Autosensitization to human chorionic gonadotropin: etiology, role in reproductive loss, and approaches to therapy
Daria V. Tkhai , Sergey V. Chepanov , Olga N. Arzhanova , Olesya N. Bespalova , Sergey A. Selkov
Journal of obstetrics and women's diseases ›› 2023, Vol. 72 ›› Issue (3) : 85 -94.
Autosensitization to human chorionic gonadotropin: etiology, role in reproductive loss, and approaches to therapy
The important role of human chorionic gonadotropin in pregnancy suggests the occurrence of reproductive disorders due to the circulation of specific antibodies, especially in early pregnancy, which can lead to a cascade of pathological reactions such as implantation failure, placentation, trophoblast invasion, and ultimately fetal rejection. The lack of knowledge and the complexity of diagnosing and treating this autoimmune pathology in reproductive medicine and obstetrics negatively affects both the outcomes of each individual pregnancy and the demographic situation as a whole. This review article highlights the main ideas about the causes of human chorionic gonadotropin antibody occurrence, the pathological mechanisms, the reproductive and obstetric complications associated with human chorionic gonadotropin autoantibodies, diagnostic methods, and therapeutic approaches.
antibodies to human chorionic gonadotropin / miscarriage / infertility
| [1] |
Sidelnikova VM. Nevynashivanie beremennosti: rukovodstvo dlya praktikuyushchikh vrachey. Moscow: Med inform. Agentstvo; 2011. (In Russ.) |
| [2] |
Сидельникова В.М. Невынашивание беременности: руководство для практикующих врачей. Москва: Мед. информ. агентство, 2011. |
| [3] |
Braunstein GD, Bloch SK, Rasor JL, et al. Characterization of antihuman chorionic gonadotropin serum antibody appearing after ovulation induction. J Clin Endocrinol Metab. 1983;57(6):1164–1172. DOI: 10.1210/jcem-57-6-1164 |
| [4] |
Braunstein G.D., Bloch S.K., Rasor J.L., et al. Characterization of antihuman chorionic gonadotropin serum antibody appearing after ovulation induction // J. Clin. Endocrinol. Metab. 1983. Vol. 57. No. 6. P. 1164–1172. DOI: 10.1210/jcem-57-6-1164 |
| [5] |
Keay SD, Vatish M, Karteris E, et al. The role of hCG in reproductive medicine. BJOG. 2004;111(11):1218–1228. DOI: 10.1111/j.1471-0528.2004.00412.x |
| [6] |
Keay S.D., Vatish M., Karteris E., et al. The role of hCG in reproductive medicine // BJOG. 2004. Vol. 111. No. 11. P. 1218–1228. DOI: 10.1111/j.1471-0528.2004.00412.x |
| [7] |
Afshar Y, Stanculescu A, Miele L, et al. The role of chorionic gonadotropin and Notch1 in implantation. J Assist Reprod Genet. 2007;24(7):296–302. DOI: 10.1007/s10815-007-9149-2 |
| [8] |
Afshar Y., Stanculescu A., Miele L., et al. The role of chorionic gonadotropin and Notch1 in implantation // J. Assist. Reprod. Genet. 2007. Vol. 24. No. 7. P. 296–302. DOI: 10.1007/s10815-007-9149-2 |
| [9] |
Borisova MA, Moiseenko DY, Smirnova OV. Human chorionic gonadotropin: unknown about known. Fiziol Cheloveka. 2017;43(1):97–110. DOI 10.7868/S0131164616060059. (In Russ.) |
| [10] |
Борисова М.А., Моисеенко Д.Ю., Смирнова О.В. Хорионический гонадотропин человека: неизвестное об извест ном // Физиология человека. 2017. Т. 43. № 1. C. 97–110. DOI 10.7868/S0131164616060059 |
