New IVF Guidelines Urge Cutting Embryo Transfers

OB/GYN News, Dec 15, 1999 by Kathryn Demott

Two embryo transfers for some women.

New in vitro fertilization guidelines recommend cutting back the maximum number of embryos transferred from three to two among young women who stand the best chance of becoming pregnant.

If followed, that advice would virtually eliminate the occurrence of higher-order multiple gestations among the estimated 20% of IVF patients with the best prognosis, while only slightly impairing their shot at pregnancy, said Dr. Phil McNamee, president of the Society for Assisted Reproductive Technology (SART). The society issued the guidelines jointly with American Society for Reproductive Medicine (ASRM) last month.

Still, the guidelines aren't likely to make much of a dent in the overall rate of higher-order multiples, which spiked alarmingly in the last decade.

IVF really isn't a big contributor to the rate of higher-order multiples, Dr. McNamee said. Even among women in the youngest age groups--who are at the greatest risk of higher-order multiple gestations--the risk of triplets from IVF is only about 10% Overall, the risk of triplets arising from IVF is 6%.

By far, the vast majority of higher-order multiple gestations are due to superovulation. But given the extreme maternal and fetal risks involved, "if we have any higher-order multiples, we want to stop [them]," Dr. McNamee said.

The guidelines address traditional IVF procedures in which embryos are transferred on day 3. They do not address the newer blastocyst transfer procedure, in which embryos are transferred on day 5, allowing clinicians to more accurately predict which embryos have the best implantation potential, Dr. McNamee said. At many clinics that offer the blastocyst procedure, the transfer of two blastocysts is already the norm.

ASRM and SART were spurred to revise their IVF guidelines, initially released in 1998, by findings from a recent study conducted by investigators with the Centers for Disease Control and Prevention.

In that study, Laura A. Schieve, Ph.D., and her colleagues analyzed 35,554 IVF cycles to determine how various factors, including age and the number of embryos transferred, affected the chances of pregnancy and the risk of higher-order multiple gestations and births (JAMA 282[19l]:1832-38, 1999).

Overall, women in the two youngest age groups, 20-29 and 30-34, had higher pregnancy rates than older women. Furthermore, the best pregnancy rates in these young women were among those who had leftover embryos available for cryopreservation; presumably, higher quality embryos were used for transfer in these women.

Women in the two youngest age groups who had embryos available for preservation achieved live-birth rates of 43% and 36%, respectively when just two embryos were transferred.

Those rates were "more than double" those observed among women of the same age when two embryos were transferred but cryopreservation wasn't an option.

Transferring three embryos did not significantly improve live-birth rates in young women. In fact, among women aged 20-29 and 30-34, the rates of triplet births were 10% and 7%, respectively when three embryos were transferred.

In other words, when two embryos are transferred to women in the very best prognosis group "you give up very little in terms of pregnancy rate, and you really cut the risk of higher-order multiples to almost nothing," Dr. McNamee said.

That may be true, said Dr. Amin Milki, director of the IVF program at Stanford (Calif.) University, but it's still going to be a hard sell to IVF recipients, many of whom are paying for the procedure out-of-pocket and want the best odds of becoming pregnant. Preventing higher-order multiple gestations is seen by many of these women as a lower priority, he said.

Since most patients do not have several good-quality embryos when performing traditional IVF, "we rarely put back just two," Dr. Milki said. When more than two embryos are of high quality, we suggest culturing the embryos until the fifth day when it is easier to select the best two embryos for transfer. In this fashion the agonizing decision of selective reduction can be avoided without compromising the chance of pregnancy.

Only about 10% of couples are unwilling to have selective reduction performed if they become pregnant with higher-order multiples, but no one is ever fully comfortable with that option, he added.

CDC study findings may have a more powerful impact on persuading people that pregnancy can be achieved with only two embryos, Dr. Milki noted.

For all other women--those in the youngest age groups who don't have preservable embryos and for older women undergoing IVF--the study confirmed the appropriateness of the original recommendations, which are as follows:

* For women under age 35 without preservable embryos, usually no more than three quality embryos should be transferred.

* For women aged 35-40, usually no more than four quality embryos should be transferred.

* For women older than 40 or who have failed multiple cycles, usually no more than five quality embryos should be transferred.