичного сокультивирования эмбриона с клетками кумулюса и новой технологии переноса CAT. Клинический случай
Рождение здорового ребенка в программе вспомогательных репродуктивных технологий после аутологичного сокультивирования эмбриона с клетками кумулюса и новой технологии переноса CAT. Клинический случай
Асфарова Г.Р., Смольникова В.Ю., Макарова Н.П., Драпкина Ю.С., Сысоева А.П., Лобанова Н.Н., Калинина Е.А. Рождение здорового ребенка в программе вспомогательных репродуктивных технологий после аутологичного сокультивирования эмбриона с клетками кумулюса и новой технологии переноса CAT. Клинический случай. Гинекология. 2021; 23 (3): 270–274. DOI: 10.26442/20795696.2021.3.200876
DOI: 10.26442/20795696.2021.3.200876
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DOI: 10.26442/20795696.2021.3.200876
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Кумулюсные клетки имеют важное значение во время роста и развития ооцитов, а также в процессе их созревания и оплодотворения. Результаты исследований показали, что сокультивирование эмбриона с аутологичными клетками кумулюса повышает частоту формирования бластоцист, а также улучшает эффективность программ вспомогательных репродуктивных технологий (ВРТ). Перенос эмбриона в таких программах рекомендовано осуществлять с помощью технологии САТ (Cumulus-Aided embryo Transfer), включающей в себя культивирование эмбриона на слое кумулюсных клеток и проведение переноса эмбриона с некоторым количеством разреженных клеток кумулюса. В отделение обратилась пациентка Г., 38 лет, с жалобами на отсутствие наступления беременности в течение 15 лет и несколькими неудачными попытками ВРТ в анамнезе. Пациентке была проведена программа ВРТ с использованием аутологичного сокультивирования эмбрионов с клетками кумулюса и новой технологии переноса CAT. У пациентки наступила беременность, закончившаяся своевременными оперативными родами. На момент написания публикации ребенок соматически здоров, развивается соответственно возрасту. Использование аутологичных клеток кумулюса в качестве источника биологически активных веществ способствует улучшению эмбриологического этапа, а также повышает частоту имплантации в программах ВРТ. Сокультивирование эмбриона с кумулюсными клетками особенно актуально пациентам с несколькими неудачными попытками ВРТ в анамнезе. Данная методика может стать достойной альтернативой для оптимизации системы культивирования эмбрионов человека в программах ВРТ.
Ключевые слова: вспомогательные репродуктивные технологии, клетки кумулюса, технология САТ, сокультивирование, ростовые факторы, эмбрион, ооцит, имплантация эмбриона, неудачные попытки вспомогательных репродуктивных технологий
with autologous cumulus cells increases the frequency of blastocyst formation, and also improves the effectiveness of ART programs. Embryo transfer in such programs is recommended to be carried out using the CAT technology (Cumulus-Aided embryo Transfer), which includes embryo cultivation on a layer of cumulus cells and embryo transfer with a certain amount of diluted cumulus cells. Patient G., 38 years old, came to the department with infertility for 15 years and recurrent implantation failure in history. The patient had ART program with autologous co-cultivation of embryos with cumulus cells and a new CAT transfer technology. The patient fell pregnant and gave birth to a healthy child. Autologous cumulus cells can be a source of biologically active substances and improve embryological parameters and implantation rate in ART programs. Embryo co-cultivation with cumulus cells is especially important for patients with recurrent implantation failure. This technique can become an alternative for optimizing human embryos culturing.
Keywords: assisted reproductive technologies, cumulus cells, CAT technology, co-cultivation, growth factors, embryo, oocyte, embryo implantation, recurrent implantation
failure
Ключевые слова: вспомогательные репродуктивные технологии, клетки кумулюса, технология САТ, сокультивирование, ростовые факторы, эмбрион, ооцит, имплантация эмбриона, неудачные попытки вспомогательных репродуктивных технологий
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with autologous cumulus cells increases the frequency of blastocyst formation, and also improves the effectiveness of ART programs. Embryo transfer in such programs is recommended to be carried out using the CAT technology (Cumulus-Aided embryo Transfer), which includes embryo cultivation on a layer of cumulus cells and embryo transfer with a certain amount of diluted cumulus cells. Patient G., 38 years old, came to the department with infertility for 15 years and recurrent implantation failure in history. The patient had ART program with autologous co-cultivation of embryos with cumulus cells and a new CAT transfer technology. The patient fell pregnant and gave birth to a healthy child. Autologous cumulus cells can be a source of biologically active substances and improve embryological parameters and implantation rate in ART programs. Embryo co-cultivation with cumulus cells is especially important for patients with recurrent implantation failure. This technique can become an alternative for optimizing human embryos culturing.
