We are in the midst of a worldwide epidemic of infertility. Ironically, even in countries with severe overpopulation, one of the most common reasons for a visit to the doctor is the inability to have children. Twenty-five percent of modern couples in their mid-thirties are infertile. From our teen years (when the last thing we really want is a child) to our mid-thirties (when we finally feel emotionally and financially secure enough to start a family), there is a twenty-five-fold decline in our ability to get pregnant. Let me explain.
Infertility is the inability to conceive despite a year or more of regular intercourse (without using birth control). The incidence of infertility in teenagers is rare. For women in their early twenties, only 1 to 2 percent are infertile. In their late twenties, 16 percent of women are infertile, and in their mid- to late thirties, 25 percent are infertile. By age forty, more than half of women are infertile, and pregnancy beyond age forty-three is very uncommon. If you are in your thirties, have been working hard to establish yourself, and are now just casually thumbing through this chapter at a local bookstore because you’re thinking maybe in a few years you might like to start a family, you should realize that there is a 25 percent chance you will not be able to do so without medical intervention.
These startling figures originally came from the National Center for Health Statistics and were presented to the United States Congress through a panel assembled by the Congressional Office of Technology Assessment in 1988. I was one of five physicians on that Congressional Advisory Panel. We had witnessed an explosive increase since the 1970s in the number of couples desperately struggling to have a child, but it wasn’t until these statistics were formally assembled that we were stunned to find out just how staggering the problem was. What accounts for this dramatic increase in infertility over the last forty years? The major reason for this huge increase is the woman’s biological clock, as couples delay the age at which they try to conceive from their early twenties until their mid- to late thirties.
We could speculate about other causes: the increase in sexually transmitted diseases, environmental pollution, declining sperm count from absorption of toxic substances, and even the increased tension and anxiety of modern life. These may be modestly contributing factors, but the major reason is simply that by the time the modern couple decides to have children, usually in their thirties, the human animal is just not as fertile as it was fifteen years earlier.
I have spent some time studying aboriginal societies, most recently the Hadzi bushmen, a forty-thousand-year-old hunter-gatherer culture in a remote region of western Tanzania. These people own nothing, sleep outside without any hut or tent, and lead a tenuous existence. They marry at age thirteen or fourteen, have children, and usually die in their thirties. I asked them about infertility, and they had never heard of such a thing. Some women might stop bearing children in their mid- to late twenties, but every woman was apparently able to have children. The biology of fertility in humans has not changed in the last forty thousand years. What has changed in the last few centuries is our life span and the age at which we first try to conceive.
One of the views of the Congressional Advisory Panel (which consisted of lawyers, psychologists, sociologists, and religious leaders as well as doctors) was that society clearly benefited from people putting off childbearing until their thirties. Both men and women are now able to obtain fuller educations, develop themselves in their careers, and contribute dramatically to the intellectual and economic prosperity of the modern world. This would not occur so readily if we were saddled with children as teenagers or in our early twenties. So if society is collectively making a decision to delay childbearing, it should be no one’s position to advise couples patronizingly just to “hurry up” and have children when they’re young.
With dramatic new technology, virtually any couple (with a few exceptions) can have a child. But you must understand the myriad complexities of your reproductive system in order to get the right help instead of the wrong help, and to deal with the emotional and financial costs (more information) the process might cause if you are not savvy. Most important, you need to understand your biological clock [see video] and how to manage it. My intention in this book is (1) to teach you how to manage your biological clock so that you won’t need technology to get pregnant, and (2) to explain how you can use technology safely to get pregnant if that is currently your only option.
The Importance of Understanding Your Biological Clock
In the New York Times Magazine in December of 1989, a forty-one-year-old writer named Paulette conveyed her sense of loss at trying to have a child in her late thirties, not succeeding, and now finding herself a successful forty-one-year-old writer who sadly “will probably never have a baby.” It wasn’t until she reached age thirty-eight that she decided to stop using birth control pills and tried to get pregnant. She read a book called Fertility Awareness and hoped she could get pregnant “naturally” with just a little bit of help from knowing more about the timing of her cycle and the quality of her cervical mucus. She did not understand her biological clock. It wasn’t until she reached forty that she saw a local doctor who began “fertility testing,” including mucus testing, hormone testing, and “two endometrial biopsies” (a tiny piece of the lining of the uterus is sampled to see if it is capable of sustaining a pregnancy). None of this plodding got her any closer to getting pregnant.
She was then given a grand diagnosis of “luteal phase defect.” This was a very popular diagnosis fifteen years ago, and many women were treated with progesterone supplementation in the second half of their cycle in an effort to “overcome” this problem. That is worthless treatment. Later she was given a mild ovulatory stimulant pill, Clomid, because of the view that luteal phase defect “might be” caused by a subtle “ovulation defect.” But she had no way of knowing that her biologic clock was too far along for Clomid to be of any use. She then went through a procedure called “intrauterine insemination” in which her husband’s sperm was placed directly inside her uterus even though previous testing had shown that her cervical mucus was quite able to allow his sperm to penetrate on its own. These are simple, old methods of treatment that sometimes work and might possibly make sense in a young woman trying to have a baby. But not for Paulette.
