medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2020-4-16-26medalphabet-1449Research ArticleСтатьиДефицит 21-гидроксилазы и фертильность21-hydroxylase deficiency and fertilityАмираслановаМ. М.AmiraslanovaM. M.

врач – акушер-гинеколог клиники акушерства и гинекологии имени В. Ф. Снегирева, Университетская клиническая больница № 2

г. Москва

Moscow

КузнецоваИ. В.KuznetsovaI. V.

д. м. н., проф., рук. направления «гинекологическая эндокринология»

г. Москва

Moscow

ФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова (Сеченовский университет)» Минздрава РоссииРоссияFirst Moscow State Medical University n. a. I. M. SechenovRussian FederationНОЧУ ДПО «Высшая медицинская школа»РоссияHigher Medical SchoolRussian Federation20201206202004Современная гинекология1626Copyright © Амирасланова М.М., Кузнецова И.В., 20202020Амирасланова М.М., Кузнецова И.В.Amiraslanova M.M., Kuznetsova I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/1449

Дефицит 21-гидроксилазы является самым распространенным генетически обусловленным дефектом стероидогенеза в надпочечниках. Одним из следствий заболевания, развивающегося в результате этого дефекта, – врожденной дисфункции коры надпочечников (ВДКН) – становится снижение фертильности в виде бесплодия или ранних потерь беременности. Проблема снижения фертильности, ассоциированного с ВДКН, до сих пор не преодолена ввиду отсутствия понимания причин негативных исходов беременности или происхождения бесплодия при сохраненной овуляторной функции яичников. Вероятным фактором снижения фертильности у больных ВДКН является гиперандрогенизм. Но попытки его терапии глюкокортикоидами не увенчались клиническим успехом. Таким образом, вопросы восстановления фертильности у женщин, больных ВДКН, остаются актуальными. На текущий момент единственным методом предотвращения привычного выкидыша и других осложнений беременности у больных ВДКН является использование прогестагенов при условии их раннего, преконцепционного назначения.

21-hydroxylase deficiency is the most common genetically determined adrenal steroidogenesis defect. One of the consequences of the disease developing as a result of this defect, congenital dysfunction of the adrenal cortex (CDAC), is a decrease in fertility in the form of infertility or early pregnancy loss. The problem of reducing the fertility associated with CDAC is still not overcome due to a lack of understanding of the causes of negative pregnancy outcomes or the origin of infertility with preserved ovulatory function of the ovaries. A likely factor in reducing fertility in patients with CDAC is hyperandrogenism. But attempts at his glucocorticoid therapy have not been clinically successful. Thus, the issues of fertility restoration in women with CDAC are still relevant. At the moment, the only method of preventing the usual miscarriage and other complications of pregnancy in patients with CDAC is the use of progestogens, subject to their early, preconception purpose.

врожденная дисфункция коры надпочечниковдефицит 21-гидроксилазыфертильностьбесплодиебеременностьпривычный выкидышгиперандрогенизмглюкокортикоидыпрогестагеныcongenital adrenal cortical dysfunction21-hydroxylase deficiencyfertilityinfertilitypregnancymiscarriagehyperandrogenismglucocorticoidsprogestogensReferencesШмидт А. А., Замятнин С. А., Гончар И. С., Коровин А. Е., Городнюк И. О., Коцур А. В. Эпидемиология бесплодия в России и за рубежом. Клиническая патофизиология. 2019; 25 (1): 9–12.Шмидт А. А., Замятнин С. А., Гончар И. С., Коровин А. Е., Городнюк И. О., Коцур А. В. Эпидемиология бесплодия в России и за рубежом. Клиническая патофизиология. 2019; 25 (1): 9–12.Inhorn MC, Patrizio MC. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015; 21 (4): 411–426.Inhorn MC, Patrizio MC. