Фолликулярная жидкость и исходы программ вспомогательных репродуктивных технологий (обзор литературы)
Фолликулярная жидкость и исходы программ вспомогательных репродуктивных технологий (обзор литературы)
Бурдули А.Г., Кициловская Н.А., Сухова Ю.В. и др. Фолликулярная жидкость и исходы программ вспомогательных репродуктивных технологий (обзор литературы). Гинекология. 2019; 21 (6): 36–40.
DOI: 10.26442/20795696.2019.6.190663
Фолликулярная жидкость и исходы программ вспомогательных репродуктивных технологий (обзор литературы)
Бурдули А.Г., Кициловская Н.А., Сухова Ю.В. и др. Фолликулярная жидкость и исходы программ вспомогательных репродуктивных технологий (обзор литературы). Гинекология. 2019; 21 (6): 36–40.
DOI: 10.26442/20795696.2019.6.190663
В обзоре представлены данные о метаболитах фолликулярной жидкости (ФЖ) с позиций репродуктивной медицины и их использовании с целью предикции исходов программ вспомогательных репродуктивных технологий (ВРТ). Рассматриваются различные составляющие данной биологической среды (гормоны, липиды, мелатонин и др.) с оценкой их предиктивной значимости в прогнозировании эффективности программ экстракорпорального оплодотворения (ЭКО). Приведены данные об экспериментальных направлениях в этой области и перспективах их использования в клинической практике. Подчеркивается необходимость расширения и интенсификации исследований в области анализа состава ФЖ вследствие растущей клинической потребности и нерешенности задачи повышения эффективности программ ВРТ. Материалы и методы. В обзор включены данные зарубежных и отечественных статей, найденных в PubMed по данной теме, опубликованных в последние годы. Результаты. В качестве неинвазивных маркеров качества ооцитов/эмбрионов активно изучаются различные метаболиты ФЖ, учитывая установленный факт прямого влияния ее состава на рост и созревание ооцитов, а в последующем и на процесс фертилизации. Приведены данные об экспериментальных направлениях в этой области и перспективах их использования в клинической практике. Однако данные клинических исследований в отношении связи уровней различных метаболитов ФЖ и исходов программ ЭКО противоречивы. Заключение. Необходимы расширение и интенсификация исследований в области поиска и применения надежных предикторов в прогнозировании исходов программ ВРТ вследствие больших экономических затрат на дорогостоящее лечение бесплодия методом ЭКО.
The review presents data on metabolites in the follicular fluid (FF) from the perspective of reproductive medicine and their use in order to predict outcomes of assisted reproductive technology (ART) programs. It considers various components of this biological medium (hormones, lipids, melatonin, etc.) with an assessment of their predictive value in prognosis of the effectiveness of in vitro fertilization (IVF) programs. The data on experimental directions in this field and the prospects for their use in clinical practice are presented. The article emphasizes that the growing clinical need and the unsolved problem of increasing the effectiveness of ART programs determine the need for further studies of the FF composition. Materials and methods. The review includes data related to this topic from foreign and Russian articles found in PubMed which were published in recent years. Results. Given the established fact of a direct effect of FF composition on growth and maturation of oocytes, and further, on the fertilization process, various FF metabolites are actively investigated as non-invasive markers of quality of oocytes/embryos. The article provides data on the experimental directions in this field and the prospects for their use in clinical practice. However, clinical studies of a relation between various FF metabolites levels and outcomes of IVF programs are contradictory. Conclusion. Owing large economic cost for treatment of infertility with IVF, there is need for expansion and intensification of studies to identify and use reliable predictors in prognosis of ART programs outcomes.
1. Hennet M, Combelles C. The antral follicle: a microenvironment for oocyte differentiation. Int J Dev Biol 2012; 56: 819–31.
2. Edwards R. Follicular fluid. Reproduction 1974; 37 (1): 189–219.
3. Rodgers R, Irving-Rodgers H. Formation of the ovarian follicular antrum and follicular fluid. Biol Reprod 2010; 82: 1021–9.
4. Basuino L, Silveira C. Human follicular fluid and effects on reproduction. JBRA Assist Reprod 2016; 20 (1): 38–40.
5. Lebbe M, Taylor AE, Visser JA et al. The steroid metabolome in the isolated ovarian follicle and its response to androgen exposure and antagonism. Endocrinology 2017; 158: 1474–85.
6. Handelsman D. Mass spectrometry, immunoassay and valid steroid measurements in reproductive medicine and science. Hum Reprod 2017; p. 1–4.
