Publication Date: Wednesday Apr 8, 1998

INFERTILITY: In-vitro process improved

Holly Rodriguez had tried for four years to get pregnant with her first child. Both she and her husband, Terry Stover, faced several obstacles: a blocked fallopian tube, a thin cervical lining and low sperm count.

On five occasions they had tried inner uterine inseminations, a process in which sperm was inserted into the uterus around the time of ovulation. None of the attempts were successful.

"It was a roller coaster every month for me," recalled 39-year-old Rodriguez. "I never knew when I was going to ovulate, so life was really disrupted."

The couple eventually decided to opt for in-vitro fertilization (IVF), in which Holly's egg and her husband's sperm would be fertilized in a lab environment, instead of the fallopian tubes, and then transferred to the uterus.

They chose to enlist the services of Dr. Amin Milki, director of the Stanford IVF program and associate professor of gynecology and obstetrics. Under his care, they opted to try a new technology that minimizes the odds of multiple pregnancies.

Stanford is the first medical center to use the new approach more routinely in patients. The approach uses a chemical medium to keep artificially fertilized embryos growing in the lab for a longer period of time. The additional time (about two days) allows more embryos to reach a developmental milestone called the blastocyst stage. At that point, around day 5, it is much easier for scientists to discern which embryos are most viable. Consequently, only embryos that have reached the blastocyst stage are transferred to the uterus.

Milki said doctors don't try to rejuvenate weaker embryos. "It's a medium that mimics the natural environment of the fallopian tube and is very hospitable for embryo growth. And it buys more time for the embryos to display their actual potential for implantation."

Up until about two years ago, the culture used to grow embryos was not optimal enough to allow a high percentage of embryos to survive until the fifth day. Consequently, embryos would be transferred to the uterus early, on the second day, to give them the best chance at survival. This contradicted the natural sequence of events, since the embryo is normally still in the fallopian tube on Day 2.

Today, due to an improvement in culture techniques, 90 percent of IVF programs culture embryos through the third day. However, even though viable embryos are narrowed down at this later stage, reproductive specialists might still transfer four to six embryos to the woman's uterus. A significant number of such cases result in high-order multiple pregnancies (quadruplets or more) that are often beset by complications. Couples would then face the dilemma of proceeding with a risky pregnancy or considering selective reduction, where doctors remove one or more embryos to give the pregnancy a better chance of succeeding.

Thanks to the new culture, Stanford's IVF program can offer couples the option of nurturing their embryos to the fifth day (provided they have more than three embryos on day 3) in order to limit the numbers transfered, and reduce the incidence of high-order multiple births.

The ethical dilemma surrounding selective reduction is substantially minimized or even erased.

Rodriguez had 10 eggs harvested on Feb. 25 and nine fertilized. Six embryos made it to day 3. At that point, the most viable ones could not be discerned and it was not certain that the embryos would last until day 5. She entertained the notion of transfering all six on day 3.

"But we thought it was better to wait until day 5 and have a more realistic perspective," said the Pleasanton resident. "It was easier to accept the numbers going down if they're not inside you."

By day 5, two embryos had advanced to the blastocyst stage, and were transfered to Rodriguez' uterus. Another embryo eventually did reach the blastocyst stage; it was frozen for a subsequent pregnancy.

Rodriguez is now five weeks pregnant.

Selective reduction was never an issue for Menlo Park resident Catherine McMillan, who underwent IVF in January under Dr. Milki's care. Out of seven fertilized embryos, six were still viable on day 3. By day 5, only two had reached the critical blastocyst stage.

"My husband and I felt lucky that we didn't have to choose among them or freeze them," said 38-year-old McMillan, the mother of a three-and-a-half-year-old daughter. "The ethical side was taken care of. It wouldn't have been the case if they didn't have this five-day transfer."

Today, McMillan is nine weeks pregnant.

Except for one patient who may be carrying triplets, all of Stanfords patients have either singletons or twins. Both McMillan and Rodriguez appear to be carrying only one child.

The two women are part of a group of 10 women (out of 12 patients, aged 30-40) who have shown positive pregnancy tests since the new IVF procedure began at Stanford in December. Of these 10, eight women have viable pregnancies. Two other women had miscarriages, while two did not conceive.

"Based on these initial patients," said Milki, "this technique allows us to limit the numbers of embryos transfered without any jeopardy to the pregnancy rate. The success rate may be even higher than for the third day transfer, perhaps because we're transferring them to the uterus on day 5, when they would naturally implant there. However this theory can't be confirmed by just 12 patients."

So far, 100 percent of Milki's patients were able to have a fifth day transfer, and all had at least two blastocysts available. Chances are, however, that with more subjects, there may be some people who won't have any embryos to put back by day 5, Milki cautions.

Given the success so far, Milki hopes that the blastocyst culture will become routine in most IVF programs.

"When I started doing IVF a few years ago, a good clinic would have a 25 percent pregnancy rate," said Andrea Speck-Zulac, a Stanford nurse practitioner and IVF coordinator. "But since we've been doing the blastocyst transfer, the pregnancy rate has been over 80 percent. Most of the time I'm calling with good news," she said. 

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