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Treating Severe Cases of Male Infertility

Posted Aug 24 2008 1:49pm
MARK POCHAPIN, MD: Hi. Welcome to our show. We're going to talk about infertility. In fact, infertility is a very common problem affecting up to 15% of couples. In women approaching the age of 40 and above, about 25% can have a problem with infertility.

We're going to focus specifically on male infertility problems, known as the male factor infertility. We're going to focus on very severe male infertility, in essence, a zero sperm count.

With me today are two experts in the field. Sitting to my left is Dr. Steven Hirschberg. Dr. Hirschberg is currently the Director of Male Infertility at the Toll Center for Reproductive Sciences and Abington Medical Hospital in Abington, Pennsylvania. He is the male reproductive urologist at the two largest in vitro fertilization programs in the Philadelphia area and works hand-in-hand with 10 reproductive endocrinologists. Welcome.

Sitting next to him is Dr. Lawrence Grunfeld. He's a Clinical Association Professor of Obstetrics and Gynecology at the Mount Sinai School of Medicine in New York, and is associated with the Institute for Reproductive Medicine and Sciences at St. Barnabas in Livingston, New Jersey. He is also a specialist in reproductive endocrinology. Welcome.

When we talk about severe male factor infertility, or in essence, zero sperm count, Larry, what does that mean, and what can be done about that?

LAWRENCE GRUNFELD, MD: It's always a shock for the couple because there is no way that the couple can sense that there is a zero sperm count. Typically, when there is a zero sperm count, the man has a normal sensation for ejaculation. I think it's important here to have the couple understand that there are two components to the semen. There is a liquid component, which they can sense, and then there is the microscopic component which is made in the testicles, which they would have no way of knowing about. So these couples have no way of knowing there is a problem, but when we evaluate the sperm under the microscope, we see normal fluid, but no sperm inside the fluid.

The other subcategory is the dry ejaculate. Sometimes couples present and the husband knows that there is no fluid coming out in the ejaculation. That's a more obvious problem to the couple.

In either one of those cases, the guy has to be sent directly to a urologist with a speciality in male fertility such as Steve.

MARK POCHAPIN, MD: So what happens now? The man comes to you Steve. What can be done?

STEVEN HIRSHBERG, MD: I think it is important to note that men are not necessarily going to know that there is a problem. By and large, most of the men that I see who have zero sperm, for whatever reason it is, are young, healthy men with no significant medical problems. They never really suspect that they are going to have a problem. So really part of the testing part and getting involved in the whole infertility testing once they sense there might be a problem with the couple is important.

A mainstay of the evaluation of the man who comes in with no sperm is based upon the physical examination. There are two main categories of men that have no sperm. There is really only two reasons that men are going to have no sperm. Either they are being made, but they are not coming out into the ejaculate because either they are going to the wrong place or there is a blockage preventing them from coming through. Or a more severe problem is the men that really don't make enough sperm or don't make any sperm at all for them to end up in the outside world where we can look at them under the microscope.

Part of my suspicion as to which one of these two major categories it is is based on the man's physical examination. One thing I need to make sure is he has a vas. The vas is the tube that we commonly, as urologists, do a vasectomy on. It's the tube that brings the sperm from the testicle up to the outside world.

MARK POCHAPIN, MD: Can you see a vas? Or is it something that just a doctor can really examine?

STEVEN HIRSHBERG, MD: You can't see a vas, and there are really no tests, no CAT scans or ultrasounds that really tell us whether it's there or not. It's what we call a clinical diagnosis. The diagnosis is determined when we examine the man and feel his scrotum and feel for that little tube. It actually feels like a hard piece of linguini, but of course, you have to know what you're feeling there.

But some men are actually born without that tube. It's what we call in the medical community vasal agenesis. Some men can be born without one tube. Some men can be born without both tubes. If they are born without both tubes, that essentially means that the man is born with a vasectomy, and there is no way for the sperm to get out. Fortunately, like we're going to talk about in a few minutes, there are very reasonable ways of treating that problem.

There are other types of blockages, and vasal agenesis or lack of the vas is considered a blockage type of phenomenon. There are other reasons that men could have blockages. The most common one that we would see are men that come in who have had a vasectomy. Maybe it's somebody who is remarried or someone that had it done as a method of birth control in younger years now comes in and wants to know what options are open for them, a man that's had a vasectomy and there is no sperm coming out in the ejaculate.

MARK POCHAPIN, MD: You mentioned that there are two classes. One is that there is a blockage problem and that blockage is internal. That man has no idea there is a blockage of the sperm.

STEVEN HIRSHBERG, MD: Right. Usually there is no pain or discomfort associated with it.

MARK POCHAPIN, MD: What is the other part?

STEVEN HIRSHBERG, MD: The other part is what we call nonobstructive or non-blockage azoospermia. Lack of sperm in the ejaculate. These are the men with what we consider testicular failure. There is really a problem with the testicles themselves producing the sperm. Sometimes I'll get a clue on this when I examine the man based on how his testicle feels, on the size of the testicle. If they are a quarter of the normal size, that pretty much is going to tell me that that man does not have adequate sperm production, and that there probably is a problem with the testicles. There is also one critical hormone that sometimes clues us in too that this may be a sperm production problem. That's a hormone called FSH. It's a hormone that is released from the pituitary gland, a very common blood test that we'll get.

If a man comes in with no sperm in the ejaculate and his blood test is abnormal, that pretty much tells us this is going to be a problem with sperm production rather than a blockage type of phenomenon.

MARK POCHAPIN, MD: So now we have these two classes. It sounds pretty grim. The man has no sperm, yet there is apparently some incredible things that can be done now.


MARK POCHAPIN, MD: From your perspective, what can be done?

STEVEN HIRSHBERG, MD: We're very excited when we get the diagnosis of obstructive azoospermia because that's a guarantee that we're going to do okay. This is a couple who comes to us distraught and very unhappy. We turn around and say, "Don't worry. We can fix this. This is something that we have wonderful success with."

MARK POCHAPIN, MD: It's sort of good news in a sense.

LAWRENCE GRUNFELD, MD: Yes. This is a plumbing problem. The problem is that sperm are not getting from the testicle directly into the egg. We are terrific at fixing that.

The one point that I want to make about this is that there is a very important preconception diagnosis that one has to rule out here. Quite often the cause of this congenital absence of the vas deferens is a genetic illness. It's often a manifestation of cystic fibrosis, so one of the things we always do as a team is we'll evaluate both the male and the female for the cystic fibrosis gene because that's really important as a preconception diagnosis.

Once we've done that, this is where the team effort really has to mesh together. The gynecologist is collecting the eggs from the women, the urologist, such as Steve, will collect the sperm from the guy through some sort of surgical aspiration technique, and there is a third part of the team – usually working very closely with the two of us – called the embryologist.

The embryologist is not an MD. It's typically under the direction of the PhD, and the job of the embryologist is to work with sperm and the eggs in a laboratory. We, the reproductive endocrinologists responsible for getting those eggs out of the women at the right time and handing them over to the embryologist. What the embryologist then does is pokes the sperm directly into the egg. Now that's a really interesting technique. It was invented by accident. They didn't know they were going to do that. They accidentally poked into the egg trying to do a different procedure. Low and behold, the sperm got right into the egg and fertilized. This occurred in the mid-80s. Because of that, we were able to get the first IVF baby through ICSI (Intracytoplasmic Sperm Injection).

Since the mid-90s, ICSI has flourished and really become a routine part of the IVF procedure. This procedure is only about five or six years old.

MARK POCHAPIN, MD: So when you talk about IVF, which is in vitro fertilization, are you talking the technique of actually taking the egg and sperm out of the bodies of the two recipients and putting it together? Or is there something more to it?

LAWRENCE GRUNFELD, MD: That's right Steve. What in vitro means is in a dish, in glass. What we are doing is we are physically putting the sperm and the egg into a dish. It's not glass. It's plastic. But we're physically putting the sperm directly into the egg, developing it into an embryo and watching it. We take over the job of the woman's fallopian tube where the sperm and egg meet in the body, grow it for anywhere from three to five days and then we transfer several of those embryos back into the woman's uterus in the hopes that one of those embryos will implant into the uterine lining.

MARK POCHAPIN, MD: You mentioned that obviously you need a sperm to put into the egg.

STEVEN HIRSHBERG, MD: Right. How do we get the sperm? There are many different methods, and it depends on the philosophy of the individual center or the individual urologist who is doing this type of procedure. I think that by and large urologists are the ones who usually do this just because we're most familiar with the male anatomy.

