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Embryos on Ice May Provide More Successful IVF

Image of Cyropreservation

Think Ice, Ice … Baby.

If you are a couple considering in vitro fertilization (IVF), you may want to ask your fertility doctor about the possibility of freezing all of the embryos and transferring one later in a frozen embryo transfer (FET). Why? Spanish researchers have presented the first meta-analysis that indicates that the chance of a clinical pregnancy is around 30 percent higher when all embryos are frozen for later transfer than with fresh embryo transfer. And Australian researchers who analyzed more than 50,000 births between 2004 and 2008 say that a policy of single embryo transfer (SET) is associated with a reduction in perinatal mortality in infants born as a a result of IVF and intracytoplasmic sperm injection (ICSI).

Both studies were presented at the European Society of Human Reproduction and Embryology (ESHRE) conference in Istanbul, Turkey, in July.

"It has become very routine for us in the last year to incorporate preimplantation genetic screening (PGS), and we do the embryo testing at the blastocyst stage for PGS and PGD procedures," says Brad Hurst, M.D., Director of Assisted Reproduction with the Center for Reproductive Medicine at Carolinas Medical Center's Women's Institute. "Typically we'll vitrify the embryos and come back later and do a frozen embryo transfer. We're using PGS also to help us do more single embryo transfer procedures."

PGS is a laboratory procedure in which the embryologist extracts cells from the developing embryo and tests them to make sure the embryo is chromosomally normal. Then, the fertility doctor can transfer only the healthiest embryo(s) that has the best chance for implantation.

"There have been a number of studies comparing frozen embryo transfer to fresh embryo transfer that show the risk of birth defects is lower, and the birth weight of the baby is higher with frozen vs. fresh," Dr. Hurst explains.

The Most Recent Frozen Embryo Transfer Study

In the most recent study led by Professor Miguel Angel Checa from the Hospital Universitari del Mar in Barcelona, Spain, researchers did a systematic review of 64 relevant studies — including three randomized trials — performed before December 2011. The review was based on information from 633 IVF/ICSI cycles in which 316 were randomized to fresh embryo transfer and 317 to frozen embryo transfer. The results showed, based on a relative risk calculation, that the probability of a clinical pregnancy is significantly higher from freeze-all cycles than in fresh embryo transfers. The miscarriage rates did not show significantly differences between the two groups.

What is the difference between a fresh embryo cycle and a frozen one? The embryos generated in a stimulated IVF cycle are cryopreserved and then transferred in a later, less stimulated or non-stimulated cycle. This approach avoids the ill effects fertility drugs may have on the lining of the uterus (endometrium) and its ability to receive the embryo for implantation.

"The endometrium is better prepared for a frozen embryo transfer," says Dr. Hurst. "When we do an IVF, the woman's estrogen levels may be 10 times what they normally may be, and progesterone levels are different, so the uterus just isn't ideally prepared to accept the pregnancy. The endometrium can potentially have implications on how the babies develop.

"With frozen embryo transfer, what we do is prescribe estrogen and progesterone to control the cycle, and many of the studies have shown that what we consider a programmed FET cycle has a little bit higher success rate than a natural cycle," Dr. Hurst continues. "It used to be that we would prescribe progesterone shots, but now we do most FETs with vaginal progesterone."

Dr. Hurst does say that the fertility clinic environment must be right in order to have success with FET. The ability to test the embryos at the blastocyst stage via PGS to see if there are chromosomal abnormalities is key. "Culture environment that supports embryo development, the freezing and thawing techniques, there's a lot of infrastructure that's important to be able to successfully do an FET," he says.

The Success of Single Embryo Transfer

In the single embryo transfer study presented to ESHRE, the researchers found that births following the transfer of two embryos had a significantly higher perinatal mortality rate (19.1 per 1,000 births) than births following SET (13.2 per 1,000 births). The risk of perinatal mortality for all births following two embryo transfer was 53 percent higher than those following SET. Interestingly, the difference was especially apparent in births following the transfer of fresh (and not frozen) embryos — births following the transfer of two fresh embryos had s 74 percent higher risk of perinatal mortality than births following fresh SET.

Australia and New Zealand have voluntary adopted an IVF policy of single embryo transfer, and the policy has been associated with a reduction in overall perinatal mortality for all babies conceived by assisted reproduction methods.

"The data is pretty conclusive that single babies are healthier than twins, and studies have shown that intellectual development and behavioral development is better with single babies," Dr. Hurst says. "So if we can avoid twins, that's better."

He says that in his practice during 2012, there were probably only 10 percent of patients under 35 who did a single embryo transfer. "But we're moving more into that direction," he says. "When we incorporate PGS into the process, most of those are done as single embryo transfer."

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