The possible and the probable in human reproduction at the new millenniumBy Sharon W. Linsker
Over the past few years, headlines about sexual reproduction techniques and practices have grabbed the public's attention: "Voluptuous fashion models auction eggs online for $150,000 ..." "Ovaries transplanted into patient's arm ..." "Scientists experiment with artificial uterus ..."
Despite the sci-fi hype, researchers have made extraordinary progress in solving infertility problems, in extending the reproductive lives of women, and in screening for genetic abnormalities.
A dishy babe
Remember the excitement in 1978 when the first in vitro fertilization (IVF) was performed in the United Kingdom? Louise Brown, the baby who was born when an egg and a sperm were combined in a laboratory dish, is now an adult. For parents today, birth through IVF seems no less a miracle, but the procedure has become common.
According to the Center for Reproductive Medicine and Infertility (CRMI) at Weill Cornell Medical Center, more than 60,000 babies have been born using IVF in the United States.
It's through IVF that Lisa Green's baby came into the world less than two years ago. (Her name has been changed.) Although the little girl looks just like her mom -- blond hair and blue eyes -- her eggs were donated by Green's sister, who shares the same coloring. Green went the IVF route because a birth defect left her unable to conceive normally. She has two uteri, one ovary, and one fallopian tube, which never developed fully.
When Green failed to get pregnant after two rounds of IVF, her 21-year-old sister agreed to donate her own eggs, which involved a series of painful injections to prepare the eggs for retrieval. Although seven eggs were successfully fertilized when mixed with the sperm of Green's husband, only two embryos were of good enough quality to implant in Green's uterus. The result -- nine months later -- was a healthy baby girl.
"I am so thrilled," says Green, 34, who'd always wanted to have children. "My sister is really close to my daughter. But my baby couldn't be more mine because I carried her and I'm her mom."
The first physician in the United States to use a donor egg in the treatment of infertility was Zev Rosenwaks, M.D., director of the Center for Reproductive Medicine and Infertility at Weill Cornell. According to Dr. Rosenwaks, strides in the infertility field in the past 25 years have been enormous.
"Before IVF, we were able to successfully achieve pregnancies in 65 percent of couples presenting with infertility. These included couples where donor sperm were used for male infertility," says Dr. Rosenwaks. "Today, with innovations in assisted reproductive technologies, such as intracytoplasmic sperm injection (ICSI), we can help 90 percent of the remaining 35 percent. It should be emphasized, however, that these couples must be willing to undergo all currently available techniques (including egg donation and gestational carrier)."
Dr. Rosenwaks attributes great strides in IVF to new drugs that allow better control of the ovarian stimulation process. He also points to improvements in pregnancy rates resulting from new laboratory innovations, one of which is the new human endometrial cell coculture technique. This technique endeavors to take a woman's own uterine cells and permits the growth of the embryos in the presence of those cells. This is particularly useful to improve embryo quality in cases in which IVF has failed previously.
The male factor
Infertility affects one in six couples who are trying to conceive. Not so long ago, society blamed infertility on the woman. But in at least half of all cases of infertility, a major contributing cause is the male, says Marc Goldstein, director of the Center for Male Reproductive Medicine and Reproductive Surgery, also at Weill Cornell.
Improvements in treating men have been dramatic. Less than a decade ago, men with severe sperm production problems were routinely consigned to donor sperm or adoption. But now, says Dr. Goldstein, "any patient who presents with infertility, even the most severe form of zero sperm count, is told there is hope."
The most severe form of male infertility occurs in men who have no sperm at all in their semen. The causes can be divided into two major categories: Either the men are not producing any sperm at all, or they're producing sperm that can't get out because there's a blockage.
Ironically, of the most common operations for men with blocked ducts is a vasectomy reversal. Approximately 500,000 men undergo vasectomy each year for permanent birth control. But with the high rate of divorce and remarriage in the United States, demand for reversal of this procedure is growing. "Ten years ago, I thought a success rate of 86 percent was good, but now, thanks to improvements in microsurgery, the success rate has increased to 99 percent. The resulting pregnancy rates have jumped from 40 to 50 percent to almost 70 percent," says Dr. Goldstein.
In another microsurgical procedure, known as intracytoplasmic sperm injection (ICSI), a surgeon is able to extract sperm from blocked ducts. Then, in the laboratory, an embryologist can inject a single sperm right into a woman's egg for possible fertilization.
"By far the most exciting new development in the field of male infertility is the ability to treat men with severe sperm production problems," says Dr. Goldstein. "Even though these men may have no sperm in their semen, we can now find sperm between the cells of the testicles in almost half these cases." The procedure is called testicular sperm extraction, or TESE.
In a world in which science fiction seems to become reality with the flip of a calendar page, researchers anticipate being able to take any tissue in a man's body and induce these cells to fertilize an egg using an advanced version of ICSI. Male infertility would be a problem of the past.
