Yale Bulletin and Calendar

March 23, 2007|Volume 35, Number 22

Ob/Gyn researchers announce new
findings at recent scientific meeting

Researchers from Yale's Department of Obstetrics, Gynecology & Reproductive Sciences (Yale Ob/Gyn) presented the following abstracts about their work at the Society for Gynecologic Investigation's 54th annual Scientific Meeting March 14-17 in Reno, Nevada.

Procedure predicts embryos most likely to result in pregnancy

To address the high rate of multiple births resulting from in-vitro-fertilization (IVF), researchers at the Yale School of Medicine and McGill University have developed a procedure that estimates the reproductive potential of individual embryos, possibly leading to a decrease in multiple-infant births and a higher success rate in women undergoing IVF.

Over 100,000 in-vitro fertilization procedures are performed each year in the United States. In 2002, 3.1 embryos on average were transferred in IVF cycles, but only 34.3% resulted in pregnancies. Of those successful pregnancies, 29% resulted in multiple births. These statistics remained unchanged within the last decade, suggesting to scientists that an improvement is needed over the current methodology used for embryo evaluation.

"The main reason for multiple gestations following in-vitro fertilization is the inability to precisely estimate the reproductive potential of individual embryos," says Dr. Emre Seli, assistant professor in Yale Ob/Gyn, who led the study. "The successes of in-vitro fertilization often result from simultaneous transfer of multiple embryos with the hope that at least one will lead to a pregnancy."

By comparing the content of the successful and unsuccessful embryos, the team established a metabolic profile of embryos that resulted in pregnancies as well as ones that did not. "We found that proton NMR, a non-invasive nuclear magnetic resonance form of spectroscopy, will determine the metabolic profile of the embryo and accurately predict its reproductive potential," says Seli, who plans to confirm the findings in a larger trial.

Other authors on the abstract included Denny Sakkas, Richard Scott, Lucy Botros and David H. Burns.

Proteins that cause blood vessel damage in preeclampsia identified

Proteins released by the placenta may damage blood vessels in women with preeclampsia (PE), according to Yale researchers. In PE, a complication of pregnancy linked to life-threatening increases in high blood pressure after 20 weeks of gestation, it has long been recognized that substances called "microparticles" released by the placenta damage maternal blood vessels.

Researchers at Yale and from Berne, Switzerland -- led by Seth Guller of Yale -- sought to detect whether specific proteins were found in microparticles. They studied placentas obtained from patients with preeclampsia who had uncomplicated pregnancies delivered at term by cesarean section. They found that microparticles released from the placenta contain a protein that regulates clot formation (plasminogen activator inhibitor-1). They also found that microparticles contain soluble Flt-1, which inhibits blood vessel growth, and that microparticles contain extremely high levels of plasminogen activator inhibitor-2, a placental protein with no known function.

"In this study, we demonstrate for the first time that microparticles released by the placenta may contain factors that damage maternal blood vessels in preeclampsia," says Guller, associate professor in Yale Ob/Gyn.

In this study, the team only detected whether specific proteins were found in microparticles, says Guller. "In the future, we will determine whether they are biologically active -- promote damage in vessel culture models -- and whether they are present in the blood of women with preeclampsia."

Other authors on the abstract included Yuehong Ma, Stefano Di Santo, Graciela Krikun, Antoine Malek and Henning Schneider.

Genetic variation in Hispanic women linked to spontaneous preterm birth

Yale researchers have found that in Hispanic women, four gene variants are linked to spontaneous preterm birth, a major cause of illness and death in newborns.

A genetic cause of preterm birth was suggested by racial disparity, a tendency to occur within families and a high rate of recurrence, according to Dr. Errol Norwitz, associate professor in Yale Ob/Gyn and the study's lead investigator.

Norwitz and his team prepared DNA samples from 102 mothers with a spontaneous unexplained preterm birth and 408 mothers who delivered at term with no complications. They then compared the distribution of 128 well-known genetic variations, known as single nucleotide polymorphisms, in 77 genes between the two groups.

"Our analysis demonstrates that, in an Hispanic population, mothers who carried any one of four polymorphisms were significantly more likely to have a spontaneous preterm birth," says Norwitz.

The risk of preterm birth was highest among women with the ENPP1 polymorphism variant.

"The strong association of ENPP1 was particularly compelling, but how this variant functions and why it predisposes preterm births still needs to be determined," says Norwitz.

In another abstract using the same study subjects, Norwitz and colleagues explored whether polymorphisms in the gene that encodes the progesterone receptor may identify women at risk for preterm birth. The team found no such association.

"Progesterone supplementation may prevent preterm birth in about 30% to 40% of women at high risk by virtue of a prior preterm birth, but exactly how progesterone supplementation works is still unknown," says Norwitz. "While this was a negative finding, it was an important question to answer."

Other authors on both abstracts included Thomas Morgan, Victoria Snegovskikh, Edward Kuczynski, Hee Joong Lee, Frederick Schatz, Se-Te Joseph Huang, Catalin Buhimschi, Edmund Funai, Irina Buhimschi, Antonette Dulay, Guoyang Luo, Sonya Abdel-Razeq and Charles Lockwood.

-- All Stories by Karen Peart

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Ob/Gyn researchers announce new findings at recent scientific meeting