Trends in Immunotherapy

Review

Immunological Consequences of Infertility: From Immune Basis to Immunotherapy for Miscarriage and Infertility

Downloads

Kalmatov, R., Rahim, F., Zhainagul Abdirasulovna, A., Gozin, S., Rakhima Momunovna, A., & Aizhan Nurlanovna, O. (2025). Immunological Consequences of Infertility: From Immune Basis to Immunotherapy for Miscarriage and Infertility. Trends in Immunotherapy, 9(2), 13–26. https://doi.org/10.54963/ti.v9i2.999

Authors

  • Roman Kalmatov

    International Medical Faculty, Osh State University, Osh City 723500, Kyrgyzstan
  • Fakher Rahim

    Department of Medical Biotechnology, Internal Medicine Faculty, Osh state University, Osh City 723500, Kyrgyzstan
  • Abdirasulova Zhainagul Abdirasulovna

    Department of Medical Sciences, International Medical Faculty, Osh State University, Osh City 723500, Kyrgyzstan
  • Shamim Gozin

    Department of General Medicine, Faculty of Medicine, Istanbul Atlas University, Istanbul, Turkey
  • Azhimamatova Rakhima Momunovna

    Department of Clinical Disciplines 1, International Medical Faculty, Osh State University, Osh City 723500, Kyrgyzstan
  • Omorova Aizhan Nurlanovna

    Department of Clinical Disciplines 1, International Medical Faculty, Osh State University, Osh City 723500, Kyrgyzstan

One of the causes of infertility and recurrent miscarriage is immunological factors or factors related to the immune system. Several immunological issues, for instance autoantibodies and alterations in the level of uterine immune cells, play a crucial role in immune-related infertility. This review evaluated all available immunological bases in female reproductive disorders, especially infertility and miscarriage to provide optimal diagnostic strategies for patients. NK cells are considered important elements of the innate immune system, ensuring that there is tolerance between the mother and child’s immune systems. Touching on the adaptive immune system, Th cells not only are able to impart directional structure on incoming lymphocytes draining from the periphery but also categorize into different subsets depending on where they are located within peripheral blood. During pregnancy, the immune system is skewed toward a type 2 T helper response, while fetal rejection is associated with a type 1 response The rules of organ transplantation require that the host’s immunological mechanisms, based on the incompatibility of antigens of the histocompatibility system, recognize the transplanted piece and ultimately reject it. Among the various therapeutic options, lymphocyte immunotherapy (LIT) stands out as a promising solution based on immunological principles. Some studies have shown that the success rate of LIT is 69%, but other studies have shown that the success rate has increased to 80%. On the other hand, controlled clinical trials are needed to further investigate immunomodulatory therapeutic strategies to help treat this disorder. Therefore, further studies are needed to achieve standardized diagnostic and immunological therapeutic approaches to increase the effectiveness of therapeutic interventions and increase the success rate of assisted reproductive technology (ART) cycles in these women.

Keywords:

Recurrent Spontaneous Abortion; Lymphocyte Transfusion; Lymphocyte Immunotherapy (LIT); Infer‑ tility; Miscarriage

Highlights

Received: 8 February 2025; Revised: 24 February 2025; Accepted: 27 February 2025; Published: 7 May 2025