| [11] |
Zamorina SA, Gorbunova OL, Shirshev SV. Khorionicheskii gonadotropin kak regulyator fenotipicheskogo sozrevaniya intaktnykh i interleikin- 2-aktivirovannykh NK- i NKT-kletok. Vestnik Permskogo universiteta. Seriya: Biologiya. 2010;1(1):77–80. (In Russ.) |
| [12] |
Заморина С.А., Горбунова О.Л., Ширшев С.В. Хорионический гонадотропин как регулятор фенотипического созревания интакт ных и интерлейкин- 2-активированных NK- и NKT-клеток // Вестник Пермского университета. Серия: Биология. 2010. Т. 1. № 1. С. 77–80. |
| [13] |
Nair RR, Verma P, Singh K. Immune-endocrine crosstalk during pregnancy. Gen Comp Endocrinol. 2017;242:18–23. DOI: 10.1016/j.ygcen.2016.03.003 |
| [14] |
Nair R.R., Verma P., Singh K. Immune-endocrine crosstalk during pregnancy // Gen. Comp. Endocrinol. 2017. Vol. 242. P. 18–23. DOI: 10.1016/j.ygcen.2016.03.003 |
| [15] |
Gridelet V, Perrier d’Hauterive S, Polese B, et al. Human chorionic gonadotrophin: new pleiotropic functions for an “old” hormone during pregnancy. Front Immunol. 2020;11. DOI: 10.3389/fimmu.2020.00343 |
| [16] |
Gridelet V., d’Hauterive P.S., Polese B., et al. Human chorionic gonadotrophin: new pleiotropic functions for an “old” hormone during pregnancy // Front. Immunol. 2020. Vol. 11. P. 1–13. DOI: 10.3389/fimmu.2020.00343 |
| [17] |
Akoum A, Metz CN, Morin M. Marked increase in macrophage migration inhibitory factor synthesis and secretion in human endometrial cells in response to human chorionic gonadotropin hormone. J Clin Endocrinol Metab. 2005;90(5):2904–2910. DOI: 10.1210/jc.2004-1900 |
| [18] |
Akoum A., Metz C.N., Morin M. Marked increase in macrophage migration inhibitory factor synthesis and secretion in human endometrial cells in response to human chorionic gonadotropin hormone // J. Clin. Endocrinol. Metab. 2005. Vol. 90. No. 5. P. 2904–2910. DOI: 10.1210/jc.2004-1900 |
| [19] |
Dong M, Ding G, Zhou J, et al. The effect of trophoblasts on T lymphocytes: possible regulatory effector molecules – a proteomic analysis. Cell Physiol Biochem. 2008;21(5–6):463–472. DOI: 10.1159/000129639 |
| [20] |
Dong M., Ding G., Zhou J., et al. The effect of trophoblasts on T lymphocytes: possible regulatory effector molecules – a proteomic analysis // Cell Physiol. Biochem. 2008. Vol. 21. No. 5–6. P. 463–472. DOI: 10.1159/000129639 |
| [21] |
Sel’kov SA, Pavlov OV. Rol’ matochno-platsentarnykh makrofagov v reproduktivnoi patologii. Journal of Obstetrics and Women’s Diseases. 2010;59(1):122–130. (In Russ.) |
| [22] |
Сельков С.А., Павлов О.В. Роль маточно-плацентарных макрофагов в репродуктивной патологии // Журнал акушерства и женских болезней. 2010. Т. 59. № 1. С. 122–130. |
| [23] |
Elmaagacli AH, Ditschkowski M, Steckel NK, et al. Human chorionic gonadotropin and indolamine 2,3-dioxygenase in patients with GVHD. Bone Marrow Transplant. 2014;49(6):800–805. DOI: 10.1038/bmt.2014.59 |
| [24] |
Elmaagacli A.H., Ditschkowski M., Steckel N.K., et al. Human chorionic gonadotropin and indolamine 2,3-dioxygenase in patients with GVHD // Bone Marrow Transplant. 2014. Vol. 49. No. 6. P. 800–805. DOI: 10.1038/bmt.2014.59 |
| [25] |
