Lymphocyte Immunization Therapy in Recurrent Pregnancy Loss - Is There a Place for This Treatment?

The efficacy of lymphocyte immunotherapy (LIT) in the prevention of pregnancy loss still remains to be controversial. It was initially introduced in the 1980’s, with several investigators proposing that recurrent pregnancy losses (RPL) were due to failure of induction of protective immune responses in some cases of women with unexplained RPL. It was proposed that with the effective presentation of paternal antigens, this could be overcome. LIT could enhance the development of “blocking” antibodies during pregnancy. This was further supported by studies showing lower levels of these antibodies in those with RPL compared to controls and these antibodies increased after LIT. Most trials on LIT have shown success rate of ~70%. However, control groups in various studies have also shown success rates ranging from 29-79%.

A Cochrane meta-analysis in 2006 found an odds ratio (OR) for live birth after paternal LIT of 1.23 (95% CI 0.89-1.70) and for donor LIT 1.39 (95% CI 0.68-2.82) and concluded that neither provided significant benefit over placebo in preventing miscarriages. An updated Cochrane meta-analysis in 2014 yielded same results, not surprisingly since no new study after 2004 was included in this review. This meta-analysis, however, only included a few studies and it has been argued by a few that therapeutic benefits with LIT may be more significant with the addition of other studies. Moreover, the inclusion of the study by Ober et al added significant heterogeneity in the results of the meta-analysis. The Ober study used varying routes of administration which is questionable in its capacity to induce protective immune responses. It also stored some of the lymphocytes overnight in cold temperatures, which could possibly deteriorate its effectiveness. These, together with its large sample size could have significantly affected the results of the meta-analysis.

While LIT is still not an approved treatment option in the US and parts of Europe, other parts of the world still continue to use this as an option. Only a few studies have come out since then and many investigators recognize the need to come up with a consistent and effective protocol to allow integration of data across trials.