New insights into mechanisms behind miscarriage

Abstract

Sporadic miscarriage is the most common complication of early pregnancy. Two or three consecutive pregnancy losses is a less common phenomenon, and this is considered a distinct disease entity. Sporadic miscarriages are considered to primarily represent failure of abnormal embryos to progress to viability. Recurrent miscarriage is thought to have multiple etiologies, including parental chromosomal anomalies, maternal thrombophilic disorders, immune dysfunction and various endocrine disturbances. However, none of these conditions is specific to recurrent miscarriage or always associated with repeated early pregnancy loss. In recent years, new theories about the mechanisms behind sporadic and recurrent miscarriage have emerged. Epidemiological and genetic studies suggest a multifactorial background where immunological dysregulation in pregnancy may play a role, as well as lifestyle factors and changes in sperm DNA integrity. Recent experimental evidence has led to the concept that the decidualized endometrium acts as biosensor of embryo quality, which if disrupted, may lead to implantation of embryos destined to miscarry. These new insights into the mechanisms behind miscarriage offer the prospect of novel effective interventions that may prevent this distressing condition.

Figure 1

The pregnancy loss iceberg: an overview of the outcome of spontaneous human conceptions. It is estimated that 70% of conceptions are lost prior to live birth. The majority of these losses occur prior to implantation or before the missed menstrual period, and since they are not revealed to the woman they are termed preclinical. In the pregnancy loss ‘iceberg’, they are therefore below the ‘waterline’. Figure reproduced with permission from Oxford University Press [37].

Figure 2

The migration zone after adding a high-quality, low-quality or no embryo. The migratory response of decidualized human embryonic neural stem cells (H-EnSCs) from normally fertile (A-C) and recurrent miscarriage (RM) women (D-F) was analyzed in absence of a human embryo (A,D), in presence of a high-quality embryo (B,E) or a low-quality embryo (C,F). Phase contrast pictures were taken 18 h after creating the migration zone. The dotted line represents the front of the migration zone directly after its creation. As a reference for the position of the embryo, the bottom of the plate was marked. The arrows indicate the position of the embryo. All pictures were taken with 25 × magnification. (Reproduced from Weimar et al. [26]).