#Grand Rounds

How Effective are Treatments for Unexplained Recurrent Miscarriage?

BACKGROUND AND PURPOSE:

Recurrent pregnancy loss (RPL) is unexplained in approximately 50% of cases
- RPL is estimated to vary between 0.5% and 2.3% in different populations
- RPL definitions are not consistent as some define RPL as ≥3 losses before gestational week 22 while some use ≥2 losses
Evidence based treatment is limited but there have been several suggested treatments that includes
- Acetylsalicylic acid | Low molecular weight heparin | Progesterone | Intravenous immunoglobulin | Corticosteroids | Leukocyte immune therapy | Pre-implantation genetic screening | tender loving care
Roepke et al. (Acta Obstetricia et Gynecologica Scandinavica, 2018) contrasted treatment efficacies in women with unexplained recurrent pregnancy loss

Systematic review and meta-analysis
Literary search included 21 randomized controlled trials (RCTs) with women who had ≥3 miscarriages and treated with one of the following
- Acetylsalicylic acid
- Low molecular weight heparin
- Progesterone
- Intravenous immunoglobulin
- Leukocyte immune therapy
Outcomes
- Live birth; at gestational age ≥ 22 completed weeks
- Complications or side effects
Only studies with outcome of live birth and/or complication were included
The study quality was assessed and data was extracted independently by at least two authors

There was no significant difference in live birth rates between acetylsalicylic acid, low molecular weight heparin or placebo
Meta-analysis of low molecular weight heparin vs. control found no significant differences in live birth rate
- Risk ratio (RR) 1.47 (95% CI, 0.83-2.61)
Treatment with progesterone starting in the luteal phase seemed effective in increasing live birth rate
- RR 1.18 (95% CI 1.09-1.27)
- There was no benefit to progesterone when started after conception
Intravenous immunoglobulin showed no effect on live birth rate compared with placebo
- RR 1.07 (95% CI 0.91-1.26)
Paternal immunization compared with autologous immunization showed a significant difference in outcome, although the studies were small and at high risk of bias
- RR 1.8 (95% CI 1.34-2.41)

While the studies had strengths, the authors acknowledge that
- Not including large RCTs that used a ≥2 losses definition rather than 3 could impact results
- Overall, studies suffer from low quality and bias
- Progesterone administered at ovulation and continued through the luteal phase was the only significant treatment for idiopathic recurrent pregnancy loss
They suggest that treatments for recurrent pregnancy loss should be used within the context of RCTs

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