References

  1. Kirovakov, Z.; Konova, E.; Hinkova, N.; et al. Immunological Risk Factors in Recurrent Pregnancy Loss in Patients With Hereditary Thrombophilia. Cureus 2024, 16, e56555.
  2. Hara, A.; Iwasa, Y.; Autoimmune Diseases Initiated by Pathogen Infection: Mathematical modeling. J. Theor. Biol. 2020, 498, 110296.
  3. Pisetsky, D.S. Pathogenesis of Autoimmune disease. Nat. Rev. Nephrol. 2023, 19, 509–524.
  4. Jörg, S.; Grohme, D.A.; Erzler, M.; et al. Environmental Factors in Autoimmune Diseases and Their role in Multiple Sclerosis. Cell. Mol. Life Sci. 2016, 73, 4611–4622.
  5. Gratiela Gradisteanu, P.; Octavian, S.; Grigore, M.; et al. Dysbiosis, Tolerance, and Development of Autoimmune Diseases. In: Immunology of the GI Tract - Recent Advances; Rijeka, L., Eds.; IntechOpen: Rijeka, Licko-Senjska, Croatia, 2022; Volume 4, pp. 2–23.
  6. Siu, K.K.; Serrão, V.H.B.; Ziyyat, A.; et al. The Cell Biology of Fertilization: Gamete Attachment and fusion. J. Cell Biol. 2021, 220, e202102146
  7. Wu, H.M.; Chen, L.H.; Hsu, L.T.; et al. Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles. Int. J. Mol. Sci. 2022, 23, 13382.
  8. Ma, J.; Gao, W.; Li, D. Recurrent Implantation Failure: A Comprehensive Summary From Etiology to Treatment. Front. Endocrinol. 2022, 13, 1061766.
  9. Hamadi, G.M.; Lafta, S.F. Immunological Parameters of Recurrent Miscarriages Among Women in Thi-Qar Province. J. Med. Life 2022, 15, 635–639.
  10. Zhang, S.; Lin, H.; Kong, S.; et al. Physiological and Molecular Determinants of Embryo Implantation. Mol. Aspects Med. 2013, 34, 939–980.
  11. Simon, A.; Laufer, N. Assessment and Treatment of Repeated Implantation Failure (RIF). J. Assist. Reprod. Genet. 2012, 29, 1227–1239.
  12. Quenby, S.; Gallos, I.D.; Dhillon-Smith, R.K.; et al. Miscarriage Matters: The Epidemiological, Physical, Psychological, and Economic Costs of Early Pregnancy loss. Lancet 2021, 397, 1658–1667.
  13. Genovese, H.G.; McQueen, D.B. The Prevalence of Sporadic and Recurrent Pregnancy Loss. Fertil. Steril. 2023, 120(5), 934–936.
  14. Turesheva, A.; Aimagambetova, G.; Ukybassova, T.; et al. Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box. J. Clin. Med. 2023, 12, 4074.
  15. Mendes, D.C.G.; Fonseca, A.; Cameirão, M.S. The Relationship Between Healthcare Satisfaction After Miscarriage and Perinatal Grief Symptoms: A Cross-Sectional Study on Portugal Residents. Soc. Sci. Med. 2024, 353, 117037.
  16. Dawe, G.S.; Tan, X.W.; Xiao, Z.C. Cell Migration From Baby to Mother. Cell Adhes. Migrat. 2007, 1, 19–27.
  17. O’Donoghue, K. Fetal Microchimerism and Maternal Health During and After Pregnancy. Obstet. Med. 2008, 1, 56–64.
  18. Shrivastava, S.; Naik, R.; Suryawanshi, H.; et al. Microchimerism: A New Concept. J. Oral Maxillofac. Pathol. 2019, 23, 311.
  19. Gammill, H.S.; Nelson, J.L. Naturally Acquired Microchimerism. Inter. J. Dev. Biol. 2010, 54, 531–543.
  20. Kammala, A.K.; Lintao, R.C.V.; Hoy, R.; et al. Fetal Microchimeric Cells Influence Maternal Lung Health Following Term and Preterm births. Sci. Rep. 2024, 14, 28417.
  21. Pandey, M.K. Immunological harmony: the dynamic influence of cellular and humoral immunity on pregnancy success. Discov. Immun. 2024, 1, 2.
