Time Warner Bookmark presents: Dr. Sherman Silber
Author of “How to Get Pregnant With the New Technology
July 13, 2000

(For more questions and answers, visit Dr. Silber’s Frequently Asked Questions page. Also check out Dr. Silber’s online chat from Mom.com)
Dr. Sherman Silber discusses the advances in fertility treatments related in his book, “How to Get Pregnant.”

TWBookmark: Welcome to Time Warner Bookmark! Warner Books is proud to present Dr. Sherman Silber, author of “How to Get Pregnant With the New Technology.” The revised and updated paperback includes important information on the latest hi-tech findings, tests, and procedures from one of the world’s most renowned fertility specialists. Welcome, Dr. Silber!

Dr. Silber: It’s great to be back, and I would like to just remind everyone that infertility is really the modern epidemic, and that although only 2 percent of couples in their early 20s are infertile, close to 25 percent of couples in their mid-thirties are infertile. Two percent of all men on Earth are born with 0 sperm production, that is, azospermic, and approximately 20 percent of men have severe sperm production defects.

With modern technology, we are overcoming these problems. It really behooves everyone suffering from infertility to be knowledgeable enough so that they can separate the widely available “quack” remedies and inappropriate treatments from what really works. I’d be happy to answer questions or talk to anyone. I guess this is the time for me to just mention that the Time Warner book of mine, “How To Get Pregnant With The New Technology” is updated and will probably be a big starting point for couples to understand what they have to do so solve the problem. They can go to the Time Warner website at www.timewarner.com or they can go to my website at www.infertile.com to begin their exploration. But in the meantime, why don’t we just answer some questions and open it up!

TWBookmark: How widespread is infertility? Is it usually a problem just for women?

Dr. Silber: No. By most of our estimates, the infertility is a problem of the couple. Now it is true that in about 10 percent of cases, the woman has blocked tubes and it is clearly a female problem. And in about 10 percent of cases, the male has almost zero sperm, and then it is pretty clearly a male problem. But in 80 percent of cases, it’s a problem of the couple that requires both of them to participate in order to have a baby.

This problem is pretty equivalent throughout the world. For example, in China, which is the world’s most populated country – 1/4th of the entire world’s population is in China – and yet 10 percent of those 1.2 billion people suffer from infertility and can’t have any children without medical help. In India, which is the second-most overcrowded, populated country in the world, the number one reason for visiting a doctor is infertility. So, wherever you look, even in places where you wouldn’t anticipate fertility to be a problem, it is pervasive and not limited to the US, Europe or the Western World.

Icee Mocha: What are the newest advances in this technology and what fertility problems do they help the most?

Dr. Silber: Well, the biggest problem for the previous 40 years, even after the refinement of IVF, has been male infertility. There have been so many treatments proposed to try to improve the sperm count in men with deficient sperm production, including hormones, nutritional supplements, varicose vein surgery, even cold temperature athletic supporters, to name a few, and none of these treatments have had any impact on the infertile male, despite being proposed widely. But the breakthrough came in 1992 and 1993 when, in collaboration with the Dutch-speaking Free University in Brussels, Belgium, we developed the procedures referred to as ICSI and Sperm Retrieval. What this means is that in men with poor fertility, where the sperm would not fertilize the wife’s eggs, even in vitro, we developed a method of retrieving these sperm even from men who appeared to have no sperm at all in the ejaculate, in the most tiny numbers, and inject an individual sperm into an individual egg.

Using this approach, we can get pregnancy rates for IVF no different than in men with completely normal sperm counts. The idea behind this thinking is that even when men have zero sperm in their ejaculate, the majority still have a minute number of sperm hiding, so to speak, in their testicles, and even one sperm with this technology, is all that you need for a pregnancy. Prior to the ICSI and Sperm Retrieval, microsurgery for vasectomy reversal was able to help men who were sterile because of a vasectomy to get their wives pregnant naturally, without even resorting to IVF, and this still represents a tremendous advance. But now with ICSI, even men who had no chance for correcting their azospermia, or men with extremely low amounts of sperm in their ejaculate, were able to father children.

