Deborah Holman discusses fertility preservation guidelines, potential risks and barriers to fertility preservation, and the role of the oncology nurse in discussing fertility with male and female cancer patients.
Back to Symposium Page »
so I would like to introduce our next guest. We're switching gears again. And the last topic for this symposium is gonna be regarding Uncle Fertility. And our next guest is Deborah Holman. Um, Deborah received her undergraduate nursing degree from the University of Toronto in Toronto, Canada, and her MSN and W h N P. From the University of Texas Health Science Center at Houston. Ah, School of Nursing. Miss Holman earned her postgraduate certificate and oncology advanced practice nursing from the University of Texas Health Science Center at Houston School of Nursing. She's also completed her a PRN Fellowship at India Anderson Cancer Center. Deborah has over 30 years of experience working in infertility with the last seven years focused on Anka fertility. So please help me welcome Deborah Holman. Thank you. Hi, everyone. I just wanna thank the organizers for inviting me to speak at this conference and to talk to you about Uncle Fertility. Um, I want to thank the audience for hanging in there until the very last lecture. It's, uh, almost night in the central time zone in the eastern time zone. So I really appreciate you hanging around. I have great respect for highest respect for all of you oncology providers. You just do an awesome job with patients and often help me with my job. And we've heard a lot of great presentations today, so I feel like I have a very big shoes to fill. Um, and the whole cove it pandemic has had a big effect on fertility practice to because we find that there's a whole new level of anxiety for expectant moms. And nobody really knows what the long term effects of this viral infection will be on their babies if they became infected during pregnancy. Um, a couple more people. I want to thank Scott and Justin with broadcast med for their patients with me and the mute button, which will be the legacy of my experience with Zoom. I know for sure, so I have no disclosures. I will discuss some off label and experimental procedures and treatments, and they should be identified with this blue highlight, although I did find one spot where I forgot to do that. But it does say it's experimental. Uncle Fertility combines the art and science of reproductive endocrinology and infertility. Aziz Well is the art and science of oncology practice toe, educate cancer patients to preserve or expand their reproductive options. And this is another conversation that needs to happen. We've heard this in a couple of the talks today, and it's just a important for fertility. So today I'm gonna explain why it's important to have the conversation review for fertility preservation guidelines from ASCO and from the American Society for Reproductive Medicine. Explain fertility risks for men and for women with cancer treatment. Discuss post treatment family building options. Discussed barriers to fertility preservation and to describe the role of the nurse in the conversation about fertility and not just the nurse but any oncology provider. So the good thing is that there's good survival from childhood cancer and for people between 15 and 39 years old who are diagnosed with cancer and the potential whilst the fertility could be more stressful than the cancer diagnosis itself. We've actually had a few people who declined cancer treatment because of the potential effect on their fertility, and that is sad. Um, decisions about fertility preservation, as you are probably fully aware, are made at a time of emotional fragility. We've had patients say I had testing last week for whatever symptom I have. On Monday, I got a diagnosis of cancer. On Wednesday, I was here and Friday I'm talking to you about the impact of my cancer treatment on my ability to have Children in the future. So we know this is just ah, busy graph that talks about the most common cancer diagnosis in females and males between the ages of 15 and 39 are most common. Referrals come from breast lymphoma, G I oncology, gastrointestinal oncology and actually from our own grouping. Gynecologic oncology. In the conversation matters because Live Strong, which is a very important support group for people with cancer. They report that fewer than 50% of patients recall getting any information from their oncologist about the effects of their cancer treatment on fertility. And I've actually talked to patients who said nobody said anything to me. But I have seen it documented in the chart that the oncology oncology provider actually did discuss something with them, and they just don't recall because they're so overwhelmed with all of the information they're receiving. 