  22. Davies, C. Why is the fetal allograft not rejected? J. Anim. Sci. 2007, 85, E32–E35.
  23. Kinder, J.M.; Stelzer, I.A.; Arck, P.C.; et al. Immunological implications of pregnancy-induced microchimerism. Nat. Rev. Immunol. 2017, 17, 483–494.
  24. Nakamura, T.; Shirouzu, T.; Nakata, K.; et al. The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage. Int. J. Mol. Sci. 2019, 20, 4544.
  25. Szekeres-Bartho, J. Immunological Relationship Between the Mother and the Fetus. Int. Rev. Immunol. 2002, 21, 471–495.
  26. Grunstra, N.D.S.; Betti, L.; Fischer, B.; et al. There is an Obstetrical Dilemma: Misconceptions About the Evolution of Human Childbirth and Pelvic Form. Am. J. Biol. Anthropol. 2023, 181, 535–544.
  27. Shibahara, H.; Wakimoto, Y.; Fukui, A.; et al. Anti-sperm Antibodies and Reproductive Failures. Am. J. Reprod. Immunol. 2021, 85, e13337.
  28. Mettler, L.; Skrabei, H. Isolation of Human Spermatozoa Membrane Antigens Binding Sperm-Immobilizing and Sperm-Agglutinating Antibodies. Int. J. Fertil. 1979, 24, 44–48.
  29. Burger, D.; Chicheportiche, R.; Giri, J.G.; et al. The Inhibitory Activity of Human Interleukin-1 Receptor Antagonist is Enhanced by Type II Interleukin-1 Soluble Receptor and Hindered by Type I Interleukin-1 Soluble Receptor. J. Clin. Investig 1995, 96, 38–41.
  30. Prince, L.R.; Allen, L.; Jones, E.C.; et al. The Role of Interleukin-1beta in Direct and Toll-Like Receptor 4-Mediated Neutrophil Activation and Survival. Am. J. Pathol. 2004, 165, 1819–1826.
  31. Lindhard, A.; Bentin-Ley, U.; Ravn, V.; et al. Biochemical Evaluation of Endometrial Function at the Time of Implantation. Fertil. Steril. 2002, 78, 221–233.
  32. Boraschi, D. What Is IL-1 for? The Functions of Interleukin-1 Across Evolution. Front. Immunol. 2022, 13, 872155.
  33. Saito, S.; Tsukaguchi, N.; Hasegawa, T.; et al. Distribution of Th1, Th2, and Th0 and the Th1/Th2 Cell Ratios in Human Peripheral and Endometrial T Cells. Am. J. Reprod. Immunol. 1999, 42(4), 240–245.
  34. Sykes, L.; MacIntyre, D.A.; Yap, X.J.; et al. Changes in the Th1:Th2 Cytokine bias in Pregnancy and the Effects of the Anti-Inflammatory Cyclopentenone Prostaglandin 15-Deoxy-Δ(12,14)-Prostaglandin J2. Mediat. Inflamm. 2012, 2012, 416739.
  35. Raghupathy, R.; Al-Mutawa, E.; Al-Azemi, M.; et al. Progesterone-Induced Blocking Factor (PIBF) Modulates Cytokine Production by Lymphocytes From Women with Recurrent Miscarriage or Preterm Delivery. J. Reprod. Immunol. 2009, 80, 91–99.
  36. Jasinski-Bergner, S.; Eckstein, M.; Taubert, H.; et al. The Human Leukocyte Antigen G as an Immune Escape Mechanism and Novel Therapeutic Target in Urological Tumors. Front. Immunol. 2022, 13, 811200.
  37. Zhuang, B.; Shang, J.; Yao, Y. HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance. Front. Immunol. 2021, 12, 744324.
  38. Uța, C.; Tîrziu, A.; Zimbru, E.L.; et al. Alloimmune Causes of Recurrent Pregnancy Loss: Cellular Mechanisms and Overview of Therapeutic Approaches. Medicina 2024, 60, 1896.