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015; 21 (4): 411–426.Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clinical Biochemistry. 2018; 62: 2–10.Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clinical Biochemistry. 2018; 62: 2–10.Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat. World Population Prospects: The 2012 Revision. New York, 2013; 18 p.Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat. World Population Prospects: The 2012 Revision. New York, 2013; 18 p.Третьякова О. С., Заднипряный И. В. Гиперандрогения как базис формирования бесплодия и акне у женщин репродуктивного возраста. Крымский журнал экспериментальной и клинической медицины. 2015; 5 (3): 65–71.Третьякова О. С., Заднипряный И. В. Гиперандрогения как базис формирования бесплодия и акне у женщин репродуктивного возраста. Крымский журнал экспериментальной и клинической медицины. 2015; 5 (3): 65–71.Legro RS, Brzyski RG, Diamond MP, et al. The Pregnancy in Polycystic Ovary Syndrome II study: base-line characteristics and effects of obesity from a multicenter randomized clinical trial. Fertil Steril. 2014; 101 (1): 258–269.Legro RS, Brzyski RG, Diamond MP, et al. The Pregnancy in Polycystic Ovary Syndrome II study: base-line characteristics and effects of obesity from a multicenter randomized clinical trial. Fertil Steril. 2014; 101 (1): 258–269.Nascimento ML. Cristiano ANB, de Campos T. Tenyear evaluation of a Neonatal Screening Program for congenital adrenal hyperplasia. Arq Brasil Endocrinol Metab. 2014; 58 (7): 765–771.Nascimento ML. Cristiano ANB, de Campos T. Tenyear evaluation of a Neonatal Screening Program for congenital adrenal hyperplasia. Arq Brasil Endocrinol Metab. 2014; 58 (7): 765–771.Kopacek C, de Castro SM, Prado MJ, et al. Neonatal screening for congenital adrenal hyperplasia in Southern Brazil: a population based study with 108,409 infants. BMC Pediatrics. 2017; 17 (1): 22.Kopacek C, de Castro SM, Prado MJ, et al. Neonatal screening for congenital adrenal hyperplasia in Southern Brazil: a population based study with 108,409 infants. BMC Pediatrics. 2017; 17 (1): 22.Tsuji A, Konishi K, Hasegawa S, et al. Newborn screening for congenital adrenal hyperplasia in Tokyo, Japan from 1989 to 2013: a retrospective population-based study. BMC Pediatrics. 2015; 15: 209.Tsuji A, Konishi K, Hasegawa S, et al. Newborn screening for congenital adrenal hyperplasia in Tokyo, Japan from 1989 to 2013: a retrospective population-based study. BMC Pediatrics. 2015; 15: 209.Kaur G, Thakur K, Kataria S, et al. Current and future perspective of newborn screening: an Indian scenario. JPEM. 2016; 29 (1): 5–13.Kaur G, Thakur K, Kataria S, et al. Current and future perspective of newborn screening: an Indian scenario. JPEM. 2016; 29 (1): 5–13.Мельниченко Г. А., Трошина Е. А., Молашенко Н. В., и др. Клинические рекомендации Российской ассоциации эндокринологов по диагностике и лечебно-профилактическим мероприятиям при врожденной дисфункции коры надпочечников у пациентов во взрослом возрасте. Consilium Medicum. 2016; 18 (4): 8–19.Мельниченко Г. А., Трошина Е. А., Молашенко Н. В., и др. Клинические рекомендации Российской ассоциации эндокринологов по диагностике и лечебно-профилактическим мероприятиям при врожденной дисфункции коры надпочечников у пациентов во взрослом возрасте. Consilium Medicum. 2016; 18 (4): 8–19.Turcu AF, Auchus RJ. Adrenal steroidogenesis and congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 2015; 44: 275–296.Turcu AF, Auchus RJ. Adrenal steroidogenesis and congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 2015; 44: 275–296.Trapp CM, Oberfield CM. Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): an update. Steroids. 2012; 77 (4): 342–346.Trapp CM, Oberfield CM. Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): an update. Steroids. 2012; 77 (4): 342–346.New MI, Abraham M, Gonzalez B, et al. Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Proc Nat Acad Sci. 2013; 110 (7): 2611–2616.New MI, Abraham M, Gonzalez B, et al. Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Proc Nat Acad Sci. 2013; 110 (7): 2611–2616.Speiser PW, Arlt W, Auchus RJ, et al. White Guidelines on Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2018; 103 (11): 4043–4088.Speiser PW, Arlt W, Auchus RJ, et al. White Guidelines on Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2018; 103 (11): 4043–4088.Sarafoglou K, Banks K, Gaviglio A, et al. Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia. Pediatrics. 2012; 130(5): e1261–1268.Sarafoglou K, Banks K, Gaviglio A, et al. Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia. Pediatrics. 2012; 130(5): e1261–1268.Hannah-Shmouni F, Morissette F, Sinaii N, et al. Revisiting the prevalence of nonclassic congenital adrenal hyperplasia in US Ashkenazi Jews and Caucasians. Genetics Med. 2017; 19 (11): 1276–1279.Hannah-Shmouni F, Morissette F, Sinaii N, et al. Revisiting the prevalence of nonclassic congenital adrenal hyperplasia in US Ashkenazi Jews and Caucasians. Genetics Med. 2017; 19 (11): 1276–1279.Kamrath C, Hochberg Z. Increased activation of the alternative “backdoor” pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis. J Clin Endocrinol Metab. 2012; 97 (3): E 367–375.Kamrath C, Hochberg Z. Increased activation of the alternative “backdoor” pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis. J Clin Endocrinol Metab. 2012; 97 (3): E 367–375.El-Maouche D, Arlt W, Merke DP. Congenital adrenal hyperplasia. Lancet. 2017; 390 (10108): 2194–2210.El-Maouche D, Arlt W, Merke DP. Congenital adrenal hyperplasia. Lancet. 2017; 390 (10108): 2194–2210.Sharma R, Seth A. Congenital adrenal hyperplasia: issues in diagnosis and treatment in children. Ind J Pediatr. 2014; 81 (2): 178–185.Sharma R, Seth A. Congenital adrenal hyperplasia: issues in diagnosis and treatment in children. Ind J Pediatr. 2014; 81 (2): 178–185.Trapp CM, Speiser PW, Oberfield SE. Congenital adrenal hyperplasia: an update in children. Curr Opin Endocrinol Diabet Obes. 2011; 18 (3): 166–170.Trapp CM, Speiser PW, Oberfield SE. Congenital adrenal hyperplasia: an update in children. Curr Opin Endocrinol Diabet Obes. 2011; 18 (3): 166–170.Falhammar H, Nordenström A. Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome. Endocrine. 2015; 50 (1): 32–50.Falhammar H, Nordenström A. Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome. Endocrine. 2015; 50 (1): 32–50.Martin KA, Anderson RR, Chang RJ, et al. Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103 (4): 1233–1257.Martin KA, Anderson RR, Chang RJ, et al. Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103 (4): 1233–1257.Yu H, Bian J, Liu X, et al. Pregnancy outcomes of eight pregnant women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Zhonghua Fu Chan Ke Za Zhi. 2012; 47 (9): 651–654.Yu H, Bian J, Liu X, et al. Pregnancy outcomes of eight pregnant women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Zhonghua Fu Chan Ke Za Zhi. 2012; 47 (9): 651–654.Arlt W, Willis DS, Wild SH, et al. Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab. 2010; 95 (11): 5110–5121.Arlt W, Willis DS, Wild SH, et al. Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab. 2010; 95 (11): 5110–5121.Lekarev O, Lin-Su K, Vogiatzi M. G. Infertility and Reproductive Function in Patients with Congenital Adrenal Hyperplasia. Endocrinol Metabol Clinics of North America. 2015; 44 (4): 705–722.Lekarev O, Lin-Su K, Vogiatzi M. G. Infertility and Reproductive Function in Patients with Congenital Adrenal Hyperplasia. Endocrinol Metabol Clinics of North America. 