Technique Aids Pregnancy in Women Over 40
Physicians using sophisticated reproductive technologies have enabled some menopausal women over age 40 to bear children, according to a report in today’s New England Journal of Medicine.
The achievement, which involves eggs transferred from another woman, hormonal supplements and test tube fertilization, is the latest in a fast-moving field that has pushed back the limits of pregnancy. It opens up the possibility of childbearing well into middle age but also promises to spark legal questions and debate about the ethics of giving birth late in life.
“The limits on the childbearing years are now anyone’s guess,” Dr. Marcia Angell, the executive editor of the New England Journal, observed. “Perhaps they will have more to do with the stamina required for labor and 2 a.m. feedings than with reproductive function.”
A team of USC physicians reports success in taking eggs from women in their early thirties, fertilizing them in the laboratory with sperm donated by the husbands of women in their forties and implanting the embryos in the uteri of the older women.
The women--all of whom had ovarian failure, or menopause--were given hormone supplements so that the embryos would attach to the wall of the uterus and develop normally. Five of the seven women established viable pregnancies.
In an editorial, Angell wrote: “The possibilities and permutations seem endless. A woman can become a mother but avoid pregnancy, if she chooses, by hiring a birth mother. Or she can give birth late in life, if she chooses, by buying (eggs) from another woman.”
A similar success in a woman who gave birth two months shy of her 50th birthday was reported in September by physicians at the Bay Area Fertility Medical Group in Walnut Creek. This is apparently the oldest successful pregnancy using the technology, which is known as embryo donation.
“With the ability to use donor eggs, we theoretically can produce pregnancies at almost unlimited age ranges . . . even 55 or 60,” said Dr. Donald I. Galen, one of the Walnut Creek physicians.
Although a handful of pregnancies have been reported with unfertilized eggs that were frozen and thawed, researchers have yet to perfect this technique. When they do, young women could conceivably bank their own eggs, as some men bank sperm, and then use them at a later time--whenever they wanted to start a family.
In a related report, a team of Israeli physicians wrote in the New England Journal that fresh human embryos created by fertilizing eggs with sperm in the laboratory were more likely to produce a pregnancy than embryos that had been frozen. Worldwide, there are about 15,000 frozen human embryos in storage.
The ability to extend reproductive potential for menopausal women focuses attention on the risks of pregnancy at advanced age and the wisdom of childbearing beyond the limits that had been set by a woman’s individual biology.
Other studies have shown that the risks of both infant and maternal death are increased for women 40 or older and that their delivery complication rate may be higher than for younger women.
Arthur Caplan, director of the Center for Biomedical Ethics at the University of Minnesota, said there was “nothing ethically wrong with a woman of age 45 or 50 or beyond having a child.” He explained: “We certainly have not moved to prohibit men in their 60s, 70s or 80s from having children.”
But Caplan added that he was troubled that many older women might not fully understand what they were getting into and questioned whether extending the boundaries of fertility should become “a top social priority.”
There is also substantial legal uncertainty about the status of pregnancies using donated eggs.
Earlier this week, in an Orange County case that attracted national attention, a Superior Court judge rejected arguments that a surrogate mother who was genetically unrelated to the child she carried acquired parental rights by virtue of having given birth to the child.
It is unclear how this situation, where the surrogate mother initially agreed to give up the child but then changed her mind, relates to embryo donation. When an embryo is donated, the woman who carries the child is not the biological mother but plans to keep the child, not give it up.
“I wouldn’t advise anyone to use a donated egg if they live in Orange County,” said Alexander Capron, a bioethics expert at the USC Law Center. Capron said that while a sperm donor usually relinquishes his parental rights, there are no comparable laws governing egg donation in California or other states.
Some experts, such as Capron and John Robertson of the University of Texas Law School in Austin, feel that similar legal standards should apply to sperm and egg donation.
Menopause develops as hormone production by a woman’s ovaries decreases. Eventually, the release of eggs and menstrual periods cease. This typically occurs between the ages of 48 and 51, yet there is wide variation.
