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How to Get Pregnant with the New Technology
By Sherman J. Silber
Warner BooksCopyright © 1998 Dr. Sherman Silber
All right reserved.
Chapter OneHow Does the New Technology Work?
Solving Seemingly Impossible Infertility Problems With The New Technology
In the mid-1980s I saw a lovely woman who had undergone surgery by a well-meaning gynecologist for severe pelvic adhesions (scarring) caused by previous infections. (Nowadays if I were to see a woman with such severe adhesions in the pelvis, I wouldn't even attempt to try to solve her problem surgically, but would go straight to in vitro fertilization [IVF], a relatively simple, outpatient procedure.)
At the time, the surgeon who explored her felt that her only option would be an effort to free up the adhesions to her fallopian tubes and ovaries. Unfortunately, the doctor performing the surgery got into some problems with bleeding that were beyond his ability to handle and the only way he could solve the dilemma was by removing the woman's uterus (she was only twenty-five years of age). The doctor who removed her uterus did not feel the sense of tragedy he should have, because he was not aware that this lady could have gotten pregnant with in vitro fertilization without ever attempting the hopeless operation to open her completely cemented-down tubes and ovaries. If he had only known that all this lady needed was a uterus in order to get pregnant with the new technology, he might have avoided this foolhardy operation, sent her to a proper IVF program, and she could have had her baby. Now she could not even get pregnant with IVF.
Miraculously, four years later, I called this lady back to tell her what seemed absolutely incredible, that she could have a baby after all even without her uterus. She had to find a close friend who would be willing to carry her baby for nine months and then return her baby to her. Her own eggs and her husband's sperm would be used to get her friend pregnant using IVF or GIFT. Then, nine months later, her friend would give her baby back to her.
This is not the same as the infamous "surrogate motherhood" cases that have appeared in the media. "Surrogate motherhood" involves no medical technology whatsoever and is a procedure of highly questionable ethics. With the "surrogate motherhood" case you may have popularly read about involving "Baby M," a volunteer is artificially inseminated with sperm from a couple's husband and then paid to carry a baby who is genetically the surrogate's (not the infertile wife's). Nine months later the surrogate is required to give this baby (which is hers) up for adoption to the couple.
What I am referring to is something entirely different. A friend would simply voluntarily carry the genetic baby of the woman who has no uterus. The friend, who would be paid nothing other than normal medical expenses, would then return the baby to her infertile friend.
Couples who wait too long can even get pregnant after menopause. The only problem is it will require the donation of an egg either from an anonymous donor or from a good friend or younger sister, or even a niece, who has not yet gone through menopause herself. Most women go through menopause between the ages of forty-five and fifty-five but about 5 percent will run out of eggs well before the age of forty.
What about Paulette (to whom I referred in the Preface), who wrote the stirring article in the New York Times Magazine? Her biological clock is ticking and she's going to run out of fertilizable eggs fairly soon. That does not mean the end of her chance to get pregnant. A proper lining of the womb (endometrium) can easily be created by giving her the right hormones in the proper sequence to simulate a normal cycle, and put her husband's sperm along with one or more eggs from a good friend (or anonymous donor if she so prefers) into her fallopian tube at exactly the right time of her artificially induced cycle, and quite amazingly, she can still get pregnant and carry and deliver a normal baby, virtually at any age!
Speaking of getting pregnant at an older age, the first case of a grandmother giving birth to her own grandchildren, using her daughter's eggs and her son-in-law's sperm, was reported in 1989. This procedure was necessitated because her daughter had no uterus. The grandmother was forty-eight years old, and her daughter was twenty-five. Their cycles were synchronized with hormones quite easily (as will be described in later chapters), and her daughter's eggs with her daughter's husband's sperm were used to create three embryos in a culture dish. A11 three embryos were then placed in the uterus (womb) of the grandmother-to-be and she got pregnant with triplets. Thus, in one delivery the grandmother gave birth to her own three grandchildren.
