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Особенности цитокинового профиля семенной плазмы и наступление беременности при проведении программы вспомогательных репродуктивных технологий
Особенности цитокинового профиля семенной плазмы и наступление беременности при проведении программы вспомогательных репродуктивных технологий
Донцова Т.В., Бабаян А.А., Николаева М.А. и др. Особенности цитокинового профиля семенной плазмы и наступление беременности при проведении программы вспомогательных репродуктивных технологий. Гинекология. 2019; 21 (4): 9–13.
DOI: 10.26442/20795696.2019.4.190233
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Аннотация
Цель. Оценить эффективность программы вспомогательных репродуктивных технологий (ВРТ) с учетом особенностей цитокинового профиля семенной плазмы (СП), поступающей в репродуктивные пути женщин при половых контактах.
Материалы и методы. В проспективном исследовании приняли участие 33 супружеские пары, обратившиеся для лечения бесплодия путем экстракорпорального оплодотворения/ИКСИ (ICSI – IntraCytoplasmic Sperm Injection). Пациентам был рекомендован режим половой жизни без ограничения контактов во время лечения, последний половой акт – за 3 дня до предполагаемой трансвагинальной пункции (ТВП). Определение уровня цитокинов [трансформирующий фактор роста b1, интерферон (ИФН)-g, интерлейкин (ИЛ)-33, ИЛ-6, ИЛ-8, ИЛ-23, ИЛ-10, фактор некроза опухоли a, ИЛ-18, ИЛ-17А, ИФН-a, ИЛ-12p, моноцитарный хемотаксический протеин-1) в образцах СП партнеров, полученных в день ТВП, было проведено с помощью мультиплексного анализа с использованием наборов LegendPlex (BioLegend, США).
Результаты. При сравнении цитокинового профиля СП между группами с ненаступившей (n=25) и наступившей беременностью (n=8) было выявлено повышенное содержание ИЛ-18 и пониженное содержание ИЛ-10 в СП в группе с наступившей беременностью (p=0,017 и p=0,01 соответственно). Для оценки клинической значимости содержания цитокинов в СП использовалось построение характеристических кривых (Receiver Operating Characteristics – ROC). Установлено, что наибольшую диагностическую значимость имеет определение концентрации ИЛ-18 в СП (площадь под кривой составила 0,792±0,107, чувствительность теста – 62,5%, специфичность – 95,24% при пороговом значении концентрации более 210,43 пг/мл). Частота наступления беременности при концентрации ИЛ-18 выше пороговой составляла 83,3%, в то время как при пониженной концентрации ИЛ-18 наступление беременности наблюдалось лишь у 13,0% женщин.
Заключение. Повышенный уровень ИЛ-18 и пониженный уровень ИЛ-10 в СП партнеров пациенток с разрешенной половой жизнью во время лечения бесплодия с помощью ВРТ являются благоприятными факторами для наступления беременности.
Ключевые слова: семенная плазма, интерлейкин-10, интерлейкин-18, исходы вспомогательных репродуктивных технологий.
Materials and methods. 33 married couples who applied for a treatment of infertility by means of in vitro fertilization /ICSI (Intracytoplasmic Sperm Injection) were included in the prospective study. Patients were recommended to have sexual intercourse with no restrictions during treatment and to have the last sexual intercourse 3 days before an intended transvaginal puncture (ITP). Testing of cytokines (transforming growth factor (TGF)-b1, interferon (IFN)-g, interleukin (IL)-33, IL-6, IL-8, IL-23, IL-10, tumor necrosis factor (TNF)-a, IL-18, IL- 17A, IFN-a, IL-12, monocyte chemotactic protein-1) levels in samples of partners’ SP obtained on the day having ITP were carried out using multiplex analysis with LegendPlex kits (BioLegend, USA).
Results. When comparing a cytokine profile of SP in couples who did not become pregnant (n=25) and couples who become pregnant (n=8) increased IL-18 and reduced IL-10 levels (p=0.017 and p=0.01 respectively) were revealed in the group which got pregnant. To assess a clinical relevance of cytokine content in SP ROC (Receiver Operating Characteristics) curve was used. It was established that determining of IL-18 concentration in SP has the greatest diagnostic significance (the area under a curve was 0.792±0.107, test sensitivity – 62.5%, test specificity – 95.24% at threshold concentration >210.43 pg/ml). Incidence of pregnancy at IL-18 concentration above threshold levels was 83.3% while at lower concentrations of IL-18 pregnancy occurred only in 13.0% of women.
