Live Birth Rates after Active Immunization with Partner Lymphocytes

Abstract

Although many potential causes have been established for recurrent implantation failure (RIF) and recurrent miscarriage (RM), about 50% of these remain idiopathic. Scientific research is focused on immunological risk factors. In the present study, we aim to evaluate live birth rates after immunization with paternal lymphocytes (lymphocyte immunotherapy (LIT)). This retrospective study consisted of 148 couples with a history of RM and/or RIF. The women underwent immunization with lymphocytes of their respective partners from November 2017 to August 2019. Fifty-five patients (43%) had live births. Stratified by indication (RM, RIF, combined), live birth rates in the RM and the combined group were significantly higher than that in the RIF group (53%, 59% and 33%, respectively, p = 0.02). The difference was especially noticeable during the first 90 days after immunization (conception rate leading to live births: 31%, 23% and 8% for RM, the combined group and RIF, respectively; p = 0.005), while there was no difference between groups during the later follow-up. LIT was associated with high live birth rates, especially in women with recurrent miscarriage. In view of the limited data from randomized studies, LIT cannot be recommended as routine therapy. However, it may be considered in individual cases.

Keywords: immunization; implantation failure; live birth rate; paternal lymphocytes; recurrent miscarriage.

Figure 1

Schematic sequence of immunization. Abbreviations: ART: assisted reproductive technology, HLA: human leukocyte antigen, HPA: human platelet antigen, CMV: cytomegalovirus.

Figure 2

Conception rate after immunization resulting in a live birth. (A): The pregnancy rate leading to live birth was lower in patients with implantation failure only (overall p = 0.02, p = 0.03 compared to patients with recurrent miscarriage, p = 0.008 compared to patients with combined recurrent miscarriage and implantation failure), but not different between patients with recurrent miscarriage and those with combined recurrent miscarriage and implantation failure (p = 0.65). (B): Pregnancy rates differred mainly during the first 90 days after immunization, with lower rates in patients with implantation failure only (overall p = 0.005; p = 0.001 compared to patients with recurrent miscarriage, p = 0.04 compared to patients with combined recurrent miscarriage and implantation failure), but no significant difference was observed between patients with recurrent miscarriage and patients with combined recurrent miscarriage and implantation failure (p = 0.49). (C): There was no significant difference in pregnancy rates leading to live birth after day 90 post immunization (overall p = 0.18).