Her clock is ticking
But even as researchers are solving problems of infertility at the new millennium, women in their late 30s and 40s continue to delay having children -- risking being unable to get pregnant when they want to. "We were always told to have a career, that there will always be time to get pregnant, that we shouldn't get married right out of college," says Marcelle Cedars, M.D., who is in her mid-40s. "The bottom line is that I have a lot of friends who are still single, never got married, and never had kids." Dr. Cedars is director of the Center for Reproductive Medicine at the University of Colorado Health Sciences Center.
Talking of her peers, Dr. Cedars adds, "Having a baby was part of their big master plan. It's just when we finally had success in our careers and got married, we weren't fertile anymore."
Indeed, researchers are learning that there is a group of older women who are reproductively less fertile, even though they are still having regular periods. "This group -- usually in their late 30s to mid-40s -- is probably beyond the point where we can help them get pregnant without oocyte [egg] donation," comments Dr. Cedars. "And so, one of the big issues of the future is education. We're trying to start a campaign to say 'sooner is better.'"
Scientists are looking at several new ways to preserve a woman's ability to have children:
Egg cryopreservation. Scientists are looking at the possibility of allowing a woman to harvest her own eggs and freeze them until she is ready to get pregnant. Recently, a few babies have been born from relatively mature eggs that have been thawed for in vitro fertilization and injected directly with sperm. But unlike sperm and embryo freezing, which are widespread and very successful, completely immature unfertilized eggs present a problem, since researchers have not yet found a way to mature them in the laboratory.
Ovarian cryopreservation. Another approach, sometimes used these days when women of childbearing age face the loss of ovarian function because of impending chemotherapy or other procedures that would destroy tissue, is cryopreservation of all or part of an ovary. The ovarian tissue is removed, sliced into thin sections containing the microscopic eggs, placed in a solution, and frozen. The cryopreserved tissue can later be thawed and replaced in the bed from which it was taken, with the hope of restoring reproductive and endocrine function. To date, however, no human pregnancies have occurred from this method.
Discussing progress in the field of freezing eggs and ovaries, Dr. Cedars concludes, "Cryopreservation is going to be the answer for women who want to delay childbearing, but it's not going to come tomorrow."
Even more astonishing developments have taken place with genetic manipulation. Obviously, these developments have required review into professional and personal ethics for both the scientists and the potential parents. Nevertheless, the future of biogenetics promises advancements that could change childbearing altogether.
Preimplantation genetic diagnosis (PGD)
One new development that has arrived is genetic manipulation, which is changing the way people think about hereditary risk. Preimplantation genetic diagnosis (PGD) allows a physician to identify genetic diseases before the embryo is transferred to the uterus. The process begins with in vitro fertilization. Then embryologists examine the makeup of the newly formed cells to look for genetic abnormalities. This procedure could eliminate the anguish a couple experiences when prenatal tests indicate a genetic problem in a fetus. Until now, the only solution has been to terminate the pregnancy. The major indication for PGD has been sex-linked recessive diseases carried on the X (female) chromosome, such as Duchenne muscular dystrophy and hemophilia. Several other genetic disorders, including Huntington disease and sickle cell anemia, can be diagnosed as well.
A girl or a boy?
And what about the age-old dream of choosing the sex of a child? It's now possible, says the Genetics & IVF Institute, a provider of infertility and genetics services with main facilities in Fairfax, Virginia. In 1996, the institute reported the first human birth following a procedure called MicroSort, in which X and Y chromosome-bearing sperm cells are separated and sorted and then, depending on the desired sex of the child, an egg is fertilized with sperm containing either X or Y chromosomes.
The approach had been used for more than a decade to determine the sex of cows, horses, and pigs. MicroSort is still in clinical trial on humans, but that hasn't stopped couples from flocking to the institute with the promise of getting their wish for a girl 90 percent of the time and a boy 73 percent.
Pure whim? Not quite. Though MicroSort helps satisfy a couple's long-held wish to have a baby girl -- or a boy -- the procedure can also help families avoid sex-linked genetic diseases for which their offspring could be at risk.
And then there's cloning -- some scientists' dream and some ethicists' nightmare. In 1997, researchers in Scotland announced the stunning news that they had cloned a lamb, Dolly, from the cells of a mature sheep. With Dolly in the pasture, politicians, scientists, and ethicists have begun to consider the possibility of human cloning -- and the moral implications.
The ethics of reproduction
As for ethical issues around human reproduction, we don't have to look to the future. Surrogate mothers battle genetic parents. Hospital ethics boards debate the disposal of unclaimed frozen embryos. Universities criticize couples who advertise in campus newspapers for would-be egg donors -- for a fee of $10,000 or more. Advocacy groups decry that costly procedures like IVF, which run $12,000 to $15,000 for a single attempt, are not covered by most insurance policies and are therefore available only to those who are financially well-off.
There is no doubt that reproduction in the new millennium presents perplexing new problems and extraordinary new opportunities. Some people will act to avoid disease, others for personal economic gain or out of vanity, and still others, out of altruism. But for parents who have yearned for a healthy child, the possibilities have never been so exciting.
Several medical centers that offer Assistive Reproductive Technology (ART ) also have very informative websites that decipher the jargon around IVF, GIFT (gamete intrafallopian transfer), ZIFT (zygote intrafallopian transfer), and other new fertility procedures: