Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Эффективность внутриматочного введения аутологичных мононуклеарных клеток периферической крови перед переносом эмбриона у пациенток с повторными неудачами имплантации в программах вспомогательных репродуктивных технологий
Эффективность внутриматочного введения аутологичных мононуклеарных клеток периферической крови перед переносом эмбриона у пациенток с повторными неудачами имплантации в программах вспомогательных репродуктивных технологий
Амян Т.С., Перминова С.Г., Кречетова Л.В., Вторушина В.В. Эффективность внутриматочного введения аутологичных мононуклеарных клеток периферической крови перед переносом эмбриона у пациенток с повторными неудачами имплантации в программах вспомогательных репродуктивных технологий. Гинекология. 2018; 20 (2): 28–33.
DOI: 10.26442/2079-5696_2018.2.28-33
________________________________________________
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Цель исследования – оценить эффективность внутриматочного введения аутологичных мононуклеарных клеток периферической крови (МКПК) перед переносом эмбриона у пациенток с повторными неудачами имплантации в программах вспомогательных репродуктивных технологий.
Материал и методы. В исследование включены 129 пациенток с повторными неудачами имплантации в программе экстракорпорального оплодотворения: 1-я группа – 42 женщины, которым перед переносом эмбриона проводилось внутриматочное введение аутологичных МКПК, активированных хорионическим гонадотропином человека – ХГЧ (Прегнил 500 МЕ); 2-я группа – 42 пациентки, которым проводилось внутриматочное введение аутологичных МКПК без активации ХГЧ, 3-я группа (плацебо) – 45 участниц, которым проводилось внутриматочное введение физиологического раствора.
Результаты. В группе пациенток с внутриматочным введением МКПК, активированными ХГЧ, частота положительного анализа крови на ХГЧ, имплантации и наступления клинической беременности была значимо выше по сравнению с аналогичными показателями в группе пациенток с внутриматочным введением МКПК без активации ХГЧ и в группе плацебо как в стимулированном, так и криоцикле (р≤0,05).
Заключение. Внутриматочное введение аутологичных МКПК перед переносом эмбриона в программе экстракорпорального оплодотворения/ИКСИ (интрацитоплазматическая инъекция сперматозоида в яйцеклетку) повышает эффективность программ вспомогательных репродуктивных технологий у пациенток с повторными неудачами имплантации в анамнезе.
Ключевые слова: повторные неудачи имплантации, внутриматочное введение, аутологичные мононуклеарные клетки периферической крови, хорионический гонадотропин человека.
Materials and methods. The study enrolled 129 patients with recurrent implantation failures in an IVF programme. Group 1 – 42 patients who had intrauterine administration of autologous PBMC activated with hCG (Pregnyl 500 IU). Group 2 – 42 patients who had intrauterine administration of autologous PBMC without hCG activation. Group 3 (placebo) – 45 patients who had intrauterine administration of saline.
Study results. In the hCG-activated PBMC group, the rates of positive blood hCG tests, implantation, and clinical pregnancy were significantly higher than the respective rates in the non-activated PBMC group and in the placebo group, both in a stimulated cycle and in an FET cycle (р≤0.05).
Conclusion. Intrauterine administration of autologous PBMC prior to embryo transfer in an IVF/ICSI programme increases the efficacy of IVF program in patients with a history of recurrent implantation failures.
Key words: recurrent implantation failures, intrauterine administration, autologous peripheral blood mononuclear cells, hCG.
Материал и методы. В исследование включены 129 пациенток с повторными неудачами имплантации в программе экстракорпорального оплодотворения: 1-я группа – 42 женщины, которым перед переносом эмбриона проводилось внутриматочное введение аутологичных МКПК, активированных хорионическим гонадотропином человека – ХГЧ (Прегнил 500 МЕ); 2-я группа – 42 пациентки, которым проводилось внутриматочное введение аутологичных МКПК без активации ХГЧ, 3-я группа (плацебо) – 45 участниц, которым проводилось внутриматочное введение физиологического раствора.
Результаты. В группе пациенток с внутриматочным введением МКПК, активированными ХГЧ, частота положительного анализа крови на ХГЧ, имплантации и наступления клинической беременности была значимо выше по сравнению с аналогичными показателями в группе пациенток с внутриматочным введением МКПК без активации ХГЧ и в группе плацебо как в стимулированном, так и криоцикле (р≤0,05).
