Twenty-eight years after the first "test-tube" baby in the United States was conceived at a lab in Norfolk, infertility treatments are still evolving and the ethical questions haven't subsided. If anything, the issues surrounding assisted reproductive technology have become increasingly complicated.
Since that birth in 1981 — three years after a birth resulting from in vitro fertilization (IVF) made history in England — IVF is still the most common fertility treatment. In these procedures, a lab prepares a fertilized embryo using a couple's egg and sperm, and the embryo is implanted in the woman through a procedure no more uncomfortable than having a Pap smear.
But now, through new research and technology, it is possible to screen embryos for certain diseases and genetic disorders. And Richmond-area labs are working toward being able to freeze not just embryos but unfertilized eggs as well, leaving open the possibility of delaying childbirth or protecting the eggs from effects of a medical treatment that may impair a woman's childbearing ability.
The screening, called preimplantation genetic diagnosis (PGD), is a process where a single cell is removed from the fertilized embryo before it is transferred to the woman to identify whether the chromosomes are affected by diseases such as cystic fibrosis or sickle cell disease. PGD also screens for genetic disorders including muscular dystrophy and Tay Sachs disease, and success rates for the process have significantly increased, says Dr. Michael C. Edelstein, a reproductive endocrinologist with the Fertility Institute of Virginia at Johnston-Willis Hospital.
Such options bring up ethical questions, including the possibility of screening to choose a child's sex, says Scott Lucidi, associate professor of reproductive endocrinology and infertility in VCU's Department of Obstetrics and Gynecology.
"I don't believe there is anyone in the Richmond area that is doing sex selection for family balancing, although there are people in the United States who will," he says. "It is deemed unethical to put the woman through all that for the purposes of family balancing."
Lucidi says that parents decide the fate of abnormal embryos. Possibilities include discarding them or donating them for research; for mild abnormalities, transferring the embryo to the uterus or freezing it are also options.
The ability to effectively freeze eggs will be one of the greatest fertility developments in this field in the next decade, Edelstein says. Labs currently are able to freeze, thaw and then implant fertilized embryos that successfully result in pregnancy, as well as successfully freeze sperm for later use. Lucidi says freezing eggs, or oocyte cryopreservation, is still an experimental process, and one that is being worked on at the Virginia IVF & Andrology Center, a Richmond lab established by a group of reproductive endocrinologists in 1998. Edelstein was among the founders, along with Dr. Dennis W. Matt, its scientific director; Dr. Kenneth Steingold, also a reproductive endocrinologist at the Fertility Institute of Virginia; and Dr. Geof Tidey, a partner at the Richmond Center for Fertility & Endocrinology.
"You would think it would be simpler to freeze an egg than a dividing embryo," Steingold says, "but it's mainly a technical issue."
Lucidi says, "When you freeze an egg, it tends to destroy the egg because of all the water expanding in it." Egg freezing and thawing has not resulted in pregnancies yet at local facilities (although one pregnancy resulted from frozen eggs sent from an out-of-state lab). He says there are accounts of pregnancies occurring elsewhere in the nation — one California lab, Frozen Egg Bank, reports 41 births since 2005.
Locally, Lucidi says, a woman would have to go through multiple cycles of egg retrieval, which involves medication to stimulate egg production and collection of eggs through a needle biopsy, to produce 100 eggs — enough for a likelihood of successful pregnancy through egg freezing.
Dr. Elizabeth McGee, director of the division of infertility at VCU Medical Center, says she counseled about 100 patients just this past year who could be aided by egg freezing. Her patients are women facing treatments such as chemotherapy, who still want hope for future pregnancies.
"We are getting to the point where oocyte freezing is not going to be considered an experimental process in the near future," Matt says. He predicts that there will be a boom of egg freezing to delay childbearing and that frozen eggs will be available from donor banks.
"That will raise a host of ethical questions [about] whether women should be banking their eggs in the concern that they might try to get pregnant for many years," Edelstein says, adding, that often ethics are "just lagging behind the technology."
Improved Lab Technology
In recent years, advances including less-painful ovary-stimulating injections also have emerged, and the chances of becoming pregnant through IVF have improved from about 20 percent in the early years to about 50 percent nationwide today. In just the last 13 years, more than 430,000 births in the United States have resulted from assisted reproductive technology (treatments where both egg and sperm are handled), according the federal Centers for Disease Control and Prevention.
"Every [successful] case was in the newspaper in the old days," Steingold says with a laugh. "But now you expect a 50-percent pregnancy rate."