Rao ChV, Li X, Manna SK, et al. Human chorionic gonadotropin decreases proliferation and invasion of breast cancer MCF-7 cells by inhibiting NF-kappaB and AP-1 activation. J Biol Chem. 2004;279(24):25503–25510. DOI: 10.1074/jbc.M400683200 |
| [26] |
Rao Ch.V., Li X., Manna S.K., et al. Human chorionic gonadotropin decreases proliferation and invasion of breast cancer MCF-7 cells by inhibiting NF-κB and AP-1 activation // J. Biol. Chem. 2004. Vol. 279. No. 24. P. 25503–25510. DOI: 10.1074/jbc.M400683200 |
| [27] |
Wass M, McCann K, Bagshawe KD. Isolation of anti bodies to HCG/LH from human sera. Nature. 1978;274(5669):369–370. DOI: 10.1038/274368a0 |
| [28] |
Wass M., Mccann K., Bagshawe K.D. Isolation of antibodies to HCG/LH from human sera // Nature. 1978. Vol. 274. No. 5669. P. 368–370. DOI: 10.1038/274368a0 |
| [29] |
Lutz HU, Miescher S. Natural antibodies in health and disease: an overview of the first international workshop on natural antibodies in health and disease. Autoimmun Rev. 2008;7(6):405–409. DOI: 10.1016/j.autrev.2008.03.005 |
| [30] |
Lutz H.U., Miescher S. Natural antibodies in health and disease: an overview of the first international workshop on natural antibodies in health and disease. // Autoimmun. Rev. 2008. Vol. 7. No. 6. P. 405–409. DOI: 10.1016/j.autrev.2008.03.005 |
| [31] |
Zaichik AM, Poletaev AB, Churilov LP. Natural autoantibodies, immunological theories and preventive medicine. Vestnik of Saint Petersburg University. Medicine. 2013;(2):3–16. (In Russ.) |
| [32] |
Зайчик А.Ш., Полетаев А.Б., Чурилов Л.П. Естественные аутоантитела, иммунологические теории и превентивная медицина // Вестник Санкт-Петербургского университета. Медицина. 2013. № 2. С. 3–16. |
| [33] |
Sidel’nikova VM. Podgotovka i vedenie beremennosti u zhenshchin s privychnym nevynashivaniem. Moscow: MEDpress-inform; 2013. (In Russ.) |
| [34] |
Сидельникова В.М. Подготовка и ведение беременности у женщин с привычным невынашиванием. Москва: МЕДпресс-информ, 2013. |
| [35] |
Spiridonova NV, Basina EI, Shchukin VYu. Natural (physiological) autoantibodies and regulation of homeostasis. Izvestia of Samara Scientific Center of the Russian Academy of Sciences. 2015;17(5(3): 861–867. (In Russ.) |
| [36] |
Спиридонова Н.В., Басина Е.И., Щукин В.Ю. Естественные (физиологические) аутоантитела и регуляция гомеостаза // Извес тия Самарского научного центра Российской академии наук. 2015. Т. 17. №. 5(3). С. 861–867. |
| [37] |
Talwar GP, Singh O, Pal R, et al. A vaccine that prevents pregnancy in women. Proc Natl Acad Sci USA. 1994;91(18):8532–8536. DOI: 10.1073/pnas.91.18.8532 |
| [38] |
Talwar G.P., Singh O., Pal R., et al. A vaccine that prevents pregnancy in women // Proc. Natl. Acad. Sci. USA. 1994. Vol. 91, No. 18. P. 8532–8536. DOI: 10.1073/pnas.91.18.8532 |
| [39] |
Talwar GP. Making of a vaccine preventing pregnancy without impairment of ovulation and derangement of menstrual regularity and bleeding profiles. Contraception. 2013;87(3):280–287. DOI: 10.1016/j.contraception.2012.08.033 |
| [40] |
Talwar G.P. Making of a vaccine preventing pregnancy without impairment of ovulation and derangement of menstrual regularity and bleeding profiles // Contraception. 2013. Vol. 87. No. 3. P. 280–287. DOI: 10.1016/j.contraception.2012.08.033 |
| [41] |