In fact, what Paulette went through is the conventional approach of trying to make a diagnosis and then using simple, non-invasive treatment appropriate to that diagnosis. The problem with this conventional view is that (1) many of these “diagnoses” are just normal variants which have nothing to do with why the woman is not getting pregnant, and (2) when time has almost run out, fiddling around for too long with the old-fashioned approaches may waste the few precious years a woman has left. We now have simple testing that could have told her (when she was younger) just when her particular clock would run out, and let her decide (while there was still time left) when to stop procrastinating.
Physicians simply have to admit that we often really don’t know why a couple isn’t getting pregnant except for the wife just being at the edge of the limits of her biological clock [see video]. Of course, a low sperm count in the husband, tubal obstruction, lesions in the uterine lining and poor ovulation can all contribute to infertility, and all those problems can be solved. But the biggest problem for a thirty-eight year-old woman is simply her age. Some women lose their fertility in their twenties and others not until their forties. In this book I will explain how you can gauge your own particular biological clock[see video], and if you are too late for that, how you can get pregnant anyway with the proper treatment. But the forty-one-year-old writer of that sad New York Times article, in 1989, did not have the availability of this knowledge.
Years ago I celebrated New Year’s with our son’s high school biology teacher and his thirty-nine-year-old wife, Pam, and their six-week-old baby, who never would have existed without IVF. Pam told me to make sure to tell everyone in this book how awful it is to go through the conventional series of “diagnostic” tests and ineffective treatments for years and years with one contradictory diagnosis after another. She had gone through seven years of this at the previous clinic she had used. She had two laparoscopic operations to remove tiny little implants of “endometriosis” and never got a satisfactory answer to her question of how her mother could have had five children despite huge implants of “endometriosis.” When surgery didn’t help, Pam was placed on progesterone, because they suddenly discovered “luteal phase defect.” Later she was given Clomid as well. She had been through literally hundreds of pills and shots and doctors’ visits and tests.
Pam and her husband finally came to me, and after a twenty-minute interview with them, I told her that I really did not know why she was not getting pregnant. But she was in her late thirties, that was enough reason for them to be infertile, and I recommended no more tests. She was thrilled when I suggested we proceed right to what was then the “new” technology of IVF. She was fed up with trying to figure out why she was infertile and getting nowhere.
Pam conceived with the IVF procedure, and she and her husband had a healthy baby, who is now a healthy teenager. She has no idea why she was infertile and neither do her original doctors who spent so much of her money on wild-goose chases. For Pam it was not too late. She had the common, “undiagnosable” age-related decline in fertility of women in their thirties. But at least she had an adequate supply of remaining eggs for IVF to work.
Misleading Diagnoses of the Cause of Your Infertility
The Simple, Unexplainable Effect of Age
Even in the best-conditioned athletes, age has a way of slowing us down, sometimes imperceptibly year by year, and it doesn’t mean that there is any particular physical ailment or diagnosis to explain that slowdown. This is usually (though, of course, not always) the case in a couple try unsuccessfully to have babies in their mid-thirties.
In 1982, the French reported in the New England Journal of Medicine a large study of 2,193 “normal” women (whose husbands had no sperm whatsoever in their ejaculate) undergoing artificial insemination with fertile donor sperm. These were “normal” women and they were being inseminated with completely normal sperm. There is no logical reason why they shouldn’t all have gotten pregnant. Yet it was very clear that the “normal” women under thirty had a high pregnancy rate, and the “normal” women over thirty showed decreasing pregnancy rates as they got older. A study from Ontario published seven years later in the Journal of Fertility and Sterility looked at more than two thousand couples with “unexplained” infertility. The chances of getting pregnant with simple, conventional methods of treatment were directly related to how young the woman was. No other factor studied was significant except for the age of the woman.
The decline in fertility as women get older is related to the aging of their eggs. You are born with all the eggs you will ever have, about two hundred thousand to four hundred thousand by the time of puberty, and every month about a thousand of them die. Thus as you get older, your eggs will decrease in both number and quality. Yet some women remain fertile into their forties, and others lose their fertility in their twenties. Chapter 3 of this book shows you how to determine at what particular age you will lose your fertility, so that you can plan to avoid Paulette’s dilemma.
A woman I first saw in 1990 is typical of many I see every week. Tammy got pregnant very easily as a young teenager after her first sexual experience and gave the child up for adoption. Five years later, again she got pregnant quite easily and kept this baby as a single mother. She continued to have completely regular, normal periods for six more years, got married, and then used condoms for birth control for three years until she and her husband were certain that their marriage was a stable one. By the time they finally decided to try to have children, she was thirty-three years old, and her menstrual cycles had become irregular, varying from twenty-five to thirty-two days. All of her tests were normal, but now she couldn’t get pregnant.
What happened to her subsequently is a terrifying story that exemplifies the pitfalls I am hoping to help you avoid with this book. She saw a doctor who performed major surgery to remove the “endometriosis” and release the adhesions. This only served to reduce her remaining supply of eggs even further, making it even harder for her to get pregnant.
As long as insurance companies require a “pathological diagnosis” in order to pay for treatment, and as long as major surgery results in no difficulty in getting insurance payment (whereas in vitro fertilization usually is not covered), women like Tammy run a good chance of being mistreated in this fashion.