Conclusion. Elevated IL-18 levels and decreased IL-10 levels in SP of female patients’ partners who don’t have restriction of sexual life when treating infertility with ART are favorable factors for a pregnancy to occur.
Key words: seminal plasma, interleukin-10, interleukin-18, outcomes of assisted reproductive technologies.
Материалы и методы. В проспективном исследовании приняли участие 33 супружеские пары, обратившиеся для лечения бесплодия путем экстракорпорального оплодотворения/ИКСИ (ICSI – IntraCytoplasmic Sperm Injection). Пациентам был рекомендован режим половой жизни без ограничения контактов во время лечения, последний половой акт – за 3 дня до предполагаемой трансвагинальной пункции (ТВП). Определение уровня цитокинов [трансформирующий фактор роста b1, интерферон (ИФН)-g, интерлейкин (ИЛ)-33, ИЛ-6, ИЛ-8, ИЛ-23, ИЛ-10, фактор некроза опухоли a, ИЛ-18, ИЛ-17А, ИФН-a, ИЛ-12p, моноцитарный хемотаксический протеин-1) в образцах СП партнеров, полученных в день ТВП, было проведено с помощью мультиплексного анализа с использованием наборов LegendPlex (BioLegend, США).
Результаты. При сравнении цитокинового профиля СП между группами с ненаступившей (n=25) и наступившей беременностью (n=8) было выявлено повышенное содержание ИЛ-18 и пониженное содержание ИЛ-10 в СП в группе с наступившей беременностью (p=0,017 и p=0,01 соответственно). Для оценки клинической значимости содержания цитокинов в СП использовалось построение характеристических кривых (Receiver Operating Characteristics – ROC). Установлено, что наибольшую диагностическую значимость имеет определение концентрации ИЛ-18 в СП (площадь под кривой составила 0,792±0,107, чувствительность теста – 62,5%, специфичность – 95,24% при пороговом значении концентрации более 210,43 пг/мл). Частота наступления беременности при концентрации ИЛ-18 выше пороговой составляла 83,3%, в то время как при пониженной концентрации ИЛ-18 наступление беременности наблюдалось лишь у 13,0% женщин.
Заключение. Повышенный уровень ИЛ-18 и пониженный уровень ИЛ-10 в СП партнеров пациенток с разрешенной половой жизнью во время лечения бесплодия с помощью ВРТ являются благоприятными факторами для наступления беременности.
Ключевые слова: семенная плазма, интерлейкин-10, интерлейкин-18, исходы вспомогательных репродуктивных технологий.
________________________________________________
Materials and methods. 33 married couples who applied for a treatment of infertility by means of in vitro fertilization /ICSI (Intracytoplasmic Sperm Injection) were included in the prospective study. Patients were recommended to have sexual intercourse with no restrictions during treatment and to have the last sexual intercourse 3 days before an intended transvaginal puncture (ITP). Testing of cytokines (transforming growth factor (TGF)-b1, interferon (IFN)-g, interleukin (IL)-33, IL-6, IL-8, IL-23, IL-10, tumor necrosis factor (TNF)-a, IL-18, IL- 17A, IFN-a, IL-12, monocyte chemotactic protein-1) levels in samples of partners’ SP obtained on the day having ITP were carried out using multiplex analysis with LegendPlex kits (BioLegend, USA).
Results. When comparing a cytokine profile of SP in couples who did not become pregnant (n=25) and couples who become pregnant (n=8) increased IL-18 and reduced IL-10 levels (p=0.017 and p=0.01 respectively) were revealed in the group which got pregnant. To assess a clinical relevance of cytokine content in SP ROC (Receiver Operating Characteristics) curve was used. It was established that determining of IL-18 concentration in SP has the greatest diagnostic significance (the area under a curve was 0.792±0.107, test sensitivity – 62.5%, test specificity – 95.24% at threshold concentration >210.43 pg/ml). Incidence of pregnancy at IL-18 concentration above threshold levels was 83.3% while at lower concentrations of IL-18 pregnancy occurred only in 13.0% of women.
Conclusion. Elevated IL-18 levels and decreased IL-10 levels in SP of female patients’ partners who don’t have restriction of sexual life when treating infertility with ART are favorable factors for a pregnancy to occur.
Key words: seminal plasma, interleukin-10, interleukin-18, outcomes of assisted reproductive technologies.
Полный текст
Список литературы
1. Mascarenhas MN, Flaxman SR, Boerma T et al. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med 2012; 9 (12): e1001356.
2. Fox C, Morin S, Jeong JW et al. Local and systemic factors and implantation: what is the evidence? Fertil Steril 2016; 105 (4): 873–84.
3. Schjenken JE, Robertson SA. Seminal fluid and immune adaptation for pregnancy – comparative biology in mammalian species. Reprod Domest Anim 2014; 49 (Suppl. 3): 27–36.
4. Juyena N, Stelletta C. Seminal Plasma: An Essential Attribute to Spermatozoa. J Androl 2012; 33: 536–51.
5. Robertson SA, Guerin LR, Bromfield JJ et al. Seminal fluid drives expansion of the CD4þCD25þ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol Reprod 2009; 80: 1036–45.
6. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016; 106 (3): 511–9.
7. Politch JA, Tucker L, Bowman FP, Anderson DJ. Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 2007; 22: 2928–35.
8. McGraw LA, Suarez SS, Wolfner MF. On a matter of seminal importance. Bioessays 2015; 37: 142–7.
9. Wolff M, Rösner S, Germeyer A et al. Intrauterine instillation of diluted seminal plasma at oocyte pick-up does not increase the IVF pregnancy rate: a double-blind, placebo controlled, randomized study. Hum Reprod 2013; 28: 3247–52.
10. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
11. Meuleman T, Snaterse G, van Beelen E et al. The immunomodulating effect of seminal plasma on T cells. J Reprod Immunol 2015; 110: 109–16.
12. Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol 2000; 12 (1); 59–63.
13. Anderson DJ, Politch JA. Role of seminal plasma in human female reproductive failure: immunomodulation, inflammation, and infections. Adv Exp Med Biol 2015; 868: 159–69.
14. Nikolaeva MA, Babayan AA, Stepanova EO et al. The relationship of seminal transforming growth factor-β1and IL-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment. J Reprod Immunol 2016; 117: 45–51.
15. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 1999; 11 (3): 307–11.
16. Sharkey DJ, Macpherson AM, Tremellen KP et al. TGF-beta mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 2012; 189: 1024–35.
17. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
18. Abbas A, Ghandi S, Tabibnejad N. The Effect of Intercourse around Embryo Transfer on Pregnancy Rate in Assisted Reproductive Technology Cycles. Int J Fertil Steril 2009; 2 (4): 169–72.
19. Matalliotakis IM, Cakmak H, Fragouli Y et al. Increased IL-18 levels in seminal plasma of infertile men with genita ltract infections. Am J Reprod Immunol 2006; 55 (6): 428–33.
20. Lédée-Bataille N et al. Detectable levels of interleukin-18 in uterine luminal secretions at oocyte retrieval predict failure of the embryo transfer. Hum Reprod 2004; 19: 968–73.
21. Ouyang W, Rutz S, Crellin NK et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71–109.
22. Moreau P, Adrian-Cabestre F, Menier C et al. IL-10 selectively includes HLA-G expression in human trophoblasts and monocytes. Int Immunol 1999; 11 (5): 803–11.
23. Sharkey DJ, Schjenken JE, Mottershead DG et al. Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells. Mol Cell Endocrinol 2015; 417: 178–90.
24. Nikolaeva MA, Babayan AA, Stepanova EO et al. The link between cytokine IL-18, female circulating regulatory T cells, and IVF/ICSI success. Reprod Sci 2018. Oct 16: 1933719118804404.
2. Fox C, Morin S, Jeong JW et al. Local and systemic factors and implantation: what is the evidence? Fertil Steril 2016; 105 (4): 873–84.
3. Schjenken JE, Robertson SA. Seminal fluid and immune adaptation for pregnancy – comparative biology in mammalian species. Reprod Domest Anim 2014; 49 (Suppl. 3): 27–36.
4. Juyena N, Stelletta C. Seminal Plasma: An Essential Attribute to Spermatozoa. J Androl 2012; 33: 536–51.
5. Robertson SA, Guerin LR, Bromfield JJ et al. Seminal fluid drives expansion of the CD4þCD25þ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol Reprod 2009; 80: 1036–45.
6. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016; 106 (3): 511–9.
7. Politch JA, Tucker L, Bowman FP, Anderson DJ. Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 2007; 22: 2928–35.
8. McGraw LA, Suarez SS, Wolfner MF. On a matter of seminal importance. Bioessays 2015; 37: 142–7.
9. Wolff M, Rösner S, Germeyer A et al. Intrauterine instillation of diluted seminal plasma at oocyte pick-up does not increase the IVF pregnancy rate: a double-blind, placebo controlled, randomized study. Hum Reprod 2013; 28: 3247–52.
10. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
11. Meuleman T, Snaterse G, van Beelen E et al. The immunomodulating effect of seminal plasma on T cells. J Reprod Immunol 2015; 110: 109–16.
12. Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol 2000; 12 (1); 59–63.
13. Anderson DJ, Politch JA. Role of seminal plasma in human female reproductive failure: immunomodulation, inflammation, and infections. Adv Exp Med Biol 2015; 868: 159–69.
14. Nikolaeva MA, Babayan AA, Stepanova EO et al. The relationship of seminal transforming growth factor-β1and IL-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment. J Reprod Immunol 2016; 117: 45–51.
15. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 1999; 11 (3): 307–11.
16. Sharkey DJ, Macpherson AM, Tremellen KP et al. TGF-beta mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 2012; 189: 1024–35.
17. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
18. Abbas A, Ghandi S, Tabibnejad N. The Effect of Intercourse around Embryo Transfer on Pregnancy Rate in Assisted Reproductive Technology Cycles. Int J Fertil Steril 2009; 2 (4): 169–72.
19. Matalliotakis IM, Cakmak H, Fragouli Y et al. Increased IL-18 levels in seminal plasma of infertile men with genita ltract infections. Am J Reprod Immunol 2006; 55 (6): 428–33.
20. Lédée-Bataille N et al. Detectable levels of interleukin-18 in uterine luminal secretions at oocyte retrieval predict failure of the embryo transfer. Hum Reprod 2004; 19: 968–73.
21. Ouyang W, Rutz S, Crellin NK et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71–109.
22. Moreau P, Adrian-Cabestre F, Menier C et al. IL-10 selectively includes HLA-G expression in human trophoblasts and monocytes. Int Immunol 1999; 11 (5): 803–11.
23. Sharkey DJ, Schjenken JE, Mottershead DG et al. Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells. Mol Cell Endocrinol 2015; 417: 178–90.
24. Nikolaeva MA, Babayan AA, Stepanova EO et al. The link between cytokine IL-18, female circulating regulatory T cells, and IVF/ICSI success. Reprod Sci 2018. Oct 16: 1933719118804404.
2. Fox C, Morin S, Jeong JW et al. Local and systemic factors and implantation: what is the evidence? Fertil Steril 2016; 105 (4): 873–84.
3. Schjenken JE, Robertson SA. Seminal fluid and immune adaptation for pregnancy – comparative biology in mammalian species. Reprod Domest Anim 2014; 49 (Suppl. 3): 27–36.
4. Juyena N, Stelletta C. Seminal Plasma: An Essential Attribute to Spermatozoa. J Androl 2012; 33: 536–51.
5. Robertson SA, Guerin LR, Bromfield JJ et al. Seminal fluid drives expansion of the CD4þCD25þ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol Reprod 2009; 80: 1036–45.
6. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016; 106 (3): 511–9.
7. Politch JA, Tucker L, Bowman FP, Anderson DJ. Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 2007; 22: 2928–35.
8. McGraw LA, Suarez SS, Wolfner MF. On a matter of seminal importance. Bioessays 2015; 37: 142–7.
9. Wolff M, Rösner S, Germeyer A et al. Intrauterine instillation of diluted seminal plasma at oocyte pick-up does not increase the IVF pregnancy rate: a double-blind, placebo controlled, randomized study. Hum Reprod 2013; 28: 3247–52.
10. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
11. Meuleman T, Snaterse G, van Beelen E et al. The immunomodulating effect of seminal plasma on T cells. J Reprod Immunol 2015; 110: 109–16.
12. Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol 2000; 12 (1); 59–63.
13. Anderson DJ, Politch JA. Role of seminal plasma in human female reproductive failure: immunomodulation, inflammation, and infections. Adv Exp Med Biol 2015; 868: 159–69.
14. Nikolaeva MA, Babayan AA, Stepanova EO et al. The relationship of seminal transforming growth factor-β1and IL-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment. J Reprod Immunol 2016; 117: 45–51.
15. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 1999; 11 (3): 307–11.
16. Sharkey DJ, Macpherson AM, Tremellen KP et al. TGF-beta mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 2012; 189: 1024–35.
17. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
18. Abbas A, Ghandi S, Tabibnejad N. The Effect of Intercourse around Embryo Transfer on Pregnancy Rate in Assisted Reproductive Technology Cycles. Int J Fertil Steril 2009; 2 (4): 169–72.
19. Matalliotakis IM, Cakmak H, Fragouli Y et al. Increased IL-18 levels in seminal plasma of infertile men with genita ltract infections. Am J Reprod Immunol 2006; 55 (6): 428–33.
