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Review

Exploring the Immunological Aspects and Treatments of Recurrent Pregnancy Loss and Recurrent Implantation Failure

by
Jenny Valentina Garmendia
1,
Claudia Valentina De Sanctis
1,
Marián Hajdúch
1,2,3 and
Juan Bautista De Sanctis
1,2,*
1
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic
2
Czech Advanced Technology and Research Institute, Palacky University, 77900 Olomouc, Czech Republic
3
Laboratory of Experimental Medicine, University Hospital Olomouc, 779 00 Olomouc, Czech Republic
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(3), 1295; https://doi.org/10.3390/ijms26031295
Submission received: 31 December 2024 / Revised: 26 January 2025 / Accepted: 30 January 2025 / Published: 3 February 2025
(This article belongs to the Section Molecular Immunology)

Abstract

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses before 24 weeks of gestation. It affects 3–5% of women who are attempting to conceive. RPL can stem from a variety of causes and is frequently associated with psychological distress and a diminished quality of life. By contrast, recurrent implantation failure (RIF) refers to the inability to achieve a successful pregnancy after three or more high-quality embryo transfers or at least two instances of egg donation. RIF shares several causative factors with RPL. The immunological underpinnings of these conditions involve alterations in uterine NK cells, reductions in M2 macrophages and myeloid-derived suppressor cells, an increased Th1/Th2 ratio, a decreased Treg/Th17 ratio, the presence of shared ≥3 HLA alleles between partners, and autoimmune disorders. Various therapeutic approaches have been employed to address these immunological concerns, achieving varying degrees of success, although some therapies remain contentious within the medical community. This review intends to explore the immunological factors implicated in RPL and RIF and to analyze the immunological treatments employed for these conditions, which may include steroids, intravenous immunoglobulins, calcineurin inhibitors, anti-TNF antibodies, intralipid infusions, granulocyte colony-stimulating factor, and lymphocyte immunotherapy.
Keywords: recurrent pregnancy loss; recurrent implantation failure; NK cells; T regulatory cells; Th17; Th1; Th2; macrophages; cytokines; HLA recurrent pregnancy loss; recurrent implantation failure; NK cells; T regulatory cells; Th17; Th1; Th2; macrophages; cytokines; HLA

Share and Cite

MDPI and ACS Style

Garmendia, J.V.; De Sanctis, C.V.; Hajdúch, M.; De Sanctis, J.B. Exploring the Immunological Aspects and Treatments of Recurrent Pregnancy Loss and Recurrent Implantation Failure. Int. J. Mol. Sci. 2025, 26, 1295. https://doi.org/10.3390/ijms26031295

AMA Style

Garmendia JV, De Sanctis CV, Hajdúch M, De Sanctis JB. Exploring the Immunological Aspects and Treatments of Recurrent Pregnancy Loss and Recurrent Implantation Failure. International Journal of Molecular Sciences. 2025; 26(3):1295. https://doi.org/10.3390/ijms26031295

Chicago/Turabian Style

Garmendia, Jenny Valentina, Claudia Valentina De Sanctis, Marián Hajdúch, and Juan Bautista De Sanctis. 2025. "Exploring the Immunological Aspects and Treatments of Recurrent Pregnancy Loss and Recurrent Implantation Failure" International Journal of Molecular Sciences 26, no. 3: 1295. https://doi.org/10.3390/ijms26031295

APA Style

Garmendia, J. V., De Sanctis, C. V., Hajdúch, M., & De Sanctis, J. B. (2025). Exploring the Immunological Aspects and Treatments of Recurrent Pregnancy Loss and Recurrent Implantation Failure. International Journal of Molecular Sciences, 26(3), 1295. https://doi.org/10.3390/ijms26031295

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