Обоснование. Медикаментозная поддержка лютеиновой фазы (ЛФ) является важным этапом эффективности программ вспомогательных репродуктивных технологий (ВРТ). Цель. Представить современные данные относительно эффективности гормональной поддержки ЛФ при проведении циклов ВРТ, а также провести сравнительный анализ эффективности различных гестагенных препаратов. 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 8 лет. В обзор были включены статьи из рецензируемой литературы. Результаты. Медикаментозная поддержка ЛФ цикла становится необходимым этапом лечения бесплодия в различных программах ВРТ. Хотя инъекции препарата хорионического гонадотропина человека в течение посттрансферного периода приводят к активации синтеза эндогенных стероидных гормонов, в настоящее время предпочтение отдается использованию экзогенных гормонов вследствие отсутствия влияния на риск развития синдрома гиперстимуляции яичников. Заключение. Многообразие различных препаратов прогестерона сочетается с отсутствием алгоритмов их использования при различных клинических ситуациях. Требуется проведение дальнейших исследований по оценке эффективности препаратов прогестерона, в том числе в различных подгруппах пациенток.
Background. Luteal phase (LP) drug support is an important step in assisted reproductive technology (ART) programs efficacy. Aim. To present up-to-date data on an efficacy of LP hormonal support during ART cycles as well as to conduct a comparative analysis of various gestagen drug effectiveness. Materials and methods. To write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, eLibrary, etc.) for the last 8 years. The review includs articles from peer-reviewed literature. Results. LP drug support becomes an essential step in infertility treatment in various ART programs. Although human chorionic gonadotropin drug injections in the posttransfer period leads to an activation of endogenous steroid hormones synthesis, exogenous hormones use is currently preferred because of not having a risk of ovarian hyperstimulation syndrome. Conclusions. The variety of progesterone drugs is accompanied by a lack of algorithms for their use in various clinical situations. Further studies are required to evaluate progesterone drugs efficacy for various subgroups of patients.
Key words: infertility, assisted reproductive technologies, in vitro fertilization, gestagens.
1. Child T, Leonard SA, Evans JS, Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted. Reprod Biomed Online. Elsevier Ltd, 2018. https://doi.org/10.1016/j.rbmo.2018.02.001
2. Mesen T, Young S. HHS Public Access. Obs Gynecol Clin North Am 2015; 25 (4): 368–79.
3. Maher MA. Luteal phase support may improve pregnancy outcomes during intrauterine insemination cycles. Eur J Obstet Gynecol Reprod Biol 2011; 157 (1): 57–62.
4. Karadag B, Dilbaz B, Karcaaltincaba D et al. The effect of luteal-phase support with vaginal progesterone on pregnancy rates in gonadotropin and clomiphene citrate/intra-uterine insemination cycles in unexplained infertility: A prospective randomised study. J Obstet Gynaecol (Lahore) 2016; 36 (6): 794–9.
5. Elgindy EA, Sibai H, Mostafa MI et al. Towards an optimal luteal support modality in agonist triggered cycles: a randomized clinical trial. Hum Reprod England 2018; 33 (6): 1079–86.
6. Мартазанова Б.А., Мишиева Н.Г., Ведихина И.А. и др. Гормональный профиль после замены триггера овуляции у женщин с высоким риском развития синдрома гиперстимуляции яичников. Акушерство и гинекология. 2015; 6: 84–90.
[Martazanova B.A., Mishieva N.G., Vedikhina I.A. et al. Gormonal'nyi profil' posle zameny triggera ovuliatsii u zhenshchin s vysokim riskom razvitiia sindroma giperstimuliatsii iaichnikov. Akusherstvo i ginekologiia. 2015; 6: 84–90 (in Russian).]
7. Benadiva C, Engmann L. Luteal phase support after gonadotropin-releasing hormone agonist triggering: does it still matter? Fertil Steril United States 2018; 109 (5): 763–7.
8. Bergh C, Lindenberg S. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection. Hum Reprod 2012; 27 (12): 3467–73.
9. Alsbjerg B, Polyzos NP, Elbaek HO et al. Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate. Reprod Biomed Online 2013; 26 (2): 133–7. http://dx.doi.org/10.1016/j.rbmo.2012.10.012
10. Silverberg KM, Vaughn TC, Hansard LJ et al. Vaginal (Crinone 8%) gel vs. intramuscular progesterone in oil for luteal phase support in in vitro fertilization: A large prospective trial. Fertil Steril 2012; 97 (2): 344–8. http://dx.doi.org/10.1016/j.fertnstert.2011.11.018
11. Tomic V, Tomic J, Klaic DZ et al. Oral dydrogesterone versus vaginal progesterone gel in the luteal phase support: Randomized controlled trial. Eur J Obstet Gynecol Reprod Biol 2015; 186: 49–53. http://dx.doi.org/10.1016/j.ejogrb.2014.11.002
12. Michnova L, Dostal J, Kudela M et al. Vaginal use of micronized progesterone for luteal support.A randomized study comparing Utrogestan(R) and Crinone(R) 8. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017; 161 (1): 86–91.
