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Stanford Report, August 11, 1999

Two-embryo transfer is as effective as three in new IVF procedure

BY RUTHANN RICHTER

Women who have undergone a new in vitro fertilization (IVF) procedure known as blastocyst transfer are just as likely to get pregnant if doctors transfer two embryos into the womb, as opposed to three, according to a new study by Stanford researchers. The study indicates that the new IVF approach can virtually eliminate the chance of triplets ­ which can be risky to the pregnancy ­ while maintaining, or possibly even increasing, a woman's chances of getting pregnant, said Amin Milki, MD, associate professor of gynecology and obstetrics and the lead author on the study.

"There are two major gambles with IVF," said Milki, medical director of Stanford's IVF program. "The first gamble is getting pregnant versus not getting pregnant. Once you achieve a pregnancy, the woman's second worry begins ­ how pregnant am I? This technique won't decrease her odds of conceiving and at the same time avoids her risk of having triplets."

The study involved 55 Stanford patients who chose to undergo blastocyst transfer in 1998, when Stanford first began offering the procedure. During the procedure, the embryo is bathed in a culture of nutrients for five days until it reaches a developmental landmark known as the blastocyst stage. At this point, doctors can discern which embryos are most likely to thrive and make their selection for transfer into the uterus.

Traditionally, doctors have performed transfers on day three, often implanting four or more embryos in the hope that some will do well and develop into a healthy fetus. However, the traditional approach sometimes can lead to the conception of three or more fetuses ­ a number that threatens the pregnancy and may force women to opt for selective reduction, the removal of one or more embryos to give the pregnancy a better chance of success. With the blastocyst method, doctors can transfer just two or three embryos, with a good chance of success.

In the study, Stanford researchers set out to determine whether two embryos might serve the purpose as well as three, avoiding the need for selective reduction, Milki said.

Indeed, their results showed that women who had two embryos transferred had just as good ­ in fact slightly better ­ chances of getting pregnant as those who had three embryos transferred. Of the 29 patients who chose to have a two-embryo transfer, 62 percent achieved a viable pregnancy, with all of them passing the first trimester mark. Among the 24 women who chose a three-embryo transfer, 58 percent conceived a viable pregnancy, the researchers reported in the August issue of the journal Fertility and Sterility.

"We've shown that with two embryos transferred, we're approximating the time when we can get a single-embryo transfer, which is incredible. Nobody previously thought we could transfer fewer embryos and get a higher pregnancy rate," said Barry Behr, PhD, assistant professor of gynecology and obstetrics and a co-author on the report.

Behr, director of the Stanford's IVF and Assisted Reproductive Technology Laboratory, developed the special culture used to nurture the embryos in
the laboratory.

The results suggest there is no value in transferring more than two embryos ­ and there is a benefit in that the technique can avoid high-risk, triplet births. Among the women who had two-embryo transfers, 39 percent conceived more than one fetus (all twins). Among those who had a three-embryo transfer, 79 percent conceived more than one fetus ­ 50 percent twins and the other 29 percent triplets. The patients who chose to transfer three embryos were counseled about the risks associated with multiple gestations. All those who conceived triplets elected to selectively reduce one embryo to minimize the overall risk of the pregnancy, Milki said.

Since the researchers compiled data on the initial 55 patients, Milki said the Stanford IVF Clinic has performed blastocyst transfer on an additional 55 women, with similar results.

He noted that success rates have been high in part because of patient selection. Blastocyst transfer has been offered to patients who produce more than three eight-cell embryos by day three ­ embryos considered likely to do well. But a separate study by Milki and his colleagues suggests that patient selection alone isn't the key. Extending embryo growth for another two days ­ until day five ­ confers a special advantage, they found. Among women whose embryos were nurtured for five days before being transferred, the pregnancy rate was 68 percent, he said. Among those who chose to have the embryos transferred on day three ­ before they reached the blastocyst stage ­ the pregnancy rate was 46 percent, Milki said.

In the latest study, the research team included Jeffrey Fisch, MD, a fellow in reproductive endocrinology. The study was funded by Stanford. SR