The Endometriosis Myth
The most commonly, overused “diagnosis” for infertility is “endometriosis.” Endometriosis is a condition whereby some of the lining of the uterus has leaked back into the abdominal cavity and has implanted in little tiny nodules either in the abdominal wall, on the outside of the fallopian tube, or possibly in the ovary. When doctors perform a “laparoscopy” as part of an infertility investigation to see if the woman has a normal uterus, tubes, and ovaries, most of the time the examination is normal. Nonetheless the diagnosis of “endometriosis” is frequently inserted in the operative note just because the insurance company is much happier to pay for laparoscopy when they see a “pathological” diagnosis, and doctors feel more comfortable that way. The euphemism that avoids outright self-deception is to call it “minimal lesion” endometriosis. Doctors are often so anxious to find a diagnosis to determine the “cause” of infertility (not to mention the desire for patients to get insurance reimbursement) that many couples walk out of their long series of expensive infertility tests thinking incorrectly that they now know why they haven’t gotten pregnant. This might be harmless if it weren’t for the fact that it may lead to unnecessary or improper treatment, and could delay further the proper treatment. With infertility in older women, any delay caused by foolish treatments is devastating.
The “Male Factor” and “Varicocele” Myth
There are many other popular “diagnoses” which may lead to inappropriate treatment. The doctor may obtain a sperm count on the husband and find that it is “low.” The husband may then be put on all kinds of totally ineffective drug treatments such as Clomid, Pergonal, human chorionic gonadotropin, or testosterone. But worst of all, he may be given that all too common diagnosis of “varicocele [PDF File of a scientific paper].” Very few men escape seeing a urologist for infertility without suffering through this “diagnosis.”
A varicocele is a varicose vein of the testicle (usually on the left side) that is present in 15 percent of all males on the planet. It is just a common, normal anatomic variant but it has been argued that 40 percent of infertile men have varicoceles, and it is implied, therefore, that varicocele is the cause of the infertility. But most of these so-called minimal lesion varicoceles are not really varicoceles at all, and are no different from what is found in a normal, fertile population.
The varicocele has little to do with male infertility. A careful study of 651 infertile couples with varicocele was published in theBritish Medical Journal by the Australians in 1985 demonstrating absolutely no difference in pregnancy rate among couples whose husbands had the varicocele operated on versus those who did not have the varicocele operated on. Similar studies have been repeated in Belgium, Sweden, and Germany. Furthermore, fifteen percent of men who request a vasectomy (because they already have had all the children they want) are found on physical examination to have an obvious varicocele, and in my experience, that is the same as the incidence of varicocele in infertile couples.
What happens to infertile couples once the diagnosis of varicocele is made in the man? Typically, the men get operated on, sometimes on one side, sometimes on both sides, and then they wait six months to see if the sperm count improves. Since sperm counts, like the weather, vary from month to month around a mean average value, it only makes sense that if you get one or two sperm counts before this unnecessary surgery, and one or two sperm counts after this unnecessary surgery, at least half of the men will appear to have some improvement. But this is just an illusion created by the variability of sperm counts, and the failure to make equal note of those whose sperm counts seem to have actually gone down after varicocelectomy. Because of the intrinsic variability of sperm counts, half of the patients will appear to have reduced counts after treatment, and half will appear to have improved counts.
Furthermore, many couples can conceive naturally in spite of the husband’s very low sperm count. Manuel and Flora were a couple from South America who were married twenty-two years earlier, when she was only seventeen years old. Four years later she became pregnant and had a wonderful little baby boy, but she was never able to become pregnant again. A sperm count performed in their local city was zero. It wasn’t until eighteen years later, when Flora was thirty-nine years old and Manuel was forty-five, that they came to see me in St. Louis, and the enigma was solved. Manuel had zero sperm on the first semen analysis; however, after performing many semen analyses over a period of time, we finally found a few rare motile sperm on just one of those occasions. Testicle biopsy revealed that almost the entire testicle was nonfunctioning, except for a tiny island of normal sperm-producing tubules. Obviously, when Flora was very young, at age twenty-one, after four years of regular intercourse, a single sperm from Manuel was finally able to fertilize one of her eggs, resulting in a baby boy. As she became older, however, Manuel’s extremely severe infertility, compounded by the naturally decreasing quality of her eggs[also see video], made this couple infertile.
IVF and ICSI Bypass Everything That Can Go Wrong No Matter What the So-called Diagnosis Is
In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) solve the quandary presented by our frequent ignorance of why couples are not getting pregnant. If the cause of infertility really is low sperm count, the sperm can be microinjected directly into the egg. If the cause of the problem is poor ovulation, the hormonal stimulation and aspiration of eggs from the ovaries removes the need for ovulation. If the issue is poor cervical mucus blocking the entrance of sperm into the womb, these new technologies can bypass that problem as well. If the problem is endometriosis (a highly questionable but very popular diagnosis), again IVF overcomes the unfavorable environment for fertilization that endometriosis supposedly creates in the woman’s pelvis. If the problem is poor pickup of the egg by the fallopian tube from the surface of the ovary (a tricky feat in which the fallopian tube has to “reach over” and grab the egg by twisting back on itself), IVF, as well as gamete intrafallopian transfer (GIFT), once again bypasses this event.