Заключение. Внутриматочное введение аутологичных МКПК перед переносом эмбриона в программе экстракорпорального оплодотворения/ИКСИ (интрацитоплазматическая инъекция сперматозоида в яйцеклетку) повышает эффективность программ вспомогательных репродуктивных технологий у пациенток с повторными неудачами имплантации в анамнезе.
Ключевые слова: повторные неудачи имплантации, внутриматочное введение, аутологичные мононуклеарные клетки периферической крови, хорионический гонадотропин человека.
________________________________________________
Materials and methods. The study enrolled 129 patients with recurrent implantation failures in an IVF programme. Group 1 – 42 patients who had intrauterine administration of autologous PBMC activated with hCG (Pregnyl 500 IU). Group 2 – 42 patients who had intrauterine administration of autologous PBMC without hCG activation. Group 3 (placebo) – 45 patients who had intrauterine administration of saline.
Study results. In the hCG-activated PBMC group, the rates of positive blood hCG tests, implantation, and clinical pregnancy were significantly higher than the respective rates in the non-activated PBMC group and in the placebo group, both in a stimulated cycle and in an FET cycle (р≤0.05).
Conclusion. Intrauterine administration of autologous PBMC prior to embryo transfer in an IVF/ICSI programme increases the efficacy of IVF program in patients with a history of recurrent implantation failures.
Key words: recurrent implantation failures, intrauterine administration, autologous peripheral blood mononuclear cells, hCG.
Полный текст
Список литературы
1. Zeyneloglu HB, Onalan G. Remedies for recurrent implantation failure. Semin Reprod Med 2014; 32: 297–305.
2. Yoshinaga K. Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system. Semin Cell Dev Biol 2008; 19, 161–9.
3. Huang P. Effects of intrauterine perfusion of human chorionic gonadotropin in women with different implantation failure numbers. Am J Reprod Immunol 2018; 79 (2).
4. Stephenson M, Fluker M. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertil Steril 2000; 74 (6): 1108–13.
5. Yu N, Yang J, Guo Y et al. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity with embryonic implantation dysfunction. Am J Reprod Immunol 2014; 71: 24–33.
6. Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril 2012; 97 (5): 1039–43.
7. Makrigiannakis A, BenKhalifa M, Vrekoussis T et al. Gurgan: repeated implantation failure: a new potential treatment option. Eur J Clin Invest 2011; 45: 380–4.
8. Takabatake K, Fujiwara H, Goto Y et al. Splenocytes in early pregnancy promote embryo implantation by regulating endometrial differentiation in mice. Hum Reprod 1997; 12: 2102–7.
9. Nakayama T, Fujiwara H, Maeda M et al. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: hCG enhances the effects of PBMC. Hum Reprod 2002; 17: 207–12.
10. Lea RG, Sandra O. Immunoendocrine aspects of endometrial function and implantation. Reproduction 2007; 134: 389–404.
11. Yoshioka S, Fujiwara H, Nakayama T et al. Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod 2006; 21: 3290–4.
12. Okitsu O, Kiyokawa M, Oda T et al. Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 2011; 92: 82–7.
13. Santibañez A, García J, Pashkova O et al. Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study. Reprod Biol Endocrinol 2014; 12 (1): 9.
14. Fujiwara H. Do circulating blood cells contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period? Mol Hum Reprod 2009; 15: 335–43.
15. RoqueM, Lattes K, Serra S et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2013; 99 (1): 156–62.
16. Hammer A. Immunological regulation of trophoblast invasion. J Reprod Immunol 2011; 90: 21–8.
17. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010; 63: 601–10.
18. Imakawa K, Bai R, Fujiwara H, Kusama K. Conceptus implantation and placentation: molecules related to epithelial-mesenchymal transition, lymphocyte homing, endogenous retroviruses, and exosomes. Reprod Med Biol 2015; 14: 1–11.
19. Volovsky M, Healey M. Should intrauterine human chorionic gonadotropin infusions ever be used prior to embryo transfer? Assist Reprod Genet 2018; 35: 273–8. DOI: 10.1007/s10815-017-1049-5
20. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update 2003; 9 (6): 515–22.