Hearn JP. Immunological interference with the maternal recognition of pregnancy in primates. Ciba Found Symp. 1978;(64):353–375. DOI: 10.1002/9780470720479.ch15 |
| [42] |
Hearn J.P. Immunological interference with the maternal recognition of pregnancy in primates // Ciba Found. Symp. 1978. Vol. 64. P. 353–375. DOI: 10.1002/9780470720479.ch15 |
| [43] |
Dhar R, Karmakar S, Sriraman R, et al. Efficacy of a recombinant chimeric anti-hCG antibody to prevent human cytotrophoblasts fusion and block progesterone synthesis. Am J Reprod Immunol. 2004;51(5):358–363. DOI: 10.1111/j.1600-0897.2004.00169.x |
| [44] |
Dhar R., Karmakar S., Sriraman R., et al. Efficacy of a recombinant chimeric anti-hCG antibody to prevent human cytotrophoblasts fusion and block progesterone synthesis // Am. J. Reprod. Immunol. 2004. Vol. 51. No. 5. P. 358–363. DOI: 10.1111/j.1600-0897.2004.00169.x |
| [45] |
Pavlov OV, Sel’kov SA. Platsentarnye makrofagi: morfofunk tsional’nye kharakteristiki i rol’ v gestatsionnom protsesse. Saint Petersburg: Eco-Vector; 2018. (In Russ.) |
| [46] |
Павлов О.В., Сельков С.А. Плацентарные макрофаги: морфофункциональные характеристики и роль в гестационном процессе. Санкт Петербург: Эко-Вектор, 2018. |
| [47] |
Amato F, Warnes GM, Kirby CA, et al. Infertility caused by HCG autoantibody. J Clin Endocrinol Metab. 2002;87(3):993–997. DOI: 10.1210/jcem.87.3.8334 |
| [48] |
Amato F., Warnes G.M., Kirby C.A., et al. Infertility caused by HCG autoantibody // J. Clin. Endocrinol. Metab. 2002. Vol. 87. No. 3. P. 993–997. DOI: 10.1210/jcem.87.3.8334 |
| [49] |
Dubossarskaya ZM, Duka YM. Experience of conducting pregnancy at the sensitization to the horionichesky gonadotrophin of the person. Obstetrics, Gynecology and Reproduction. 2016;10(3):18–23. (In Russ.) DOI: 10.17749/2313-7347.2016.10.2.018-023 |
| [50] |
Дубоссарская З.М., Дука Ю.М. Опыт ведения беременности при сенсибилизации к хорионическому гонадотропину человека // Акушерство, Гинекология и Репродукция. 2016. Т. 10. № 3. С. 18–23. DOI: 10.17749/2313-7347.2016.10.2.018-023 |
| [51] |
Kiryushchenkov PA. Osobennosti vedeniya zhenshchin s autosensibilizatsiey k khorionicheskomu gonadotropinu cheloveka. Gynecology. 2003;5(5):222–224. (In Russ.) |
| [52] |
Кирющенков П.А. Особенности ведения женщин с аутосенсибилизацией к хорионическому гонадотропину человека // Гинекология. 2003. Т. 5. № 5. С. 222–224. |
| [53] |
Menzhinskaya IV, Vanko LV. Complement activation in women with early pregnancy loss and autoantibodies against phospholipids and chorionic gonadotropin. Russian Journal of Allergy. 2018;15(1S):58–60. (In Russ.) DOI: 10.36691/RJA50 |
| [54] |
Менжинская И.В., Ванько Л.В. Активация комплемента у женщин с ранней потерей беременности и аутоантителами к фосфолипидам и хорионическому гонадотропину // Российский Аллергологический Журнал. 2018. Т. 15. № 1S. C. 58–60. DOI: 10.36691/RJA50 |
| [55] |
Toulis KA, Goulis DG, Venetis CA, et al. Thyroid autoimmunity and miscarriages: the corpus luteum hypothesis. Med Hypotheses. 2009;73(6):1060–1062. DOI: 10.1016/j.mehy.2009.05.012 |
| [56] |
Toulis K.A., Goulis D.G., Venetis C.A., et al. Thyroid autoimmunity and miscarriages: the corpus luteum hypothesis // Med. Hypotheses. 2009. Vol. 73. No. 6. P. 1060–1062. DOI: 10.1016/j.mehy.2009.05.012 |