7. De Sutter P, Dhont M, Vanluchene E et al. Correlations between follicular fluid steroid analysis and maturity and cytogenetic analysis of human oocytes that remained unfertilized after in vitro fertilization. Fertil Steril 1991; 55: 958–63.
8. Rosen M, Zamah A, Shen S et al. The effect of follicular fluid hormones on oocyte recovery after ovarian stimulation: FSH level predicts oocyte recovery. Reprod Biol Endocrinol 2009; 7: 35.
9. Wen X, Li D, Tozer A et al. Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles. Reprod Biol Endocrinol 2010; 8: 117.
10. Kushnir M, Naessen T, Wanggren K et al. Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment. J Steroid Biochem Mol Biol 2016; 162: 126–33.
11. Walters K, Eid S, Edwards M et al. Steroid profiles by liquid chromatography-mass spectrometry of matched serum and single dominant ovarian follicular fluid from women undergoing IVF. Reproductive BioMedicine Online 2018. DOI:10.1016/j.rbmo.2018.10.006
12. Kedem-Dickman A, Maman E, Yung Y et al. Anti-Mullerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes. Reprod BioMed Online 2012; 24 (5): 540–6.
13. Kim J, Lee J, Chang H et al. Anti-Mullerian hormone levels in the follicular fluid of the preovulatory follicle: a predictor for oocyte fertilization and quality of embryo. J Korean Med Sci 2014; 29 (9): 1266–70.
14. Nagy B, Poto L, Farkas N et al. Follicular fluid progesterone level associated with fertilization outcome during in vitro fertilization: a systematic review and meta-analysis. Reproductive BioMedicine Online 2019. DOI: 10.1016/j.rbmo.2018.12.045
15. O'Brien Y et al. Anti-Müllerian hormone and progesterone levels in human follicular fluid are predictors of embryonic development. Reprod Biol Endocrinol 2019; 17 (1): 47. DOI: 10.1186/s12958-019-0492-9
16. Emori M, Drapkin R. The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis. Reprod Biol Endocrinol 2014; 12: 60. DOI: 10.1186/1477-7827-12-60
17. De los Santos M, Garcia-Laez V, Beltran-Torregrosa D et al. Hormonal and molecular characterization of follicular fluid, cumulus cells and oocytes from pre-ovulatory follicles in stimulated and unstimulated cycles. Hum Reprod 2012; 27: 1596–605.
18. Polyzos N, Anckaert E, Guzman L et al. Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI. Hum Reprod 2014; 29: 2032–40.
19. Van de Vijver A, Drakopoulos P, Van Landuyt L et al. Vitamin D deficiency and pregnancy rates following frozen–thawed embryo transfer: a prospective cohort study. Hum Reprod 2016; 31: 1749–54.
20. Vanni V, Vigano P, Somigliana E et al. Vitamin D and assisted reproduction technologies: current concepts. Reprod Biol Endocrinol 2014; 12: 47.
21. Lv S, Ji Y, Wang X et al. Serum vitamin D status and in vitro fertilization outcomes: a systematic review and meta-analysis. Arch Gynecol Obstet 2016; 293: 1339–45.
22. Zhao J, Huang X, Xu B et al. Whether vitamin D was associated with clinical outcome after IVF/ICSI: a systematic review and meta-analysis. Reprod Biol Endocrinol 2018; 16 (1).
23. Shehadeh A et al. A shift in follicular fluid from triacylglycerols to membrane lipids is associated with positive pregnancy outcome. FASEB J 2019: fj201900318RR. DOI: 10.1096/fj.201900318RR
24. Browne R, Bloom M, Shelly W et al. Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF. J Assist Reprod Genet 2009; 26: 557.
25. Cordeiro F, Montani D, Pilau E et al. Ovarian environment aging: follicular fluid lipidomic and related metabolic pathways. J Assist Reprod Genet 2018; 35: 1385.
26. Cataldi T, Cordeiro F, Costa Ldo V et al. Lipid profiling of follicular fluid from women undergoing IVF: young poor ovarian responders versus normal responders. Hum Fertil 2013; 16: 269–77.
27. Cordeiro F, Cataldi T, do Vale Teixeira da Costa L et al. Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment. J Assist Reprod Genet 2015; 32: 45–5.
28. Ruebel M, Cotter M, Sims C et al. Obesity modulates inflammation and lipid metabolism oocyte gene expression: a single-cell transcriptome perspective. J Clin Endocrinol Metab 2017; 102: 2029–38.
