The effectiveness of assisted reproductive technologies immunological prediction

Cover Page

Cite item


The high frequency of infertility is a significant medical and social problem in many countries of the world; assisted reproductive technologies (ART) are actively used to solve it. Given that immune responses play an important role in the development and maintenance of pregnancy, the study of changes in immune parameters is relevant in different trimesters of pregnancy, as well as at the stage of preconception preparation. It is believed that the maternal-fetal relationship is not limited to the development of maternal tolerance to fetal antigens, but is complemented by complex cytokine interactions that control selective immune regulation, control of adhesion and vascularization processes during embryo implantation and pregnancy. The purpose of the review was to analyze the available scientific data on the use of immune parameters to predict the effectiveness of ART. A review of Russian and foreign scientific papers on prevalence, immunopathogenetic mechanisms, and infertility diagnostics was carried out. A multi-criteria search was carried out for inventions, abstracts of patent documents on immunological prediction of the effectiveness of ART. As predictors, immunocompetent cells (CD3+-, CD4+-, CD3-CD16+56+-venous blood lymphocytes, CD95+ macrophages of endometrial biopsy), cytokines, pregnancy glycoproteins, autoantibodies, immunogenetic markers are presented. The study of the quantitative level of cytokines in blood serum, ovarian follicular fluid and endometrium as mediators of intercellular and intertissue interactions is of undoubted scientific and practical interest in terms of establishing their discriminatory levels specific to different trimesters of a normal pregnancy, the threat of miscarriage, and infertility. There was an association with non-occurrence of pregnancy due to in vitro fertilization of an increased content of interleukin (IL)-2 and interferon (IFN)-γ in the follicular fluid, and a soluble receptor IL-2-α, IL-8 and lactoferrin in the blood serum. The immunosuppressive effects of pregnancy-associated α2-glycoprotein, trophoblastic β1-glycoprotein, α-fetoprotein, α2-macroglobulin contribute to the development and maintenance of pregnancy, but their prognostic value is not unambiguous. The study of the content of immunoglobulins G to α2-macroglobulin, lactoferrin, progesterone, estradiol, cardiolipin in the follicular fluid and blood serum makes it possible to predict the result of ART. Conclusion. The study of immune parameters, especially in combination with sex hormones and characteristics of the state of the embryo, in infertile women has diagnostic value and prognostic significance, and can contribute to the timely correction of therapy and the ART program.

About the authors

Ljubov V. Matveeva

Ogarev Mordovia State University

Author for correspondence.
ORCID iD: 0000-0001-9342-3157
SPIN-code: 6017-0118
Saransk, Russian Federation

