Features of the profile of serum autoantibodies to reproductive hormones and steroidogenic enzymes in patients with endometriosis-related infertility and infertile patients without endometriosis
Menzhinskaya I.V., Ermakova D.M., Pavlovich S.V., Dolgushina N.V.
Female infertility is a pressing issue in reproductive medicine, marked by a rising number of patients and increased need for assisted reproductive technologies (ART). There is a well-established association between infertility and endometriosis, which is characterized by a diverse repertoire of autoantibodies, including those against hormones.
Objective: This study aimed to compare the profiles of autoantibodies to reproductive hormones and steroidogenic enzymes in patients with endometriosis-associated infertility and those without endometriosis.
Materials and methods: We used enzyme-linked immunosorbent assays to determine serum antibodies to steroid and gonadotropic hormones, anti-Müllerian hormone (AMH), and steroidogenic enzymes (21-hydroxylase, aromatase, and cholesterol side-chain cleavage enzyme) in patients with endometriosis-associated infertility (group 1, n=44) and those without endometriosis (group 2, n=44) prior to ART cycles.
Results: Group 1 exhibited a high detection rate of IgG antibodies to estradiol, progesterone, and aromatase (>20%), while group 2 showed a high detection rate of IgG antibodies to FSH and AMH (>30%). When comparing the two groups, IgG antibodies to estradiol were detected more frequently in group 1, whereas IgG antibodies to AMH were more prevalent in group 2. IgG antibodies to hormones and steroidogenic enzymes were detected in 9 of 10 women with reduced ovarian reserves.
Conclusion: The identified features of the autoantibody profile can improve the efficiency of diagnostics, facilitate personalized therapy prescriptions, and optimize ART programs. Prospective studies are necessary to assess the impact of autoantibodies on reproductive outcomes and explore effective immunosuppressive and immunotherapies.
Authors' contributions: Menzhinskaya I.V., Pavlovich S.V., Dolgushina N.V. – conception and design of the study; Menzhinskaya I.V., Ermakova D.M. – material collection and processing, statistical analysis, drafting of the manuscript; Pavlovich S.V., Dolgushina N.V. – editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was conducted in accordance with state assignment No. 122020900125-8, entitled "Development of a differentiated approach to the management of patients of reproductive age with different forms of endometriosis".
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Menzhinskaya I.V., Ermakova D.M., Pavlovich S.V., Dolgushina N.V. Features of the profile of
serum autoantibodies to reproductive hormones and steroidogenic enzymes in patients
with endometriosis-related infertility and infertile patients without endometriosis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (12): 128-138 (in Russian)
https://dx.doi.org/10.18565/aig.2024.296
Keywords
infertility
endometriosis
assisted reproductive technologies
autoantibody profile
autoantibodies to hormones and steroidogenic enzymes
References
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Женское бесплодие. 2024. [Ministry of Health of the Russian Federation. Clinical guidelines. Female infertility. 2024. (in Russian)].
- Российская Ассоциация Репродукции Человека. Регистр ВРТ. Отчет за 2022 год. Доступно по: https://www.rahr.ru/d_registr_otchet/RegistrVRT_2022.pdf [Russian Association of Human Reproduction. ART register. 2022 report. Available at: https://www.rahr.ru/d_registr_otchet/RegistrVRT_2022.pdf (in Russian)].
- Российская Ассоциация Репродукции Человека. Регистр ВРТ. Отчет за 2019 год. Доступно по: https://www.rahr.ru/d_registr_otchet/RegistrART2019.pdf [Russian Association of Human Reproduction. ART register. 2019 report. Available at: https://www.rahr.ru/d_registr_otchet/RegistrART2019.pdf (in Russian)].
- Leone Roberti Maggiore U., Chiappa V., Ceccaroni M., Roviglione G., Savelli L., Ferrero S. et al. Epidemiology of infertility in women with endometriosis. Best Pract. Res. Clin. Obstet. Gynaecol. 2024; 92: 102454. https://dx.doi.org/10.1016/j.bpobgyn.2023.102454.
- Дубровина С.О., Беженарь В.Ф., ред. Эндометриоз. Патогенез, диагностика, лечение. М.: ГЭОТАР-Медиа; 2020. 352 с. [Dubrovina S.O., Bezhenar V.F., eds. Endometriosis. Pathogenesis, diagnosis, treatment. Moscow: GEOTAR-Media; 2020. 352 p. (in Russian)].
- Goyri E., Kohls G., Garcia-Velasco J. IVF stimulation protocols and outcomes in women with endometriosis. Best Pract. Res. Clin. Obstet. Gynaecol. 2024; 92: 102429. https://dx.doi.org/10.1016/j.bpobgyn.2023.102429.
- Tian Z., Zhang Y., Zhang C., Wang Y., Zhu H.L. Antral follicle count is reduced in the presence of endometriosis: a systematic review and meta-analysis. Reprod. Biomed. Online 2021; 42(1): 237-47. https://dx.doi.org/10.1016/j.rbmo.2020.09.014.
- Muzii L., Di Tucci C., Di Feliciantonio M., Galati G., Di Donato V., Musella A. et al. Antimullerian hormone is reduced in the presence of ovarian endometriomas: a systematic review and meta-analysis. Fertil. Steril. 2018; 110(5): 932-940 e1. https://dx.doi.org/10.1016/j.fertnstert.2018.06.025.
- Gajbhiye R.K. Endometriosis and inflammatory immune responses: indian experience. Am. J. Reprod. Immunol. 2023; 89(2): e13590. https://dx.doi.org/10.1111/aji.13590.
