50A - Progesterone Treatment Does Not Help Recurrent Miscarriage Patients

Summary

Recurrent miscarriage, defined as the loss of three or more consecutive early pregnancies, affects 1-2% of the population. In at least 50% of cases this is due to recurrent fetal aneuploidy. Despite numerous proposed aetiologies (endocrine; immune and anatomical), only obstetric antiphospholid syndrome has withstood critical evaluation over an extended period – 30 years. Progesterone, secreted by the corpus luteum, is recognised to play a cardinal role in early pregnancy. Its actions are mediated through both genomic (via nuclear and membrane bound receptors) and non-genomic mechanisms which include modulation of the maternal immune response, promotion of a TH2 cytokine response and up-regulation of Tissue Factor and PAI-1 activity. A murine knockout model of progesterone receptor A demonstrates impaired endometrial decidualisation and implantation failure. Seminal work by Robert Casper reported that progesterone secretion by the corpus luteum is an absolute requirement for a successful pregnancy. Lutectomy before 8 weeks of pregnancy results in a decrease in progesterone levels and miscarriage. Pregnancy is rescued by the administration of exogenous progesterone. Administration of an anti-progesterone, Mifepristone, leads to pregnancy loss. Progesterone levels are lower in pregnancies that miscarry compared to those that are on-going.