Placental proteins in the diagnosis and evaluation of the "elusive" early pregnancy

Abstract

For many many years much time and effort has been invested to identify, purify, and quantify markers of significant reproductive events. The search for such markers has been recently intensified with the widespread acceptance of IVF and ET as a treatment regimen for the management of certain causes of infertility. Now it is possible to monitor ovarian folliculogenesis and time of ovulation, successful fertilization, and subsequent nidation and the ensuing pregnancy. Following successful fertilization and zygote development, EPF, a protein complex which suppresses in vitro lymphocyte rosette formation can be detected within 24 hours. Shortly after implantation hCG can be measured in the maternal circulation. The developing trophoblastic tissue continues to synthesize and secrete into the maternal circulation many varied proteins including SP1, PAPP-A, and PP5. To date hCG is the mainstay of rapid and early pregnancy diagnosis and is an accepted biochemical marker of successful implantation and trophoblastic activity. Combination of hCG and EPF measurement offers the clinician new insight into his infertile patient for now it is possible to monitor successful fertilization and implantation as separate independent events. Such diagnostic assays should also provide new insight into early embryo mortality rate at the pre- and postimplantation stage and hence indicate the selection pressures acting on an embryo. It is the application of these assays which has led to the definition of subclinical abortions and to the description of biochemical pregnancies. The value of these proteins for the management of compromised early pregnancies has to be more fully examined. Although the differentiation between a normal and abnormal pregnancy is more readily ascertained by serial sampling and analysis of the time taken for circulating levels to double (3). Preliminary data suggest the potential of EPF and PAPP-A measurement in such clinical conditions is enormous. Our studies suggest that PAPP-A, at present, is the only biochemical marker which can predict pregnancy abortion, even in the presence of normal ultrasound scans, many weeks prior to the event, thus implying a vital biological role for PAPP-A in normal pregnancy (52). Despite the need for more intensive evaluation of these early pregnancy indicators the search for that "demmed elusive" marker has more than "Those Frenchies" earnestly looking for him here and there.