- Greenbaum H., Galper B.-E.L., Decter D.H., Eisenberg V.H. Endometriosis and autoimmunity: Can autoantibodies be used as a non-invasive early diagnostic tool? Autoimmun. Rev. 2021; 20(5): 102795. https://dx.doi.org/10.1016/j.autrev.2021.102795.
- Shigesi N., Kvaskoff M., Kirtley S., Feng Q., Fang H., Knight J.C. et al. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Hum. Reprod. Update 2019; 25(4): 486-503. https://dx.doi.org/10.1093/humupd/dmz014.
- Simopoulou M., Sfakianoudis K., Maziotis E., Grigoriadis S., Giannelou P., Rapani A. et al. The impact of autoantibodies on IVF treatment and outcome: a systematic review. Int. J. Mol. Sci. 2019; 20(4): 892. https://dx.doi.org/10.3390/ijms20040892.
- Pires E.S., Parikh F.R. The status of anti-ovarian antibody immunoassays: Valid or invalid, in or out? Am. J. Reprod. Immunol. 2023; 89(2): e13617. https://dx.doi.org/10.1111/aji.13617.
- Menzhinskaya I.V., Pavlovich S.V., Melkumyan A.G., Chuprynin V.D., Yarotskaya E.L., Sukhikh G.T. Potential significance of serum autoantibodies to endometrial antigens, α-enolase and hormones in non-invasive diagnosis and pathogenesis of endometriosis. Int. J. Mol. Sci. 2023; 24(21): 15578. https://dx.doi.org/10.3390/ijms242115578.
- Adamyan L.V., Menzhinskaya I.V., Antonova A.A., Tonoyan N.M., Sukhikh G.T. Diagnostic value of autoantibodies against steroidogenic enzymes and hormones in infertile women with premature ovarian insufficiency. Int. J. Mol. Sci. 2024; 25(12): 6545. https://dx.doi.org/10.3390/ijms25126545.
- Cotellessa L., Giacobini P. Role of anti-Müllerian hormone in the central regulation of fertility. Semin. Reprod. Med. 2024; 42(1): 34-40.https://dx.doi.org/10.1055/s-0044-1786050.
- Bedenk J., Vrtačnik-Bokal E., Virant-Klun I. The role of anti-Müllerian hormone (AMH) in ovarian disease and infertility. J. Assist. Reprod. Genet. 2020; 37(1): 89-100. https://dx.doi.org/10.1007/s10815-019-01622-7.
- Менжинская И.В., Мелкумян А.Г., Павлович С.В., Чупрынин В.Д., Кречетова Л.В. Сравнение профиля сывороточных аутоантител у женщин при разных формах эндометриоза. Акушерство и гинекология. 2023; 8: 78-85. [Menzhinskaya I.V., Melkumyan A.G., Pavlovich S.V., Chuprynin V.D., Krechetova L.V. Comparison of the profile of serum autoantibodies in women with different forms of endometriosis. Obstetrics and Gynecology. 2023; (8): 78-85. (in Russian)]. https://dx.doi.org/10.18565/aig.2023.105.
- Bulun S.E., Yilmaz B.D., Sison C., Miyazaki K., Bernardi L., Liu S. et al. Endometriosis. Endocr. Rev. 2019; 40(4): 1048-79. https://dx.doi.org/10.1210/er.2018-00242.
- Di Clemente N., Racine C., Pierre A., Taieb J. Anti-müllerian hormone in female reproduction. Endocr. Rev. 2021; 42(6): 753-82. https://dx.doi.org/10.1210/endrev/bnab012.
- Савина В.А., Потин В.В., Тарасова М.А. Роль ароматазы в патогенезе первично-овариальной недостаточности. Журнал акушерства и женских болезней. 2010; 59(6): 85-93. [Savina V.A., Potin V.V., Tarasova M.A. The role of aromatase in the pathogenesis of primary ovarian insufficiency (literature review). Journal of Obstetrics and Women's Diseases. 2010; 59(6): 85-93.(in Russian)].
- Barbotin A.L., Mimouni N.E.H., Kuchcinski G., Lopes R., Viard R., Rasika S. et al. Hypothalamic neuroglial plasticity is regulated by anti-Müllerian hormone and disrupted in polycystic ovary syndrome. EBioMedicine. 2023; 90: 104535. https://dx.doi.org/10.1016/j.ebiom.2023.104535.
Received 20.11.2024
Accepted 29.11.2024
About the Authors
Irina V. Menzhinskaya, Dr. Med. Sci., Leading Researcher, Laboratory of Clinical Immunology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, Russia, 117997, +7(495)438-11-83, i_menzinskaya@oparina4.ru,https://orcid.org/0000-0002-5385-0370
Daria M. Ermakova, PhD, Researcher, Center for Scientific and Clinical Research, Obstetrician-Gynecologist, Department of Gynecological Endocrinology, Academician
V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, Russia, 117997,
+7(495)438-85-41, d_ermakova@oparina4.ru, https://orcid.org/0000-0002-8558-4687
Stanislav V. Pavlovich, PhD, Academic Secretary, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, Russia, 117997, +7(495)438-52-25, s_pavlovich@oparina4.ru, https://orcid.org/0000-0002-1313-7079
Nataliya V. Dolgushina, Dr. Med. Sci., Professor, Deputy Director for Science, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, Russia, 117997, +7(495)438-49-77, n_dolgushina@oparina4.ru, https://orcid.org/0000-0003-1116-138X
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