  39. Meuleman, T.; van Beelen, E.; Kaaja, R.J.; et al. HLA-C Antibodies in Women with Recurrent Miscarriage Suggests that Antibody Mediated Rejection is One of the Mechanisms Leading to Recurrent Miscarriage. J. Reprod. Immunol. 2016, 116, 28–34.
  40. Motlagh Asghari, K.; Novinbahador, T.; Mehdizadeh, A.; et al. Revolutionized Attitude Toward Recurrent Pregnancy Loss and Recurrent Implantation Failure Based on Precision Regenerative Medicine. Heliyon 2024, 10, e39584.
  41. Yatsenko, S.A.; Rajkovic, A. Genetics of Human Female Infertility. Biol. Reprod. 2019, 101, 549–566.
  42. Bohn, C.; Vogel, M.; Poulain, T.; et al. Birth Weight Increases with Birth Order Despite Decreasing Maternal Pregnancy Weight Gain. Acta Paediatr. 2021, 110, 1218–1224.
  43. Vidarsson, G.; Dekkers, G.; Rispens, T. IgG subclasses and allotypes: from structure to effector functions. Front. Immunol. 2014, 5, 520.
  44. Eidizadeh, A.; Papert, S.; Valk, J.; et al. Adverse Drug Reactions Following Lymphocyte Immunotherapy for the Treatment of Infertility: A Retrospective Study. J. Obstet. Gynaecol. Res. 2022, 48, 2571–2582.
  45. Saremi, A.T.; Sanaye Naderi, M.; Pooladi, A.; et al. Evaluations of WBC Cross-Match Results After Lymphocyte Immunization in Women with Recurrent Spontaneous Abortion in Sarem Women’s Hospital %J Sarem. J. Med. Res. 2017, 2, 19–23.
  46. Chighizol, C.B.; Lonati, P.A.; Trespidi, L.; et al. The Complement System in the Pathophysiology of Pregnancy and in Systemic Autoimmune Rheumatic Diseases During Pregnancy. Front. Immunol. 2020, 11, 2084.
  47. Salmon, J.E.; Girardi, G. Antiphospholipid Antibodies and Pregnancy Loss: A Disorder of Inflammation. J. Reprod. Immunol. 2008, 77, 51–56.
  48. Skoura, R.; Andronikidi, P.E.; Anestakis, D.; et al. Antiphospholipid Syndrome and Preeclampsia in Pregnancy: A Case Report. Cureus 2022, 14, e28458.
  49. Liu, T.; Guo, X.; Liao, Y.; et al. Correlation Between the Presence of Antinuclear Antibodies and Recurrent Pregnancy Loss: A Mini Review. Front. Endocrinol. 2022, 13, 873286.
  50. Kolatorova, L.; Vitku, J.; Suchopar, J.; et al. Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine. Int. J. Mol. Sci. 2022, 23, 7989.
  51. Santana-Sánchez, P.; Vaquero-García, R.; Legorreta-Haquet, M.V.; et al. Hormones and B-cell development in health and autoimmunity. Front. Immunol. 2024, 15, 1385501.
  52. Xie, J.; Jiang, L.; Sadhukhan, A.; et al. Effect of Antithyroid Antibodies on Women with Recurrent Miscarriage: A Meta-Analysis. Am. J. Reprod. Immunol. 2020, 83, e13238.
  53. Sarkar, D. Recurrent Pregnancy Loss in Patients with Thyroid Dysfunction. Indian J. Endocrinol. Metab. 2012, 16, S350–S351.
  54. Liu, S.; Gu, X.; Weng, R. Clinical Effect of Lymphocyte Immunotherapy on Patients with Unexplained Recurrent Spontaneous Abortion. Immun. Inflamm.Dis. 2021, 9, 1272–1278.
  55. Seles, L.; Zaha, I.A.; Luncan, M.; et al. Immunomodulatory Treatment Impact on IVF Outcomes in KIR AA Genotype: Personalized Fertility Insights. Medicina 2024, 60, 948.
  56. Aslanian-kalkhoran, L.; Kamrani, A.; Alipourfard, I.; et al. The Effect of Lymphocyte Immunotherapy (LIT) in Modulating Immune Responses in Patients with Recurrent Pregnancy Loss (RPL). Int. Immunopharmacol. 2023, 121, 110326.