| [57] |
Chen L, Hu R. Thyroid autoimmunity and miscarriage: a meta-analysis. Clin Endocrinol (Oxf). 2011;74(4):513–519. DOI: 10.1111/j.1365-2265.2010.03974.x |
| [58] |
Chen L., Hu R. Thyroid autoimmunity and miscarriage: a meta-analysis // Clin. Endocrinol. (Oxf). 2011. Vol. 74. No. 4. P. 513–519. DOI: 10.1111/j.1365-2265.2010.03974.x |
| [59] |
Recurrent pregnancy loss causes, controversies, and treatment. Ed. by H. Carp. London: CRC Press; 2020. |
| [60] |
Recurrent pregnancy loss causes, controversies, and treatment / Ed. by H. Carp. London: CRC Press; 2020. |
| [61] |
Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2(2):76–83. |
| [62] |
Ford H.B., Schust D.J. Recurrent pregnancy loss: etiology, diagnosis, and therapy // Rev. Obstet. Gynecol. 2009. Vol. 2. No. 2. P. 76–83. |
| [63] |
Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite anti phospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306. DOI: 10.1111/j.1538-7836.2006.01753.x |
| [64] |
Miyakis S., Lockshin M.D., Atsumi T., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome // Thromb. Haemostasis. 2006. Vol. 4. P. 295–306. DOI: 10.1111/j.1538-7836.2006.01753.x |
| [65] |
Zou SH, Yang ZZ, Zhang P, et al. Autoimmune disorders affect the in vitro fertilization outcome in infertile women. Zhonghua Nan Ke Xue. 2008;14(4):343–346. |
| [66] |
Zou S.H., Yang Z.Z., Zhang P., et al. Autoimmune disorders affect the in vitro fertilization outcome in infertile women // Zhonghua Nan Ke Xue. 2008. Vol. 14. No. 4. P. 343–346. |
| [67] |
Bansal AS, Bora SA, Saso S, et al. Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy. Expert Rev Clin Immunol. 2012;8(8):747–753. DOI: 10.1586/eci.12.77 |
| [68] |
Bansal A.S., Bora S.A., Saso S., et al. Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy // Expert. Rev. Clin. Immunol. 2012. Vol. 8. No. 8. P. 747–753. DOI: 10.1586/eci.12.77 |
| [69] |
Menzhinskaya IV, Beznoshchenko OS, Saroyan TT, et al. Antibodies to reproductive hormones as a possible risk factor for poor outcome of in vitro fertilization cycles. Obstetrics and Gynecology. 2012;(2):41–45. (In Russ.) |
| [70] |
Менжинская И.В., Безнощенко О.С., Саронян Т.Т., и др. Антитела к гормонам репродуктивной системы как возможный фактор риска неблагоприятного исхода в циклах экстракорпорального оплодотворения // Акушерство и гинекология. 2012. № 2. С. 41–45. |
| [71] |
Menzhinskaya IV, Beznoshcenko OS, Kiryushchenkov PA, et al. The clinical value of gonadotropic hormone autoantibodies in female reproductive dysfunction. Obstetrics and Gynecology. 2011;(1):47–51. (In Russ.) |
| [72] |
Менжинская И.В., Безнощенко О.С., Кирющенков П.А., и др. Клиническое значение аутоантител к гонадотропным гормонам при нарушениях репродуктивной функции у женщин // Акушерство и гинекология. 2011. № 1. С. 47–51. |
| [73] |
Talwar GP. Vaccines for control of fertility and hormone-dependent cancers. Immunol Cell Biol. 1997;75(2):184–189. DOI: 10.1038/icb.1997.26 |
| [74] |
Talwar G.P. Vaccines for control of fertility and hormone-dependent cancers // Immunol. Cell Biol. 1997. Vol. 75. No. 2. P. 184–189. DOI: 10.1038/icb.1997.26 |
| [75] |