Maybe I’ve gone on too long on this, but the next major area of advance currently taking place is related to our collaboration with the human genome project. And we are rapidly, every month, finding the sequence for the various genes that promote sperm production. And we see genetic diagnoses and cures almost around the corner now for what was previously this impossible problem of male infertility. Maybe I should just stop there. There are many more advances and I’d like to take some additional questions.

Thunderbird5: I see your book covers info on ovarian tissue freezing. What is this procedure?

Dr. Silber: This is a tremendous breakthrough developed by Roger Gosden from England, and what is involves is for women who are undergoing cancer chemotherapy or bone marrow transplantation that would completely destroy their ovaries and make it impossible for them to have children even if they are cured of their cancer, we can successfully remove their ovary, either one or both, dissect out the very outer, thin 1 millimeter, which is where all the eggs are located, discard the inconsequential center of the ovary, and then freeze this outer–it’s like a membrane almost–where all the eggs are, the same way we would freeze embryos. And quite remarkably, you can preserve over 75 percent of the ovary with this approach. Then she can undergo her otherwise sterilizing but curative cancer treatment, and some time in the future when it is clear that she is cured, and the ovarian tissue can be tested to make sure there are no cancer cells in it, it can be transplanted back to her very simply. Much like a skin graft. And it will then develop into a normal ovary again. It’s a tremendous technique for this small group of young women who suffer from the most common cancers of Hodgkin’s Disease and leukemia or bone cancer, and when we interview these women in their early 20s, they are all very optimistic about being cured of cancer and they are generally quite brave about what they are about to undergo. But their biggest fear is that once they are cured, they won’t be able to have children. The ovarian tissue freezing, though there are still some wrinkles in it, represents tremendous hope. I think it is important that all young women undergoing cancer treatment be given the option of having this ovarian tissue freezing in the modern era. Many women don’t find out about this until it is too late.

Now another possible use of ovarian tissue freezing is for women with intractable endometriosis or other such diseases who cannot have children at present but wish to have children in the future, and who may benefit from removal of the ovaries, can have the ovaries frozen and then transplanted back at a later date when they are ready to have children. By the way, such an approach is now available also for men, as testicular tissue freezing, particularly for young pre-pubertal boys who are undergoing cancer treatment.

Godess Xena: My sister has polycystic ovaries and her husband and her want to have children. They have been trying for over 7 years do they have any hope?

Dr. Silber: I think polycystic ovaries don’t have to be the real problem that they sometimes pose. You have to understand that a polycystic ovary simply means that follicles are developing which then cannot ovulate, and that’s where these multiple little cysts in the ovary come from. This results in, or can be the result of, increased male hormone in her system. It can result from, and this is relatively new information, insulin resistance, so that you can often dramatically ameliorate the polysistic ovary problem by putting these women on anti-diabetic drugs, such as Metformin. By breaking the insulin resistance, the polysistic ovary will often return to normal function on its own. Even if it doesn’t, there can be enough improvement that stimulation with ovulatory drugs can be more successful.

So, I would think their condition is far from hopeless. So, let me elaborate a little further on this condition. If the couple has to go through IVF, typically the eggs from polycystic ovaries are not of great quality. And there are 2 reasons for that. One is the high male hormone level that can be toxic to the eggs and two is the fact that the eggs are coming from follicles which are abnormal and under-developed for a long period of time. Typically, you get many eggs from such a patient but most of the eggs are not very good. If she is placed, however, on insulin-enhancing drugs such as Metformin, and if her ovary is suppressed for a long enough period of time, for example, with Lupron, then stimulation of her ovaries is much more likely to lead to the retrieval of good quality eggs.

Alliekins: Do you have any ideas on if polycystic ovarian syndrome is a genetic condition?