Almost anything that can go wrong in the arduous process which sperm and eggs normally have to go through can be bypassed with IVF and ICSI. If the couple is committed to several treatment cycles, and the woman is not too far along on her biological clock [see video], most will get pregnant no matter what the diagnosis and no matter how severe the problem.
ICSI (sperm injection) is explained in detail in chapter 11, but essentially this is how the technique works: With ultramicromanipulative instruments attached to special microscopes, the woman’s otherwise invisible egg can actually be held secure with a microscope “holding” pipette, and an even tinier micropipette can be used to inject a sperm through the hard outer shell of the egg so that this one sperm is literally forced to fertilize the egg. Can you imagine the delicacy of this type of manipulation? The sperm head is no more than 4 to 6 microns in diameter (that’s approximately 1⁄4,000 of an inch), and an egg is approximately 100 microns in diameter (1⁄200 of an inch). It took years of painstaking research in Brussels and in St. Louis to perfect it.
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 naïve 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.
Even poor sperm have normal DNA sufficient for making a normal baby and the only thing wrong with poor sperm (with an occasional exception) is simply that they cannot get into the egg. The incredible complexity of sperm physiology, which will be discussed later in this book, appears to serve no purpose other than to mechanically get the package of DNA which the sperm contains into the egg. Once that package of DNA is inserted into the egg, all the processes of fertilization and embryo formation leading to a baby can take care of themselves.
Even Men Who Don’t Make Sperm Can Have Children
In 1985, a young couple, both twenty-two years of age, from New York, came to see me in St. Louis because he had azoospermia (no sperm in the ejaculate) and needed a testicle biopsy to see whether he had an obstruction that could be corrected with microsurgery. In those days, we always prayed that the biopsy would show normal sperm production, because our success rate with microsurgery to correct obstruction in male infertility was over 95 percent. But we could do nothing at that time for couples if the men weren’t making sperm at all.
His biopsy revealed what we call “maturation arrest.” This means that the early precursors for sperm production were present in the testicle, but there was no continuation of sperm production beyond these early stages. This man was by all definitions 100 percent sterile, and it was my unfortunate job to explain to this otherwise wide-eyed, cheerful young couple (who were looking forward so much to having a family) that they couldn’t have children.
But this couple never gave up hope. Ten years later, they came back after they had heard about ICSI. By now we were having exciting success in using ICSI for men with extremely poor sperm counts, and in men with irreparable obstruction requiring retrieval of testicular sperm from blocked but otherwise normally functioning testicle. But could it possibly work for men who were apparently not making any sperm at all. This determined couple helped us to embark upon a new theory with startling consequences.
When I had looked back to my research from the early 1980s on quantitative testicle biopsy, I discovered a phenomenon that had previously eluded my attention. Even in men with zero sperm in the ejaculate, and apparently no sperm production, if one looked carefully throughout the testicular specimens, an occasional sperm precursor could be found that had the same number of chromosomes and the same basic appearance as a normal sperm. Based on this finding, this couple was our first case of a man who appeared to be making no sperm but in whom we were able to find just a few sperm “hiding” in his testicles. We injected these hidden sperm into his wife’s eggs, and normal fertilization occurred. They had a happy baby girl who is now in her teens.
Another patient treated around the same time had, as a child, undescended testicles that were brought down surgically into the scrotum very late in his childhood. As is often the case with such men, he was clearly producing no sperm. When we operated on his testis to see if any sperm could be found (under the same theory, that any man with a testicle may have some sperm somewhere), indeed we were again able to find just a few sperm. We injected his wife’s eggs with those testicular sperm and again obtained normal fertilization and pregnancy. This young man had been known to be sterile ever since he was a teenager. Yet, during extensive exploration of his testicle, we found sufficient sperm to perform ICSI, and he could have a normal family.
The question that might occur now to every such couple is: Will my baby be normal? The fear might arise that abnormal sperm in men with low sperm counts will cause a higher risk of producing abnormal babies. We have now studied this in over seven thousand such children born through the ICSI procedure as we performed it, and the news is great. The children are normal, and there is no greater incidence of chromosomal or congenital abnormalities than in the children of normally fertile couples conceiving without any kind of reproductive treatment. There may be occasional exceptions, related to the age of the wife, but not to the IVF or ICSI treatment at all. The offspring are more likely to be infertile (like their parents) but otherwise are normal, healthy children.
Poor sperm production represents up to half of the infertility cases in the world, causing couples in the past to undergo billions of dollars’ worth of ineffective, unscientific, and frankly stupid surgical and hormonal treatment. ICSI now solves that problem in most couples, but a genetic cure would still be preferable. Our research in conjunction with the human genome project, the Howard Hughes Institute at MIT, and the University of Amsterdam, thus far indicates that sperm production in men is controlled genetically by many different genes on the Y chromosome and elsewhere in the genome. We have now completely sequenced the Y chromosome and have located the areas on the Y chromosome where sperm production in these men is regulated, and we have described many of the genes that control spermatogenesis. This discovery means that in the future we may have a genetic cure for male infertility, i.e., replacing the missing gene (or genes) so that these men will be able to resume normal spermatogenesis, thereby in the future, eliminating the need for ICSI.
