Dr. Silber Extends Fertility with New, Innovative Methods
(Excerpted from Wall Street Journal, Front Page, April 26, 2007)
Doctor Pioneers New Way to Extend Fertility: Freeze Ovary Tissue
By Sylvia Pagán Westphal
Wall Street Journal
Stored at subzero temperatures in a laboratory at St. Luke’s Hospital in St. Louis are eight tiny strips of tissue that were once part of Amy Johnson’s ovaries.
Ms. Johnson, 34 years old, plans to keep the tissue frozen and transplant it back into her ovaries if she has a hard time getting pregnant in the future when she might be too old. Back inside her body, the strips would produce young, healthy eggs — even if Ms. Johnson is in her 40s or even if she has reached menopause.
For women who want to delay child-rearing, technology is presenting an intriguing option. Evidence is rising that women who receive a transplant of their own (previously frozen) transplanted ovarian tissue, can once again start ovulating and get pregnant with “young” eggs that have not aged. Dr. Sherman Silber, Ms. Johnson’s surgeon in St. Louis, is the leading pioneer of the technique and believes it should be available broadly. “Patients have to be informed and know what their options are, but if they make an informed decision who would deny them the right to preserve their fertility?” he asks.
“This has the potential to be one of the largest breakthroughs for reproductive choice in women,” says Pamela Madsen, executive director of the American Fertility Association, a patient-advocacy organization. “For women to be able to bank their tissue [see video] and then come back when they are ready in their lives to have their children is tremendous.”
A woman is born with roughly a million immature eggs in her ovaries. Each month, beginning with puberty, one will mature for ovulation. But hundreds of the immature eggs will also die every month. A woman in her teens has about 400,000 immature eggs in her ovaries. That dwindles to 25,000 by age 37, and about 1,000 by 51. Cells surrounding the eggs contain the hormones that drive ovulation. Once they run out, the hormones do too, and a woman enters menopause.
As years go by, the quality of the remaining eggs also declines [see video], making it harder to get pregnant with a healthy baby. “The most heartbreaking thing is speaking to 38, 39 and 40-year-old women who find out that their ovarian reserve is low or nonexistent and that the only way they could have a child is through egg donation,” says Ms. Madsen of the patient-advocacy organization.
The point of ovarian-tissue freezing is to bypass this otherwise inescapable drop in the quantity and quality of eggs. Doctors remove the millimeter-thick outer shell of the ovary, which contains the immature eggs. They divide the shell into strips and place the strips in a kind of antifreeze, and then chill it to about minus 180 degrees Celsius. The frozen immature eggs within the frozen ovarian tissue retain their youth indefinitely. When reimplanted back into the woman, these strips of tissue recruit their own blood supply and once again start producing healthy mature eggs. The frozen ovary of a 30 year old remains 30 years old even though she may be 40 or 50.
Dr. Silber, who treated Ms. Johnson and directs the Infertility Center of St. Louis at St. Luke’s Hospital in St. Louis, believes the procedure will work fine if women freeze tissue in their 20s or early 30s. If they wait till their late 30’s or 40’s, it would be problematic.
One basis for that judgment is his success in ovarian tissue transplants between identical twins. In this surgery, a woman who has become infertile receives tissue from her fertile twin. The difference with Ms. Johnson’s procedure is that the tissue did not have to be frozen first. But new freezing techniques minimize the loss of eggs from the freezing process anyway.
In 2005, Dr. Silber and his colleagues reported in the New England Journal of Medicine a successful pregnancy and birth in such a twin. Stephanie Yarber had undergone menopause prematurely in her teens. She received ovarian tissue from her identical twin sister at age 24. Not long thereafter she started to ovulate – the eggs came from her sister’s tissue – and she got pregnant during her second menstrual cycle, giving birth to a healthy baby girl.