Keywords: assisted reproductive technologies, cumulus cells, CAT technology, co-cultivation, growth factors, embryo, oocyte, embryo implantation, recurrent implantation
failure
Полный текст
Список литературы
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14. Benkhalifa M, Demirol A, Sari T, et al. Autologous embryo-cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study. Zygote. 2012;20(2):173-80. DOI:10.1017/S0967199411000062
15. Vendrell-Flotats M, García-Martínez T, Martínez-Rodero I, et al. In vitro maturation in the presence of Leukemia Inhibitory Factor modulates gene and miRNA expression in bovine oocytes and embryos. Sci Rep. 2020;10(1):17777. DOI:10.1038/s41598-020-74961-6
16. Mo C, Chearwae W, Bright JJ. PPARgamma regulates LIF-induced growth and self-renewal of mouse ES cells through Tyk2-Stat3 pathway. Cell Signal. 2010;22(3):495-500. DOI:10.1016/j.cellsig.2009.11.003
17. Cihangir N, Görkemli H, Ozdemir S, et al. Influence of cumulus cell coculture and cumulusaided embryo transfer on embryonic development and pregnancy rates. J Turk Ger Gynecol Assoc. 2010;11(3):121-6. DOI:10.5152/jtgga.2010.017
18. Levitas E, Lunenfeld E, Har-Vardi I, et al. Blastocyst-stage embryo transfer in patients who failed to conceive in three or more day 2–3 embryo transfer cycles: a prospective, randomised study. Fertil Steril. 2004;81(3):567-71. DOI:10.1016/j.fertnstert.2003.08.031
19. Parikh F, Nadkarni SG, Naik NJ, et al. Cumulus coculture and cumulus-aided embryo transfer increase pregnancy rates in patients undergoing in vitro fertilization. Fertil Steril. 2006;86(4):839-47. DOI:10.1016/j.fertnstert.2006.03.028
20. Тимофеева А.В., Калинина Е.А., Драпкина Ю.С., и др. Оценка качества эмбриона по профилю экспрессии малых некодирующих РНК в культуральной среде эмбриона в программах вспомогательных репродуктивных технологий. Акушерство и гинекология. 2019;6:79-86 [Timofeeva AV, Kalinina EA, Drapkina IuS, et al. Embryo quality assessment by the small noncoding RNA expression profile in an embryo culture medium in assisted reproductive technology programs. Akusherstvo i Ginekologiya. 2019;6:79-86 (in Russian)]. DOI:10.18565/aig.2019.6.79-86
21. Lin YH, Hwang JL, Seow KM, et al. Effects of growth factors and granulosa cell co-culture on in-vitro maturation of oocytes. Reprod Biomed Online. 2009;19(2):165-70. DOI:10.1016/s1472-6483(10)60068-5
22. Godard NM, Pukazhenthi BS, Wildt DE, Comizzoli P. Paracrine factors from cumulus-enclosed oocytes ensure the successful maturation and fertilization in vitro denuded oocytes in the cat model. Fertil Steril. 2009;91(Suppl. 5):2051-60. DOI:10.1016/j.fertnstert.2008.05.069
2. Bongso A, Ng SC, Fong CY, Ratnam S. Cocultures: a new lead in embryo quality improvement for assisted reproduction. Fertil Steril. 1991;56(2):179-91.