29. Manchester L, Coto-Montes A, Boga J et al. Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J Pineal Res 2015; 59: 403–19.
30. Reiter R, Tamura H, Tan D et al. Melatonin and the circadian system: contributions to successful female reproduction. Fertil Steril 2014; 102: 321–8.
31. Tong J, Sheng S, Sun Y et al. Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve. Reproduction 2017; 153 (4): 443–51.
32. Zheng M, Tong J, Li W-P et al. Melatonin concentration in follicular fluid is correlated with antral follicle count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive technology (ART) procedures. Gynecol Endocrinol 2017; 34 (5): 446–50.
33. Fang L, Hu X, Cui L et al. Serum and follicular fluid fetuin-B levels are correlated with fertilization rates in conventional IVF cycles. J Assist Reprod Genet 2019; 36: 1101.
34. Li Zewu et al. Leukaemia inhibitory factor in serum and follicular fluid of women with polycystic ovary syndrome and its correlation with IVF outcome. Reproductive BioMedicine Online 2018; 36 (Issue 4): 483–9.
35. Alfaidy N, Baron Ch, Antoine Y et al. Prokineticin 1 (PROK1) is a new biomarker of human oocyte competence: expression and hormonal regulation throughout late folliculogenesis. Biol Reprod 2019; pii: ioz114.
36. Rao M, Zhou F, Tang L et al. Follicular fluid humanin concentration is related to ovarian reserve markers and clinical pregnancy after IVF–ICSI: a pilot study. Reproductive BioMedicine Online 2018. DOI: 10.1016/j.rbmo.2018.11.002
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1. Hennet M, Combelles C. The antral follicle: a microenvironment for oocyte differentiation. Int J Dev Biol 2012; 56: 819–31.
2. Edwards R. Follicular fluid. Reproduction 1974; 37 (1): 189–219.
3. Rodgers R, Irving-Rodgers H. Formation of the ovarian follicular antrum and follicular fluid. Biol Reprod 2010; 82: 1021–9.
4. Basuino L, Silveira C. Human follicular fluid and effects on reproduction. JBRA Assist Reprod 2016; 20 (1): 38–40.
5. Lebbe M, Taylor AE, Visser JA et al. The steroid metabolome in the isolated ovarian follicle and its response to androgen exposure and antagonism. Endocrinology 2017; 158: 1474–85.
6. Handelsman D. Mass spectrometry, immunoassay and valid steroid measurements in reproductive medicine and science. Hum Reprod 2017; p. 1–4.
7. De Sutter P, Dhont M, Vanluchene E et al. Correlations between follicular fluid steroid analysis and maturity and cytogenetic analysis of human oocytes that remained unfertilized after in vitro fertilization. Fertil Steril 1991; 55: 958–63.
8. Rosen M, Zamah A, Shen S et al. The effect of follicular fluid hormones on oocyte recovery after ovarian stimulation: FSH level predicts oocyte recovery. Reprod Biol Endocrinol 2009; 7: 35.
9. Wen X, Li D, Tozer A et al. Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles. Reprod Biol Endocrinol 2010; 8: 117.
10. Kushnir M, Naessen T, Wanggren K et al. Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment. J Steroid Biochem Mol Biol 2016; 162: 126–33.
11. Walters K, Eid S, Edwards M et al. Steroid profiles by liquid chromatography-mass spectrometry of matched serum and single dominant ovarian follicular fluid from women undergoing IVF. Reproductive BioMedicine Online 2018. DOI: 10.1016/j.rbmo.2018.10.006
12. Kedem-Dickman A, Maman E, Yung Y et al. Anti-Mullerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes. Reprod BioMed Online 2012; 24 (5): 540–6.
13. Kim J, Lee J, Chang H et al. Anti-Mullerian hormone levels in the follicular fluid of the preovulatory follicle: a predictor for oocyte fertilization and quality of embryo. J Korean Med Sci 2014; 29 (9): 1266–70.
14. Nagy B, Poto L, Farkas N et al. Follicular fluid progesterone level associated with fertilization outcome during in vitro fertilization: a systematic review and meta-analysis. Reproductive BioMedicine Online 2019. DOI: 10.1016/j.rbmo.2018.12.045
15. O'Brien Y et al. Anti-Müllerian hormone and progesterone levels in human follicular fluid are predictors of embryonic development. Reprod Biol Endocrinol 2019; 17 (1): 47. DOI: 10.1186/s12958-019-0492-9
16. Emori M, Drapkin R. The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis. Reprod Biol Endocrinol 2014; 12: 60. DOI: 10.1186/1477-7827-12-60
17. De los Santos M, Garcia-Laez V, Beltran-Torregrosa D et al. Hormonal and molecular characterization of follicular fluid, cumulus cells and oocytes from pre-ovulatory follicles in stimulated and unstimulated cycles. Hum Reprod 2012; 27: 1596–605.
