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Cedars-Sinai to Study Causes of IVF-Related Pregnancy Complications

NEW YORK (GenomeWeb News) – Scientists at Cedars-Sinai Medical Center in Los Angeles have received a $3.4 million grant from the National Institutes of Health to investigate possible genetic and epigenetic explanations for why pregnancies resulting from fertility treatments – particularly in vitro fertilization – are at increased risk for complications.

Cedars-Sinai said the five-year study, funded by the Eunice Kennedy Shriver National Institute of Child Health and Development, aims to determine if genetic or epigenetic factors may heighten the risk of adverse outcomes in pregnancies that result from assisted reproductive technologies (ART).

ART-derived pregnancies are at increased risk of several complications, including low birth weight, pre-eclampsia, placental abruption, placenta previa, preterm delivery, perinatal mortality, major structural birth defects, and other consequences. Many of these problems may be attributed to abnormalities of placentation and trophoblast differentiation in the first trimester.

"We are trying to understand what is causing the increased risk of problems for pregnancies achieved by in vitro fertilization," Margareta Pisarska, director of the Fertility and Reproductive Medicine Center at Cedars-Sinai and principal investigator on the project, said in a statement. "This study is so unique, and the first of its kind in humans, because we will be able to look at the earliest point in human pregnancy, when the fertilized egg implants, to determine if the adverse outcomes are the result of the genetic make-up of the parents that led to problems conceiving in the first place, or whether it is the result of the infertility treatments themselves."

The investigators will use samples from discarded tissues through Cedars-Sinai's Prenatal Biorepository, and they will couple those samples with a database of pregnancy-related data and clinical outcome information from the same pregnancies. This will enable the team to examine first-trimester trophoblasts that were obtained ruing the placentation period.

The researchers will use genome-wide genetic, epigenetic, and gene expression profiling to differentiate the impact of infertility genetics and IVF-induced epigenetic changes on placental function and fetal development. Specifically, they plan to quantify and compare gene expression and DNA methylation, as well as use genome-wide SNP and CNV profiles and exome-wide SNP profiles in samples from pregnancies that were conceived by in vitro methods and compare them to in vivo fertilization.

"We will be able to look at genes that get turned on right at the beginning of a pregnancy when the fertilized egg implants and compare that to genes that are turned on at the end of pregnancy to give us a snapshot of what is happening in utero. This will give us the ability, not only to look at the pregnancies that are achieved in couples with infertility, but it will also shed light on how normal pregnancies develop in the womb and how the intrauterine environment may affect the overall health of the infant, child, and adult, something called fetal origins of adult diseases," Pisarska explained.

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