With the advent of ICSI, there is now only an occasional need for donor sperm, but there is still a strong need for donor eggs. It is my hope that women who read this book and learn how to plot their own biological clock will be able to avoid having to resort to egg donation by planning their life more knowledgeably. However, an older woman who has already run out of her own supply of fertile eggs can still get pregnant (using her husband’s sperm, of course) with embryos derived from the eggs of a younger woman. Egg donation is much more readily accepted emotionally by couples than sperm donation, because the woman still gets to carry and deliver the baby. Because the woman carries the baby, emotional bonding is rarely adversely affected by its having been derived from a donor egg. Follow-up on the children who have resulted from egg donation, and on their parents, is wonderful. These are really happy families.
The question, whose baby is it? creeps into every aspect of egg donation, gestational surrogacy, and adoption controversies. Adopting eggs, i.e., using donated eggs, is much more secure for the infertile couple than struggling and traveling around the world to try to find a baby to adopt (a baby that could possibly be taken away in the future) at enormous cost. With donor eggs, which are legally recognized in every state, there is no risk (as with adoption) that the egg donor could ever interfere or lay claim to the child or to the embryos. I will discuss the issue of bonding and the question of whose child it is in chapters 16 and 17.
Even for a woman without a uterus, it is possible for her mother or a very close friend, or a sister, to carry her biological child for her and then give that child back to her after the delivery. This is called “gestational surrogacy.” It is possible to arrange legal “adoption” from the surrogate even before the delivery. These procedures are medically and legally extremely safe and reliable.
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. The surgeon who explored her decided to try to release the adhesions on 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 safely 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 in those days, before IVF was so routine, she could not have had children anyway. He was not aware that this woman, in the future, could have gotten pregnant easily with IVF without the need for the hopeless operation to open her completely cemented-down tubes and ovaries. If this woman had only known that all she needed in order to get pregnant with IVF was a uterus, she might have avoided this foolhardy operation.
Miraculously, four years later, I called this woman back to tell her what, at the time, seemed absolutely incredible: that she could have a baby after all, even without her uterus. We could use her eggs and her husband’s sperm and put the fertilized embryo into her own mother’s uterus. Then, nine months later, her mother would give her newly delivered baby back to her. We now have helped so many women who have no uterus, or for whom pregnancy would be dangerous, have their babies this way. In many cases, their mother carried their baby, and in other cases, a sister, an aunt, or a close friend. Thus, a mother can give birth to her own grandchildren, and a sister can give birth to her own nieces and nephews.
Can You Save Your Eggs for Later?
Although human embryos can be successfully frozen and thawed, and can result in happy, healthy babies, eggs (unfertilized), until very recently, could not be very successfully frozen and thawed. The success rate in freezing eggs had always been extremely low, but this has all changed now. For young female cancer patients, whose ovaries would surely be destroyed by heavy chemotherapy and radiation, we can now remove an ovary, freeze it, and save it to be grafted back to the woman after she has been cured of the cancer. We can do the same with her individual eggs, and save them for subsequent IVF. Both egg and ovary freezing are also available for women who feel a need to delay childbearing until their late thirties and forties, by which time their egg supply will very likely have been depleted. These are wonderful options for the woman who wants her own genetic child but does not anticipate starting a family for many years. Watch a video where Dr. Silber explains egg and ovary banking to preserve fertility [see video].
For many years we have been able to use cryogenic technology to freeze and store embryos derived from IVF in order that women not have to risk having a dangerous multiple pregnancy. The embryos can be thawed safety at a later date, and the pregnancy rate with these frozen embryos is still very high. That is nothing new. We have been able to do this since 1983, and long-term follow up shows no deleterious effect on subsequent offspring. In fact, young couples who are happily married, but want to put off childbearing until later, can readily have their embryos (derived from the husband’s sperm and the wife’s eggs) frozen and saved for later, so that they do not sacrifice their chances for later parenthood.
However, freezing embryos for a future date does not solve the problem for unmarried women who want to have children in the future but have not yet met the right man. For these women, freezing their eggs, or even an entire ovary, would be the ideal solution. Until very recently, this holy grail of IVF was unattainable. The reason is that in order for fertilizable eggs to be retrieved, they must be in a mature state of development, with a complex alignment of chromosomes, and this makes them susceptible to even the slightest ice-crystal damage. However, with a new technique of vitrification, recently refined in Japan, ice-crystal formation is avoided completely, and early results indicate that high pregnancy rates can now be achieved with frozen eggs. Thus, a woman who knows that she is nearing a time when she will lose her fertility because of her biologic clock [see video] can freeze her eggs, or a piece of one ovary, and have her babies later.
In St. Louis, we have now demonstrated for the first time that an entire ovary can be removed, and grafted back after freezing and thawing [see video] so that even a menopausal woman can gain back her youthful fertility many years later. This new capability will be especially important to women undergoing treatment for cancer, because all the eggs that might have been lost to chemotherapy can be preserved by removing, freezing and storing her ovary for later use.
If you are considering freezing your unfertilized eggs, or one of your ovaries, the best approach is to first determine just where you are on your biological clock [see video] so that you can know when it’s time to worry. You can now monitor your own biological clock from your early twenties on, so you can decide when you ought to try to have a baby naturally. I will show you exactly how you can do this in chapter 3 of this book. If you find out that your biological clock is more advanced than you feel comfortable with, you now have the additional alternative of freezing an ovary or eggs and saving them until you are finally ready to have a child.
