Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Abstract

Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

Keywords: RPL; RPL management; miscarriage; pregnancy loss; recurrent miscarriage; recurrent pregnancy loss.

Figure 1

Studies selection flow-chart.

Figure 2

Etiology and risk factors of recurrent pregnancy loss. Figure legend: FOXP3—forkhead 3 box protein; FVL—factor V Leiden; HLA—human leukocyte antigen; MTHFR—methylenetetrahydrofolate reductase; NK—natural killer cells; PAI-1—plasminogen activator inhibitor-1; VDR—vitamin D receptors.

Figure 3

Recurrent pregnancy loss diagnostic and management algorithm. Figure legend: LA—lupus anticoagulant; ACA—anticardiolipin antibodies; anti-β2-GPA—anti-β2 glycoprotein antibodies; APA—antiphospholipid antibodies; APS—antiphospholipid syndrome; FVL—factor V Leiden; HLA—human leukocyte antigens; HS—hysteroscopy; MI—minimally invasive; MTHFR—methylenetetrahydrofolate reductase; LMWH—low-molecular-weight heparin; POC—products of conception; PAI-1—plasminogen activator inhibitor-1; PG—prothrombin gene; PGT—preimplantation genetic testing; RPL—recurrent pregnancy loss; TSH—thyroid-stimulating hormone; US—ultrasound.