Dr. Silber: We think that – we will call it PCO to make it easier – we think that PCO is a genetic condition. In fact, we can generalize that a great many cases of infertility that we didn’t previously think of as genetic, really are genetic in truth. And it’s been easiest for us initially to attack the problem of male infertility with the human genome project because it is so easy simple to categorize infertile men by their sperm count, and in so doing we are uncovering a host of genes that are mutated in varying degrees in different infertile men. Most likely, the same phenomenon is occurring with PCO or many other types of female infertility. The reason that infertility is on the increase is that when you are young many of these genetic defects do not stop you from getting pregnant, for reasons I will elaborate on in a minute, but when you are older, when you combine aging eggs with these other genetic problems, whether in the male or female, that’s when you have infertility. Now, probably the major reason that infertility is on the rise throughout the world is that couples are putting off child bearing from their early 20s to their late 30s. As I mentioned before, there is over a 25 fold decline in fertility as you pass from the early 20s to the mid to late 30s. The major reason for this decline in fertility is genetic in the following way. The eggs from older women have a much higher incidence of chromosomal errors. The reason is that when the eggs or in fact sperm from men undergo the process called meiosis. The normal 46 chromosomes that make up the egg and every cell in your body separate off into 23 chromosomes. That way the egg, which has only 23 chromosomes, can be fertilized by the sperm which has only 23 chromosomes, and this results in an embryo with a normal number of 46 chromosomes. It’s this division from 46 to 23 chromosomes, the meiosis process, that is so fragile particularly in the egg, it is the cause of Down’s Syndrome. It is the cause of Turner Syndrome. And it is the cause of most miscarriages.

More importantly, perhaps, it is the cause of genetic errors so profound that the fertilized egg cannot possibly develop, even far enough to result in an early pregnancy. In young women, meiosis occurs in a normal fashion. Each chromosomal pair divides evenly and cleanly so that you have an egg that is left with exactly the right number of chromosomes and genes and just 50 percent, exactly, of what any other normal cell would have. But when you get older and the eggs get older, the matrix on which these chromosomes divide becomes defective, perhaps sticky, if you will, and then instead of having an even separation of these like chromosomes, for example, instead of having one copy of chromosome 21 going to the egg and one copy of chromosome 21 going to the polar body, and this occurring in proper fashion for all 23 pairs of chromosomes, instead, you may have what scientists refer to as “nondisjunction”. This means that you might get two copies of 21 in the egg or two copies of chromosome 16 in the egg. Then when that chromosomally abnormal egg is fertilized even by a normal sperm, the resulting embryo will have more than the appropriate number of chromosomes and genes and this will be lethal for the embryo.

So, in a sense, most infertility that is age-related may not have been inherited from parents, but it is still quite clearly genetic. And so the future for treating infertility even more effectively both in the male and in the female is going to be modern, molecular genetics which we have been interested in, specifically with male infertility, since the early ’90s.

Sammiegurl: How do they tell if it is the man or the woman with the fertility problem? Who should get tested first?

Dr. Silber: Very often, mistaken judgments are made about whether it is the man or the woman. They both should be tested first. In other words, the man must get a sperm count, or better yet, 3 or 4, because a sperm count can be variable, and the woman must have her ovulation checked and she must have a hysterosalpingogram (x-ray of her uterus and fallopian tubes) because these are very classic tests that will immediately tell you whether it is one of those 10 percent of cases that is strictly male, or one of those 10 percent of cases that is strictly female.

For example, if the tubes are blocked or the uterus is scarred, there is nothing subtle about that. It is quite clearly female. If the sperm count is zero or close to zero, once again, there is nothing subtle about that. It is male. With sperm counts that are moderately low, or even with women who ovulate only some of the time, it becomes very difficult to try to pin the “blame” on either partner. And the only treatment that works is treatment that involves both the husband and the wife.