21. Haouzi D, Assou S, Mahmoud K et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod 2009; 24 (6): 1436–45.
22. Istanbul consensus workshop on embryo assessment (ESHRE, 2011).
2. Yoshinaga K. Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system. Semin Cell Dev Biol 2008; 19, 161–9.
3. Huang P. Effects of intrauterine perfusion of human chorionic gonadotropin in women with different implantation failure numbers. Am J Reprod Immunol 2018; 79 (2).
4. Stephenson M, Fluker M. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertil Steril 2000; 74 (6): 1108–13.
5. Yu N, Yang J, Guo Y et al. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity with embryonic implantation dysfunction. Am J Reprod Immunol 2014; 71: 24–33.
6. Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril 2012; 97 (5): 1039–43.
7. Makrigiannakis A, BenKhalifa M, Vrekoussis T et al. Gurgan: repeated implantation failure: a new potential treatment option. Eur J Clin Invest 2011; 45: 380–4.
8. Takabatake K, Fujiwara H, Goto Y et al. Splenocytes in early pregnancy promote embryo implantation by regulating endometrial differentiation in mice. Hum Reprod 1997; 12: 2102–7.
9. Nakayama T, Fujiwara H, Maeda M et al. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: hCG enhances the effects of PBMC. Hum Reprod 2002; 17: 207–12.
10. Lea RG, Sandra O. Immunoendocrine aspects of endometrial function and implantation. Reproduction 2007; 134: 389–404.
11. Yoshioka S, Fujiwara H, Nakayama T et al. Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod 2006; 21: 3290–4.
12. Okitsu O, Kiyokawa M, Oda T et al. Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 2011; 92: 82–7.
13. Santibañez A, García J, Pashkova O et al. Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study. Reprod Biol Endocrinol 2014; 12 (1): 9.
14. Fujiwara H. Do circulating blood cells contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period? Mol Hum Reprod 2009; 15: 335–43.
15. RoqueM, Lattes K, Serra S et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2013; 99 (1): 156–62.
16. Hammer A. Immunological regulation of trophoblast invasion. J Reprod Immunol 2011; 90: 21–8.
17. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010; 63: 601–10.
18. Imakawa K, Bai R, Fujiwara H, Kusama K. Conceptus implantation and placentation: molecules related to epithelial-mesenchymal transition, lymphocyte homing, endogenous retroviruses, and exosomes. Reprod Med Biol 2015; 14: 1–11.
19. Volovsky M, Healey M. Should intrauterine human chorionic gonadotropin infusions ever be used prior to embryo transfer? Assist Reprod Genet 2018; 35: 273–8. DOI: 10.1007/s10815-017-1049-5
20. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update 2003; 9 (6): 515–22.
21. Haouzi D, Assou S, Mahmoud K et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod 2009; 24 (6): 1436–45.
22. Istanbul consensus workshop on embryo assessment (ESHRE, 2011).
2. Yoshinaga K. Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system. Semin Cell Dev Biol 2008; 19, 161–9.
3. Huang P. Effects of intrauterine perfusion of human chorionic gonadotropin in women with different implantation failure numbers. Am J Reprod Immunol 2018; 79 (2).
4. Stephenson M, Fluker M. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertil Steril 2000; 74 (6): 1108–13.
5. Yu N, Yang J, Guo Y et al. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity with embryonic implantation dysfunction. Am J Reprod Immunol 2014; 71: 24–33.
6. Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril 2012; 97 (5): 1039–43.
7. Makrigiannakis A, BenKhalifa M, Vrekoussis T et al. Gurgan: repeated implantation failure: a new potential treatment option. Eur J Clin Invest 2011; 45: 380–4.
8. Takabatake K, Fujiwara H, Goto Y et al. Splenocytes in early pregnancy promote embryo implantation by regulating endometrial differentiation in mice. Hum Reprod 1997; 12: 2102–7.
9. Nakayama T, Fujiwara H, Maeda M et al. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: hCG enhances the effects of PBMC. Hum Reprod 2002; 17: 207–12.
10. Lea RG, Sandra O. Immunoendocrine aspects of endometrial function and implantation. Reproduction 2007; 134: 389–404.
11. Yoshioka S, Fujiwara H, Nakayama T et al. Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod 2006; 21: 3290–4.
12. Okitsu O, Kiyokawa M, Oda T et al. Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 2011; 92: 82–7.
13. Santibañez A, García J, Pashkova O et al. Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study. Reprod Biol Endocrinol 2014; 12 (1): 9.