2015; 44 (4): 705–722.Eyal O, Ayalon-Dangur I, Segev-Becker A, Schachter-Davidov A, Israel S, Weintrob N. Pregnancy in women with nonclassic congenital adrenal hyperplasia: time to conceive and outcome. Clin Endocrinol (Oxf). 2017; 87 (5): 552–556.Eyal O, Ayalon-Dangur I, Segev-Becker A, Schachter-Davidov A, Israel S, Weintrob N. Pregnancy in women with nonclassic congenital adrenal hyperplasia: time to conceive and outcome. Clin Endocrinol (Oxf). 2017; 87 (5): 552–556.Nasir H, Ali SI, Haque N, et al. Compound heterozygosity for a whole gene deletion and p.R 124C mutation in CYP21A2 causing nonclassic congenital adrenal hyperplasia. Ann Pediatr Endocrinol Metab. 2018; 23 (3): 158–161.Nasir H, Ali SI, Haque N, et al. Compound heterozygosity for a whole gene deletion and p.R 124C mutation in CYP21A2 causing nonclassic congenital adrenal hyperplasia. Ann Pediatr Endocrinol Metab. 2018; 23 (3): 158–161.Sparrow R. Gender eugenics? The ethics of PGD for intersex conditions. Am J Bioeth. 2013; 13 (10): 29–38.Sparrow R. Gender eugenics? The ethics of PGD for intersex conditions. Am J Bioeth. 2013; 13 (10): 29–38.Simpson JL, Rechitsky S. Preimplantation diagnosis and other modern methods for prenatal diagnosis. J Steroid Biochem Mol Biol. 2017; 165 (Pt A): 124–130.Simpson JL, Rechitsky S. Preimplantation diagnosis and other modern methods for prenatal diagnosis. J Steroid Biochem Mol Biol. 2017; 165 (Pt A): 124–130.Soto-Lafontaine M, Dondorp W, Provoost V, de Wert G. Dealing with treatment and transfer requests: how PGD-professionals discuss ethical challenges arising in everyday practice. Med Health Care Philos. 2018; 21 (3): 375–386.Soto-Lafontaine M, Dondorp W, Provoost V, de Wert G. Dealing with treatment and transfer requests: how PGD-professionals discuss ethical challenges arising in everyday practice. Med Health Care Philos. 2018; 21 (3): 375–386.Hill M, Finning K, Martin P, Hogg J, Meaney C, Norbury G, Daniels G, Chitty LS. Non-invasive prenatal determination of fetal sex: translating research into clinical practice. Clin Genet. 2011; 80 (1): 68–75.Hill M, Finning K, Martin P, Hogg J, Meaney C, Norbury G, Daniels G, Chitty LS. Non-invasive prenatal determination of fetal sex: translating research into clinical practice. Clin Genet. 2011; 80 (1): 68–75.Tardy-Guidollet V, Menassa R, Costa J-M, et al. New management strategy of pregnancies at risk of congenital adrenal hyperplasia using fetal sex determination in maternal serum: French cohort of 258 cases (2002–2011). J Clin Endocrinol Metab. 2014; 99 (4): 1180–1188.Tardy-Guidollet V, Menassa R, Costa J-M, et al. New management strategy of pregnancies at risk of congenital adrenal hyperplasia using fetal sex determination in maternal serum: French cohort of 258 cases (2002–2011). J Clin Endocrinol Metab. 2014; 99 (4): 1180–1188.Eunice M, Ammini AC. Prenatal treatment of mothers with fetuses at risk for congenital adrenal hyperplasia: how relevant is it to Indian context? Indian J Endocrinol Metab. 2013; 17 (3): 373–375.Eunice M, Ammini AC. Prenatal treatment of mothers with fetuses at risk for congenital adrenal hyperplasia: how relevant is it to Indian context? Indian J Endocrinol Metab. 2013; 17 (3): 373–375.New MI, Abraham M, Yuen T, Lekarev O. An update on prenatal diagnosis and treatment of congenital adrenal hyperplasia. Semin Reprod Med. 2012; 30 (5): 396–399.New MI, Abraham M, Yuen T, Lekarev O. An update on prenatal diagnosis and treatment of congenital adrenal hyperplasia. Semin Reprod Med. 2012; 30 (5): 396–399.Gorduza D, Tardy-Guidollet V, Robert E, et al. Late prenatal dexamethasone and phenotype variations in 46, XX CAH: concerns about current protocols and benefits for surgical procedures. J Pediatr Urol. 2014; 10 (5): 941–947.Gorduza D, Tardy-Guidollet V, Robert E, et al. Late prenatal dexamethasone and phenotype variations in 46, XX CAH: concerns about current protocols and benefits for surgical procedures. J Pediatr Urol. 2014; 10 (5): 941–947.Kemp MW, Newnham JP, Challis JG, et al. The clinical use of corticosteroids in pregnancy. Hum Reprod Update. 