How Can I Be Sure My Baby Will Be Normal?
Why is the egg of an aging female less likely to result in a pregnancy and more likely to result in miscarriage or an abnormal baby than that of a younger woman? Why is it that a young egg placed into an older woman results in a high pregnancy rate, while an egg from an older woman results in an extremely low pregnancy rate? How can we now prevent Down syndrome, or other genetic diseases,without the need for amniocentesis and pregnancy terminations? It’s all in the DNA.
In this book, I will explain, in terms you can fully understand, the emergence of DNA technology, and how it can ensure that you have a healthy baby. Otherwise fertile couples who are carriers of genetic diseases such as Tay-Sachs, cystic fibrosis, retinitis pigmentosa, hemophilia, and so on, can now use this technology to be assured that they will have normal children. We can easily screen married couples for such genetic risks, and if they have a risk, pre-implantation evaluation of the embryos can save them from having a child who would otherwise be certain to die, or be handicapped with severe defects.
Several years ago, a twenty-seven-year-old woman with Marfan’s disease [see video] (inherited from her father) came to my office with her fiancé. She was told quite correctly by her doctors that a pregnancy could easily be fatal to her because of her condition (which results in a weakened main blood vessel in the chest and leaky heart valves). She was about to be married the following year, and she came in with her mother and father, proposing that her mother be a surrogate and carry her baby via IVF. She was surprised when we told her that not only could her mother be a surrogate and carry her baby, but that as long as we were doing IVF anyway, we could test her embryos (derived from her eggs and her husband’s sperm) before placing them into her mother, and transfer only the healthy ones. Thus, not only could we allow this woman to have a child via IVF, but also we could assure her of having a baby that would not carry her disease.
Most patients who had previously delivered a child with Down syndrome or had elected to have such a pregnancy terminated simply would not ever try again to get pregnant and undergo the risk of enduring this agony once more. Even patients with cystic fibrosis, who are managing to survive with modern medical treatment, tell us that they don’t want their baby to have cystic fibrosis. Using IVF, we can test their embryos and put back only the healthy ones, thereby avoiding these heart-wrenching problems. For obvious ethical reasons, the unhealthy but viable embryos can be frozen and saved for a future date when gene therapy would be able to correct the genetic defect.
There are many couples in their twenties and early thirties who are married and committed to each other, but just don’t want children yet. But they are afraid to put off having children into their late thirties or early forties for two reasons. (1) They are afraid that with their biological clock ticking, they will not be able to have children if they wait another ten years. (2) They are afraid that if they do get pregnant they will be in an age category where this poses a high risk of abnormal embryos, and chromosomal defects in their children, for reasons I will explain in chapter 12. These couples can undergo IVF while they are still young, and have their embryos successfully frozen and stored. At a later date the embryos can be thawed, and the wife can get pregnant even when she is older, with no increased risk of Down’s syndrome. Furthermore, these embryos can be tested genetically just to be sure. Alternatively, they can have the wife’s ovarian reserve tested (again, see chapter (3), and can then make a more informed decision about when they should actually begin to have children naturally.
Achieving Pregnancy Without the New Technology
Do not misinterpret the focus of what I am saying. It is better just to avoid the need for infertility treatment, and in this book I will give you tools for doing just that.
In one couple who had been infertile for many years, the wife ovulated perfectly on day fourteen of every twenty-eight-day cycle like clockwork. In fact, because her ovulatory cycle was so perfect and so regular, she always ovulated on Tuesday or Wednesday. Her husband, who was a traveling workaholic businessman, was only in town on the weekends. So for years they never got pregnant simply because they were having sex only on the weekends. A simple rescheduling of their intercourse resulted in her getting pregnant rather quickly without any high technology. But simple approaches like this only work if you have not yet reached the descending point in your biological clock.
One lady begged me to review her case even though she and her husband could not travel to our clinic in St. Louis. At that time, we were estimating the quality and time of ovulation from basal body temperature charts (rather than ultrasound and simple LH urine testing). Her basal body temperature charts clearly showed poor ovulation, but her doctor had insisted on not treating her because he felt the husband’s low sperm count was the problem. In fact, the local urologist had put the husband on the male hormone testosterone, which would only make his muscles bigger but would certainly lower rather than raise his sperm count. After her husband discontinued taking these steroids and she went on Clomid, she promptly became pregnant. I still receive a Christmas card every year from her despite the fact that we never met. There are countless, similar stories in which very simple approaches work, but only if you learn about your own particular fertility clock.
The problem of infertility in our modern society is getting worse, and the simpler methods do not work well for the advancing age of would-be parents. These simpler methods should be discontinued after they have been shown not to be effective for a couple, and the newer technology used before too much time, energy, emotion, and money have been wasted on old-fashioned approaches. However, it is my goal that by knowing where you are on your own particular biological clock [seevideo], you will be able to have your family naturally, without having to resort to the high technology.
When patients contemplate IVF, their first reaction is often the fear of daily injections of hormones for months, the incredibly high cost of the drugs, the risk of multiple pregnancy and consequent prematurity, side effects related to high levels of estrogen resulting from large numbers of eggs, hyperstimulation syndrome, and the prospect of painful daily progesterone injections for a full ten weeks even after the IVF procedure. Mini-IVF is a very unique approach developed by our colleagues in Japan to circumvent these problems and to simplify IVF for patients, reducing the cost while maintaining comparable success rates.
