IMMUNOTHERAPY FOR RECURRENT PREGNANCY LOSS - ANALYSIS OF RESULTS FROMCLINICAL-TRIALS

PROBLEM: Up to 80% of unexplained recurrent spontaneous abortions (RSA ) are thought to have an immunologic mechanism. Yet clinical trials us ing immunotherapy to treat women experiencing RSA have low treatment e ffects. The present study was undertaken to explain the low treatment effects. METHODS: Results of clinical trials using allogeneic leukocyt e immunization and intravenous (TV) immunoglobulin (Ig) are compared. The mechanisms of pregnancy loss are reviewed in light of data on freq uency of karyotype abnormalities in trophoblast of failing pregnancies . RESULTS: Results of two independent analyses using allogeneic leukoc yte immunization as immunotherapy for ail women with RSA revealed live birth ratios of 1.16 (P = 0.03) and 1.21 (P = 0.02). When the analysi s was limited to primary aborters, the live birth ratio increased to 1 .46 (P = 0.006). Live birth ratio after immunotherapy for all RSA usin g IVIg was 1.88 (P = 0.04). Because of low treatment effects, confound ers to treatment success of maternal age and number of previous aborti ons were studied. Chromosomal abnormalities have been identified in 55 % of concepti from RSA. The frequency of chromosomal abnormalities rem ained constant for up to six pregnancy losses. Women with a history of primary compared to secondary RSA had a higher frequency of karyotypi cally abnormal concepti (chi(2) = 4.54, P < 0.05). Risk factors for RS A also include number of previous losses. CONCLUSION: Chromosomal abno rmalities are a significant confounder when evaluating efficacy of imm unotherapy for treatment of RSA. Some women with RSA have a high risk of recurrent chromosomal problems.