13. Tomic V, Tomic J, Klaic DZ. Oral micronized progesterone combined with vaginal progesterone gel for luteal support. Gynecol Endocrinol 2011; 27 (12): 1010–3.
14. Campaña-Seoane M, Peleteiro A, Laguna R, Otero-Espinar FJ. Bioadhesive emulsions for control release of progesterone resistant to vaginal fluids clearance. Int J Pharm 2014; 477 (1–2): 495–505. http://dx.doi.org/10.1016/j.ijpharm.2014.10.066
15. Wang Y, He Y, Zhao X et al. Crinone gel for luteal phase support in frozen-thawed embryo transfer cycles: A prospective randomized clinical trial in the Chinese population. PLoS One 2015; 10 (7): 1–9.
16. Merriam KS, Leake KA, Elliot M et al. Sexual absorption of vaginal progesterone: A randomized control trial. Int J Endocrinol 2015; 2015: 685281. DOI: 10.1155/2015/685281
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1. Child T, Leonard SA, Evans JS, Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted. Reprod Biomed Online. Elsevier Ltd, 2018. https://doi.org/10.1016/j.rbmo.2018.02.001
2. Mesen T, Young S. HHS Public Access. Obs Gynecol Clin North Am 2015; 25 (4): 368–79.
3. Maher MA. Luteal phase support may improve pregnancy outcomes during intrauterine insemination cycles. Eur J Obstet Gynecol Reprod Biol 2011; 157 (1): 57–62.
4. Karadag B, Dilbaz B, Karcaaltincaba D et al. The effect of luteal-phase support with vaginal progesterone on pregnancy rates in gonadotropin and clomiphene citrate/intra-uterine insemination cycles in unexplained infertility: A prospective randomised study. J Obstet Gynaecol (Lahore) 2016; 36 (6): 794–9.
5. Elgindy EA, Sibai H, Mostafa MI et al. Towards an optimal luteal support modality in agonist triggered cycles: a randomized clinical trial. Hum Reprod England 2018; 33 (6): 1079–86.
6. Martazanova B.A., Mishieva N.G., Vedikhina I.A. et al. Gormonal'nyi profil' posle zameny triggera ovuliatsii u zhenshchin s vysokim riskom razvitiia sindroma giperstimuliatsii iaichnikov. Akusherstvo i ginekologiia. 2015; 6: 84–90 (in Russian).
7. Benadiva C, Engmann L. Luteal phase support after gonadotropin-releasing hormone agonist triggering: does it still matter? Fertil Steril United States 2018; 109 (5): 763–7.
8. Bergh C, Lindenberg S. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection. Hum Reprod 2012; 27 (12): 3467–73.
9. Alsbjerg B, Polyzos NP, Elbaek HO et al. Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate. Reprod Biomed Online 2013; 26 (2): 133–7. http://dx.doi.org/10.1016/j.rbmo.2012.10.012
10. Silverberg KM, Vaughn TC, Hansard LJ et al. Vaginal (Crinone 8%) gel vs. intramuscular progesterone in oil for luteal phase support in in vitro fertilization: A large prospective trial. Fertil Steril 2012; 97 (2): 344–8. http://dx.doi.org/10.1016/j.fertnstert.2011.11.018
11. Tomic V, Tomic J, Klaic DZ et al. Oral dydrogesterone versus vaginal progesterone gel in the luteal phase support: Randomized controlled trial. Eur J Obstet Gynecol Reprod Biol 2015; 186: 49–53. http://dx.doi.org/10.1016/j.ejogrb.2014.11.002
12. Michnova L, Dostal J, Kudela M et al. Vaginal use of micronized progesterone for luteal support.A randomized study comparing Utrogestan(R) and Crinone(R) 8. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017; 161 (1): 86–91.
13. Tomic V, Tomic J, Klaic DZ. Oral micronized progesterone combined with vaginal progesterone gel for luteal support. Gynecol Endocrinol 2011; 27 (12): 1010–3.
14. Campaña-Seoane M, Peleteiro A, Laguna R, Otero-Espinar FJ. Bioadhesive emulsions for control release of progesterone resistant to vaginal fluids clearance. Int J Pharm 2014; 477 (1–2): 495–505. http://dx.doi.org/10.1016/j.ijpharm.2014.10.066
15. Wang Y, He Y, Zhao X et al. Crinone gel for luteal phase support in frozen-thawed embryo transfer cycles: A prospective randomized clinical trial in the Chinese population. PLoS One 2015; 10 (7): 1–9.
16. Merriam KS, Leake KA, Elliot M et al. Sexual absorption of vaginal progesterone: A randomized control trial. Int J Endocrinol 2015; 2015: 685281. DOI: 10.1155/2015/685281
Авторы
А.Г. Сыркашева*, Я.А. Петросян, Н.В. Долгушина
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. академика В.И.Кулакова» Минздрава России, Москва, Россия
*a_syrkasheva@oparina4.ru
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Anastasia G. Syrkasheva*, Yana A. Petrosyan, Natalia V. Dolgushina
V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Moscow, Russia
*a_syrkasheva@oparina4.ru