V.F.Snegirev Archives of Obstetrics and GynecologyV.F.Snegirev Archives of Obstetrics and GynecologyАрхив акушерства и гинекологии им. В.Ф. Снегирева2313-87262687-1386Eco-Vector10090810.17816/2313-8726-2022-9-1-13-21ReviewsНаучные обзорыReview ArticleTreatment of habitual pregnancy miscarriage of various originsЛечение привычного невынашивания беременности различного генезаhttps://orcid.org/0000-0002-2283-2356UnanyanAra L.УнанянАра Леонидович
Russian Federation

MD, Dr. Sci. (Med.), professor

д.м.н., профессор

9603526@mail.ruhttps://orcid.org/0000-0002-6844-3321PivazyanLaura G.ПивазянЛаура Горовна
Russian Federation

V-year student

студентка V курса

laurapivazyan98@gmail.comhttps://orcid.org/0000-0003-0919-465XZakaryanAraksya A.ЗакарянАракся Аршаковна
Russian Federation

IV-year student

студентка IV курса

araksya.zakaryan99@mail.ruSiordiyaArchil A.СиордияАрчил Александрович
Russian Federation

MD, Cand. Sci. (Med.), assistant professor

к.м.н., доцент

9603526@mail.ruIshchenkoAnatoliy I.ИщенкоАнатолий Иванович
Russian Federation

MD, Dr. Sci. (Med.), Professor, Head of the Department of Obstetrics and Gynecology

д.м.н., профессор, зав. кафедрой акушерства и гинекологии

9603526@mail.ruI.M. Sechenov First Moscow State Medical UniversityПервый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет)150120229113211602202216022022Copyright ©; 2022, Eco-VectorCopyright ©; 2022, ООО "Эко-Вектор"2022Eco-VectorООО "Эко-Вектор"https://archivog.com/2313-8726/article/view/100908

Habitual pregnancy miscarriage is one of the serious problems of reproductive health in the modern world. Habitual miscarriage is defined as the spontaneous termination of two or more pregnancies before the fetus reaches viability from conception to 24 weeks of pregnancy. However, some differences of opinion are determined among specialists in habitual miscarriage. Some experts in their clinical practice for habitual miscarriages use the definition of three or more consecutive miscarriages. Habitual miscarriage occurrence varies from 0.5 to 2.3%, but the exact prevalence is very difficult to estimate, which depends on the used definition. The pathogenesis of habitual miscarriage is determined based on the age of the mother and the gestational age of the fetus. Habitual miscarriage can be caused by chromosomal errors, autoimmune disorders, endometrial dysfunction, endocrinopathies, hormonal and metabolic disorders, infections, and uterine anatomical defects. Currently available treatments target suspected risk factors for miscarriage, although the effectiveness of many medical interventions appears to be controversial.

This study aimed to evaluate the effectiveness of treatments for habitual miscarriage of various origins, such as antiphospholipid syndrome, subclinical hypothyroidism, and idiopathic habitual miscarriage.

Привычное невынашивание беременности (ПНБ) ― одна из серьёзных проблем репродуктивного здоровья в современном мире. ПНБ определяется как самопроизвольное прекращение двух беременностей или более до того момента, как плод достигнет жизнеспособности (с момента зачатия до 24 недель беременности). Однако существуют некоторые расхождения во мнениях среди специалистов относительно данного определения, некоторые из них в своей клинической практике для ПНБ применяют определение трёх или более последовательных невынашиваний беременности. Встречаемость ПНБ варьирует от 0,5 до 2,3%, однако точную распространённость очень трудно оценить, и это зависит от используемого определения. Патогенез ПНБ определяется в зависимости от возраста матери и гестационного возраста плода. ПНБ может быть вызвано хромосомными ошибками, аутоиммунными нарушениями, дисфункцией эндометрия, эндокринопатиями, гормональными и метаболическими нарушениями, инфекциями и анатомическими дефектами матки. Доступные в настоящее время методы лечения нацелены на предполагаемые факторы риска невынашивания беременности, хотя эффективность многих медицинских вмешательств представляется спорной.

Целью данного обзора является оценка эффективности способов лечения ПНБ различного генеза, таких как антифосфолипидный синдром, субклинический гипотиреоз и идиопатическое привычное невынашивание беременности.