2016; 22 (2): 240–259.Kemp MW, Newnham JP, Challis JG, et al. The clinical use of corticosteroids in pregnancy. Hum Reprod Update. 2016; 22 (2): 240–259.Moran C, Azziz R. Reproductive outcome of women with 21-hydroxylase-deficient nonclassic adrenal hyperplasia. J Clin Endocrinol Metab. 2006; 91 (9): 3451–3456.Moran C, Azziz R. Reproductive outcome of women with 21-hydroxylase-deficient nonclassic adrenal hyperplasia. J Clin Endocrinol Metab. 2006; 91 (9): 3451–3456.Mesiano S, Jaffe RB. The Endocrinology of Human Pregnancy and Fetal-Placental Neuroendocrine Development. In Yen and Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. 7th ed., Philadelphia: Elsevier/ Saunders 2014; 327–366.Mesiano S, Jaffe RB. The Endocrinology of Human Pregnancy and Fetal-Placental Neuroendocrine Development. In Yen and Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. 7th ed., Philadelphia: Elsevier/ Saunders 2014; 327–366.Manojlović-Stojanoski MN, Filipović BR, Nestorović NM, Šošić-Jurjević BT, Ristić NM, Trifunović SL, Milošević VLj. Morphofunctional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure. Steroids. 2014; 84: 22–29.Manojlović-Stojanoski MN, Filipović BR, Nestorović NM, Šošić-Jurjević BT, Ristić NM, Trifunović SL, Milošević VLj. Morphofunctional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure. Steroids. 2014; 84: 22–29.Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95 (9): 4133–4160.Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95 (9): 4133–4160.Skuladottir H, Wilcox AJ, Ma C, et al. Corticosteroid use and risk of orofacial clefts Birth Defects. Res A Clin Mol Teratol. 2014; 100 (6): 499–506.Skuladottir H, Wilcox AJ, Ma C, et al. Corticosteroid use and risk of orofacial clefts Birth Defects. Res A Clin Mol Teratol. 2014; 100 (6): 499–506.Rijk Y, van Alfen-vander Velden J, Claahsen-vander Grinten HL. Prenatal Treatment with dexamethasone in suspected congenital adrenal hyperplasia and or ofacial cleft: a case report and review of the literature. Pediatr Endocrinol Rev. 2017; 15 (1): 21–25.Rijk Y, van Alfen-vander Velden J, Claahsen-vander Grinten HL. Prenatal Treatment with dexamethasone in suspected congenital adrenal hyperplasia and or ofacial cleft: a case report and review of the literature. Pediatr Endocrinol Rev. 2017; 15 (1): 21–25.Grunt S, Steinlin M, Weisstanner C, Schoning M, Mullis PE, Fluck CE. Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight. Horm Res Paediatr. 2013; 80 (1): 57–63.Grunt S, Steinlin M, Weisstanner C, Schoning M, Mullis PE, Fluck CE. Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight. Horm Res Paediatr. 2013; 80 (1): 57–63.Food and Drug Administration, Health and Human Services. Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Fed Regist. 2014; 79 (233): 72063–72103.Food and Drug Administration, Health and Human Services. Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Fed Regist. 2014; 79 (233): 72063–72103.Braun T, Challis JR, Newnham JP, Sloboda DM. Early-life glucocorticoid exposure: the hypothalamic-pituitary-adrenal axis, placental function, and long-term disease risk. Endocr Rev. 2013; 34 (6): 885–916.Braun T, Challis JR, Newnham JP, Sloboda DM. Early-life glucocorticoid exposure: the hypothalamic-pituitary-adrenal axis, placental function, and long-term disease risk. Endocr Rev. 2013; 34 (6): 885–916.Burton GJ, Fowden AL, Thornburg KL. Placental Origins of Chronic Disease. Physiol Rev. 2016; 96 (4): 1509–1565.Burton GJ, Fowden AL, Thornburg KL. Placental Origins of Chronic Disease. Physiol Rev. 2016; 96 (4): 1509–1565.Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011; 59 (3): 279–289.Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011; 59 (3): 279–289.Tseng WN, Chen CC, Yu HR, Huang LT, Kuo HC. Antenatal dexamethasone exposure in preterm infants is associated with allergic diseases and the mental development index in children. Int J Environ Res Public Health. 2016; 13 (12): E 1206.Tseng WN, Chen CC, Yu HR, Huang LT, Kuo HC. Antenatal dexamethasone exposure in preterm infants is associated with allergic diseases and the mental development index in children. Int J Environ Res Public Health. 2016; 13 (12): E 1206.Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: outcomes. Nat Rev Endocrinol. 2014; 10 (7): 391–402.Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: outcomes. Nat Rev Endocrinol. 2014; 10 (7): 391–402.Damsted SK, Born AP, Paulson OB, Uldall P. Exogenous glucocorticoids and adverse cerebral effects in children. Eur J Paediatr Neurol. 2011; 15 (6): 465–477.Damsted SK, Born AP, Paulson OB, Uldall P. Exogenous glucocorticoids and adverse cerebral effects in children. Eur J Paediatr Neurol. 2011; 15 (6): 465–477.Peffer ME, Zhang JY, Umfrey L, Rudine AC, Monaghan AP, DeFranco DB. Minireview: the impact of antenatal therapeutic synthetic glucocorticoids on the developing fetal brain. Mol Endocrinol. 2015; 29 (5): 658–666.Peffer ME, Zhang JY, Umfrey L, Rudine AC, Monaghan AP, DeFranco DB. Minireview: the impact of antenatal therapeutic synthetic glucocorticoids on the developing fetal brain. Mol Endocrinol. 2015; 29 (5): 658–666.Hirvikoski T, Lindholm T, Lajic S, Nordenstrom A. Gender role behaviour in prenatally dexamethasone-treated children at risk for congenital adrenal hyperplasia – a pilot study. Acta Paediatr. 2011; 100 (9): e112–e119.Hirvikoski T, Lindholm T, Lajic S, Nordenstrom A. Gender role behaviour in prenatally dexamethasone-treated children at risk for congenital adrenal hyperplasia – a pilot study. Acta Paediatr. 2011; 100 (9): e112–e119.Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95 (9): 4133–4160.Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95 (9): 4133–4160.Hirvikoski T, Nordenstrom A, Wedell A, Ritzen M, Lajic S. Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint. J Clin Endocrinol Metab. 2012; 97 (6): 1881–1883.Hirvikoski T, Nordenstrom A, Wedell A, Ritzen M, Lajic S. Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint. J Clin Endocrinol Metab. 2012; 97 (6): 1881–1883.Dorr HG, Binder G, Reisch N, Gembruch U, Oppelt PG, Wieacker P, Kratzsch J. Experts’ opinion on the prenatal therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency – guideline of DGKED in cooperation with DGGG (S 1level, AWMF registry no.174/013, July 2015). Geburtshilfe Frauenheilkd. 2015; 75 (12): 1232–1238.Dorr HG, Binder G, Reisch N, Gembruch U, Oppelt PG, Wieacker P, Kratzsch J. Experts’ opinion on the prenatal therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency – guideline of DGKED in cooperation with DGGG (S 1level, AWMF registry no.174/013, July 2015). Geburtshilfe Frauenheilkd. 2015; 75 (12): 1232–1238.Miller WL, Witchel SF. Prenatal treatment of congenital adrenal hyperplasia: risks out weigh benefits. Am J Obstet Gynecol. 2013; 208 (5): 354–359.Miller WL, Witchel SF. Prenatal treatment of congenital adrenal hyperplasia: risks out weigh benefits. Am J Obstet Gynecol. 2013; 208 (5): 354–359.Bidet M, Bellanne-Chantelot C, Galand-Portier M-B, et al. Fertility in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2010; 95 (3): 1182–1190.Bidet M, Bellanne-Chantelot C, Galand-Portier M-B, et al. Fertility in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2010; 95 (3): 1182–1190.Georgiou EX, Lei K, Lai PF, et al. The study of progesterone action in human myometrial explants. Mol Hum Reprod. 