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

METHODS: 

• 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 

RESULTS: 

• 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) 

CONCLUSION: 

• 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 

Learn More – Primary Sources: 

Treatment efficacy for idiopathic recurrent pregnancy loss – a systematic review and meta-analyses.