Recurrent miscarriage and hCG supplementation: a review and metaanalysis

Human chorionic gonadotropin (hCG) has been used to prevent subsequent miscarriages after previous recurrent miscarriages. In addition to the luteotrophic effects, hCG has uterine immune and autocrine actions. hCG also affects cytokine expression. A Cochrane database systematic review has indicated that hCG seems to prevent further miscarriages, (OR for miscarriage = 0.26, 95% CI 0.14-0.52). However, the trials in the Cochrane database were not matched for the number of miscarriages, 1°, 2° or 3° aborter status, maternal age, etc. and no account was made for chromosomally abnormal pregnancies. All of these impact on the subsequent prognosis and may confound the results. The previous trials in the literature all assessed urinary (u-hCG) rather than recombinant hCG (r-hCG), raising the question whether the effect on pregnancy outcome is due to hCG itself, or other urinary proteins present in u-hCG. A new trial is indicated in which r-hCG is compared to u-hCG and the most effective compared to placebo. Treatment and placebos arms should be stratified for the prognostic factors above and the results corrected for fetal chromosomal aberrations. Until such a trial is carried out, the use of hCG supplementation is empiric.