18. Polyzos N, Anckaert E, Guzman L et al. Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI. Hum Reprod 2014; 29: 2032–40.
19. Van de Vijver A, Drakopoulos P, Van Landuyt L et al. Vitamin D deficiency and pregnancy rates following frozen–thawed embryo transfer: a prospective cohort study. Hum Reprod 2016; 31: 1749–54.
20. Vanni V, Vigano P, Somigliana E et al. Vitamin D and assisted reproduction technologies: current concepts. Reprod Biol Endocrinol 2014; 12: 47.
21. Lv S, Ji Y, Wang X et al. Serum vitamin D status and in vitro fertilization outcomes: a systematic review and meta-analysis. Arch Gynecol Obstet 2016; 293: 1339–45.
22. Zhao J, Huang X, Xu B et al. Whether vitamin D was associated with clinical outcome after IVF/ICSI: a systematic review and meta-analysis. Reprod Biol Endocrinol 2018; 16 (1).
23. Shehadeh A et al. A shift in follicular fluid from triacylglycerols to membrane lipids is associated with positive pregnancy outcome. FASEB J 2019: fj201900318RR. DOI: 10.1096/fj.201900318RR
24. Browne R, Bloom M, Shelly W et al. Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF. J Assist Reprod Genet 2009; 26: 557.
25. Cordeiro F, Montani D, Pilau E et al. Ovarian environment aging: follicular fluid lipidomic and related metabolic pathways. J Assist Reprod Genet 2018; 35: 1385.
26. Cataldi T, Cordeiro F, Costa Ldo V et al. Lipid profiling of follicular fluid from women undergoing IVF: young poor ovarian responders versus normal responders. Hum Fertil 2013; 16: 269–77.
27. Cordeiro F, Cataldi T, do Vale Teixeira da Costa L et al. Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment. J Assist Reprod Genet 2015; 32: 45–5.
28. Ruebel M, Cotter M, Sims C et al. Obesity modulates inflammation and lipid metabolism oocyte gene expression: a single-cell transcriptome perspective. J Clin Endocrinol Metab 2017; 102: 2029–38.
29. Manchester L, Coto-Montes A, Boga J et al. Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J Pineal Res 2015; 59: 403–19.
30. Reiter R, Tamura H, Tan D et al. Melatonin and the circadian system: contributions to successful female reproduction. Fertil Steril 2014; 102: 321–8.
31. Tong J, Sheng S, Sun Y et al. Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve. Reproduction 2017; 153 (4): 443–51.
32. Zheng M, Tong J, Li W-P et al. Melatonin concentration in follicular fluid is correlated with antral follicle count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive technology (ART) procedures. Gynecol Endocrinol 2017; 34 (5): 446–50.
33. Fang L, Hu X, Cui L et al. Serum and follicular fluid fetuin-B levels are correlated with fertilization rates in conventional IVF cycles. J Assist Reprod Genet 2019; 36: 1101.
34. Li Zewu et al. Leukaemia inhibitory factor in serum and follicular fluid of women with polycystic ovary syndrome and its correlation with IVF outcome. Reproductive BioMedicine Online 2018; 36 (Issue 4): 483–9.
35. Alfaidy N, Baron Ch, Antoine Y et al. Prokineticin 1 (PROK1) is a new biomarker of human oocyte competence: expression and hormonal regulation throughout late folliculogenesis. Biol Reprod 2019; pii: ioz114.
36. Rao M, Zhou F, Tang L et al. Follicular fluid humanin concentration is related to ovarian reserve markers and clinical pregnancy after IVF–ICSI: a pilot study. Reproductive BioMedicine Online 2018. DOI: 10.1016/j.rbmo.2018.11.002
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. академика В.И. Кулакова» Минздрава России, Москва, Россия
*burdulianna@gmail.com
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Anna G. Burduli*, Natalia A. Kitsilovskaya, Yuliya V. Sukhova, Irina A. Vedikhina, Tatiana Y. Ivanets, Vitaliy V. Chagovets, Nataliia L. Starodubtseva, Vladimir E. Frankevich
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
*burdulianna@gmail.com