Since then, Dr. Silber has worked with seven other sets of twins. In a report last month in the New England Journal of Medicine, he wrote that all women began to get their periods and ovulate within months of receiving ovarian tissue. Five of those six conceived, and Ms. Yarber got pregnant again.
A recent study by researchers at the University of Valencia in Spain corroborates Silber’s work. Dr. Silber’s clinic is a rare example of a major U.S. clinic offering ovarian tissue freezing to healthy women who plan to get pregnant later in life. Doctors in the field say they don’t know of anyone else doing that. “What is the difference between losing your fertility from aging of your ovary or from cancer treatment? Either way you are losing your fertility, and freezing either your eggs or your ovarian tissue can preserve that fertility,” says Dr. Silber.
A perpetually busy 65-year-old, he works some 80 to 100 hours a week and travels constantly. Colleagues describe him as an exceptionally skilled surgeon, stitching together some of the body’s smallest and thinnest structures. In the 1970s, Dr. Silber pioneered vasectomy reversals, testicle transplants, and tubal ligation reversals. He also pioneered a technique for microsurgically locating sperm in the testis of men who otherwise were considered sterile, and fertilizing the wife’s eggs with those few microsurgically retrieved sperm.
Earlier this year he successfully transplanted an intact whole ovary [see technical video] from one woman to her infertile sister, a challenging procedure because the vessels used to reattach the organ are extremely small. A whole-ovary transplant, by ensuring an immediate blood supply, could provide longer duration of function than an ovarian-tissue transplant, but the surgery is so difficult that it’s unclear if it can ever become widely used.
Ms. Johnson, a self-described biology buff, considers herself a well-informed patient. She says Dr. Silber fully explained to her all the pros and cons of the procedure. One option that Ms. Johnson and others in her position typically consider is freezing mature eggs. This is different from freezing ovarian tissue, which contains thousands of immature eggs but none that are ready to be fertilized by sperm. The end result, however, is similar. Both procedures enable women to take advantage of the fertility of their younger years when they’re older. Dr. Silber also offers egg freezing to women who wish to preserve their fertility, using the new vitrification process [see video] of the Kato Clinic in Japan, with whom they have a close scientific collaborative relationship.
For egg freezing, in order to boost their production of mature eggs, women undergo rounds of hormone shots. Doctors then retrieve the eggs with a minimally invasive procedure and freeze them. When the woman is ready to get pregnant, sperm are introduced to the eggs through in-vitro fertilization, and the resulting embryo is implanted in the womb. It is the patient’s choice which approach she wishes.
Dreading her body’s reaction to the hormone treatments, Ms. Johnson decided against egg freezing. Cost was also an issue. She paid about $5,000 for the ovarian banking procedure, while egg-freezing treatments can cost $15,000 or more.
Other challenges remain. As many as one third of the immature eggs in transplanted ovarian tissue die after it is reattached, limiting the life of the transplant somewhat. Freezing and thawing the tissue may also reduce the egg number, but new techniques like vitrification obviate that problem.
The biggest threat to egg survival is lack of blood flow to the tissue in the first day or two after surgery, before new blood vessels grow into the transplant. Ms. Yarber began to run out of eggs three years after her first transplant from her twin sister. This can be solved by Silber’s difficult technique of intact whole ovary transplantation.
Dr. Silber’s collaborators around the world are now solving any remaining problems. The new freezing technique called vitrification is yielding encouraging results in blocking ice crystals from forming in the eggs and results in very little loss of eggs therefore. Also, the new technique for whole ovary freezing called unidirectional solidification is being currently perfected.
Perhaps the biggest obstacle to the technique’s widespread adoption is a social one. “We’ve had people in their late 30s and early 40s say they want to store their tissue, but by then it’s too late,” says Roger Gosden, laboratory director at Cornell University’s Center for Reproductive Medicine and Infertility. “The technique needs to be taken up at a younger age, and whether young women will be sufficiently concerned [about fertility] in their early 20s, I don’t know.”