DOI:10.1016/s0015-0282(16)54468-9
3. Safronova NA, Kalinina EA, Donnikov AE, et al. Prospects for studying cumulus cell markers to assess the quality of oocytes and embryos in assisted reproductive technology programs. Akusherstvo i ginekologiya. 2015;12:21-5 (in Russian)
4. Ebert P, Völklein K. Choosing a culture medium: making informed choices. Fertil Steril. 2010;93(6):e25; author reply e26. DOI:10.1016/j.fertnstert.2009.12.048
5. Ebner T, Moser M, Sommergruber M, et al. Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development. Hum Reprod. 2006;21(11):2972-7. DOI:10.1093/humrep/del272
6. Karakaya C, Guzeloglu-Kayisli O, Uyar A, et al. Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells. Fertil Steril. 2015;103(6):1469-76.e1-3. DOI:10.1016/j.fertnstert.2015.02.035
7. De Geyter C, Calhaz-Jorge C, Kupka MS, et al. ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2018;33(9):1586-1601. DOI:10.1093/humrep/dey242
8. Van Landuyt L, De Vos A, Joris H, et al. Blastocyst formation in in vitro fertilization versus intracytoplasmic sperm injection cycles: influence of the fertilization procedure. Fertil Steril. 2005;83(5):1397-403. DOI:10.1016/j.fertnstert.2004.10.054
9. Sapandorfer SD, Pascal P, Parks J, et al. Autologous endometrial coculture in patients with IVF failure: outcome of the first 1,030 case. J Reprod Med. 2004;49(6):463-7.
10. Kattal N, Cohen J, Barmat LI. Role of coculture in human in vitro fertilization: a meta-analysis. Fertil Steril. 2008;90(4):1069-76. DOI:10.1016/j.fertnstert.2007.07.1349
11. Eyheremendy V, Raffo FGE, Papayannis M, et al. Beneficial effect of autologous endometrial cell coculture in patients with repeated implantation failure. Fertil Steril. 2010;93(3):769-73. DOI:10.1016/j.fertnstert.2008.10.060
12. Quinn P, Margalit R. Beneficial effect of coculture with cumulus cells on blastocyst formation in prospective trial with supernumerary human embryos. J Assist Reprod Genet. 1996;13(1):9-12. DOI:10.1007/BF02068862
13. Asfarova GR, Smolnikova VYu, Makarova NP, et al. Autologous embryo-cumulus cell co-culturing in ART programs. Akusherstvo i Ginekologiya. 2018;11:10-4 (in Russian)
DOI:10.18565/aig.2018.11.10-14
14. Benkhalifa M, Demirol A, Sari T, et al. Autologous embryo-cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study. Zygote. 2012;20(2):173-80. DOI:10.1017/S0967199411000062
15. Vendrell-Flotats M, García-Martínez T, Martínez-Rodero I, et al. In vitro maturation in the presence of Leukemia Inhibitory Factor modulates gene and miRNA expression in bovine oocytes and embryos. Sci Rep. 2020;10(1):17777. DOI:10.1038/s41598-020-74961-6
16. Mo C, Chearwae W, Bright JJ. PPARgamma regulates LIF-induced growth and self-renewal of mouse ES cells through Tyk2-Stat3 pathway. Cell Signal. 2010;22(3):495-500. DOI:10.1016/j.cellsig.2009.11.003
17. Cihangir N, Görkemli H, Ozdemir S, et al. Influence of cumulus cell coculture and cumulusaided embryo transfer on embryonic development and pregnancy rates. J Turk Ger Gynecol Assoc. 2010;11(3):121-6. DOI:10.5152/jtgga.2010.017
18. Levitas E, Lunenfeld E, Har-Vardi I, et al. Blastocyst-stage embryo transfer in patients who failed to conceive in three or more day 2–3 embryo transfer cycles: a prospective, randomised study. Fertil Steril. 2004;81(3):567-71. DOI:10.1016/j.fertnstert.2003.08.031
19. Parikh F, Nadkarni SG, Naik NJ, et al. Cumulus coculture and cumulus-aided embryo transfer increase pregnancy rates in patients undergoing in vitro fertilization. Fertil Steril. 2006;86(4):839-47. DOI:10.1016/j.fertnstert.2006.03.028
20. Timofeeva AV, Kalinina EA, Drapkina IuS, et al. Embryo quality assessment by the small noncoding RNA expression profile in an embryo culture medium in assisted reproductive technology programs. Akusherstvo i Ginekologiya. 2019;6:79-86 (in Russian) DOI:10.18565/aig.2019.6.79-86
21. Lin YH, Hwang JL, Seow KM, et al. Effects of growth factors and granulosa cell co-culture on in-vitro maturation of oocytes. Reprod Biomed Online. 2009;19(2):165-70. DOI:10.1016/s1472-6483(10)60068-5
22. Godard NM, Pukazhenthi BS, Wildt DE, Comizzoli P. Paracrine factors from cumulus-enclosed oocytes ensure the successful maturation and fertilization in vitro denuded oocytes in the cat model. Fertil Steril. 2009;91(Suppl. 5):2051-60. DOI:10.1016/j.fertnstert.2008.05.069
2. Bongso A, Ng SC, Fong CY, Ratnam S. Cocultures: a new lead in embryo quality improvement for assisted reproduction. Fertil Steril. 1991;56(2):179-91.