Tkhay DV. Antitela k KhGCh v geneze reproduktivnykh neudach. In: Tezisy III Obshcherossiyskoy nauchno-prakticheskoy konferentsii dlya akusherov-ginekologov “Ottovskie chteniya”, Saint Petersburg, 12–13 Nov 2021. Moscow;2021:72–73. |
| [76] |
Тхай Д.В. Антитела к ХГЧ в генезе репродуктивных неудач // Тезисы III Общероссийской научно-практической конференции для акушеров-гинекологов «Оттовские чтения», Санкт-Петербург, 12–13 ноября 2021 года. Москва: StatusPraesens, 2021. С. 72–73. |
| [77] |
Tkhay DV, Kotova KE. Antitela k khorionicheskomu gonadotropinu cheloveka i antifosfolipidnye antitela kak nezavisimye faktory patologii beremennosti. In: Fundamental’naya nauka i klinicheskaya medi tsina: materialy nauchnoy konferentsii. Saint Petersburg, 24 april, 2021. Saint Petersburg; 2021. P. 172–173. |
| [78] |
Тхай Д.В., Котова К.Е. Антитела к хорионическому гонадотропину человека и антифосфолипидные антитела как независимые факторы патологии беременности // Фундаментальная наука и клиническая медицина материалы научной конференции, Санкт-Петербург, 24 апреля 2021 года. Санкт-Петербург: Сциентиа, 2021. С. 172–173. |
| [79] |
Rossiiskoe obshchestvo akusherov-ginekologov. Privychnyi vykidysh. Klinicheskie rekomendatsii. 2022. (In Russ.) [cited 2023 Mar 12]. Available from: https://roag-portal.ru/recommendations_obstetrics |
| [80] |
Российское общество акушеров-гинекологов. Привычный выкидыш. Клинические рекомендации. 2022 [дата обра щения: 12.03.2023]. Доступ по ссылке: https://roag-portal.ru/recommendations_obstetrics |
| [81] |
Muller V, Ob’edkova K, Krikheli I, et al. Successful pregnancy outcome in women with recurrent IVF failure and anti-hCG autoimmunity: a report of three cases. Case Reports Immunol. 2016;2016. DOI: 10.1155/2016/4391537 |
| [82] |
Muller V., Ob’edkova K., Krikheli I., et al. Successful pregnancy outcome in women with recurrent IVF failure and anti-hCG autoimmunity: a report of three cases // Case Reports Immunol. 2016. Vol. 2016. DOI: 10.1155/2016/4391537 |
| [83] |
Stephenson MD, Kutteh WH, Purkiss S, et al. Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial. Hum Reprod. 2010;25(9):2203–2209. DOI: 10.1093/humrep/deq179 |
| [84] |
Stephenson M.D., Kutteh W.H., Purkiss S., et al. Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial. // Hum. Reprod. 2010. Vol. 25. No. 9. P. 2203–2209. DOI: 10.1093/humrep/deq179 |
| [85] |
Ensom MH, Stephenson MD. A two-center study on the pharmacokinetics of intravenous immunoglobulin before and during pregnancy in healthy women with poor obstetrical histories. Hum Reprod. 2011;26(9):2283–2288. DOI: 10.1093/humrep/der227 |
| [86] |
Ensom M.H., Stephenson M.D. A two-center study on the pharmacokinetics of intravenous immunoglobulin before and during pregnancy in healthy women with poor obstetrical histories // Hum. Reprod. 2011. Vol. 26, No. 9. P. 2283–2288. DOI: 10.1093/humrep/der227 |
| [87] |
Sel’kov SA, Sokolov DI, Chepanov SV. Immunoregulatory effects of intravenous immunoglobulins. Med. Immunol. 2013;15(1):5–12. (In Russ.) |
| [88] |
Сельков С.А., Соколов Д.И., Чепанов С.В. Иммунорегуляторные эффекты иммуноглобулинов для внутривенного введения // Медицинская иммунология. 2013. Т. 15. № 1. С. 5–12. |
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