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

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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

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 63% (33 of 52) and 2% (1 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 Cushing’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.

Section snippets

Patients

A diagnosis of IRM was based on a documented history of at least three spontaneous, consecutive miscarriages before 15 weeks’ gestation with the same partner; this was consistent with the American College of Obstetricians and Gynecologists definition (1). A total of 210 consecutive women who visited our outpatient clinic for recurrent miscarriages between March 2000 and February 2005 were included. All women underwent a standard diagnostic workup to rule out the presence of antiphospholipid

Results

Patient characteristics are given in Table 1. No significant difference was found in pregnancy rates between women who were treated with the combination treatment and those who were not treated during the study period (52 of 80 [65%] vs. 74 of 130 [57%]; P=1.0). Fifty-two of 80 women (65%) became pregnant using the combination treatment and were assigned to the treatment group. The 52 women who became pregnant without treatment during the same observation period were assigned to the control

Discussion

This study demonstrates that a combination treatment consisting of prednisone, aspirin, progesterone, and folate results in a higher live birth rate than no treatment in women with IRM. Women who were treated with this combination had a 42% higher live birth rate than controls. In addition, we did not note a higher rate of preterm birth or intrauterine growth restriction among the treatment group. Our results are in accordance with previously reported data by Réznikoff-Etievant et al. (7) and

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Copyright © 2006 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.