DOI:10.1016/s0015-0282(16)54468-9
3. Сафронова Н.А., Калинина Е.А., Донников А.Е., и др. Перспективы исследования маркеров клеток кумулюса для оценки качества ооцитов и эмбрионов в программах вспомогательных репродуктивных технологий. Акушерство и гинекология. 2015;12:21-5 [Safronova NA, Kalinina EA, Donnikov AE, et al. Prospects for studying cumulus cell markers to assess the quality of oocytes and embryos in assisted reproductive technology programs. Akusherstvo i ginekologiya. 2015;12:21-5 (in Russian)].
4. Ebert P, Völklein K. Choosing a culture medium: making informed choices. Fertil Steril. 2010;93(6):e25; author reply e26. DOI:10.1016/j.fertnstert.2009.12.048
5. Ebner T, Moser M, Sommergruber M, et al. Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development. Hum Reprod. 2006;21(11):2972-7. DOI:10.1093/humrep/del272
6. Karakaya C, Guzeloglu-Kayisli O, Uyar A, et al. Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells. Fertil Steril. 2015;103(6):1469-76.e1-3. DOI:10.1016/j.fertnstert.2015.02.035
7. De Geyter C, Calhaz-Jorge C, Kupka MS, et al. ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2018;33(9):1586-1601. DOI:10.1093/humrep/dey242
8. Van Landuyt L, De Vos A, Joris H, et al. Blastocyst formation in in vitro fertilization versus intracytoplasmic sperm injection cycles: influence of the fertilization procedure. Fertil Steril. 2005;83(5):1397-403. DOI:10.1016/j.fertnstert.2004.10.054
9. Sapandorfer SD, Pascal P, Parks J, et al. Autologous endometrial coculture in patients with IVF failure: outcome of the first 1,030 case. J Reprod Med. 2004;49(6):463-7.
10. Kattal N, Cohen J, Barmat LI. Role of coculture in human in vitro fertilization: a meta-analysis. Fertil Steril. 2008;90(4):1069-76. DOI:10.1016/j.fertnstert.2007.07.1349
11. Eyheremendy V, Raffo FGE, Papayannis M, et al. Beneficial effect of autologous endometrial cell coculture in patients with repeated implantation failure. Fertil Steril. 2010;93(3):769-73. DOI:10.1016/j.fertnstert.2008.10.060
12. Quinn P, Margalit R. Beneficial effect of coculture with cumulus cells on blastocyst formation in prospective trial with supernumerary human embryos. J Assist Reprod Genet. 1996;13(1):9-12. DOI:10.1007/BF02068862
13. Асфарова Г.Р., Смольникова В.Ю., Макарова Н.П., и др. Аутологичное сокультивирование эмбрионов с клетками кумулюса в программах ВРТ. Акушерство и гинекология. 2018;11:10-4 [Asfarova GR, Smolnikova VYu, Makarova NP, et al. Autologous embryo-cumulus cell co-culturing in ART programs. Akusherstvo i Ginekologiya. 2018;11:10-4 (in Russian)]. DOI:10.18565/aig.2018.11.10-14
14. Benkhalifa M, Demirol A, Sari T, et al. Autologous embryo-cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study. Zygote. 2012;20(2):173-80. DOI:10.1017/S0967199411000062
15. Vendrell-Flotats M, García-Martínez T, Martínez-Rodero I, et al. In vitro maturation in the presence of Leukemia Inhibitory Factor modulates gene and miRNA expression in bovine oocytes and embryos. Sci Rep. 2020;10(1):17777. DOI:10.1038/s41598-020-74961-6
16. Mo C, Chearwae W, Bright JJ. PPARgamma regulates LIF-induced growth and self-renewal of mouse ES cells through Tyk2-Stat3 pathway. Cell Signal. 2010;22(3):495-500. DOI:10.1016/j.cellsig.2009.11.003
