Immunization with refrigerated paternal cells did not prevent recurrent miscarriage

OBJECTIVE To evaluate the effectiveness of pre-pregnancy immunization with paternal cells in increasing the chance of a successful pregnancy in women with recurrent miscarriage. DESIGN Multicentre, randomized, double-blind, placebo-controlled trial. Allocation was blocked and stratified by centre, using scaled envelopes. SETTING Six hospitals in the USA and Canada. SUBJECTS 183 non-pregnant women aged ≤40 (mean 33) years, with unexplained recurrent miscarriage (≥3 miscarriages), ≤1 live birth, and no anti-HLA antibodies. The mean number of previous miscarriages was 4.3, range 3-13. 26% of women had had a previous livebirth. INTERVENTION Ninety-one women were randomized to receive immunization with mononuclear cells from their male partner. The cells were removed from 1 unit of whole blood and refrigerated overnight. Approximately 200 million lymphocytes in 5 mL saline were administered intravenously, subcutaneously and intradermally. 92 women were treated similarly with saline (donated blood was discarded). Immunization was repeated after 6 months if not pregnant. MAIN OUTCOME MEASURES Odds ratio (OR, 95% CI) for successful pregnancy (at least 28 weeks gestation), adjusted for maternal age and number of previous miscarriages and livebirths. MAIN RESULTS Excluded from the analysis were four women who did not receive treatment, and eight who were not reimmunized after 6 months. 31/86 women (36%) in the treatment group and 41/85 (48%) in the control group had successful pregnancies (P = 0.06, OR 0.54, CI 0.28-1.02). Considering only women who became pregnant, the success rates were 31/68 (46%) and 41/63 (65%), respectively (P = 0.02, OR 0.40, CI 0.19-0.84). The results were similar when only women with primary recurrent miscarriage (no previous livebirth) were considered. The mean (SD) duration of gestation at miscarriage was 8.9 (4.5) weeks in the treatment group and 6.2 (1.5) weeks in the control group (P = 0.002). All pregnancy losses in the control group occurred prior to 10 weeks, but 16% of losses in the treatment group occurred between 10 and 28 weeks gestation. CONCLUSION In women with unexplained recurrent miscarriage, pre-pregnancy immunization with refrigerated paternal cells decreased the chance of successful pregnancy, compared to placebo.