Leslie R. Schover, Ph.D.
Professor
Behavioral Science
The University of Texas MD Anderson Cancer Center
Hi I'm Dr. Leslie Schover. I'm a professor in the Department of Behavioral Science here at MD Anderson Cancer Center. And I've spent a lot of my career helping cancer patients deal with some of the problems that they have in their reproductive lives. And part of that has been helping them decide on whether it's worthwhile to do fertility preservation and also on understanding the options for being a parent after cancer treatment.
In general, you might wonder, do our younger cancer survivors want to be parents? Maybe they've had enough trauma and problems in their lives and that makes them less likely to want to be parents. Well, in our surveys, that certainly doesn't seem to be true. In fact, young cancer survivors, men and women, place increased value on family ties and intimacy. And in several surveys, 75 percent of childless patients or of teen girls want to have children in the future. And what I think my experience has been, is that if the oncology team does not really discuss the risks of infertility, survivors may have prolonged anger and grief that really affects their quality of life.
If they think there was something that could have been done and they didn't have a chance, or even if nothing could have been done but they wanted to know. And you know, part of the problem is that men and women have a very narrow window of time after their cancer is diagnosed and when their treatment plan is being made, to do anything to try to preserve their fertility. And once you start cancer treatment, chemotherapy or radiation therapy to the pelvic area or surgery, you can't go back and we don't have a time machine.
So, how do we get this information to people when they need it? Unfortunately, about a third to a half of patients will not recall being told that their cancer treatment could damage their ability to become a parent even though they were in a group where that is true.
And that has been true in the number of surveys now. This is just a list of various surveys done in the last 10 years and you can see that whether it was mixed diagnoses, or breast cancer, or kids with cancer, that usually only a minority recall fertility being discussed. Now, we are doing a little bit better job with breast cancer patients or with teenage girls.
But it's important to know that in those surveys, especially the breast cancer patients, the rate of discussion of fertility was higher because they brought up the topic themselves, not because their oncologist brought it up. And, in general, these samples tended to be very well educated Caucasian women who are more likely to look on the internet or be told--join advocacy groups and know about some of the options that they have.
So, unfortunately, most patients still are not getting the information that they need to make an informed choice about whatever options we do have to preserve fertility.
Now, some cancer treatments have been modified to spare fertility and that's usually true when the cancer is early stage or when we're very successful at treating it. For example, for Hodgkin's disease where chemotherapy has been so successful, regimens like ABVD, that are a lot less toxic to male or female gonads can be substituted, and then only if the patient has a recurrence or progression of their disease, do the more alkylating chemotherapies that are more destructive to ovaries or testes be used. Also before radiation therapy to the pelvis for things like some types of Hodgkin's disease or for--even for cervical cancer, the ovaries can be moved up and away to the sides of the pelvis out of the radiation field and about half of women seem to recover menstrual cycles after that type of treatment. It's important to do this very quickly before the start of radiation because unfortunately, the ovaries have a tendency to fall back into the pelvis. So, sometimes in the past it was done because they needed to do a laparoscopy for some other reason, and now it's more likely to be done all by itself. Also when ovarian tumors are very early stage or when they're borderline or slow growing tumors, sometimes just one ovary and tube can be removed and the uterus and other side can be preserved so that a woman can have a pregnancy. Some women with very early stage uterine cancer or hyperplasia can take progesterone therapy and avoid surgery although eventually after they have a child, they're still recommended to have a hysterectomy. For women with very early stage cervical cancer, there is a modification of surgery called trachelectomy where the uterus is preserved and a new kind of a cervix is created and women can get pregnant and carry a pregnancy, but because the cervix has a tendency to dilate during the pregnancy, they have to have cerclage, and there is a higher rate of premature low birth weight babies. But it's still a big advance for those women who are eligible and it's a difficult surgery to do, so it's not available everywhere. There was a lot of hope that drugs that were LHRH agonists or antagonists that actually keep the pituitary gland from telling the ovaries to produce estrogen and progesterone, would actually put the ovaries into a kind of arresting or temporary menopause state where they might be less damaged by chemotherapy. But the more randomized trials that are done, the less it looks like that treatment really effectively does much of anything.