14. Fujiwara H. Do circulating blood cells contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period? Mol Hum Reprod 2009; 15: 335–43.
15. RoqueM, Lattes K, Serra S et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2013; 99 (1): 156–62.
16. Hammer A. Immunological regulation of trophoblast invasion. J Reprod Immunol 2011; 90: 21–8.
17. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010; 63: 601–10.
18. Imakawa K, Bai R, Fujiwara H, Kusama K. Conceptus implantation and placentation: molecules related to epithelial-mesenchymal transition, lymphocyte homing, endogenous retroviruses, and exosomes. Reprod Med Biol 2015; 14: 1–11.
19. Volovsky M, Healey M. Should intrauterine human chorionic gonadotropin infusions ever be used prior to embryo transfer? Assist Reprod Genet 2018; 35: 273–8. DOI: 10.1007/s10815-017-1049-5
20. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update 2003; 9 (6): 515–22.
21. Haouzi D, Assou S, Mahmoud K et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod 2009; 24 (6): 1436–45.
22. Istanbul consensus workshop on embryo assessment (ESHRE, 2011).
________________________________________________
2. Yoshinaga K. Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system. Semin Cell Dev Biol 2008; 19, 161–9.
3. Huang P. Effects of intrauterine perfusion of human chorionic gonadotropin in women with different implantation failure numbers. Am J Reprod Immunol 2018; 79 (2).
4. Stephenson M, Fluker M. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertil Steril 2000; 74 (6): 1108–13.
5. Yu N, Yang J, Guo Y et al. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity with embryonic implantation dysfunction. Am J Reprod Immunol 2014; 71: 24–33.
6. Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril 2012; 97 (5): 1039–43.
7. Makrigiannakis A, BenKhalifa M, Vrekoussis T et al. Gurgan: repeated implantation failure: a new potential treatment option. Eur J Clin Invest 2011; 45: 380–4.
8. Takabatake K, Fujiwara H, Goto Y et al. Splenocytes in early pregnancy promote embryo implantation by regulating endometrial differentiation in mice. Hum Reprod 1997; 12: 2102–7.
9. Nakayama T, Fujiwara H, Maeda M et al. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: hCG enhances the effects of PBMC. Hum Reprod 2002; 17: 207–12.
10. Lea RG, Sandra O. Immunoendocrine aspects of endometrial function and implantation. Reproduction 2007; 134: 389–404.
11. Yoshioka S, Fujiwara H, Nakayama T et al. Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod 2006; 21: 3290–4.
12. Okitsu O, Kiyokawa M, Oda T et al. Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 2011; 92: 82–7.
13. Santibañez A, García J, Pashkova O et al. Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study. Reprod Biol Endocrinol 2014; 12 (1): 9.
14. Fujiwara H. Do circulating blood cells contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period? Mol Hum Reprod 2009; 15: 335–43.
15. RoqueM, Lattes K, Serra S et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2013; 99 (1): 156–62.
16. Hammer A. Immunological regulation of trophoblast invasion. J Reprod Immunol 2011; 90: 21–8.
17. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010; 63: 601–10.
18. Imakawa K, Bai R, Fujiwara H, Kusama K. Conceptus implantation and placentation: molecules related to epithelial-mesenchymal transition, lymphocyte homing, endogenous retroviruses, and exosomes. Reprod Med Biol 2015; 14: 1–11.
19. Volovsky M, Healey M. Should intrauterine human chorionic gonadotropin infusions ever be used prior to embryo transfer? Assist Reprod Genet 2018; 35: 273–8. DOI: 10.1007/s10815-017-1049-5
20. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update 2003; 9 (6): 515–22.
21. Haouzi D, Assou S, Mahmoud K et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod 2009; 24 (6): 1436–45.
22. Istanbul consensus workshop on embryo assessment (ESHRE, 2011).
Авторы
Т.С.Амян*, С.Г.Перминова, Л.В.Кречетова, В.В.Вторушина
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*amyantanya@rambler.ru
V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*amyantanya@rambler.ru
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*amyantanya@rambler.ru
________________________________________________
V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*amyantanya@rambler.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.