Success rates for pregnancy decline dramatically after age 35 and as many as 10% of women have ovarian failure by age 40. But some women over age 50 have normal ovarian function and can become pregnant.
Galen and Dr. Mark V. Sauer, the leader of the USC team, cautioned that women, regardless of their age, are carefully screened before receiving donated embryos and some are disqualified for medical, emotional or psychological reasons.
“Age is an arbitrary limit,” Sauer said. “Some women at the age of 45 or 48 would be perfectly good candidates. . . . Some women of much younger age might not fit the criteria.”
Dr. Machelle M. Seibel, a reproductive medicine expert at Harvard Medical School in Boston, said that physicians who perform embryo donation procedures should use “prudence,” establish an age cutoff, and counsel patients carefully so “they get a balanced perspective.”
While the reproductive time frame has been extended, the advance “makes it very hard for a couple to feel that they have done everything in their power (to have a child) before stopping,” Seibel said. “Is a couple a failure if they have not tried this?”
The first successful transfer of a developing embryo from one woman to another was performed at Harbor-UCLA Medical Center in 1983. Since then, techniques of egg or embryo transfer have been used hundreds of times throughout the world, primarily for women under the age of 40 with ovarian failure.
The USC report, authored by Sauer, Dr. Richard J. Paulson and Dr. Rogerio A. Lobo, is one of the most comprehensive to date on the feasibility of extending this technology to women over 40.
Since the first successful in vitro fertilization in 1978, many physicians who perform the technique had established 40 as an age cutoff. They were concerned that the success rate would be very low in older women and the complication rate high. But after the USC team was approached by a number of women over age 40 who could only become pregnant through egg donation, “we made a group decision to proceed,” Sauer said.
The team, whose in vitro fertilization program is based at California Medical Center in Los Angeles, studied seven women 40 to 44 years old “with ovarian failure who were otherwise in good physical and psychological health.”
The eggs were provided by three fertile women, ages 31 to 34, who were paid $1,500 per ovulatory cycle by the recipients.
The ovaries of these younger women were primed with hormones to produce multiple eggs. Then the eggs were harvested through a thin tube inserted through the vagina. After artificial insemination in the laboratory, the embryos were placed in the uteri of the infertile women.
In total, 28 embryos were transferred during eight transfer procedures, the report said. Six of the seven women became pregnant. One pregnancy ended in a miscarriage. Another ended in a stillbirth after 40 weeks of gestation; no cause was apparent.
The pregnancies in the other four women were normal and they all delivered normal infants, including one set of twins. The four all were delivered by Cesarean section.
In Walnut Creek, Galen said his group has been responsible for “at least a dozen pregnancies” in women over the age of 40, including the 49-year-old woman.
The new research suggests that pregnancies fail in older women because of the age of their eggs, not the age of their uteri, according to Sauer. “A healthy uterus, regardless of the woman’s age, may be susceptible to embryo implantation and development,” he said.
Times researcher Janet Lundblad assisted in the research for this story.
REPRODUCTIVE TECHNOLOGY
The new world of reproductive technology has spawned its own terms to describe medically assisted conception. Some examples: In vitro fertilization: Also known as “test tube” fertilization. A technique in which eggs are removed from a woman’s ovary and fertilized with sperm in the laboratory. The embryo is then transferred to the woman’s uterus. The procedure is usually performed because a woman’s Fallopian tubes, which connect the ovary to the uterus, are blocked.
Embryo donation: A variation of in vitro fertilization in which an egg is removed from a fertile women, fertilized with sperm in the laboratory, and then the embryo is transferred to the uterus of an infertile woman. The procedure is usually performed for a woman with ovarian failure, or menopause, who wishes to bear a child.
Surrogate mother: A woman who is artificially inseminated and carries a pregnancy to term, with the intention of relinquishing the child at birth.
Gamete intrafallopian transfer: A technique in which eggs are surgically removed from a woman’s body, and then reintroduced, together with sperm, through a thin tube threaded into the Fallopian tubes, where it is hoped fertilization will take place. The procedure is usually performed for cases of infertility due to low sperm counts and for infertility of uncertain cause.