Now for men, we for many years have had the ability to freeze sperm. And it's actually the advent of better infertility treatments for men that's made that so useful. So now, if men can have in vitro fertilization with a partner who is fertile, especially if she is under age 35, you can literally just have a handful of sperm cells, and you inject one into each egg that's recovered from the woman, and you have a very high rate of developing into embryos. So that is something that made sperm banking a lot more viable because when you freeze and thaw sperm you lose some of the sperm count and some of the motility or swimming power of the sperm. For pre-pubertal boys, there are some experimental efforts going on to try to either freeze pieces of testicular tissue that could later on be transplanted back into the testes, or maybe even onto a nude mouse to produce sperm cells, or to create suspensions of stem cells that could then be infused back and repopulate the testes with cells that would produce new mature sperm cells. But these are not ready for primetime, these are research efforts currently. For women, women who have time to do an IVF cycle, which means that they need about two weeks from day 2 or 3 of their menstrual cycle, could freeze unfertilized eggs or embryos. Embryos certainly have a higher pregnancy rate but unfertilized eggs are catching up, especially with the technique called vitrification, which is essentially like freeze drying the eggs. And also another option for either pre-pubertal girls or adult women is actually to take pieces of the cortex of the ovary that have hundreds of primordial follicles in them, freeze them, and later on transplant them back into the woman's body. Or it may be in 5 or 10 years to be able to extract those follicles and mature them in the lab which we certainly can't do now. And there have been a handful of pregnancies from cryopreserved ovarian tissue that's been auto transplanted. There have even been a few attempts to preserve the whole ovary and the advantage of that is that you could reconnect it to its blood supply . And with the ovarian tissue, it grows its own blood supply, but during the process a big chunk of the ovarian tissue dies. And so it's difficult to preserve that ovarian tissue in the body after it's transplanted. So, there are a variety of things that can be done. Now, there are also a lot of barriers.
For men, one issue is embarrassment or cultural or religious taboos about collecting semen. Typically, men are asked to masturbate and produce an ejaculation and to give that to the lab to analyze and then freeze.
In some cultures, it's considered a sin or very shameful to masturbate and so a woman partner, if the man is over 18, and the partner is over 18, can help the man through hand caressing. But in general, it's best to avoid collecting samples through intercourse because of the concern about contamination with bacteria, although sometimes in very strong religious cultures, a silicon collection condom can be used as a way to try to cryopreserve semen. Now, sperm banking works very well and, in fact, babies have been born from samples stored for 22 or 28 years and then thawed and used to create a pregnancy, but less than 20 percent of men ever return to use their samples. Some percentage of men die, larger percentage of men are able to conceive naturally, but for those men who don't recover good sperm production after cancer treatment, even banking one sample can be the difference between having the option to have a biological child or not. It's important to bank sperm before starting chemotherapy or pelvic radiation. Not all centers do that, but there is a concern, although statistics aren't really available, that a sperm that's exposed to chemotherapy or radiation could fertilize an egg, but that the baby could be born with a significant birth defect. It's very difficult to predict which men are going to recover fertility. For example, men with testes cancer are the most likely group to have very poor sperm counts and motility when their cancer is diagnosed, but they are the group that's most likely to recover good sperm counts afterwards. And as I said, we still don't really have good techniques for pre-pubertal boys.
