Evidence-based care of recurrent miscarriage

Area of Science:

• Reproductive Medicine
• Genetics
• Immunology

Background:

• Recurrent pregnancy loss (RPL) affects 0.5-1.0% of couples, defined as three or more consecutive miscarriages.
• Identified causes include genetic abnormalities (2-4%), inherited thrombophilias (Factor V Leiden, prothrombin G20210A), antiphospholipid syndrome, and uterine abnormalities.
• A significant portion of RPL cases (~50%) have no identifiable cause, leading to the exploration of novel etiologies.

Purpose of the Study:

• To review the known and proposed causes of recurrent pregnancy loss (RPL).
• To critically evaluate the scientific evidence supporting various proposed etiologies of RPL.
• To highlight the diagnostic and therapeutic challenges in managing RPL.

Main Methods:

• Literature review of studies on recurrent pregnancy loss.
• Analysis of genetic, thrombophilic, autoimmune, and uterine factors implicated in RPL.
• Examination of proposed but unvalidated causes like alloimmune incompatibility.

Main Results:

• Genetic abnormalities and inherited thrombophilias are established causes of RPL in a small percentage of couples.
• Antiphospholipid syndrome is a known cause, with thromboprophylaxis shown to reduce miscarriage risk.
• Progesterone supplementation and antenatal thromboprophylaxis for certain conditions lack robust evidence of efficacy.
• Alloimmune incompatibility remains a proposed but scientifically unvalidated cause for unexplained RPL.

Conclusions:

• RPL has diverse etiologies, ranging from well-established genetic and autoimmune conditions to unexplained cases.
• The efficacy of certain interventions like progesterone and thromboprophylaxis in specific RPL contexts requires further investigation.
• Further research is needed to validate proposed causes like alloimmune incompatibility and to improve management strategies for unexplained RPL.