  57. Sarno, M.; Cavalcante, M.B.; Niag, M.; et al. Gestational and Perinatal Outcomes in Recurrent Miscarriages Couples Treated with Lymphocyte Immunotherapy. Eur. J. Obstet. Gynecol. Reprod. Biol.:X 2019, 3, 100036.
  58. Wigby, S.; Suarez, S.S.; Lazzaro, B.P.; et al. Sperm Success and Immunity. Curr. Top. Dev. Biol. 2019, 135, 287–313.
  59. Kumar, P.; Philip, C.E.; Eskandar, K.; et al. Effect of Intravenous Immunoglobulin Therapy in Recurrent Implantation Failure: A Systematic Review and Meta-Analysis. J. Reprod. Immunol. 2024, 166, 104323.
  60. Muyayalo, K.P.; Li. Z.H.; Mor, G.; et al. Modulatory Effect of Intravenous Immunoglobulin on Th17/Treg Cell Balance in Women with Unexplained Recurrent Spontaneous Abortion. Am. J. Reprod. Immunol. 2018, 80, e13018.
  61. Aghamohammadi, A.; Farhoudi, A.; Nikzad, M.; et al. Adverse Reactions of Prophylactic Intravenous Immunoglobulin Infusions in Iranian Patients with Primary Immunodeficiency. Ann. Allergy Asthma Immunol. 2004, 92, 60–64.
  62. Nydegger, U.E.; Fierz, W.; Risch, L. Benefits and Risks of IgA in Immunoglobulin Preparations. Transfus. Apher. Sci. 2012, 46, 97–102.
  63. Li, J.; Chen, Y.; Liu, C.; et al. Intravenous Immunoglobulin Treatment for Repeated IVF/ICSI Failure and Unexplained Infertility: A Systematic review and a Meta-Analysis. Am. J. Reprod. Immunol. 2013, 70, 434–447.
  64. Ahmadi, M.; Abdolmohammadi-Vahid, S.; Ghaebi, M.; et al. Effect of Intravenous Immunoglobulin on Th1 and Th2 lymphocytes and Improvement of Pregnancy Outcome in Recurrent Pregnancy Loss (RPL). Biomed. Pharmacother. 2017, 92, 1095–1102.
  65. Jerzak, M.; Rechberger, T.; Górski, A. Intravenous Immunoglobulin Therapy Influences T cell Adhesion to Extracellular Matrix in Women with a History of Recurrent Spontaneous Abortions. Am. J. Reprod. Immunol. 2000, 44, 336–341.
  66. Ahmadi, M.; Aghdam, S.A.; Nouri, M.; et al. Intravenous Immunoglobulin (IVIG) Treatment Modulates Peripheral Blood Th17 and Regulatory T Cells in Recurrent Miscarriage Patients: Non Randomized, Open-Label Clinical Trial. Immunol. Lett. 2017, 192, 12–19.
  67. Szereday, L.; Späth, P.; Szekeres-Bartho, J. Natural Killer Cell Activity and Cytokine Production After in Vitro Immunoglobulin Treatment of Lymphocytes Derived from Pregnant Women with or Without Risk for Spontaneous Abortion. Am. J. Reprod. Immunol. 1999, 42, 282–287.
  68. Graphou, O.; Chioti, A.; Pantazi, A.; et al. Effect of Intravenous Immunoglobulin Treatment on the Th1/Th2 Balance in Women with Recurrent Spontaneous Abortions. Am. J. Reprod. Immunol. 2003, 49, 21–29.
  69. Virro, M.R.; Winger, E.E.; Reed, J.L. Intravenous Immunoglobulin for Repeated IVF Failure and Unexplained Infertility. Am. J. Reprod. Immunol. 2012, 68, 218–225.
  70. Ramos-Medina, R.; García-Segovia, A.; Gil, J.; et al. Experience in IVIg Therapy for Selected Women with Recurrent Reproductive Failure and NK Cell Expansion. Am. J. Reprod. Immunol. 2014, 71, 458–466.
  71. Toth, B.; Jeschke, U.; Rogenhofer, N.; et al. Recurrent Miscarriage: Current Concepts in Diagnosis And Treatment. J. Reprod. Immunol. 2010, 85, 25–32.
  72. Abdolmohammadi-Vahid, S.; Pashazadeh, F.; Pourmoghaddam, Z.; et al. The Effectiveness of IVIG Therapy in Pregnancy and Live Birth Rate of Women with Recurrent Implantation failure (RIF): A Systematic Review and Meta-Analysis. J. Reprod. Immunol. 2019, 134–135, 28–33.
  73. Stephenson, M.D.; Fluker, M.R. Treatment of Repeated Unexplained in Vitro Fertilization Failure with Intravenous Immunoglobulin: A Randomized, Placebo-Controlled Canadian trial. Fertil. Steril. 2000, 74, 1108–1113.
  74. Chay, J.; Lust, K.; Kubler, P.; et al. When Conventional Treatment Fails: The Role of Intravenous Immunoglobulin in Recurrent Pregnancy Loss Secondary to Antiphospholipid Syndrome. Obstet. Med. 2013, 6, 76–79.
  75. Melo, P.; Thornton, T.; Coomarasamy, A.; et al. Evidence for the Effectiveness of Immunologic Therapies in Women with Subfertility and/or Undergoing Assisted Reproduction. Fertil. Steril. 2022, 117, 1144–1159.
  76. Marzusch, K.; Dietl, J.; Klein, R.; et al. Recurrent First Trimester Spontaneous Abortion Associated with Antiphospholipid Antibodies: A Pilot Study of Treatment with Intravenous Immunoglobulin. Acta Obstet. Gynecol. Scand. 1996, 75, 922–926.
  77. Ebrahimi, R.; Asghari, K.M.; Alamdary, S.J.; et al. Intradermal lymphocyte Therapy: A Promising Treatment for Recurrent Pregnancy loss in Patients Without Anti-TPO Antibodies. Hum. Immunol. 2025, 86, 111229.
  78. Park, J.S.; Song, A.Y.; Bae, J.Y.; et al. IL-17 Producing T to Foxp3(+)CD4(+) Regulatory T Cell Ratio as a Diagnostic and Prognostic Marker in Women With Recurrent Pregnancy Loss and Its Implications for Intravenous Immunoglobulin Therapy. Am. J. Reprod. Immunol. 2024, 92, e70020.
  79. Lee, S.K.; Kim, J.Y.; Han, A.R.; et al. Intravenous Immunoglobulin G Improves Pregnancy Outcome in Women with Recurrent Pregnancy Losses with Cellular Immune Abnormalities. Am. J. Reprod. Immunol. 2016, 75, 59–68.
  80. Liang, X.; Qiu, T.; Qiu, L.; et al. Female Third Party Lymphocytes are Effective for Immunotherapy of Patients with Unexplained Primary Recurrent Spontaneous Abortion: A Retrospective Analysis of Outcomes. Eur. J. Contracept. Reprod. Health Care 2015, 20, 428–437.
  81. Ramhorst, R.; Agriello, E.; Zittermann, S.; et al. Is the Paternal Mononuclear Cells’ Immunization a Successful Treatment for Recurrent Spontaneous abortion?. Am. J. Reprod. Immunol. 2000, 44, 129–135.
  82. Pfeiffer, K.A.; Sillem, M.; Daniel, V.; et al. Activated Autologous Blood therapy in Recurrent Spontaneous Abortion--Results of a Pilot Study. Hum. Reprod. 1998, 13, 491–497.
  83. Gatenby, P.A.; Cameron, K.; Simes, R.J.; et al. Treatment of Recurrent Spontaneous abortion by Immunization with Paternal Lymphocytes: Results of a Controlled Trial. Am. J. Reprod. Immunol. 1993, 29, 88–94.
  84. Maleki-Hajiagha, A.; Razavi, M.; Rezaeinejad, M.; et al. Intrauterine Administration of Autologous Peripheral Blood Mononuclear Cells in Patients with Recurrent Implantation failure: A Systematic Review and Meta-analysis. J. Reprod. Immunol. 2019, 131, 50–56.
  85. Yang, D.N.; Wu, J.H.; Geng, L.; et al. Efficacy of Intrauterine Perfusion of peripheral Blood Mononuclear Cells (PBMC) for Infertile Women Before Embryo Transfer: Meta-Analysis. J. Obstet. Gynaecol. 2020, 40, 961–968.
  86. Pourmoghadam, Z.; Abdolmohammadi-Vahid, S.; Pashazadeh, F.; et al. Efficacy of Intrauterine Administration of Autologous Peripheral Blood Mononuclear Cells on the Pregnancy Outcomes in Patients with Recurrent Implantation Failure: A Systematic Review and Meta-Analysis. J. Reprod. Immunol. 2020, 137, 103077.
  87. Genest, G.; Banjar, S.; Almasri, W.; et al. Immunomodulation for Unexplained recurrent Implantation Failure: Where Are We Now?. Reproduction 2023, 165, R39–R60.
  88. Farifteh, F.; Fazeli, E.; Zeinab Hosseini, S.; et al. Intrauterine Administration of Autologous Peripheral Blood Mononuclear Cells Regulates the Endometrium Estrogen and Progesterone Receptor Expression: An RCT. Int. J. Reprod. Biomed. 2023, 21, 343–354.
  89. Ohams, M.; Jerzak, M.; Górski, A. Effects of Sildenafil Citrate and Etanercept Treatment on TNF-α Levels in Peripheral Blood of women with Recurrent Miscarriage. Ginekol. Pol. 2015, 86, 520–524.
  90. Berthelot, J.M.; De Bandt, M.; Goupille, P.; et al. Exposition to anti-TNF Drugs During Pregnancy: Outcome of 15 Cases and Review of the Literature. Jt. Bone Spine 2009, 76, 28–34.
  91. Lee, S.K.; Na, B.J.; Kim, J.Y.; et al. Determination of Clinical Cellular Immune Markers in Women with Recurrent Pregnancy Loss. Am. J. Reprod. Immunol. 2013, 70, 398–411.
  92. Zhang, C.; Deng, X.; Zhang, X.; et al. Association Between Serum TNF-α Levels and Recurrent Spontaneous Miscarriage: A Meta-analysis. Am. J. Reprod. Immunol. 2016, 75, 86–93.
  93. Chambers, C.D.; Johnson, D.L. Emerging Data on the use of Anti-Tumor Necrosis Factor-alpha Medications in Pregnancy. Birth Defects Res. A. 2012, 94, 607–611.
  94. Santiago, K.Y.; Porchia, L.M.; López-Bayghen, E. Endometrial Preparation with Etanercept Increased Embryo Implantation and Live Birth Rates in Women Suffering from Recurrent Implantation Failure during IVF. Reprod. Biol. 2021, 21, 100480.
  95. Winger, E.E.; Reed, J.L.; Ashoush, S.; et al. Treatment with Adalimumab (Humira) and Intravenous Immunoglobulin Improves Pregnancy rates in Women Undergoing IVF. Am. J. Reprod. Immunol. 2009, 61, 113–120.
  96. Scalea, J.R.; Levi, S.T.; Ally, W.; et al. Tacrolimus for the Prevention and Treatment of Rejection of Solid Organ Transplants. Expert Rev. Clin. Immunol. 2016, 12, 333–342.
  97. Yu, Y.; Zhong, J.; Peng, L.; et al. Tacrolimus Downregulates Inflammation by Regulating Pro‑/Anti‑Inflammatory Responses in LPS‑Induced keratitis. Mol. Med. Rep. 2017, 16, 5855–5862.
  98. Liu, J.; Farmer, J.D., Jr.; Lane, W.S.; et al. Calcineurin is a Common Target of Cyclophilin-Cyclosporin A and FKBP-FK506 Complexes. Cell 1991, 66, 807–815.
  99. Lédée, N.; Petitbarat, M.; Prat-Ellenberg, L.; et al. Endometrial Immune Profiling: A Method to Design Personalized Care in Assisted Reproductive Medicine. Front. Immunol. 2020, 11, 1032.
  100. Robertson, S.A.; Moldenhauer, L.M.; Green, E.S.; et al. Immune determinants of endometrial receptivity: a biological perspective. Fertil. Steril. 2022, 117, 1107–1120.
  101. Bashiri, A.; Halper, K.I.; Orvieto, R. Recurrent Implantation Failure-Update Overview on Etiology, Diagnosis, Treatment and Future Directions. Reprod. Biol. Endocrinol. 2018, 16, 121.