Grant: Operating Grant

Pregnancy loss is a significant health concern as 15 percent of clinically recognized pregnancies end in miscarriage, with the highest rate in the first trimester. Although finding the cause of pregnancy loss is essential for prognosis, recurrence risk counseling, and the management of all future pregnancies, the cause remains unknown in 30-50 percent of all cases. Our recent studies of sporadic and recurrent miscarriages showed that previously not described and very tiny chromosome changes, detectable only by genomic array technology, occur in 30 percent of miscarriages. In addition, our studies revealed that these tiny (submicroscopic) chromosomal abnormalities may also occur in couples with a history of recurrent pregnancy loss and may represent predisposing genetic factors for recurrent pregnancy loss (RPL). We propose to expand our screening for submicroscopic chromosomal abnormalities to additional miscarriages and couples with RPL in order to identify new genetic causes for RPL. Furthermore, we propose to determine if the function of the genes affected by these submicroscopic rearrangements (candidate miscarriage genes) is altered. We will focus on genes which have a suspected function in reproduction and early embryo/placenta development. The benefit of our study is that costly multiple testing and searching for causes of miscarriage can be eliminated for couples found to carry or transmit the candidate miscarriage genes to their pregnancies. In addition, new genes important for maintaining a successful pregnancy will be identified. The better understanding of genetic factors that contribute to pregnancy loss will pave the path for their future prevention and treatment and facilitate optimal care for reproductive health of families wishing to have a successful future pregnancy.