Fertility Services/Reproductive Endocrinology

Expert Advice On Recent Studies Challenging Long-Held Beliefs About Fertility

Howard D. McClamrock, M.D.

Recently, studies have been released that suggest fertility may be extended much longer than was thought possible and even restored in some cases. Howard McClamrock, M.D., director of the Center for Assisted Reproductive Technologies at the University of Maryland Medical Center, answers questions about these studies and addresses other fertility-related topics in the following interview.

Dr. McClamrock is an associate professor of obstetrics, gynecology and reproductive sciences at the University of Maryland School of Medicine who specializes in In-Vitro fertilization (IVF) and techniques to improve pregnancy outcomes.

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View interview with Dr. McClamrock, in which he discusses advances in treating fertility problems

In a recent study, Harvard researchers concluded that female mice produce a constant stream of new egg cells as adults, which they feel raises the possibility that women, too, may produce fresh eggs for at least the first half of their lives. If true, these findings suggest fertility may be extended much longer and that fertility may be restored in women whose ovaries have shut down. What do you make of this study/research?

The study is very significant; it's a breakthrough study because it suggests that our thinking for the past 50 years as to how women are endowed with eggs may have been incorrect. That in itself is huge, but what it will potentially do in the future remains speculation.

The idea has been that mammals are born with all the eggs they will ever have in their life and that they are lost over the lifespan of the female. This is what was thought to be true in women but this study suggests that may not be true, at least in mice, and that there are oocytes (eggs) that are being continually produced from germ or reproductive cells and matured. So that concept is novel and significant in its implications but we have to keep in mind that for the moment that it is only in mice and whether the process can be altered or extended has not been shown even in mice.

Will this study with the mice lead to studies involving women?

I believe it will, yes.

If the implications of the study are true, talk about the significance or impact this would have in terms of fertility, reproductive biology and menopause.

The possibilities are unlimited; it's just that the findings are very basic and very preliminary. But if the mechanism is true in women, then there would undoubtedly be attempts to try to alter it and delay it, delay the shutoff mechanisms of the proliferation of the stem cells to allow women to have healthy eggs at a later time in life. If that were to be done, then it would have implications because we know that the uterus itself is not a problem for having children later in life and we take advantage of that by fertilizing donor eggs and implanting them into the uteri of older women.

In regards to menopause, if you could maintain ovarian function longer it could have overall health implications such as delaying the time in which coronary artery disease starts in women. This natural ovarian function could potentially do a better and safer job than traditional hormone replacement. But it could also potentially increase women's risk of some cancers (breast, uterine) that have also been subject to concern in hormone replacement.

There was another recent report about an experimental procedure in which women in need of ovary destroying therapies for cancer and other diseases could have their fertility restored if the women's eggs and pieces of the ovaries are frozen and later transplanted into the body. This has already been done successfully in monkeys. What's your initial reaction about this?

This is clearly more advanced in the clinical scheme of things than the mouse study, and this will undoubtedly result in some pregnancies in women before long. It is certainly not efficient at the moment and a lot of work still needs to be done in order to understand how to optimize it. But the potential is there and it could become mainstream, although it's still very experimental.

What has been done and is being done more and more frequently and is perhaps even closer to coming into mainstream clinical use is the freezing of mature eggs. For many years we could not reliably freeze mature eggs and have them do what we wanted them to do when they were thawed - in other words, fertilize normally. We've been able to freeze embryos for quite a long time, and that is very common but some women are unable to freeze embryos. They may not have a partner at the current time but they want to maintain their fertility potential in the future. It's been very difficult to freeze oocytes (mature eggs) but progress has been made in that area and there have been a number of human pregnancies. It is still not mainstream, but it is being done at a few places in the U.S., and there is an institution in Italy that has considerable experience with this.

Has the UM Center For Assisted Reproductive Technologies done oocyte freezing?

We have not cryopreserved oocytes yet, but we freeze embryos routinely. In fact, we had the first birth from a frozen embryo in the state of Maryland.

Taken together, these reports point to a future in which women have more flexibility than ever regarding the timing of motherhood. Do reports like this give women the false sense that it's OK to wait longer than ever to have children?

There is the danger of that, and that danger has existed prior to these studies. Thanks largely to oocyte donation, there have been public figures who have had babies later in life than is common. Many of these births have occurred through egg donation, but that often is not part of the story. Therefore, the possibility that they used eggs from other women is often not considered by the public. The American Society for Reproductive Medicine has been attempting to educate women about age-related infertility because clinicians constantly struggle with this problem. Age-related infertility may be our most common problem.

What advice do you give to women/couples interested in starting a family about the best times to start this process? And what impact does age have, say, for a woman in her mid-30s or approaching 40?

The physiological answer to that question is really the earlier the better, but that is not what we're faced with often. There are life decisions to be made, and there are women who marry later in life and all sorts of good reasons for delaying childbearing. So we don't tell women when to have children; that's a personal decision. The only thing we want to do is educate them as to how age and fertility relate to each other.

Every person is an individual; there are some women who can conceive without significant difficulty at age 40 but most of them do not. In my practice I see many women in their mid-30s who are having age-related infertility issues, but in the general population, some women are quite fertile in their mid-30s. As age increases, the problems become more significant in every woman.

There are a couple of facts that many people don't understand. One is that if you look at embryos (fertilized eggs) in women who are 40, if they're analyzed, it has been shown that the majority of them (more than 50 percent) are genetically abnormal. Therefore, this is our baseline when we do In-Vitro fertilization (IVF) in women at age 40 and explains the need for replacing more than one embryo. This is also why fertility rates are lower and pregnancy losses are higher in women in this age group. The other thing is that in women over 42, IVF pregnancy rates are still not that good on a national basis.

It seems like we're reading more stories these days about women in their 40s and even 50s having babies, thanks to the wide array of fertility services available. Is it true these fertility services have already started to give women/couples increased flexibility in terms of when they'd like to start a family?

There is more flexibility than they would have without the services. Certainly that is true. We can help women in their late 30s and early 40s, more than they're likely to do on their own. IVF and egg donation have helped tremendously with this.

Speaking of fertility services, what should women/couples with fertility problems look for in a fertility center?

They should want a well-established program and a program that can do the majority of things that could possibly need to be done. I don't think that needs to include freezing of ovarian tissue because that still is mostly experimental. I think most of the clinics will do that when it becomes reasonable and mainstream.

Talk about the fertility services available at the University of Maryland Center for Assisted Reproductive Technologies. Anything cutting edge?

We are a full service program providing In-Vitro fertilization (IVF) as well as a donor egg program.

We also perform micromanipulation procedures such as intracytoplasmic sperm injection (ICSI), a procedure that uses microscopic instruments to enhance the chances of fertilization of the egg and involves the injection of a single sperm into the egg.

We are not at the moment freezing ovarian tissues or oocytes. That is still considered experimental in most places. One of the more cutting edge technologies we offer is pre-implantation genetic diagnosis, or pre-implantation genetic screening for women getting IVF. This technology allows an individual embryo to be tested for a specific genetic disease such as cystic fibrosis or sickle cell disease in certain populations. Also, it is at times possible to screen for conditions such as Down's syndrome. The ability to test embryos prior to implantation is important for some women and is a relatively new technology.

At our center, we try to provide a little bit more personal attention, and focus more on quality than quantity compared to some other centers. We think we do a very good job of it.

- By Michelle Murray

This page was last updated on: August 8, 2008.

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