Da. Clark et al., Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatments, HUM REP UPD, 7(5), 2001, pp. 501-511
There have been important advances in basic science investigation of mechan
isms underlying spontaneous miscarriages which lend support to empirical tr
eatments such as intravenous immunoglobulin G and allogeneic leukocyte immu
notherapy. The results from clinical trials of these and other proposed tre
atments have been problematic. There is only one published meta-analysis of
sufficient power and appropriate stratification to qualify as Level 1 evid
ence, and that deals only with leukocyte immunotherapy. Here we critically
review current trials and their flaws, update the meta-analysis, and commen
t on potential new approaches. Inadequate sample size, better definition of
heterogeneity, and proper stratification to minimize the effects of hetero
geneity remain as problems. Verification that the experimental or test trea
tment was active in producing the expected alteration in immunophysiology i
n the recipient is lacking in most trials; use of stored rather than fresh
allogeneic leukocytes appears problematic. Hidden biases that affect trial
significance emerge with critical analysis, and the focus on apparent 'high
quality' of design in published reports may be misleading. We conclude tha
t there seem to be enough patients to conduct clinical trials of sufficient
size to achieve adequate power to test therapies showing promise in pilot
studies, but at present, the only Level 1 evidence concerns leukocyte immun
otherapy which appears to increase the chance of a live birth if given to a
ppropriate patients.