Recurrent pregnancy loss: current perspectives

Abstract

Recurrent pregnancy loss is an important reproductive health issue, affecting 2%–5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy loss.

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“…Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. (El Hachem et al, 2017) It is recorded that the disorders which promote to venous thrombosis, are all named "thrombophilias," which have a role in the pathogenesis or the process of fetal loss. The great differences between theories as well as keeping in mind the correlation between such disorders and unexplained pregnancy loss suggests the presence of underlying risk modifiers (Mercier et al ., 2007).…”

Immunologic and rheumatologic causes and treatment of recurrent pregnancy loss: what is the evidence?

“…Additional proposed etiologies include inherited thrombophilia, luteal phase defect, immunologic abnormalities, and sperm DNA fragmentation. Up to half of RPL cases are unexplained (23)(24)(25).…”

The effects of DICER1 and DROSHA polymorphisms on susceptibility to recurrent spontaneous abortion

“…The etiology of RSA is not well understood although chromosomal abnormalities including translocations, inversions, deletions, and duplications are known in 50% of first trimester spontaneous abortions . Moreover, uterine anatomic anomalies, metabolic and endocrine problems, abnormal inflammation responses, thrombophilia, and infections are identified as other risk factors for the pathogenesis of RSA . However, the exact cause of RSA remains unknown in more than 50% of RSA cases classified as idiopathic unexplained RSA (URSA) …”

“…problems, abnormal inflammation responses, thrombophilia, and infections are identified as other risk factors for the pathogenesis of RSA. 3,4 However, the exact cause of RSA remains unknown in more than 50% of RSA cases classified as idiopathic unexplained RSA (URSA). 5 Genetic variations are described as other risk factors for susceptibility to idiopathic RSA.…”