While he adds that age is still the top predictor of success — something doctors can do nothing about — local professionals agree that the incremental rise in fertility success rates is primarily because of improvements in lab technology. "When IVF success rates went from 20 to 50 percent, those were largely lab-driven successes, controlling the air quality in the lab better," McGee says, adding that technology also included "better handling of the environment in which the [embryos] are stored and grow."
In addition, progressing lab technology has opened the door to ICSI (Intra Cytoplasmic Sperm Injection), a lab treatment in which a hollow needle is used to inject sperm directly into the center of an egg. Introduced in the 1990s, ICSI was a major fertility breakthrough and has proved especially valuable for treating severe male fertility problems. "Before ICSI, the sperm fertilized or didn't fertilize. And if it didn't fertilize there was nothing you can do," McGee says. "You did not know that the sperm would not fertilize until you did IVF and it failed. It was a tragedy."
But even with momentous advancements, the battle with fertility is far from solved. According to the CDC, more than 7 million women across the nation, or about 12 percent of the reproductive-age population, have difficulty becoming pregnant.
Page Hyman, a 39-year-old Richmonder, is one of these women. In 2004, Hyman was diagnosed with endometriosis, abnormal growth of tissue lining the uterus that can interfere with pregnancy. Five surgical procedures, two rounds of Intrauterine Insemination (IUI), three IVF treatments and two years later, Hyman had a life-changing conversation with her doctor, Tidey of the Richmond Center for Fertility & Endocrinology.
"I was 37, and we had a very tough meeting over at the lab," Hyman says. "They sat me down and said my two options were adoption or an egg [donor]… I completely lost it." In the discussions that followed, Hyman said she and her husband, Jeff, decided not to adopt but to pursue what Edelstein calls third-party reproduction, another procedure that has advanced greatly since it started being used in the 1980s. "Of all of the procedures we do, that generally has the highest success rate because the eggs are coming from younger woman, usually in their 20s," he says. Hyman filled out the appropriate forms, writing that health was their highest priority. "We did not care about hair color or eye color," she says, "but we were fortunate enough to have a donor who had coloring like my husband and blue eyes like me."
Hyman received the transfer in September 2006 and became pregnant. But after 10 weeks, she lost the baby. Months later, in early 2007, Hyman decided to try a second donor. "I definitely realized that this was it," she says. "Money was not an unlimited resource for us. So [if this did not work], we were going to be a very happily married couple for the rest of our lives, but we were not going to be parents."
In July 2007, she discovered she was pregnant. "Without hesitation, we would do it all over again," says Hyman, who gave birth to Peyton Elizabeth on March 3, 2008. "This child is not just a miracle because how she came about, but she is just a great kid."
The Cost of Conception
For many couples, like the Hymans, the cost of high-quality technology reaches a point of financial impossibility. For example, a single IVF process costs about $12,000, Lucidi says.
"Patients often decide what treatment to have based on what they can afford," McGee says. "It is tragic when you know what treatment someone needs and they cannot afford it. That happens daily."
In Virginia, health insurance companies are not mandated to cover fertility treatment costs; 15 other states do mandate such coverage. While many companies cover the diagnostic process, Steingold says, there are states that have mandated fertility-treatment coverage by insurance companies. Hyman adds that while her insurance did cover a portion of costs for her surgeries, she and her husband paid $100,000 out of pocket. "There should be more assistance," she says.
With little financial aid available, patients have often sought to transfer a high number of embryos during IVF or other procedures to improve their odds of success, Tidey says.
But media attention to the "Octomom" case (California resident Nadya Suleman, who gave birth to octuplets in January) has made patients more aware of the risks of multiple births. "Patients seem more aware of the possibilities of overdoing it," Tidey says. "It has made it easier to tell somebody you think they should only transfer two embryos versus three embryos."
McGee says the Octomom situation is ironic, because the fertility-treatment field nationally is moving toward a trend of caution, transferring fewer and fewer embryos. While the law does not limit embryo transfers, the American Society for Reproductive Medicine adopted guidelines in 2008 encouraging the transfer of only one embryo for women 35 or younger. "Reputable reproductive endocrinologists do follow these guidelines," Edelstein says, adding that the CDC mandates annual public lab reports from each practice.
On the other hand, Tidey says, "Avoiding triplets is just not on one's radar when they are paying a lot of money." To provide another financial option, Richmond Center for Fertility & Endocrinology, the Virginia IVF & Andrology Center, and the Fertility Institute of Virginia, as well as some other practices statewide, offer a Shared Risk Program. "The Shared IVF [Risk] Program allows people to try in vitro fertilization multiple times without paying extra each time," Tidey says. For a set rate, a couple who meets the requirements can try IVF up to four times with no additional costs.
"If they never have a baby, they are refunded," Tidey says. "Then they can use that money to pursue adoption."