Recurrent pregnancy loss (RPL), defined as multiple consecutive miscarriages, is a devastating disorder for which there are no good treatment options. Two opposing paradigms have emerged to explain RPL. The… Click to show full abstract
Recurrent pregnancy loss (RPL), defined as multiple consecutive miscarriages, is a devastating disorder for which there are no good treatment options. Two opposing paradigms have emerged to explain RPL. The prevailing clinical viewpoint is that RPL is caused by a spectrum of subclinical disorders, ranging from thrombophilia to anatomical, endocrine and immunological disorders, that somehow converge on a ‘fragile’ early pregnancy state, leading to miscarriage. A new paradigm, based on emerging concepts around early implantation events, challenges the conventional thinking around RPL. It purports that the high incidence of embryonic aneuploidies and mosaicism coupled with a cycling endometrium necessitates the introduction of multiple ‘quality control’ checkpoints in the first trimester of pregnancy to limit maternal investment in a failing pregnancy. Here we review the evidence underpinning both paradigms and examine how new thinking around RPL may lead to more effective preventative strategies.
               
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