Making babies goes high-tech

Even now, Debbie Greer can’t help but visit the infertility message boards online. Nowhere is there quite so much hope and love mingled with such heartache and desperation. It flows out from the multitude of acronyms and abbreviations: IVF, ICSI, BFP. It blinks passionately from emoticons that flash smiling icons and sobbing symbols. There are women here who suffer from polycystic ovary syndrome, women whose husbands have severe male factor infertility, women who speak of egg retrieval and follicles and embryo transfers with the familiarity of a scientist. Women who have tried every assisted reproductive technology available, over and over again, for as many as 11 years.

Only a few months ago, Greer was one of those women, and like a member of some secret society, she continues to read the message boards to remind herself how fragile the journey from infertility to parenthood is. Because in July, she became one of the lucky ones. After undergoing in vitro fertilization at the Duke Reproductive Endocrinology and Fertility division, she received what she had wanted for more than four years: a BFP-Big Fat Positive pregnancy test.

Those BFPs are better than gold to couples who struggle with infertility–and to the physicians at Duke who provide countless boxes of Kleenex each month as they shepherd their patients through the process. But Greer is doubly lucky: thanks to the pluck and prowess of the clinic’s researchers, she got pregnant after only her first cycle of IVF, and she and her husband won’t need a six-passenger minivan just to come home from the hospital next spring.

The Greers are having one baby. One, and only one. And that’s just the result Duke wants.

“There are consequences to improving fertility,” says David Walmer, MD, PhD, chief of the division. “Like improving it too much. And so our goal is to improve fertility while minimizing high-order multiple gestation. It’s one of the most important things we can work on as physicians in this field today.”

To that end, Walmer and his colleagues have made the investigation of embryo quality a specialty, coaxing hints from the little bundles of cells while they are still in the lab after fertilization. As a result, pregnancy rates at the clinic have gone from 10 percent with four or five embryos transferred a decade ago to 40 percent with just two or three embryos today.

The secret, says the clinic’s IVF program director, Grace Couchman, MD, is in the rate of cell division. In the mid-1990s, several labs around the world were trying to improve pregnancy rates by growing embryos in vitro in media that mimicked the uterine environment instead of the usual fallopian tube solution. It was an important idea: embryos that could be grown in the lab for five or six days instead of the usual three-the point at which they make the journey from the tubes to the uterus in the body-could give physicians more information to better predict their ability to become blastocysts and, eventually, full-term babies, once implanted in the mother.

But Walmer found that many of those embryos never made it to blastocysts. The result was an unacceptably high miscarriage rate among the pregnancies that took after implantation.

Couchman believed a method existed to unlock an embryo’s secrets during the commonly used three-day window. She took careful observations of the early embryos as their cells divided, looking at not only the speed and quantity, but their symmetry and fragmentation.

Bingo.

An embryo that had divided out to eight cells by day three in vitro had a far better chance of resulting in pregnancy than one that had only four cells, Couchman found. Even better were eight-cell embryos without fragmentation, or little bits of cytoplasm on the edges.

“That doesn’t mean you can’t get pregnant with a four- or five- or six-cell embryo,” says Couchman. “But the statistical likelihood is lower. We link embryo quality to pregnancy outcomes. It means that if we have ideal, eight-cell embryos … we can put back fewer numbers of embryos and lessen the chance of them having triplets and quads.”

The advancements in fertility technology can’t come quickly enough for couples who seek help, whose numbers are increasing each year. After the use of fertility drugs to stimulate ovulation, IVF is one of the most popular methods to combat infertility, and Duke now does more than 250 cycles of the procedure annually. Just two years ago, the clinic performed 100 cycles.

Next year, the Reproductive Endocrinology and Fertility main offices will move into a new state-of-the-art building near the Streets at Southpoint mall in Durham, where even the air will be part of the therapy standard. The air quality will be measured in parts-per-billion to ensure that the IVF lab cultures and embryos are protected from toxic materials in the atmosphere, improving the possibility of success for its IVF patients. If standards aren’t met during construction, Walmer says, they’ll “rip it out and start over.”

All of this is to service the 10 to 15 percent of couples nationwide who have trouble conceiving after a year of trying; in their late 30s and early 40s, as many as half struggle with fertility issues. Those numbers haven’t changed much over the years. What has increased is the number of women waiting longer to start families. Advanced maternal age, along with anovulation, are the two biggest culprits in infertility troubles, Couchman says.

“I see a lot of educated women who have no idea they are waiting too long,” she says. “Some are choosing to wait, some haven’t yet met the right individual. But I also talk to women who say, ‘If I had known that it would be this hard to get pregnant at 39, I really might have thought of doing something earlier.'”

The Duke researchers and clinicians strongly encourage women not to wait until their fertility declines in their late 30s to get pregnant, if they are sure they want children. The odds of procedures like IVF working decline with age as well, and while People magazine may have an actress over 40 who is newly pregnant in each issue, patients should remember that celebrities can afford the expense of medical interventions like IVF, which can run as much as $10,000-15,000 per cycle.

But options may soon exist for women who are making the choice to stay childless longer, as well as for cancer patients who want to have families after potentially damaging chemotherapy. Duke is working on a new technique, currently practiced with only minimal success at a handful of other centers in the country, in which women can harvest their eggs and freeze them until they are ready to become pregnant. The therapy, which Couchman expects to have available in as soon as six months-but not before its results are perfected-gives women and couples more freedom to defy the ticking biological clock. Already, men who are undergoing chemotherapy or who have had vasectomies can freeze their sperm through ejaculation or biopsies, but the fragility of women’s eggs has made them a more difficult science
to conquer.

Couchman has been on the front lines of combating the often underestimated problem of male factor infertility as well. Forty percent of couples have trouble conceiving due to low sperm counts or other male infertility issues. Before the 1990s, even IVF wasn’t useful in those situations. But Couchman has perfected an intracytoplasmic sperm injection (ICSI) program that she began at Duke in the late 1990s–now, by injecting a single sperm using a needle with a diameter of a human hair into an egg, couples can get pregnant using IVF.

“That has revolutionized male factor infertility,” says Couchman. “It’s completely changed the options for couples.”

Even patients who shy away from IVF because of cost can squelch their fears by taking advantage of Duke’s financing options. When a couple signs up for three treatment cycles through Duke’s partnership with Advanced Reproductive Care, around 85 percent of their money is refunded if they don’t go home with a child during one of them.

With so many novel treatments available, it’s hard to believe anyone would have trouble conceiving with their own eggs and sperm. But in those instances, Duke’s anonymous donor egg program, which has a success rate between 50 and 75 percent, has helped many couples achieve families. The first live birth from a donor egg in North Carolina happened through Duke on Valentine’s Day in 1990–a set of twins who kicked off a long string of babies born from the generosity of donors.

“Young ladies who are willing to donate take the patients in our program who have the lowest chance of success and elevate them to the highest,” Walmer says.

When assisted reproductive techniques are unsuccessful, some couples are more willing to consider adoption–an option that the physicians and staff, including a psychologist, counsel patients about at the outset of their relationship together. Because in fertility science, there is no such thing as a BFG–Big Fat Guarantee.

“People come here because they are seeking a child with their own gametes,” Couchman says. “But they come here mostly because they want to have a family, and we want them to reach their goal in whatever way possible.”

Article Copyright 2005 DukeMed Magazine

published in DukeMed, Fall/Winter 2005. 

 

Additional stories in this feature:

Mixing Faith and Science

One Small Step for Fertility …