EVIDENCE-BASED ANSWER
Progesterone produces a small but significant decrease in miscarriage among pregnant women with 3 or more unexplained pregnancy losses (strength of recommendation [SOR]: A, based on a meta-analysis of 3 small randomized controlled trials [RCTs] with wide confidence intervals). Human chorionic gonadotropin (HCG) reduces the rate of recurrent pregnancy loss among women with 2 or more unexplained pregnancy losses (SOR: B, based on a meta-analysis of 4 RCTs with significant methodologic weaknesses).
Four types of immunotherapy are ineffective for preventing miscarriage (SOR: A, based on RCTs and systematic reviews of RCTs). Aspirin therapy is ineffective for preventing recurrent miscarriage for women who do not have an autoimmune explanation for previous pregnancy losses (SOR: A, based on RCTs).
CLINICAL COMMENTARY
Document your patient’s understanding of the risks and benefits
Beth Damitz, MD
Medical College of Wisconsin
When discussing future childbearing with a woman who has had multiple miscarriages, there are several important issues to address. First, ask what concerns she might have about becoming pregnant again. Second, ascertain how significant another pregnancy loss would be to her. Third, outline the therapeutic options, clearly stating that they alter loss rates but do not guarantee successful delivery. Finally, fully document her understanding of the risks and benefits, including the possibility of treatment failure. Remember, even if the miscarriage rate is reduced from 25% to 20% with treatment, should your patient miscarry, her miscarriage rate is 100%!
Evidence summary
Progesterone. A Cochrane meta-analysis on the use of progesterone to prevent pregnancy loss looked at a subset of 3 small RCTs that evaluated women with 3 or more pregnancy losses. Patients with primary recurrent spontaneous abortion (RSA) (no prior live births), were not differentiated from those with secondary RSA (previous live birth with subsequent miscarriages).
Progesterone administration resulted in a significant reduction in miscarriage compared with placebo (odds ratio [OR]=0.37; 95% confidence interval [CI], 0.17–0.91), independent of administration routes (oral, vaginal, or intramuscular). This benefit was lost in the larger meta-analysis when studies containing women with fewer than 3 pregnancy losses were included.1
Human choriogonadotropin. A meta-analysis reviewed 4 trials (n=180 total) of varying methodological quality, which were constructed to determine if women, with at least 2 consecutive miscarriages of unknown cause, derive any protective effect when they receive HCG during the first trimester. Although the overall outcome favored the use of HCG (OR=0.26 compared with placebo; 95% CI, 0.14–0.52), the trials contained major methodological weaknesses (poor description of methods, no power calculations, selection and unclear randomization techniques).2
Immunotherapy. A systematic review of 22 RCTs evaluating 4 different types of immunotherapy for recurrent miscarriage found no significant improvement in live birth rates. All studies were of high quality with a low level of bias. Only one lacked double-blinding.
Immunotherapy types included: paternal leukocyte immunization (PLI) (11 trials, 596 women) (OR=1.05; 95% CI, 0.75–1.47); intravenous immune globulin (IVIG) (OR=0.98; 95% CI, 0.61–1.58); third-party donor cell immunization (3 trials, 156 women) (OR=1.39; 95% CI, 0.68–2.82); and trophoblast membrane infusion (1 trial, 37 women) (OR=0.40; 95% CI, 0.11–1.45).3