JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):17
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263538

P-05. Alloimmunotherapy in Fertility Treatment: Evidence-Based Practice or Off-Label Use?

Melanie May Chow¹, Katherine Ann Reimão Miller¹, Julia Roverso Correa Silveira¹, Gabriel Monteiro Pinheiro¹

¹Universidade Santo Amaro - São Paulo - SP - Brasil

Objective: Assisted reproductive technologies (ART) have evolved considerably over recent decades, driven by technological innovation and increasing demand related to delayed childbearing and rising infertility rates. Among various adjunctive strategies explored to improve outcomes in in vitro fertilization (IVF), alloimmunotherapy—particularly paternal lymphocyte immunotherapy (LIT)—has gained attention for its proposed role in enhancing maternal-fetal immunotolerance. LIT involves intradermal administration of the male partner’s lymphocytes with the goal of inducing regulatory immune responses in women experiencing recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Despite its immunobiological rationale, the clinical use of LIT remains controversial due to inconsistent evidence, lack of standardization, potential risks, and questions about cost-effectiveness and alignment with evidence-based and ethical practice. This study aims to critically assess the scientific, ethical, and sustainability foundations of LIT in reproductive medicine. Specifically, it explores whether the routine use of LIT is supported by robust evidence, whether it meets principles of responsible medical practice, and how its application may impact healthcare systems in terms of resource use, safety, and patient well-being.
Methods: A critical narrative literature review was conducted using data from PubMed between the years 2015 to 2025. Search terms included “lymphocyte immunotherapy,” “alloimmunotherapy,” “recurrent implantation failure,” “recurrent pregnancy loss,” and “responsible practice.” Inclusion criteria were human studies involving ART patients with RPL, RIF, or unexplained infertility, reporting clinical reproductive outcomes (implantation rate, clinical pregnancy, live birth, pregnancy loss), or addressing ethical and sustainability considerations. Out of 20 studies, 11 of them included randomized trials, cohort and case-control studies, well-described case series, systematic reviews, and guidelines. Exclusions included preclinical studies, anecdotal reports, irrelevant interventions, and methodologically limited publications. Thematic synthesis and tabulation were employed for analysis.
Results: The review found mixed evidence regarding LIT efficacy. Some observational studies (e.g., Chen et al., Fainboim et al.) reported increased pregnancy and live birth rates, especially in younger women with idiopathic RPL and multiple prior losses. However, meta-analyses of randomized controlled trials (e.g., Achilli et al.) failed to show statistically significant benefits for live birth, miscarriage reduction, or clinical pregnancy in RPL populations. Evidence in RIF was even more limited and inconsistent. Safety concerns, particularly regarding preconception protocols associated with autoantibody production and potential harm, were also highlighted. The lack of randomization, heterogeneous protocols, frequent use of co-interventions (e.g., IVIG, corticosteroids), and absence of immune stratification further limit the reliability and generalizability of findings.
Conclusion: Although LIT is biologically plausible and may be beneficial for selected patients with idiopathic RPL and defined immune abnormalities, its overall evidence base remains inconclusive and methodologically weak. Routine use of LIT in RIF or broadly across ART populations is not currently justified. Until high-quality randomized controlled trials with immune profiling are conducted, LIT should be limited to investigational settings. Personalized, evidence-based approaches—integrating immune, microbiome, and genetic assessments—are essential to ensuring that immunomodulatory therapies in reproductive care are safe, effective, and ethically sound.