Most of the cases of infertility do not have what I would think of as an absolute definable cause, with the usual diagnostic techniques. In other words, if we are honest with ourselves as physicians, then despite our routine diagnostic tests, we are stuck with not being sure in the majority of cases, what is the cause of the infertility. We have a normal uterus, normal fallopian tubes, adequate sperm count, regular menstrual cycles, ovulation at least some of the months, and yet the couple has not gotten pregnant after more than a year of unprotected intercourse.

So, to be honest, this is the commonest situation, and for this situation we have better treatment than we have diagnosis. You can stimulate ovulation in the woman with tremendous drugs these days, not only to try to get her to ovulate every month, but to improve the quality of the eggs because the hormonal stimulation in her own cycle is what prepares the eggs for this meiosis process we talked about earlier. That process of meiosis will occur more correctly if she undergoes hormonal stimulation. So it is not just a matter of getting her to ovulate. But it’s also a matter of getting better quality eggs. And this treatment is very effective even when we don’t know why the couple is infertile.

And then one can go to the ultimate step of ART, which is Assisted Reproductive Technology, which we more commonly think of as IVF or ICSI or Gift. These procedures all have the same common point of bypassing all of the difficult steps that are normally required in any human being to achieve pregnancy.

One of the points that I emphasize in my first book, “How To Get Pregnant” which was written as far back as 1980, and is frankly still a best-selling book with Time Warner, is how difficult it is if you understand and study the normal mechanism of getting pregnant. How difficult it all really is for the body to accomplish. The sperm have to manage to climb up through the harsh acid environment of the vagina which will kill all the sperm within 30 minutes that don’t successfully invade the alkaline, thick cervical mucus, and out of 100 million sperm that are ejaculated from a normal sperm count, only 100,000 ever reach the uterus. And out of those 100,000 only about 1 to 10,000 ever reach the fallopian tube. Furthermore, the egg, when it is ovulated from the ovary has to bust through the tough, outer capsule of the ovary and then get picked up actively by the fallopian tube before it otherwise simply gets lost in the abdominal area. The fallopian tube has to pick up the egg and hold it long enough for the few lucky sperm that manage to get up there, coming from the opposite direction. And if the timing is off, if the sperm come too late, or the egg comes too early, there won’t be a pregnancy. And just think of what a difficult acrobatic feat it is for the fallopian tube, which is hanging freely in the abdomen, to actively figure out where this microscopic egg is coming from and actively reach down and pick it up.

So the overall message, if you study the physiology of getting pregnant, is that it is darn hard to get pregnant. And as you get older, this feat becomes more and more difficult. So, it is with infertility that we are very often treating with techniques that bypass all these obstacles, a condition that we don’t really understand that well.

Mandybear: Have there been any breakthroughs with the treatment of Endometriosis?

Dr. Silber: Yes. Endometriosis is a very complex dilemma. And the major message to give you is that most endometriosis cases are mild. And mild endometriosis does not really appear to cause infertility. It is commonly associated with infertility, but it’s not the cause of the infertility. So, treatment of mild endometriosis, whether by hormones or laparoscopic cautery or laser, in most cases, is not going to give any higher pregnancy rate than simply conservative, watchful waiting. Severe endometriosis may cause infertility but it’s direct treatment is not very likely by itself to get the woman pregnant. Therefore it is, I believe, the modern view that over-treatment of endometriosis may be wasting very precious time when the woman should be undergoing ART. The pregnancy rate with various ART procedures, and we have known this for 15 years, is no different in woman with endometriosis than in women without endometriosis. And even when endometriosis is a cause of the infertility, bypassing everything which is the philosophy of ART, in other words, you take the egg and the sperm and you fertilize the egg with the sperm and you get embryos. You put the embryos back into the fallopian tubes and get pregnancy rates no different whether the problem was endometriosis or blocked tubes or low sperm count.

So, there is a lot of research being done on what endometriosis is all about, but for practical purposes, it’s important for a woman not to allow herself to get older, and thereby have a lower pregnancy rate with IVF because she is older, and delay IVF simply to undergo what I would consider fairly problematic treatments for endometriosis.