Mini-IVF is designed to recruit only a few (but high quality) eggs, thus avoiding the risks of hyperstimulation, reducing the cost of drugs from an average of $4,000 to closer to $400, reducing the number of injections, and completely avoiding the painful progesterone injections. This approach is not just a simple-minded reduction in hormonal stimulation. It is an ingeniously conceived and completely different approach to IVF, that saves the patient much of the complexity and cost associated with more conventional IVF protocols. Here is how it works.
On Day 3 of the menstrual cycle, you start on a low dose of Clomid (50mg), but you don’t stop the Clomid in five days as is usually the custom. You just keep taking the Clomid until ultrasound monitoring shows the follicles to be ready for ovulation. A very low “booster” dose of gonadotropin (just 150 iu of FSH), is added on Days 8, 10, and 12. Clomid not only stimulates your own pituitary to release FSH naturally (by blocking estrogen’s suppressing effect), but also staying on the Clomid (a unique new approach) blocks estrogen’s stimulation of LH release, and so also usually prevents premature ovulation. Thus, with this simple change in protocol, the old-fashioned, cheap Clomid is able to stimulate the development of great quality eggs for IVF.
Another advantage of this protocol is that you did not have to go on Lupron first to suppress the pituitary. Staying on Clomid blocks estrogen from stimulating your pituitary to release LH, and this prevents premature ovulation without your having to be suppressed. This means that you can be induced to ovulate with just a simple injection or nasal sniff of Lupron. This causes a more natural LH surge, and avoids the luteal phase defect caused by HCG that would otherwise require months of progesterone injections.
The next step is to recognize that Clomid has a negative effect on the uterine lining (because it prevents estrogen from stimulating the endometrium). That is one reason why results in the past have been so poor with the use of Clomid for ovarian stimulation. The embryos are less likely to implant in such endometrium. But that problem is solved by using the Japanese protocol for embryo freezing, “vitrification,” which I discuss elsewhere. We can now freeze the embryos almost with impunity using this approach, with only a 1% risk of loss. Then these embryos are transferred the next month in a “natural cycle” with no need for taking any hormones at all.
The frozen embryo transfers can then all be performed in a later natural cycle (without hormones). Even if you don’t normally ovulate predictably, you can be given one injection of Lupron in the follicular phase (once your follicle reaches 1.5cm) to induce natural luteinization, and still have a natural cycle embryo transfer with no hormones. The Day 3 frozen embryo would then be transferred five days later, and there is no need for your taking any hormones at all.
Even for poor prognosis cases of older women with low remaining ovarian reserve, there is an advantage to mini-IVF over high dose stimulation. Such patients normally yield very few eggs anyway even with huge megadoses of gonadotropin. If they have any quality eggs remaining, mini-IVF is just as likely to yield as many eggs (very few, of course) as giving huge megadoses of gonadotropin. Even in the worst case scenario, if there are no good eggs left at all, at least they can discover this with only $400 spent on drugs instead of $7,100 (cost of maximum dosage).
Think of this simple parable: If you are sitting under an apple tree, and wish to eat the most ripe and ready apples, you have a choice. You can chop down the tree, and look at every apple on the fallen tree to see which ones were ready. Or you can simply try to shake the lower branches and eat the one or two that have fallen. That is the idea of mini-IVF. It may not work for everyone, but for many patients, it will remove much of the aggravation and complexity associated with IVF, and also dramatically reduce the cost.
Where Do We Go for Help?
How do you decide where to go? When our U.S. Congressional Advisory Panel met back in 1988, we amassed figures which showed that of 150 IVF clinics in the United States, half of them had never achieved a pregnancy at all. Furthermore, of those that achieved pregnancies, the success rate varied from extremely low (less than 5 percent) to reasonably high (greater than 30 percent). Evaluating the quality of the clinic was an extremely muddled mess at that time. In 1984, it was reported at the World Congress in Helsinki, Finland, that of over 10,000 women entering IVF cycles, there were only 600 live births, for a success rate of only 6 percent. In the United States in 1987, out of a total of 12,000 women undergoing IVF cycles, there were a little over 1,000 live births for an overall success rate of about 9 percent. Such a low success rate would hardly be encouraging to a couple.
It was for this reason that the congressional bureaucrats who reported on the discussions of our advisory panel promulgated the claim that the success rate with this new technology is too low and the cost too high to consider it anything other than a last resort and that more resources should be spent on “conventional” therapy for infertility. The bureaucrats also refused to accept the recommendation of the advisory panel that infertility was a medical condition, which would have given strong weight to forcing insurance companies to pay for infertility treatment. The politicians were actually afraid that the female vote would be “offended” by referring to infertility as a medical condition and mandating insurance coverage. If they had not been so erroneously afraid of losing the female vote, IVF today might be affordable to more couples.