20. Lédée-Bataille N et al. Detectable levels of interleukin-18 in uterine luminal secretions at oocyte retrieval predict failure of the embryo transfer. Hum Reprod 2004; 19: 968–73.
21. Ouyang W, Rutz S, Crellin NK et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71–109.
22. Moreau P, Adrian-Cabestre F, Menier C et al. IL-10 selectively includes HLA-G expression in human trophoblasts and monocytes. Int Immunol 1999; 11 (5): 803–11.
23. Sharkey DJ, Schjenken JE, Mottershead DG et al. Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells. Mol Cell Endocrinol 2015; 417: 178–90.
24. Nikolaeva MA, Babayan AA, Stepanova EO et al. The link between cytokine IL-18, female circulating regulatory T cells, and IVF/ICSI success. Reprod Sci 2018. Oct 16: 1933719118804404.
________________________________________________
2. Fox C, Morin S, Jeong JW et al. Local and systemic factors and implantation: what is the evidence? Fertil Steril 2016; 105 (4): 873–84.
3. Schjenken JE, Robertson SA. Seminal fluid and immune adaptation for pregnancy – comparative biology in mammalian species. Reprod Domest Anim 2014; 49 (Suppl. 3): 27–36.
4. Juyena N, Stelletta C. Seminal Plasma: An Essential Attribute to Spermatozoa. J Androl 2012; 33: 536–51.
5. Robertson SA, Guerin LR, Bromfield JJ et al. Seminal fluid drives expansion of the CD4þCD25þ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol Reprod 2009; 80: 1036–45.
6. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016; 106 (3): 511–9.
7. Politch JA, Tucker L, Bowman FP, Anderson DJ. Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 2007; 22: 2928–35.
8. McGraw LA, Suarez SS, Wolfner MF. On a matter of seminal importance. Bioessays 2015; 37: 142–7.
9. Wolff M, Rösner S, Germeyer A et al. Intrauterine instillation of diluted seminal plasma at oocyte pick-up does not increase the IVF pregnancy rate: a double-blind, placebo controlled, randomized study. Hum Reprod 2013; 28: 3247–52.
10. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
11. Meuleman T, Snaterse G, van Beelen E et al. The immunomodulating effect of seminal plasma on T cells. J Reprod Immunol 2015; 110: 109–16.
12. Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol 2000; 12 (1); 59–63.
13. Anderson DJ, Politch JA. Role of seminal plasma in human female reproductive failure: immunomodulation, inflammation, and infections. Adv Exp Med Biol 2015; 868: 159–69.
14. Nikolaeva MA, Babayan AA, Stepanova EO et al. The relationship of seminal transforming growth factor-β1and IL-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment. J Reprod Immunol 2016; 117: 45–51.
15. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 1999; 11 (3): 307–11.
16. Sharkey DJ, Macpherson AM, Tremellen KP et al. TGF-beta mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 2012; 189: 1024–35.
17. Tremellen KP et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000; 15: 2653–8.
18. Abbas A, Ghandi S, Tabibnejad N. The Effect of Intercourse around Embryo Transfer on Pregnancy Rate in Assisted Reproductive Technology Cycles. Int J Fertil Steril 2009; 2 (4): 169–72.
19. Matalliotakis IM, Cakmak H, Fragouli Y et al. Increased IL-18 levels in seminal plasma of infertile men with genita ltract infections. Am J Reprod Immunol 2006; 55 (6): 428–33.
20. Lédée-Bataille N et al. Detectable levels of interleukin-18 in uterine luminal secretions at oocyte retrieval predict failure of the embryo transfer. Hum Reprod 2004; 19: 968–73.
21. Ouyang W, Rutz S, Crellin NK et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71–109.
22. Moreau P, Adrian-Cabestre F, Menier C et al. IL-10 selectively includes HLA-G expression in human trophoblasts and monocytes. Int Immunol 1999; 11 (5): 803–11.
23. Sharkey DJ, Schjenken JE, Mottershead DG et al. Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells. Mol Cell Endocrinol 2015; 417: 178–90.
24. Nikolaeva MA, Babayan AA, Stepanova EO et al. The link between cytokine IL-18, female circulating regulatory T cells, and IVF/ICSI success. Reprod Sci 2018. Oct 16: 1933719118804404.
Авторы
Т.В. Донцова*, А.А. Бабаян, М.А. Николаева, А.С. Арефьева, Е.А. Калинина, Л.В. Кречетова
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, Москва, Россия
*dr.dontsova@gmail.com
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
*dr.dontsova@gmail.com
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, Москва, Россия
*dr.dontsova@gmail.com
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Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
*dr.dontsova@gmail.com
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