17. Cihangir N, Görkemli H, Ozdemir S, et al. Influence of cumulus cell coculture and cumulusaided embryo transfer on embryonic development and pregnancy rates. J Turk Ger Gynecol Assoc. 2010;11(3):121-6. DOI:10.5152/jtgga.2010.017
18. Levitas E, Lunenfeld E, Har-Vardi I, et al. Blastocyst-stage embryo transfer in patients who failed to conceive in three or more day 2–3 embryo transfer cycles: a prospective, randomised study. Fertil Steril. 2004;81(3):567-71. DOI:10.1016/j.fertnstert.2003.08.031
19. Parikh F, Nadkarni SG, Naik NJ, et al. Cumulus coculture and cumulus-aided embryo transfer increase pregnancy rates in patients undergoing in vitro fertilization. Fertil Steril. 2006;86(4):839-47. DOI:10.1016/j.fertnstert.2006.03.028
20. Тимофеева А.В., Калинина Е.А., Драпкина Ю.С., и др. Оценка качества эмбриона по профилю экспрессии малых некодирующих РНК в культуральной среде эмбриона в программах вспомогательных репродуктивных технологий. Акушерство и гинекология. 2019;6:79-86 [Timofeeva AV, Kalinina EA, Drapkina IuS, et al. Embryo quality assessment by the small noncoding RNA expression profile in an embryo culture medium in assisted reproductive technology programs. Akusherstvo i Ginekologiya. 2019;6:79-86 (in Russian)]. DOI:10.18565/aig.2019.6.79-86
21. Lin YH, Hwang JL, Seow KM, et al. Effects of growth factors and granulosa cell co-culture on in-vitro maturation of oocytes. Reprod Biomed Online. 2009;19(2):165-70. DOI:10.1016/s1472-6483(10)60068-5
22. Godard NM, Pukazhenthi BS, Wildt DE, Comizzoli P. Paracrine factors from cumulus-enclosed oocytes ensure the successful maturation and fertilization in vitro denuded oocytes in the cat model. Fertil Steril. 2009;91(Suppl. 5):2051-60. DOI:10.1016/j.fertnstert.2008.05.069
________________________________________________
2. Bongso A, Ng SC, Fong CY, Ratnam S. Cocultures: a new lead in embryo quality improvement for assisted reproduction. Fertil Steril. 1991;56(2):179-91.
DOI:10.1016/s0015-0282(16)54468-9
3. Safronova NA, Kalinina EA, Donnikov AE, et al. Prospects for studying cumulus cell markers to assess the quality of oocytes and embryos in assisted reproductive technology programs. Akusherstvo i ginekologiya. 2015;12:21-5 (in Russian)
4. Ebert P, Völklein K. Choosing a culture medium: making informed choices. Fertil Steril. 2010;93(6):e25; author reply e26. DOI:10.1016/j.fertnstert.2009.12.048
5. Ebner T, Moser M, Sommergruber M, et al. Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development. Hum Reprod. 2006;21(11):2972-7. DOI:10.1093/humrep/del272
6. Karakaya C, Guzeloglu-Kayisli O, Uyar A, et al. Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells. Fertil Steril. 2015;103(6):1469-76.e1-3. DOI:10.1016/j.fertnstert.2015.02.035
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Авторы
Г.Р. Асфарова, В.Ю. Смольникова, Н.П. Макарова, Ю.С. Драпкина*, А.П. Сысоева, Н.Н. Лобанова, Е.А. Калинина
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России, Москва, Россия
*yu_drapkina@oparina4.ru
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
*yu_drapkina@oparina4.ru
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России, Москва, Россия
*yu_drapkina@oparina4.ru
________________________________________________
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
*yu_drapkina@oparina4.ru
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