Today your odds are very good that eventually you’ll get pregnant with IVF. But you must choose the right doctor and the right program. The Wyden bill passed by Congress in the early 1990s is not of much help. It requires that all IVF clinics report their pregnancy rates to CDC. But this still does not give you a simple answer of where to go, for the following reason: Some excellent clinics might have a lower pregnancy rate simply because they direct their attention to the most difficult cases with the longest duration of prior infertility, the greatest amount of scarring, the oldest women, the poorest sperm quality, or women with low ovarian reserve. If the clinic had the kind of expertise that suited these most difficult cases it could easily have a lower pregnancy rate than a clinic that takes on more simple, routine cases.
In fact, since the Wyden bill became enforced by SART (Society for Assisted Reproductive Technology) and by CDC (the U.S. governments main epidemiology arm), many clinics have simply “cancelled” cases with low numbers of eggs because they don’t want inclusion of such cases to lower their pregnancy rate. Pregnancy rates can easily be manipulated upward by selecting only those patients who have a large number of eggs, or not recommending continued IVF to those who do not get pregnant in the first or second cycle. By law these statistics are not supposed to be used for comparison shopping or marketing because they can be so misleading. But they always are.
We have seen many patients in St. Louis who were refused IVF treatment in their own communities because they appeared to have a dismal prognosis yet they were able to get pregnant with us and have children. I remember a forty-two-year-old woman from Canada who had gone through multiple IVF cycles when she was younger and failed to get pregnant. No credible IVF program in the United States would accept her because they were concerned about what that would do to their statistics. We warned her that her chance of pregnancy was extremely low, approximately 9 percent, because of her age and her very low ovarian reserve. Her first IVF cycle with us yielded only three eggs, and she failed to get pregnant. However, she insisted on coming back for a second cycle several months later, at which time we retrieved four eggs. This time she became pregnant and delivered a healthy little baby that has grown up to be a very fine young man. Similarly, we took care of a basketball executive and his wife who were both forty-two years old and had gone through many failed IVF cycles elsewhere in good programs. When we put her through IVF, we obtained relatively poor-quality embryos with a great deal of fragmentation, and we felt quite sure she would not get pregnant. Nonetheless, she did get pregnant with healthy twins.
These examples are not meant to imply that our program was any better than the previous IVF programs that these couples went to. The pregnancy rate in women forty-two years old with less than five eggs, even in the best IVF programs, including ours, could not be greater than 20%, and the delivery rate would only be about 10%. The only reason for citing these examples is to emphasize that even couples who are in a poor prognostic category can get pregnant but often don’t get the chance to undergo IVF because accepting such patients would lower the IVF program’s statistics and impede their marketing efforts.
Some clinics have become so commercialized that they publish misleading advertisements in local newspapers, magazines, and even in the New York Times and the Wall Street Journal. These advertisements promise high pregnancy rates based on carefully selecting only the youngest, most fertile cases, and offer money-back guarantees after overcharging for every cycle to cover the cost of rebates. Indeed, many unnecessary and expensive tests, which can total as much as $10,000 or more, are sometimes insisted upon before the first IVF, thus guaranteeing hefty revenue exclusive of any potential rebate. This commercialized “Kentucky fried” IVF franchising has become a cause of great distress and confusion for patients trying to figure out what to do. This is not meant to disparage honest clinics, which offer “insurance programs” referred to as “shared risk.” With such a program, if you are in a high prognostic category (e.g. under thirty-five and lots of eggs with no previous IVF failures), you can pay a lump sum for three cycles, and if you do not get pregnant, get 70% of your fees returned. This is more or less an insurance plan, but most couples in a high prognostic category do not care for it because it is likely to cost them more than if they just pay separately for each cycle.
Because many clinics make false claims of exaggerated pregnancy rates by selecting younger patients (with a short duration of infertility, and large ovarian reserve), published rates are simply an unreliable measure. Therefore, the patients’ only resource in deciding where to go for treatment is to understand fully how their reproductive system works, and to learn in a detailed way how IVF and ICSI work. You will need in-depth understanding in order to go through the many steps which are part of every IVF cycle. Furthermore, only with this detailed understanding will you be able to decide where to go for help. You need to learn how to pick the right place by interviewing the doctors and the nurses who are directly involved, so you can evaluate their results in a sophisticated manner.
A list of specialists or clinics is never going to be reliable. I can assure you that anyone and everyone who says that he or she is a “fertility specialist” gets on such a list. In an effort to maintain neutrality and avoid libel suits, organizations such as the American Society of Reproductive Medicine (ASRM), the American Medical Association (AMA), RESOLVE (lay organization of infertile couples), the American Fertility Association and county medical societies, as well as various books and manuals, are unable to recommend which clinic is right for you or which clinic is most likely to give a successful result.
For the energy, the time, and the money that must be put into the effort to conceive, you need to make a good choice for yourself, based on your own understanding. This book does not have to be read cover to cover, though some will wish to do so. It is designed so that you can look up in the table of contents, or in the index, the specific information that you particularly need most, and skip around if you prefer.
With the information provided in this book, you can now monitor your own biological clock [see video] from your early twenties on so that you can decide when you ought to try to have a baby naturally and avoid the need for infertility treatment altogether. Or you may decide you need to freeze your eggs, or a piece of your ovary, just to stop your biological clock. If infertility treatment does become necessary, this book explains what you should expect every step of the way. Understanding how this technology works will give you the best chances for a successful pregnancy.
Copyright © 2007 by Dr. Sherman J. Silber, M.D.
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