A combination treatment of prednisone, aspirin, folate, and progesterone in women with idiopathic recurrent miscarriage: a matched-pair study

Objective: To compare a combination treatment of prednisone, aspirin, folate, and progesterone with no treatment in women with idiopathic recurrent miscarriage (IRM). Design: Matched-pair study. Setting(s): Academic research institution. Subject(s): Women with a history of IRM, defined as three or more consecutive miscarriages before 20 weeks gestation without associated anatomic, cytogenetic, hormonal, and infectious pathologies or antiphospholipid syndrome. Intervention(s): Eighty of 210 eligible women consented to participate and were treated with prednisone (20 mg/d) and progesterone (20 mg/d) for the first 12 weeks of gestation, aspirin (100 mg/d) for 38 weeks of gestation and folate (5 mg every second day) throughout their pregnancies. Fifty of 80 women became pregnant; they were compared with 52 women with IRM (matched for age and number of miscarriages), who became pregnant without treatment during the same observation period. Main Outcome Measure(s): Live birth rate, complications of pregnancy, such as preeclampsia, premature birth, and intrauterine growth restriction, and therapy-related side effects. Result(s): The overall live birth rates of the treatment and control groups were 77% (40 of 52) and 35% (18 of 52) (P=.04). The rates of first and second trimester miscarriage among the treatment and control groups were 19% (10 of 52) and 0 (0 of 52), and 66% (33 of 520 and 2% 91 of 52), respectively (P=.09 and P=1.0, respectively). The median gestational age at birth and median birth weight did not differ between the groups. We observed two and three cases of premature birth among the treatment and control groups, respectively (P=.3) and no cases of intrauterine growth restriction and Cushling's disease. Of 80 women who started treatment, one woman had an ectopic pregnancy and one woman terminated her pregnancy due to fetal chromosome aberration (trisomy 18). Three women stopped treatment due to nausea, depression, and tachycardia. Conclusion(s): A combination treatment of prednisone, aspirin, folate, and progesterone is associated with a higher live birth rate compared with no treatment in women with IRM.