Galina V. Fominova

Ogarev Mordovia State University

ORCID iD: 0009-0004-8757-7976
SPIN-code: 6306-1864
Saransk, Russian Federation

Elena V. Gromova

Ogarev Mordovia State University

ORCID iD: 0000-0001-9255-2571
SPIN-code: 4828-4866
Saransk, Russian Federation

Elena A. Alyamkina

Ogarev Mordovia State University

ORCID iD: 0000-0003-3259-4088
SPIN-code: 1026-4723
Saransk, Russian Federation

Anastasiya S. Galynya

Ogarev Mordovia State University

ORCID iD: 0009-0001-6059-5689
SPIN-code: 8441-8731
Saransk, Russian Federation


  1. Mamiev OB, Guzhvina EN, Moroz MV, Grigoryan NV, Mamiev VO. Condition of several immunosuppressive mechanisms in the system of mother-placenta-fetus with different types of its adaptation to the birth stress. Bulletin of the Volgograd State Medical University. 2009;3(31):99–101. (In Russian).
  2. Nekrasova IV, Shirshev SV. Forming of mononuclear cells toleragenic features under the estriol influence. Russian Journal of Immunology. 2012; 6 (15): 45–50. (In Russian).
  3. Chereshnev VA, Rodionov SY, Cherkasov VA, Malyutina NN, Orlov OA. Alpha-fetoprotein. Yekaterinburg: Ural Branch of the Russian Academy of Sciences; 2004. 376 p. (In Russian).
  4. Chaouat G, Zourbas S, Ostojic S, Lappree-Delage G, Dubanchet S, Ledee N, Martal J. A brief review of recent data on some cytokine expressions at the materno-foetal interface which might challenge the classical Th1/Th2 dichotomy. J. Reprod. Immunol. 2002;53:241–256. doi: 10.1016/s0165-0378(01)00119-x
  5. WHO Newsletter. Infertility. Available from: [Accessed 2023 April 18].
  6. Russian Society of Obstetricians and Gynecologists (ROAG). Russian Association of Human Reproduction (RAHR). Clinical guidelines. female infertility. 2021. Available from:женское_бесплодие_2021.pdf. [Accessed 2023 April 18]. (In Russian).
  7. Egbe TO, Mbaki CN, Tendongfor N, Temfack E, Belley-priso E. Infertility and associated factors in three hospitals in Douala, Cameroon: a cross-sectional study. Afr. Health Sci. 2020; 20(4): 1985–1995.
  8. Rybina AN, Isenova SS, Lokshin VN. Modern aspects of assisted reproductive technologies in the world and Kazakhstan. Vestnik KazNMU. 2019;1:17–22.
  9. Akalewold M, Yohannes GW, Abdo ZA, Hailu Y, Negesse A. Magnitude of infertility and associated factors among women attending selected public hospitals in Addis Ababa, Ethiopia: a cross-sectional study. BMC Women’s Health. 2022; 22:11 p. doi: 10.1186/s12905-022-01601-8
  10. Ben Messaoud K, Bouyer J, de La Rochebrochard E. Infertility Treatment in France, 2008–2017: A Challenge of Growing Treatment Needs at Older Ages. Am. J. Public. Health. 2020;110(9):1418–1420. doi: 10.2105/AJPH.2020.305781.
  11. Lokshin VN, Korsak VS, Feldberg D, Smirnova AA, Koloda YA, Ershova A, Shurygina OV. ART in a pandemic: organization of activities ART laboratories. International meeting experts. Reproductive Medicine. 2020;2(43):61–66. doi: 10.37800/RM2020-1-18 (In Russian).
  12. Bourrion B, Panjo H, Bithorel PL, de La Rochebrochard E, François M, Pelletier-Fleury N. The economic burden of infertility treatment and distribution of expenditures overtime in France: a self-controlled pre-post study. BMC Health Services Research. 2022;22:512. doi: 10.1186/s12913-022-07725-9
  13. Malchau SS, Henningsen AA, Loft A, Rasmussen S, Forman J, Nyboe Andersen A, Pinborg A. The long-term prognosis for live birth in couples initiating fertility treatments. Hum. Reprod. 2017; 32 (7): 1439–1449. doi: 10.1093/humrep/dex096.
  14. Clinical recommendations (treatment protocol) of the Ministry of Health of the Russian Federation «Female infertility (modern approaches to diagnosis and treatment)». 2019. 70 p. (In Russian).
  15. Motovilova NO, Kogan IY, Totolian AA. Ovaries colony-stimulating factors secretion in patients with infertility in IVF cycles. Journal of obstetrics and women’s diseases. 2012; LXI (3):35–40. (In Russian).
  16. Patent RUS № 2523401 / 20.07.2014. Byul. № 20. Bogatova IK, Antsiferova JS, Bojtsova AV. Method forprediction of onset of pregnancy in females with tubal-peritoneal infertility in in vitro fertilization programme. Available from: [Accessed 2023 April 18]. (In Russian).
  17. Patent RUS № 2616240 / 13.04.2017. Byul. № 11. Gorshilova VK, Volodina MA, Tarasova NV, Vysokikh MY, Smolnikova VY, Kalinina EA, Sukhikh GT. Predicting likelihood of onset of clinical pregnancy of women with BMI 28,5 and abovein vitrofertilization programbased on estimates ofwaistcircumference and changes in share of peripheral blood monoclear with highly mitochondria as a result of superovulation. Available from: [Accessed 2023 April 18]. (In Russian).
  18. Patent RUS № 2430379 / 27.09.2011 Byul. № 27. Savel’eva GM, Shimanovskij NL, Klimenko PA, Kareva EN, Kappusheva LM, Suknovalova MV, Kramarenko MP Method of predicting pregnancy in programme of extracorporal fertilisation and transfer of embryos in standard long protocol of superovulation stimulation. Available from: [Accessed 2023 April 18]. (In Russian).