Most of us will get the sperm in these type of blockage cases from the epididymis. It's where the sperm is stored. There is more of them. They move better. If we pull a whole bunch of them out and there is a bunch of them squiggling around, it's very easy to select which one we'll use. We'll use the one that's swimming and looks relatively normal.

MARK POCHAPIN, MD: Wait a second. The epididymis we haven't talked about. We talked about the vas and the testes. Where does the epididymis sit?

STEVEN HIRSHBERG, MD: The epididymis is a little gland that sits on top of the testicle. That's where the sperm are basically stored until the man ejaculates. Now we're talking about blockage scenarios so that the sperm sort of stagnate and then they can't get out. But they are still made. They are continuously made in the testicle, and they are continuously moved to the epididymis. They just can't get out of the epididymis. That's where the blockage is.

MARK POCHAPIN, MD: Is this a surgical procedure?

STEVEN HIRSHBERG, MD: Again, it depends on the individual philosophy. There are many different procedures for this. We're not going to get into individual procedures, but there are ways of doing this under a microscope where you actually can deliver the testicle and the epididymis out and under a microscope look at the little tubes and aspirate some sperm and then freeze them. Then you can thaw the sperm out at the time they are going to be put into the eggs.

The way a lot of people prefer to do it now, rather than by surgery where you actually have to make an incision is by what's called an aspiration. Usually under local anesthesia with some numbing medicine with some sedation, we take a very small needle and puncture either into the epididymis, into these little tubules where the sperm is stored, or you could even do it directly into the testicle.

Now for in vitro, when we're going to actually put the sperm into the eggs, sometimes we only need 15 or 20 good sperm. It's as many eggs as the wife or the female partner is going to produce during that particular time while she is being stimulated by her reproductive endocrinologist.

MARK POCHAPIN, MD: So timing is everything here.

STEVEN HIRSHBERG, MD: Timing is everything. And also, if you have 4 million sperm, but you only need about 10 or 15, then you have to decide what to do with the extras, which we will commonly freeze and have for another scenario, another time when the eggs are going to come out.

But because we need less and less sperm with these newer technologies, we can do less and less evasive procedures by just putting a tiny needle in and just aspirating out enough sperm for the individual cycle. That's sort of the best case scenario; what we call the obstructive or the blockage cases.

Unfortunately, we also see the testicular failure cases where the testicles aren't producing sperm very well. Those require a little bit more invasiveness on the part of the male partner. A lot of times we'll actually have to do a biopsy ahead of time just to see if there is any sperm there. Sometimes if it's questionable at the time the eggs come out, we may actually have to have a donor as a backup to make sure there is going to be enough sperm.

MARK POCHAPIN, MD: So at some level, the man has to produce the sperm. The blockage scenario it's not coming out. But if the man is not producing any sperm anywhere, in the testes, in the vas deferens, anywhere, then is that a situation where you absolutely need a donor?

STEVEN HIRSHBERG, MD: Not absolutely. We actually have a marvelous procedure nowadays called testicular sperm extraction. If I do a testicular biopsy, remove a small piece of testicular tissue in the laboratory, we can process that tissue and sometimes find whole, complete, alive sperm that we can actually extract from the tissue itself. Not enough that we're ever going to see them on a semen analysis, but sometimes we can find enough to use in the laboratory to put into the eggs.

MARK POCHAPIN, MD: It really is quite amazing. There are so many levels of this in which you can try and extract. I guess all you really need is one sperm out of all those million.


LAWRENCE GRUNFELD, MD: You need a really sophisticated embryology lab though. In our lab we often have four embryologists work on each biopsy sample for six to eight hours. So there is a lot of time committed to find a handful of sperm. I remember one patient who we had more eggs than we had sperm. We had to throw out eggs because we didn't have enough sperm to inseminate them. But we got some beautiful embryos and beautiful babies.

MARK POCHAPIN, MD: Well, thank you both for such an enlightening and uplifting conversation. For those people who are having infertility problems, there really seems to be quite a bit of hope on the horizon. Without a doubt, it sounds like you really need to go to your physician, discuss this and get involved with a team approach, have both the male and the female factors evaluated. There really seems to be a lot that can be done.

Well, we appreciate the two of you joining us, and we appreciate our audience staying with us today.

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