You Can Save Your Eggs for Later
Because of pioneering research by Professor Roger Gosden, at the University of Leeds in the United Kingdom, we can now successfully freeze the eggs of young women before they undergo cancer chemotherapy and/or radiation (which would otherwise most likely destroy their fertility). This approach may also help women who feel a need to delay childbearing until their late thirties and forties, when their eggs will very likely have been depleted. This technology is also an option for the woman who wants her own genetic child, but does not anticipate starting a family for many years. As women get older, a thousand of their eggs degenerate every month, and the eggs which do not degenerate are less fertile with each succeeding year because of the aging process. By age 40, the likelihood that a woman can produce eggs capable of resulting in a baby has decreased significantly because it is very likely that she has run out of most, if not all, of her fertile eggs. Therefore, women who find themselves not yet married at age 35, but who still want to have children in the future, all feel the relentless ticking of the biological clock. Ovarian tissue freezing is a new solution for these women who feel that by the time they do get married, or are otherwise ready to start a family, they will have lost all of their fertile eggs due to the aging process.
For the last ten years, we have known that although human embryos can be successfully frozen and thawed, and can result in happy, healthy babies, unfertilized eggs cannot be successfully frozen and thawed (see page 304 in Chapter 11 regarding "embryo freezing"). A great deal of research has demonstrated that the reason for the poor success of egg freezing is that the eggs we retrieve through normal IVF-type processes are undergoing chromosomal division. The chromosomes of retrieved eggs are highly organized, on a complex "spindle," which is very susceptible to minor crystal damage from freezing. However, "resting" eggs in primordial follicles within an unstimulated ovary are undergoing minimal cellular activity and have no such complex spindle formation. Therefore, these immature, "resting" eggs are not easily damaged during an appropriately administered freezing procedure.
In women who are not yet married but who need to put off childbearing, and whose ovaries may be destroyed by cancer treatment, we can remove portions of ovary, or the entire ovary, perform bench microsurgery to create microstrips of tissue (to allow successful diffusion of the cryoprotectant), and successfully freeze this ovarian tissue with a well-controlled computerized methodology (see Figure 1). All of a woman's eggs can be found in the thin 1mm outer layer of the ovary, while the inside of the ovary is just pulp and blood vessels with no specific organization or function other than to feed the eggs and follicles that are located in the periphery. This structure makes it possible for an entire ovary to be removed and the periphery dissected off microsurgically. The ovarian tissue is then put through a computer controlled, gradual freezing process. At least 70 percent of the ovarian follicles survive this freeze/thaw process without damage. Transplantation of this tissue back to the patient in a relatively simple fashion can result in normal egg development and ovulation.
In the future, patients will have the option, depending upon the opinion of their oncologist, to have either transplantation of the ovary back to them, or in vitro maturation of the eggs contained in that ovarian tissue, followed by a standard ICSI-IVF procedure. Ovarian transplantation is already well established, but in vitro maturation of ovarian tissue still requires ongoing research. In either event, ovarian tissue freezing now offers a woman an opportunity to achieve motherhood many years after she will appear to have been cured of her cancer, or perhaps later in life, when she finally meets her permanent partner.
Congenital Absence of Sperm Ducts
Some types of infertility require very tricky technology and micromanipulative skill. One example is men who are born with completely absent sperm ducts. For almost twenty years, I had been bombarded by couples from all over the world for a solution to the problem of the male being born with completely absent sperm ducts. This had been a particularly frustrating condition because the man's testicles are making perfectly normal sperm, but the sperm just can't get out and there are no ducts available to connect microsurgically. These cases had previously been completely hopeless. Now, however, we have an extremely delicate method for microsurgically extracting sperm from right near the testicle, and getting the wife pregnant with it. Such sperm normally should be unable to fertilize because they have not gone through the normal pathways which are necessary for the sperm to mature and develop the ability to fertilize. However, now it is possible to inject those microsurgically extracted sperm directly into the wife's eggs, and thereby get normal fertilization and, nine months later, happy, normal babies.
