Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: A systematic review and meta‐analysis

Abstract

Problem The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting evidence on the therapeutic role of LIT, since the etiology of most cases of RPL is previously classified as idiopathic. Method of study A systematic search of PubMed and Cochrane databases was done for randomized controlled trials that assessed the efficacy of paternal lymphocyte or third donor LIT among patients with primary or secondary RPL. The primary outcome was live birth rate after LIT. Random‐effect meta‐analysis was conducted using the software RevMan 5.4. Pre‐planned subgroup analyses of source of lymphocytes, timing and frequency of administration, and concentration per immunization dose were conducted. Results Data from eight trials showed a statistically significant benefit of LIT (RR = 1.45, 95% CI 1.05‐2.01). The overall live birth rate is higher in the treatment group (65.6%) compared to placebo or no treatment (45.2%). Subgroup analysis based on source of lymphocytes revealed a trend towards benefit with paternal LIT but with wide confidence interval (RR = 1.34, 95% CI = .84‐2.14). Multiple doses of immunotherapy before pregnancy and low dose (5×106 cells) LIT showed significant benefit. Sensitivity analysis involving studies with a low risk of bias demonstrated significant benefit of increased live birth rate among patients treated with LIT compared to those who received placebo or no treatment (RR = 1.97, 95% CI = 1.53‐2.53). Conclusion LIT demonstrate benefit in improving pregnancy outcome of patients with RPL from alloimmunity.

Evaluation of Recurrent Pregnancy Loss

“…The effectiveness of these therapies remains to be demonstrated through appropriate trials with strict inclusion criteria. Although some international trials have shown a benefit of lymphocyte immunotherapy, 102,103 this therapy is not approved for use in the United States.…”

ESHRE guideline update 2022: New perspectives in the management of couples with recurrent pregnancy loss

“…Despite a substantial number of previous studies, some of them published in the American Journal of Reproductive Immunology, suggesting good efficacy and safety of immunotherapies in the management of couples with RPL, methodological quality, patient selection criteria, and protocol heterogeneity were observed as limiting factors for recommending this practice. [6][7][8][9] This new guideline recommendation suggests that understanding and controlling the immune response in reproductive failures can open new perspectives for the investigation and treatment of couples with RPL.…”