Allogenic Lymphocyte Immunotherapy for Unexplained Recurrent Spontaneous Abortion: A Meta‐Analysis

Abstract

Allogenic lymphocyte immunotherapy (LIT) as a treatment for unexplained recurrent spontaneous abortion (URSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. Eighteen randomized, placebo-controlled trials with LIT for URSA were included in the meta-analysis. Live birth rates for each group were extracted, and the overall odds ratio (OR) for LIT was calculated. The success rate of treatment group was significantly higher (OR 3.74, 95% CI 3.07 ~ 4.57). LIT performed before and during pregnancy had dramatically improved the live birth rate in women with URSA (OR 4.67, 95% CI 3.70 ~ 5.90). The overall OR was 5.25 (95% CI 4.16 ~ 6.64), which supports a low dose of lymphocytes for treating URSA. Our results indicate that LIT provides a significantly beneficial effect over placebo for URSA. LIT given before and during pregnancy is superior to LIT given only before pregnancy, and the lower doses per treatment (less than 100 × 10 lymphocytes or 100 mL peripheral blood) achieved a better outcome.

Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges

“…42,43 As pregnancy tissues are the product of both mother and father genes, LIT supports the mother's immune system in the improvement of immunologic tolerance to the genetically foreign pregnancy tissues. 42,43 As pregnancy tissues are the product of both mother and father genes, LIT supports the mother's immune system in the improvement of immunologic tolerance to the genetically foreign pregnancy tissues.…”

The sphingosine 1‐phosphate receptor agonist FTY720 interfered the distribution of dendritic cell and induced the maternal‐fetal immune tolerance

“…Our team and studies at home and abroad in the past two decades have found that the onset of URSA is mainly related to the disorder of pregnancy immune tolerance. Abnormalities in the quality and quantity of immunocompetent cells at the maternal‐fetal interface are thought to play a crucial role in the progression of URSA . Studies at home and abroad have shown that immunocompetent cells in local tissue of URSA patients are recruited from the periphery blood but not from the self‐renewal of precursor cells, while chemokines and their receptors play initiating and pivotal roles in the recruitment and differentiation of immunocompetent cells.…”

Studies on the Infants Born to the Patients with Unexplained Recurrent Abortion Who Underwent Immunotherapy using their Husband’s Lymphocytes

“…The efficacy of the immunotherapy has been controversial [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23], but a meta-analysis concerning the immunotherapy for patients with URA reported by the Recurrent Miscarriage Immunotherapy Trialists Group in 1994 [13], Clark in 2008 [7] and 2012 [14] concluded and Liu et al in 2016 [25] concluded that the immunotherapy may be highly effective. In addition, Pandey et al reported a significant improvement in pregnancy outcome in the patient group in their double-blind randomized trial of husband's lymphocyte immunization for women with recurrent spontaneous abortion [19].…”

“…Immunotherapy for these patients using their husbands' or a third party's leukocytes has been reported [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Although the efficacy of this modality has been controversial, an analysis of controlled clinical trials revealed the efficacy for patients with Unexplained Recurrent Abortion (URA) [7,14,19,26,27], especially for those who were negative for blocking antibodies evaluated by a mixed lymphocyte culture reaction between spouses (MLR-BAbs) [19,22,[28][29][30][31][32][33].…”