2016; 22: 877–889.Georgiou EX, Lei K, Lai PF, et al. The study of progesterone action in human myometrial explants. Mol Hum Reprod. 2016; 22: 877–889.Whirledge SD, Oakley RH, Myers PH, Lydon JP, De-Mayo F, Cidlowski JA. Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization. Proc Natl Acad Sci USA. 2015; 112: 15166–15171.Whirledge SD, Oakley RH, Myers PH, Lydon JP, De-Mayo F, Cidlowski JA. Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization. Proc Natl Acad Sci USA. 2015; 112: 15166–15171.Matsuzaki S, Darcha C, Maleysson E, Canis M, Mage G. Impaired down-regulation of E-cadherin and beta-catenin protein expression in endometrial epithelial cells in the mid-secretory endometrium of infertile patients with endometriosis. J Clin Endocrinol Metab. 2010; 95 (7): 3437–3445.Matsuzaki S, Darcha C, Maleysson E, Canis M, Mage G. Impaired down-regulation of E-cadherin and beta-catenin protein expression in endometrial epithelial cells in the mid-secretory endometrium of infertile patients with endometriosis. J Clin Endocrinol Metab. 2010; 95 (7): 3437–3445.Jauniaux E, Van Oppenraaij RH, Burton GJ. Obstetric outcome after early placental complications. Curr Opin Obstet Gynecol. 2010; 22(6):452-457.Jauniaux E, Van Oppenraaij RH, Burton GJ. Obstetric outcome after early placental complications. Curr Opin Obstet Gynecol. 2010; 22(6):452-457.Solano ME, Arck PC. Steroids, Pregnancy and Fetal Development. Front Immunol. 2019; 10: 3017.Solano ME, Arck PC. Steroids, Pregnancy and Fetal Development. Front Immunol. 2019; 10: 3017.Hierweger AM, Engler JB, Friese MA, Reichardt HM, Lydon J, DeMayo F, et al. Progesterone modulates the T-cell response via glucocorticoid receptor-dependent pathways. Am J Reprod Immunol. 2019; 81: e13084.Hierweger AM, Engler JB, Friese MA, Reichardt HM, Lydon J, DeMayo F, et al. Progesterone modulates the T-cell response via glucocorticoid receptor-dependent pathways. Am J Reprod Immunol. 2019; 81: e13084.Радзинский В. Е. Угроза спонтанного аборта: старые контраверсии – новые возможности. Status Praesens 2014; 6 (17): 25–31.Радзинский В. Е. Угроза спонтанного аборта: старые контраверсии – новые возможности. Status Praesens 2014; 6 (17): 25–31.Мальцева Л. И., Никогосян Д. М. Эффективность микронизированного прогестерона для профилактики невынашивания беременности. Гинекология 2015; 17 (2): 56–59.Мальцева Л. И., Никогосян Д. М. Эффективность микронизированного прогестерона для профилактики невынашивания беременности. Гинекология 2015; 17 (2): 56–59.Toth B, Jeschke U, Rogenhofer N. et al. Recurrent miscarriage: current concepts in diagnosis and treatment. J Reprod Immunol. 2010; 85: 25–32.Toth B, Jeschke U, Rogenhofer N. et al. Recurrent miscarriage: current concepts in diagnosis and treatment. J Reprod Immunol. 2010; 85: 25–32.Stephenson MD, McQuenn D, Winter M, Kliman HJ. Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss. Fertil Steril. 2017; 107 (3): 684–690.Stephenson MD, McQuenn D, Winter M, Kliman HJ. Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss. Fertil Steril. 2017; 107 (3): 684–690.Ismail AM, Abbas AM, Ali MK, Amin AF. Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial. J Matern Fetal Neonatal Med. 2018; 31 (3): 388–394.Ismail AM, Abbas AM, Ali MK, Amin AF. Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial. J Matern Fetal Neonatal Med. 2018; 31 (3): 388–394.Romero R, Conde-Agudelo A, Da Fonseca E, et al. Vaginal Progesterone for Preventing Preterm Birth and Adverse Perinatal Outcomes in Singleton Gestations with a Short Cervix: A Meta-Analysis of Individual Patient Data. Am J Obstet Gynecol. 2017 Nov 16.Romero R, Conde-Agudelo A, Da Fonseca E, et al. Vaginal Progesterone for Preventing Preterm Birth and Adverse Perinatal Outcomes in Singleton Gestations with a Short Cervix: A Meta-Analysis of Individual Patient Data. Am J Obstet Gynecol. 2017 Nov 16.Кузнецова И. В., Коновалов В. А. Значение витаминно-минеральных комплексов в обеспечении нормального течения беременности и развития плода. Гинекология. 2015; 17 (1): 60–64.Кузнецова И. В., Коновалов В. А. Значение витаминно-минеральных комплексов в обеспечении нормального течения беременности и развития плода. Гинекология. 2015; 17 (1): 60–64.Catov JM, Bodnar LM, Olsen J, Olsen S, Nohr EA. Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr. 2011; 94 (3): 906–912.Catov JM, Bodnar LM, Olsen J, Olsen S, Nohr EA. Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr. 2011; 94 (3): 906–912.Wallenstein M. B., Shaw G. M., Yang W., Carmichael S. L. Periconceptional nutrient intakes and risks of orofacial clefts in California. Pediatr Res. 2013; 74 (4): 457–465.Wallenstein M. B., Shaw G. M., Yang W., Carmichael S. L. Periconceptional nutrient intakes and risks of orofacial clefts in California. Pediatr Res. 2013; 74 (4): 457–465.Громова О. А., Торшин И. Ю., Тапильская Н. И., Галустян А. Н. Системно-биологический анализ синергичного воздействия прогестерона, витаминов и микроэлементов на нейропротекцию и развитие мозга плода. Вопросы гинекологии, акушерства и перинатологии. 2019; 18 (6): 65–75.Громова О. А., Торшин И. Ю., Тапильская Н. И., Галустян А. Н. Системно-биологический анализ синергичного воздействия прогестерона, витаминов и микроэлементов на нейропротекцию и развитие мозга плода. Вопросы гинекологии, акушерства и перинатологии. 2019; 18 (6): 65–75.Yajnik CS, Deshmukh US. Fetal programming: Maternal nutrition and role of one-carbon metabolism. Rev Endocr Metab Disord. 2012; 13: 121–127.Yajnik CS, Deshmukh US. Fetal programming: Maternal nutrition and role of one-carbon metabolism. Rev Endocr Metab Disord. 2012; 13: 121–127.Wang J, Persuitte G, Olendzki BC, et al. Dietary magnesium intake improves insulin resistance among non-diabetic individuals with metabolic syndrome participating in a dietary trial. Nutrients 2013; 5 (10): 3010–3019.Wang J, Persuitte G, Olendzki BC, et al. Dietary magnesium intake improves insulin resistance among non-diabetic individuals with metabolic syndrome participating in a dietary trial. Nutrients 2013; 5 (10): 3010–3019.Paivaa AN, Lima JG, Medeiros ACQ, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Element Med Biol 2015; 32: 66–72.Paivaa AN, Lima JG, Medeiros ACQ, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Element Med Biol 2015; 32: 66–72.Asemi Z, Karamali M, Esmaillzadeh A. Effects of calcium-vitamin D co-supplementation on glycaemic control, inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial. Diabetologia 2014; 57 (9): 1798–1806.Asemi Z, Karamali M, Esmaillzadeh A. Effects of calcium-vitamin D co-supplementation on glycaemic control, inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial. Diabetologia 2014; 57 (9): 1798–1806.Bradbury, J. Docosahexaenoic acid (DHA): An ancient nutrient for the modern human brain. Nutrients 2011, 3, 529–554.Bradbury, J. Docosahexaenoic acid (DHA): An ancient nutrient for the modern human brain. Nutrients 2011, 3, 529–554.Burchakov DI, Kuznetsova IV, Uspenskaya YB. Omega-3 Long-Chain Polyunsaturated Fatty Acids and Preeclampsia: Trials Say “No”, but Is It the Final Word? Nutrients. 2017; 9 (12): 1364–1380.Burchakov DI, Kuznetsova IV, Uspenskaya YB. Omega-3 Long-Chain Polyunsaturated Fatty Acids and Preeclampsia: Trials Say “No”, but Is It the Final Word? Nutrients. 2017; 9 (12): 1364–1380.

The authors declare that there are no conflicts of interest present.