  19. Ledee-Bataille N, Dubanchet S, Kadoch J, Castelo-Branco A, Frydman R, Chaouat G. Controlled natural in vitro fertilization may be an alternative for patients with repeated unexplained implantation failure and a high uterine natural killer cell count. Fertility Sterility. 2004;82(1):234–236. doi: 10.1016/j.fertnstert.2003.12.030
  20. Coulam CB, Goodman C. Increased pregnancy rates after IVF/ ET with intravenous immunoglobulin treatment in women with elevated circulating C56+ cells. Early Pregnancy. 2000;4:90–98.
  21. Patent RUS № 2567731/ 10.11.2015 Byul. № 3. Kozhekina Yu. N., Kovalev V.V., Chistyakova G.N., Mazurov A.D., Remizova I.I. A method for predicting the risk of early pregnancy termination after in vitro fertilization and embryo transfer in patients with tubal peritoneal infertility genesis. Available from: [Accessed 2023 April 18]. (In Russian).
  22. Abdulmedzhidova AG, Tsibizov AS, Krasnopolskaya KV, Pomerantseva EI, Krasova NK, Kushch AA. The high levels of interleukin 2 and interferon gamma in follicular fluid and blood serum correlate with decrease in efficiency of infertility treatment by method of in vitro fertilization. Russian Journal of Immunology. 2012;6(15):35–44. (In Russian).
  23. Fortunato SJ, Menon R. IL-1β is a better inducer of apoptosis in human fetal membranes than IL-6. Placenta. 2003;24(10):922–927.
  24. Fasouliotis SJ, Spandorfer SD, Witkin SS, Schattman G, Liu HC, Roberts JE, Rosenwaks Z. Maternal serum levels of interferon-gamma and interleukin-2 soluble receptor-alpha predict the outcome of early IVF pregnancies. Hum. Reprod. 2004;19(6):1357–1363. doi: 10.1093/humrep/deh169
  25. Salmassi A, Schmutzler AG, Huang L, Hedderich J, Jonat W, Mettler L. Detection of granulocyte colony-stimulating factor and its receptor in human follicular luteinized granulosa cells. Fertil. Steril. 2004;81(S1):786–91. doi: 10.1016/j.fertnstert.2003.09.039.
  26. Patent RUS № 2784576 / 28.11.2022. Byul. № 34. Nguen KT, Makhmadalieva MR, Dzhemlikhanova LK, Lesik EA, Komarova EM, Tkachenko NN, Niauri DA, Gzgzyan AM, Kogan IY. Method for prediction of the occasion of clinical pregnancy in IVF cycles in patients with a prediction of suboptimale response to controlled ovarian stimulation. Available from: [Accessed 2023 April 18]. (In Russian).
  27. Patent RUS № 2677467 / 17.01.2019. Byul. № 2. Likhacheva V.V., Zorina V.N., Andronova T.M., Zorin N.A., Shilova N.V., Likhachev A.G. A method for predicting the effectiveness of IVF programs in tubal-peritoneal infertility associated with chronic endometritis. Available from: [Accessed 2023 April 18]. (In Russian).
  28. Patent RUS № 2273031 / 27.03.2006. Byul. № 9. Kuzmin A.V., Orlov V.I., Sagamonova K. Yu., Efanova E.A., Lomteva S.V., Ermolenko E.N. Method for predicting the outcomes of the IVF and PE program. Available from: [Accessed 2023 April 18]. (In Russian).
  29. Kravtsova EI, Kolesnikova NV, Lukoshkina IN, Uryupina KV, Avakimyan VA. Immunological and immunohistochemical features of endometrial implantation factor in healthy patients of late reproductive age. RUDN Journal of Medicine. 2023; 27 (1): 46–56. doi: 10.22363/2313-0245-2023-27-1-46-56. (In Russian).
  30. Eshtemirova KA, Saijalilova DD, Ayupova DA. Changes in the level of trophoblastic β-glycoprotein in pregnant women with IVF in case of miscarriage. Proceedings of the XVII International Congress on Reproductive Medicine. M., 2023. p. 139–140. (In Russian).
  31. Mal’tseva NV, Markina LA, Bagenova LG, Chirikova TS, Belogorlova TI. Comparative analysis of human serum α2-macroglobulin and pregnancy-associated α2-glycoprotein levels in blood serum of women in extracorporeal fertilization. The Siberian Scientific Medical Journal. 2007; 4: 60–65. (In Russian).
  32. Patent RUS № 2394495 / 20.07.2010. Byul. № 20. Zorina RM, Markina LA, Zorina VN, Bazhenova LG, Polukarov AN, Medenkova NK. Method for prediction of risk of early fetal loss in IVF induced pregnancies. Available from: [Accessed 2023 April 18]. (In Russian).
  33. Menzhinskaya IV, Kraevaya EE, Kalinina EA, Vanko LV, Dolgushina NV. Prognostic value of autoimmune markers in programs of assisted reproductive technologies. Obstetrics and gynecology. 2021;3:130–137. (In Russian). doi: 10.18565/aig.2021.3.130-137
  34. Huang C, Xiang Z, Zhang Y, Tan DS, Yip CK, Liu Z, Li Y, Yu S, Diao L, Wong LY, Ling WL, Zeng Y, Tu W. Using Deep Learning in a Monocentric Study to Characterize Maternal Immune Environment for Predicting Pregnancy Outcomes in the Recurrent Reproductive Failure Patients. Front. Immunol. 2021;12:642167. doi: 10.3389/fimmu.2021.642167
  35. Patent RUS № 2474822 / 10.02.2013. Byul. № 4. Malyshkina AI, Lipin MA, Fetisova IN, Bogatova IK, Djuzhev ZA, Polumiskova EV. Method for prediction of clinical outcome of extracorporeal fertilisation and embryo transfer. Available from: [Accessed 2023 April 18]. (In Russian).
  36. Patent RUS № 2345715 / 2009. Byul. № 4. Yarygina TV, Bashmakova NV, Mazurov AD. A method for predicting the results of in vitro fertilization in patients with autoimmune diseases. Available from: [Accessed 2023 April 18]. (In Russian).

Copyright (c) 2023 Matveeva L.V., Fominova G.V., Gromova E.V., Alyamkina E.A., Galynya A.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies