Abstract

Immunological mechanisms play a critical role in the success of assisted reproductive technologies (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The female reproductive system requires a finely tuned immune balance to support implantation and pregnancy while defending against pathogens. Uterine natural killer (uNK) cells, regulatory T cells (Tregs), and macrophages are key immune cells that regulate this balance. Aberrations in their function have been linked to recurrent implantation failure (RIF), pregnancy loss, and preeclampsia. The cytokine environment, particularly the balance between Th1 (pro-inflammatory) and Th2 (anti-inflammatory) responses, is crucial; a Th2-dominant immune response supports pregnancy, whereas a Th1-skewed response is associated with adverse outcomes. Autoimmune conditions, such as antiphospholipid syndrome, further complicate ART success and pregnancy maintenance, increasing the risk of miscarriage and implantation failure. Immunomodulatory therapies, including corticosteroids, intravenous immunoglobulin (IVIG), and low-molecular-weight heparin, have shown promise in optimizing immune conditions to enhance ART outcomes. Emerging therapies targeting specific immune pathways may further improve reproductive success. Understanding the immunological interplay in ART is essential for developing personalized treatments that increase fertility and improve pregnancy outcomes. Personalized immune therapies, such as the use of autologous peripheral blood mononuclear cells (PBMCs) and platelet-rich plasma (PRP), are being explored to improve implantation success by modulating the local immune environment of the uterus.

Overall, while immunological challenges remain a significant factor in ART success, ongoing research into personalized immune profiling and targeted therapies is paving the way for more effective treatments in assisted reproduction

Keywords: Immunology, Assisted Reproduction, IVF, uNK Cells, Tregs, Th1/Th2 Balance, Cytokines, Autoimmune Disorders, Pregnancy Outcome

References

  1. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 2010;63(6):601–10. doi:10.1111/j.1600-0897.2010.00852.x
  2. Moffett A, Colucci F. Uterine NK cells: active regulators at the maternal-fetal interface. J Clin Invest. 2014;124(5):1872–9. doi:10.1172/JCI68107
  3. Kwak-Kim J, Park J, Ahn HK, Kim JW, Gilman-Sachs A. Immunological modes of pregnancy loss: Inflammation, immune effectors, and stress. Am J Reprod Immunol. 2010;63(6):611–23. doi:10.1111/j.1600-0897.2010.00846.x
  4. Polanski LT, Baumgarten MN, Quenby S, Brosens JJ. The emerging role of immunological testing and interventions in reproductive medicine. Best Pract Res Clin Obstet Gynaecol. 2019;60:77–90. doi:10.1016/j.bpobgyn.2019.07.007
  5. Zenclussen ML, Casalis PA, Jensen F, Zenclussen AC. Immunological determinants of reproductive failure in women. 2020;160(1):10–19. doi:10.1111/imm.13164
  6. Tang AW, Alfirevic Z, Turner MA, Drury JA, Small R, Quenby S. A systematic review of low-molecular-weight heparin for improving pregnancy outcomes in women with recurrent miscarriage. Hum Reprod. 2013;28(1):56–64. doi:10.1093/humrep/des329
  7. Bélanger M-C, Bahri H, Miron P, Benkhalifa M. Endometrium immunomodulation to prevent recurrent implantation failure in assisted reproductive technology. Int J Mol Sci. 2022;23(21):12787. doi:10.3390/ijms232112787​
  8. Lédée N, Petitbarat M, Prat-Ellenberg L, et al. The next frontier in ART: harnessing the uterine immune profile for improved performance. Int J Mol Sci. 2023;24(14):11322. doi:10.3390/ijms241411322
  9. Ahmadi H, Aghebati-Maleki L, Rashidiani S, Csabai T, Nnaemeka OB, Szekeres-Bartho J. Long-term effects of ART on the health of the offspring. Int J Mol Sci. 2023;24(17):13564. doi:10.3390/ijms241713564