habitual miscarriagespontaneous abortionantiphospholipid syndromesubclinical hypothyroidismidiopathic habitual miscarriageпривычное невынашивание беременностисамопроизвольный абортантифосфолипидный синдромсубклинический гипотиреозидиопатическое привычное невынашивание беременностиAtik RB, Christiansen OB, Elson J, et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open. 2018;2018(2):hoy004.Atik R.B., Christiansen O.B., Elson J., et al. ESHRE guideline: recurrent pregnancy loss // Hum Reprod Open. 2018. Vol. 2018, N 2. P. hoy004. doi: 10.1093/hropen/hoy004doi: 10.1093/hropen/hoy004Royal College of Obstetricians and Gynaecologists. RCOG Green-top Guideline No. 17: The Investigation and Treatment of Couples with Recurrent First-trimester and Second-trimester Miscarriage. April 2011. P. 1–18. [Internet] Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_17.pdf. Accessed October 30, 2019.Royal College of Obstetricians and Gynaecologists. RCOG Green top Guideline No. 17: The Investigation and Treatment of Couples with Recurrent First-trimester and Second-trimester Miscarriage. 2011:1–18. [Internet] Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_17.pdf. Accessed October 30, 2019.Rasmark Roepke E., Hellgren M., Hjertberg R., et al. Treatment efficacy for idiopathic recurrent pregnancy loss ― a systematic review and meta-analyses // Acta Obstet Gynecol Scand. 2018. Vol. 97, N 8. P. 921–941. doi: 10.1111/aogs.13352Rasmark Roepke E, Hellgren M, Hjertberg R, et al.; Treatment efficacy for idiopathic recurrent pregnancy loss ― a systematic review and meta-analyses. Acta Obstet Gynecol Scand. 2018;97(8):921+941. doi: 10.1111/aogs.13352Dong A.C., Morgan J., Kane M., Stagnaro-Green A., Stephenson M.D. Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis // Fertil Steril. 2020. Vol. 113, N 3. P. 587–600.e1. doi: 10.1016/j.fertnstert.2019.11.003Dong AC, Morgan J, Kane M, Stagnaro-Green A, Stephenson MD. Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2020;113(3):587–600.e1. doi: 10.1016/j.fertnstert.2019.11.003Liu X., Qiu Y., Yu E.D., et al. Comparison of therapeutic interventions for recurrent pregnancy loss in association with antiphospholipid syndrome: A systematic review and network meta-analysis // Am J Reprod Immunol. 2020. Vol. 83, N 4. P. e13219. doi: 10.1111/aji.13219Liu X, Qiu Y, Yu ED, et al. Comparison of therapeutic interventions for recurrent pregnancy loss in association with antiphospholipid syndrome: A systematic review and network meta-analysis. Am J Reprod Immunol. 2020;83(4):e13219. doi: 10.1111/aji.13219Mak A., Cheung M.W.L., Cheak A.A., Ho R.C. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression // Rheumatology. 2010. Vol. 49, N 2. P. 281. doi: 10.1093/rheumatology/kep373Mak A, Cheung MWL, Cheak AA, Ho RC. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology. 2010;49(2):281. doi: 10.1093/rheumatology/kep373Empson M.B., Lassere M., Craig J.C., Scott J.R. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant // Cochrane Database Syst Rev. 2005. Vol. 2, N 2. P. CD002859. doi: 10.1002/14651858.CD002859.pub2Empson MB, Lassere M, Craig JC, Scott JR. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2005;2(2):CD002859. doi: 10.1002/14651858.CD002859.pub2Bao S.H., Sheng S.L., Liao H., et al. Use of D-dimer measurement to guide anticoagulant treatment in recurrent pregnancy loss associated with antiphospholipid syndrome // Am J Reprod Immunol. 2017. Vol. 78, N 6. P. e12770. doi: 10.1111/aji.12770Bao SH, Sheng SL, Liao H, et al. Use of D-dimer measurement to guide anticoagulant treatment in recurrent pregnancy loss associated with antiphospholipid syndrome. Am J Reprod Immunol. 2017;78(6):e12770. doi: 10.1111/aji.12770Goel N., Tuli A., Choudhry R. The role of aspirin versus aspirin and heparin in cases of recurrent abortions with raised anticardiolipin antibodies // Med Sci Monit. 2006. Vol. 12, N 3. P. CR132–CR136.Goel N, Tuli A, Choudhry R. The role of aspirin versus aspirin and heparin in cases of recurrent abortions with raised anticardiolipin antibodies. Med Sci Monit. 2006;12(3):CR132–CR136.Rai R., Cohen H., Dave M., Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies) // BMJ. 1997. Vol. 14, N 7076. P. 253–257. doi: 10.1136/bmj.314.7076.253Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. 1997;14(7076):253–257.Kutteh W.H. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone // Am J Obstet Gynecol. 1996. Vol. 174, N 5. P. 1584–1589. doi: 10.1016/s0002-9378(96)70610-5doi: 10.1136/bmj.314.7076.253Mahumud R.A., Sultana M., Sarker A.R. Distribution and determinants of low birth weight in developing countries // J Prev Med Public Health. 2017. Vol. 50, N 1. P. 18–28. doi: 10.3961/jpmph.16.087Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. 1996;174(5):1584–1589. doi: 10.1016/s0002-9378(96)70610-5Stagnaro-Green A., Roman S.H., Cobin R.H., et al. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies // JAMA. 1990. Vol. 264. P. 1422–1425.Mahumud RA, Sultana M, Sarker AR. Distribution and determinants of low birth weight in developing countries. J Prev Med Public Health. 2017;50(1):18–28. doi: 10.3961/jpmph.16.087Alexander E.K., Pearce E.N., Brent G.A., et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum // Thyroid. 2017. Vol. 27. P. 315–389. doi: 10.1089/thy.2016.0457Stagnaro-Green A, Roman SH, Cobin RH, et al. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 1990;264:1422–1425.Dong A.C., Stagnaro-Green A. Differences in diagnostic criteria mask the true prevalence of thyroid disease in pregnancy: a systematic review and metaanalysis // Thyroid. 2018. Vol. 29. P. 278–289. doi: 10.1089/thy.2018.0475Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27:315–389. doi: 10.1089/thy.2016.0457Hollowell J.G., Staehling N.W., Flanders W.D., et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III) // J Clin Endocrinol Metab. 2002. Vol. 87. P. 489–499. doi: 10.1210/jcem.87.2.8182Dong AC, Stagnaro-Green A. Differences in diagnostic criteria mask the true prevalence of thyroid disease in pregnancy: a systematic review and metaanalysis. Thyroid. 2018;29:278–289. doi: 10.1089/thy.2018.0475Bernardi L.A., Cohen R.N., Stephenson M.D. Impact of subclinical hypothyroidism in women with recurrent early pregnancy loss // Fertil Steril. 2013. Vol. 100. P. 1326–1331. doi: 10.1016/j.fertnstert.2013.07.1975Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489–499. doi: 10.1210/jcem.87.2.8182Triggianese P., Perricone C., Conigliaro P., et al. Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure // Int J Immunopathol Pharmacol. 2016. Vol. 29. P. 65–75. doi: 10.1177/0394632015615130Bernardi LA, Cohen RN, Stephenson MD. Impact of subclinical hypothyroidism in women with recurrent early pregnancy loss. Fertil Steril. 2013;100:1326–1331. doi: 10.1016/j.fertnstert.2013.07.1975Stirrat G.M. Recurrent miscarriage I: definition and epidemiology // Lancet. 1990. Vol. 336, N 8716. P. 673–675. doi: 10.1016/0140-6736(90)92159-fTriggianese P, Perricone C, Conigliaro P, et al. Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure. Int J Immunopathol Pharmacol. 2016;29:65–75. doi: 10.1177/0394632015615130Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion // Fertil Steril. 2013. Vol. 99, N 1. P. 63. doi: 10.1016/j.fertnstert.2012.09.023Stirrat GM. Recurrent miscarriage I: definition and epidemiology. Lancet. 1990;336(8716):673–675. doi: 10.1016/0140-6736(90)92159-fRasmark Roepke E., Matthiesen L., Rylance R., Christiansen O.B. Is the incidence of recurrent pregnancy loss increasing? A retrospective register-based study in Sweden // Acta Obstet Gynecol Scand. 2017. Vol. 96, N 11. P. 1365–1372. doi: 10.1111/aogs.13210Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013;99(1):63. doi: 10.1016/j.fertnstert.2012.09.023Shaaban O.M., Abbas A.M., Zahran K.M., et al. Low-molecular-weight heparin for the treatment of unexplained recurrent miscarriage with negative antiphospholipid antibodies: a randomized controlled trial // Clin Appl Thromb Hemost. 2017. Vol. 23, N 6. P. 567–572. doi: 10.1177/1076029616665167Rasmark Roepke E, Matthiesen L, Rylance R, Christiansen OB. Is the incidence of recurrent pregnancy loss increasing? A retrospective register-based study in Sweden. Acta Obstet Gynecol Scand. 2017;96:1365–1372. doi: 10.1111/aogs.13210El-Zibdeh M.Y. Dydrogesterone in the reduction of recurrent spontaneous abortion // J Steroid Biochem Mol Biol. 2005. Vol. 97, N 5. P. 431–434. doi: 10.1016/j.jsbmb.2005.08.007Shaaban OM, Abbas AM, Zahran KM, et al. Low-molecular-weight heparin for the treatment of unexplained recurrent miscarriage with negative antiphospholipid antibodies: a randomized controlled trial. Clin Appl Thromb Hemost. 2017;23(6):567–572. doi: 10.1177/1076029616665167Ismail A.M., Abbas A.M., Ali M.K., Amin A.F. Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial // J Matern Fetal Neonatal Med. 2018. Vol. 31, N 3. P. 388–394. doi: 10.1080/14767058.2017.1286315El-Zibdeh MY. Dydrogesterone in the reduction of recurrent spontaneous abortion. J Steroid Biochem Mol Biol. 2005;97(5):431–434. doi: 10.1016/j.jsbmb.2005.08.007Egerup P., Lindschou J., Gluud C., Christiansen O.B. The effects of intravenous immunoglobulins in women with recurrent miscarriages: a systematic review of randomised trials with meta-analyses and trial sequential analyses including individual patient data // PloS One. 2015. Vol. 10, N 10. P. e0141588. doi: 10.1371/journal.pone.0141588Ismail 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 . 2018;31(3):388–394. doi: 10.1080/14767058.2017.1286315Egerup P, Lindschou J, Gluud C, Christiansen OB. The effects of intravenous immunoglobulins in women with recurrent miscarriages: a systematic review of randomised trials with meta-analyses and trial sequential analyses including individual patient data. PloS One. 2015;10(10):e0141588. doi: 10.1371/journal.pone.0141588