Advances like this seem to come when you least expect them. Several years ago, I had just finished telling my friend Dr. Richard Amelar (a fertility expert in New York) that a couple he had known for many years with congenital absence of the vas (and with whom he had become very close) should just give up because I didn't think the efforts in solving their problem were going anywhere. On that same day I had sent letters off to two similar patients in Colorado and Missouri, who had been repeatedly bugging me about why there couldn't be a "simple" solution to their problem. I told them that the complex requirements for maturation of sperm are beyond our understanding and that simply extracting them from near the testicle would not be of any benefit in getting the wife pregnant.
With these three patients (who were only a small number of the thousands with whom I had corresponded over the previous years) freshly in mind, I pondered how we might be able to use the new in vitro technology to approach this problem. The result was the beginning of a methodology that now allows us to successfully treat every single case of obstructive sterility, and most cases of "absolute" sterility caused by what would appear to be a complete lack of sperm production. These couples from Colorado and from Missouri were our earliest such pregnancies. Now there are thousands like them.
Surgically retrieved sperm from sterile men previously had a terribly low fertilization rate because the retrieved sperm were so weak. They looked like they were hobbling around on crutches, with big cytoplasmic blebs in their necks, all caused by the fact that they hadn't matured completely in their passage out of the testicle. Nonetheless, the DNA within all of these immature sperm was completely normal, and all that was required for these men to be able to have their own genetic offspring was the technique of IC SI, which in the early days I liked to jokingly call "fertilization by brute force."
Micromanipulation: Fertilization "by Brute Force"
Seven years ago, I wrote the following paragraphs in the first edition of How to Get Pregnant with the New Technology: "Another new development for otherwise impossible cases which requires great technical expertise is what scientists call 'micromanipulation,' but what perhaps the layman might understand better simply as 'fertilization of the egg by brute force.' The way this works is that some men have sperm counts that are so low, and motility so poor, that the sperm are incapable of penetrating the egg on their own even in the best quality laboratory setting. With ultramicromanipulative instruments that can be attached to special microscopes, the wife's egg can actually be held secure with a microholding pipette (scientific word for eye-dropper), and another micropipette can be used to literally inject a sperm through the hard outer shell of the egg (what is called the 'zona pellucida') so that this otherwise 'dead' sperm is now able to fertilize the egg.
"Can you imagine the dexterity involved in this type of manipulation? The sperm head is no more than 4 to 6 microns in diameter (that's approximately i/4,000 of an inch), and an egg is approximately 100 microns in diameter (I/200 of an inch). Thus, 'fertilization by brute force' is indeed a highly delicate procedure." It took years of painstaking research in Brussels, Belgium, and in St. Louis, Missouri, to perfect it. We called this perfected technique of sperm injection ICSI.
In November l992,in the remote town of Adelaide,Australia, a small but historic meeting of a few sperm scientists, was put together by Dr. Colin Matthews, the head of the IVF program in this relatively remote spot in Australia, to determine by consensus whether we had finally achieved a solution to the enigma of male infertility. This meeting included everyone who was feverishly working on the micromanipulation of sperm including Dr. Jacques Cohen from New York, Dr. Alan Trounson from Melbourne, Australia, Dr. Bob Edwards from Cambridge, England (the inventor of in vitro fertilization and who helped create the first IVF baby in 1978, Louise Brown), my self from St. Louis, and a rather shy, self-effacing doctor from Brussels, Belgium, Dr. Andre Van Steirteghem. It was at this meeting that a consensus was reached and spread throughout the world that with ICSI, a new era for treating infertile couples had arrived.
One of the biggest fears of those of us who were working on microinjection of sperm was that if the sperm can't get into the egg because of poor numbers or poor motility, abnormal shape, or poor maturation, then perhaps they weren't meant to get in. Perhaps it was naive to think that if such a poor sperm were injected into the egg that the chromosomes would be normal and that a normal baby could be obtained from such a procedure. Those fears proved to be completely wrong.
What is becoming apparent now is that even poor sperm have normal DNA sufficient for making a normal baby and the only thing wrong with poor sperm is simply that they cannot get into the egg.
Excerpted from How to Get Pregnant with the New Technology by Sherman J. Silber Copyright © 1998 by Dr. Sherman Silber. Excerpted by permission.
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