Now, for women, we really don't have a good analog of sperm banking, we sure wish we did. Ovarian stimulation in an IVF cycle to produce embryos or to freeze eggs, or the surgery to actually harvest and freeze ovarian tissue have much higher costs and the results aren't nearly as reliable. And unfortunately, in the USA our private insurers are not mandated to cover these procedures except in a very few states and even then it's unclear whether that applies to women with cancer. And so women might end up having an out of pocket expense of $10,000 to $15,000 dollars to do these procedures and yet end up with a very small probability of really having a live birth. And so it's very unfair and something we need to work on with legislation. Recent studies show that even teenagers diagnosed with cancer and their parents are very concerned about their future fertility. So, this is an area that really needs work.
Once someone has already had their cancer treatment and they want to be a parent, of course, one option, if they did freeze sperm or eggs or embryos, is to use that reproductive tissue. And another thing that may occur is recovery of natural fertility and that's going to depend on the type and dose of chemotherapy or dose and field of radiation therapy and patient age. In general, younger patients who are post-pubertal have a better chance of recovering fertility than older patients, but that's much more marked for women than for men. In women, being under age 35 is certainly a help in women who've had chemotherapy. It's possible, sometimes, if patients can't conceive naturally, that they may respond to infertility treatment using fresh gametes, sperm or eggs. For example, a man who has very few sperm might be able to use those sperm in an IVF cycle with intracytoplasmic sperm injection which is ICSI where they actually inject one sperm into each egg. Men who don't have any sperm in their semen may have islands of sperm production in the testes, and a surgeon may be able to do multiple biopsies, get some fresh sperm from the testes, and use that to fertilize eggs gathered from IVF. Some women may respond to IVF and actually be able to have a pregnancy even though their ovarian reserve is low. Now, what is ovarian reserve? That is how many primordial follicles are left in a woman's ovary. And even girls who have cancer treatment before puberty, if they had chemotherapy or pelvic radiation, may resume their menstrual cycles, but they are going to be more likely to have a very early premature menopause because some of their eggs were damaged. And that is something that we may be not even quite realizing until now when there are more women who have survived pediatric cancer who are getting into their early 30s, which is when we start seeing a lot of these changes. We used to just look at whether you have a menstrual period or not as indicating fertility. Now, we have some better ways of looking at a woman's ovarian reserve. One is to measure the hormone AMH, which is produced by follicles in the ovary, and if it's very, if the levels are very low, that indicates that menopause might be more eminent. There's also the possibility of using ultrasound when a woman is ovulating to look at how many follicles develop to be antral follicles, the ones just before the one that's selected for ovulation, and how big are the ovaries. And some of these measures can also give us some idea of whether a woman has normal fertility or whether her fertility is pretty impaired. Another issue is social parenthood which means parenting a child that's not yours biologically and that might involve adoption or what called third party reproduction.
Now, in the United States, third party reproduction could include using a donated sperm from a sperm donor, a donated egg from a woman who donates her eggs, a gestational carrier who's a woman who carries a pregnancy and she usually would not contribute her own egg, but she would have embryos created from a married couple, for example, with the husband's sperm and the wife's egg, planted in her uterus and then if they--that resulted in a pregnancy, she would carry the pregnancy and give birth. So she's not genetically related to the baby. Traditional surrogate mother is a woman who contributes her own egg and usually has artificial insemination with sperm from the father and the couple and then carries a pregnancy. And we have embryo adoption because a lot of couples who have IVF don't use all the embryos that they froze and store, and when they're sure they have all the children they wanted, some release their embryos for adoption and there are now websites where actually couples who want to have a pregnancy, and where the woman has a uterus and can carry a pregnancy, can actually, you know, create a connection with the couple like this and adopt their embryo. The problem is that all these kinds of third party reproduction are very expensive, especially the ones relating to women. And many survivors don't find them acceptable emotionally or from a religious or cultural point of view. So, about a quarter of men and women say that they would be willing to use some kind of third party reproduction. Sperm banking for men is actually relatively or using a sperm donor, I'm sorry, for men is actually relatively inexpensive, and most fertile women get pregnant within three to six cycles, and we're talking about maybe a $500 per cycle cost and although that's not cheap compared to $10,000 for an IVF cycle or paying a gestational carrier $25,000 to carry a pregnancy, those are much more affordable alternatives.