Thunderbird5: Do insurance companies have to cover infertility treatments? Or is that elective by company? And how does a couple convince an insurance company to cover it?

Dr. Silber: Well, that’s a very big problem and question. There are certain states that have passed legislation that require insurance companies to cover infertility. The first state to pass such a law was Maryland. There is such a law in Massachusetts. There is even such a law in Illinois, but sometimes these laws can be bypassed. For example, if the insurance company’s home base is not in that state or if the employer is self-insured. And there are a variety of other loopholes.

But nonetheless, if consumers get state legislatures to pass laws that mandate such coverage, then insurance companies have very little choice, by and large, but to cover infertility. In most states, insurance companies are not required to cover infertility and they have no desire to cover infertility. And the reason is not simply the cost of infertility treatment, but the increased obstetric costs for twins and triplets. And furthermore, they are afraid that some infertility programs may even have quintuplets. This kind of multiple pregnancy is a disaster and can cost the insurance companies many millions of dollars not only for obstetric care but for the pediatric problems it creates. So, by and large, insurance companies are very hesitant to covering it, even though the treatments alone would hardly increase their costs very much at all.

I think that it used to be easier several years ago for the couple to persuade the employer to persuade the insurance company that their infertility was a pathological condition and that it was contestable for the insurance company to arbitrarily eliminate it from coverage, any more than they could eliminate any other pathological condition. But it’s becoming more difficult now to persuade the insurance companies of anything because of the well-known negative changes that are occurring in our health care system because of the dominance of HMOs. So it becomes a political struggle now rather than a personal struggle just because these HMOs are so strong and so arrogant. That requires consumer groups banding together in as effective a way as they can.

Mandible: Does smoking reduce the chances of conceiving?

Dr. Silber: Yes. Quite definitely. The oxygen tension within the developing follicle of the ovary is very important in assuring that this meiosis takes place properly. There is a complicated word for what we call it when the meiosis doesn’t take place property and that word is aneuploidy. Aneuploidy is much more common in eggs which derive from follicles that have reduced oxygen, and smoking reduces the oxygen tension in most of the small blood vessels and vascular beds throughout the body. That is why you can always spot a chronic smoker just by looking at the ashen gray appearance of their facial skin, accompanied by perhaps premature wrinkling. I can spot with almost 100 percent assurance, chronic smokers from nonsmokers, simply by looking at what appears to be the reduced oxygen tension in their skin, which is quite visible. The same thing happens in the ovaries that happens in the skin. So although smokers can get pregnant, their rate is lower and their miscarriage rate is higher and this is not even controversial since the first surgeon general’s report in 1963.

TWBookmark: Dr. Silber, our time is almost up. Thanks so much for being with us! Any final thoughts for our audience today?

Dr. Silber: Certainly, the strongest urge that we have as humans, the greatest need we have, is to have children. So the pain of infertility is perhaps stronger than any symptom than we see in our patients. The emotional pain is great. With these scientific explanations, it almost sounds callous to sound objective about something so painful, but I want to emphasize that all couples with infertility need to study their subjects extensively. There are ridiculous treatments being offered and you have to know enough to be informed consumers and to seek the proper care from knowledgeable programs.

There is a huge amount of money being misspent and, sadly, commercialism in this field. The only way to solve this is to become knowledgeable. So, that’s why I wrote my book. I’m not trying to sell it really. You can get it at the library if you want. I know it is available through Time Warner as a great public service. I am indebted to them for making this book available, as it is not a big money making book. And I think that is where you have to start. Thank you very much.

TWBookmark: Many thanks to our audience for joining Time Warner Bookmark today, and, of course, to our special guest Dr. Sherman Silber.

Time Warner Bookmark is a production of Talk City, Inc., in association with www.twbookmark.com. Copyright 2000. All rights reserved.

(For more questions and answers, visit Dr. Silber’s Frequently Asked Questions page. Also check out Dr. Silber’s online chat from Mom.com)