Now adoption after cancer is much more endorsed by cancer survivors. About two thirds of them say if they were infertile after their cancer, they would have be willing to adopt a child, but we have the problem that adoption of a healthy infant or a young child has become very expensive with long waiting times and cancer survivors have additional barriers. Some international countries don't allow anyone with a cancer history to adopt, or they demand that someone be 5 years out, with no evidence of disease. In the US, many domestic adoptions now are done by birth parents choosing the adoptive family and some birth parents may be scared off by the idea that one of the parents has a history of cancer. These methods are very expensive and young couples who already have medical bills may not be able to afford it. And single parents need to plan to care for a child in case they die prematurely. That's true for anyone, but certainly a bit more true with cancer patients. So the one kind of adoption that's very affordable is adoption of special needs children who are in the foster care system and may have special needs in terms of their mental or physical health. And for some cancer survivors that may be a wonderful alternative, but for others, they may not have the emotional and financial resources needed to take care of a special needs child given their own history of illness.
Now we often forget that about 1 in 1000 women who gets diagnosed with cancer is pregnant at that time. And these women are often told when they first are diagnosed in the community that they should have pregnancy termination to save their life. Unfortunately, that information is very outdated and unless they have acute leukemia, is typically not true. There are no studies of the psychosocial impact of being diagnosed with cancer during a pregnancy, but it's kind of like combining a cancer diagnosis with a high risk pregnancy. If the woman continues to be pregnant and gets chemotherapy or a mastectomy, for example, during her pregnancy, if she does terminate the pregnancy or miscarry, she has that loss on top of her cancer and if she carries the pregnancy, she has all the risks of worrying about her child's health.
Many women also believe that after any type of cancer, they're going to increase their risk of recurrence if they get pregnant. And again, that's really outdated information from everything we know. Even for breast cancer which is the one where we worry the most, given high estrogen levels during a normal pregnancy that might trigger a cancer recurrence for some women, there are no studies that show that women who were diagnosed with breast cancer and then get pregnant have decreased survival. In fact, they have what they call the healthy mother effect. So if they compare a young woman who was treated successfully for breast cancer and then gets pregnant with a very similar woman who didn't get pregnant and you look at groups like that, the women who get pregnant actually have better survival. And that may be because only women with a very good prognosis try to get pregnant. It's unclear why it's true. There is a confusing fact though, if the woman has a pregnancy and within the next two years gets breast cancer, her prognosis is poorer. So there's this issue of, "What is the effect of pregnancy if it occurs before your breast cancer diagnosis versus after your breast cancer treatment"? And women have to understand that difference. Another problem is, that women who get pelvic radiation therapy as part of their cancer treatment, especially if they have it in childhood or as teens, and a group, for example, that gets a lot of this in childhood, is girls who had Wilms' tumor of the kidney. if they have radiation to the uterus, the uterus often is unusually small and it may be scarred by the radiation, so it can't expand fully. And so women who've had uterine radiation also have less blood flow to the uterus and they're at risk for either miscarrying, having a still born child, or a premature delivery, or low birth weight baby. And a lot of women don't know that, so they don't go see a high risk OB before they conceive. So that's very important. And another important reason to see a high risk OB for a cancer survivor who wants to get pregnant, is that many chemotherapies, for example, may do some damage to the heart or lungs that's not immediately apparent, but with the physical stress of pregnancy, can become a problem.
In addition, women who are going through this issue of pregnancy and cancer worry a lot about dying prematurely and leaving their child without a mother. They feel very isolated because they feel like even other young cancer patients can't relate to their experience, and certainly other pregnant women can't relate to their experience. They have long term worries about whether having chemotherapy, even during the second or third trimester, could affect their child's cognitive development, or leave learning disabilities. Although so far, the evidence looks positive that these children are doing fine. And then if they do lose their pregnancy, they may very well be infertile in the future, so they aren't necessarily going to be able to get pregnant again.
Now, cancer survivors are also very worried about their children, whether the children were conceived before or after their cancer. And we found in surveys of young survivors that they often have a really exaggerated idea of how likely it is that their cancer has an inherited component. Only 5 to 10 percent of cancers are inherited within a family, although it is true that younger people are more likely who--younger people who get cancer, are somewhat more likely to have an inherited type of cancer. But what we do know is that children who are born to parents who had cancer treatment before the child was conceived, whether it's a man or a woman, don't have any unusual rate of birth defects as far as we can measure. We always like more research, cause not that many babies are born in that circumstance. They also don't have any unusual rate of childhood cancer unless there is an inherited childhood cancer syndrome in the family. And even children exposed to chemotherapy after the first trimester, when the organs have formed, but if they're exposed in utero, they appear to do well. And we know that survivors worry too much about this issue.
So, clearly, this is an area where survivors need a lot more education and counseling. They need it to be timely, and they need it also to occur after their cancer treatment. But many physicians don't have time in a busy clinic and oncologists don't always know all of the ins and outs of these very complex issues. It is important for the oncologist to bring up this issue because the physician's endorsement is very powerful in terms of saying yes, this is an important issue, I'm going to refer you to someone who can give you the information you need to make decisions. Also allied health professionals can provide more extensive counseling and referrals.
So in an oncology clinic, a physician's assistant or advanced practice nurse, or oncology social worker can learn to do some basic infertility counseling. At diagnosis, the most important thing is to ask, "Do you still, you know, want to have children"? Maybe someone's already had two children but they really, really want to have a third, and that's still going to be a trauma for them if they can't. It's important to involve the partner. Maybe the partner feels differently about having children in the future than the patient. Or maybe they haven't really spoken about it clearly. It's important to give them the best understanding we can of the risks of infertility with their planned cancer treatment, and to find out their attitude about whatever options for fertility preservation are available to them. And then when they come back after cancer treatment for follow-up, remember to ask about, "Do they still want to have children and haven't been able to conceive. Do they need a referral either for infertility treatment or for counseling about social parenthood options"?
The best thing is to have an oncofertility program. And some cancer centers are starting to do this. To have a reproductive endocrinologist who consults in the oncology clinics on a regular basis, and to have IRB- approved protocols for experimental procedures, like collecting tissue from pre-pubertal children. To try to obtain research funding or donations to offset patient cost since so few of these procedures are covered by insurance.
To have case conferences. To keep slots open for very timely referrals for fertility preservation. You don't have time to wait three weeks to see the reproductive endocrinologist. You have to see them tomorrow or today. And also to foster collaborative research with both psychosocial and medical issues.
There are a number of patient education materials available that have been done very nicely. The organization Fertile Hope has their own website although they've now become part of the Lance Armstrong Foundation and they have a number of brochures and decision tree aids for patients. The ASCO patient guide for fertility preservation is another one. The LIVESTRONG website has some resources. The American Cancer Society, cancer.org, and there's a very good online group called Adoption After Cancer on the Yahoo group server that is open to new members, and has archives and current active discussions, and has kind of all the ins and outs about adopting a child as a cancer survivor.
So in conclusion, I think that cancer related infertility has a negative impact on quality of life, and this is particularly true for patients who really weren't finished building their families when they were diagnosed with cancer, and may be more true if they weren't properly counseled about their options. So oncologists need to help patients make informed choices about fertility preservation or even if fertility preservation is not practical, at least tell them that, so that they don't feel like they missed out on something they could have done. And we need a lot more research, not only on the techniques and their effectiveness, but on the psychosocial aspects. And we need to help long term survivors move past their grief over infertility which sometimes may be present 5 or 10 years after their cancer treatment. So thank you very much for listening to me today. And I hope this information is of help to you and your patients.
Fertility: Understanding the Options After Cancer Treatment video
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