60% of oncologists know about the ASCO guidelines, but fewer than a quarter of them follow those guidelines on a regular basis. Many patients want the option of future fertility, even if they're not sure that they want to have Children. Once someone tells them that they may not have that option, they want to explore what they could do to preserve that option. And in our experience, probably only about 10% of women with cancer decide that they're going to freeze eggs or embryos through in vitro fertilization. Many young women and men have not started or completed their family, and we see many who haven't even been thinking about having a family yet or are doing things to prevent having Children at the time on day treatment related risk is really difficult to predict exactly. And I often tell patients, You know, this job would be so much easier if I had a crystal ball and we've probably all said that at some point or another. Fertility is a concern in survivorship, and it's often a very significant cause of distress because people survived their cancers and they get three or four or five years out from finishing treatment, and they're like, Okay, now I'd really like to have a baby and Nobody told me that I might have problems. Survivors want to have Children and really talking about the risk. Fertility should be part of education and informed consent before a patient gets their cancer therapy. Several times we've received urgent concert requests that 4 30 in the afternoon. Someone is going to start their chemotherapy in the next hour or two, and nobody's talked to them that about their risk. And they're signing their consent in the pharmacist. Send us an email saying, Oh, they want to talk to you about sperm banking. Um, so it's that puts the patient and everyone in kind of a difficult position. Um, talking about it gives patients some control over the decision making. The patients who are the saddest and the angriest are the ones who never had a conversation before their cancer treatment, and it reassures patients about their future. And I've had patients say to me, You know, you, your you and your colleagues are the only ones that have really given me any hope that I might be here in five years. So fertility preservation guidelines for the fertility field the are guidelines for clinical practice and ethics. The ethics committee come from the American Society for Reproductive Medicine, and these have been updated several times. These are the latest updates, and then from the ASCO guidelines that have also been updated. And that's where we base. We based our treatment on all of these guidelines. The American Society of Clinical Oncology recommendations say that is part of education and informed consent. Before cancer therapy. Health care providers should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options and or to refer all potential patients to appropriate reproductive specialists. Whether that's a reproductive endocrinologist or urologist, they just need to get to see somebody. Although patients are often initially focused on their cancer diagnosis, the update panel encourages providers to advise advise patients regarding potential threats to fertility as early as possible in the treatment process. So it's to allow for the widest array of options for fertility preservation. And in particular, when I talk about female fertility preservation, you'll see why this is important and survivors lives are impacted by cancer. Your life is never the same once you have that diagnosis and the effects of cancer treatment can be long term and effect survivors, and they include physical effects, economic, psychological, social and sexual effects. And the whole sexuality thing could be a whole separate lecture. Loss of fertility is one negative result of cancer treatment that adversely affects the quality of life for survivors. And if there are no fertility preservation options available, we can have that conversation with them, and we can help them grieving the loss of that future fertility. That's a really important thing to do. So this is our team. We have a little card that we could give patients about the ankle fertility program with Dr Terry Woodard and Dr Lori Mackenzie and yours truly. The hair color changes every couple of years. Um, the Uncle Fertility team Doctor Woodard is a reproductive endocrinologist as his doctor Mackenzie, and they have joint appointments at M. D. Anderson and at Texas Children's Hospital, Baylor College of Medicine. And I'm a women's health nurse practitioner, and I have been in fertility treatment for a long, long time. So I respect all of you who have been in oncology for over 30 or 40 years, and our program at M. D. Anderson. We give comprehensive fertility counseling before and after cancer treatment, and sometimes during treatment, we do evaluation of baseline fertility so that we have a baseline that we can compare future results to. We discuss fertility and family building options after treatment. We streamline access to fertility preservation procedures that can be done, um, through Baylor, Texas Children's or to other fertility clinics in the Houston area, or really anywhere in the U. S. And occasionally will find clinics in other parts of the world. And, um, this could be for procedures such as sperm, freezing, Egger, embryo freezing or ovarian and testicular tissue freezing. And we collaborate very closely with the oncology team, our uncle fertility referrals. If their urgent, we can see them usually the same day or within about 24 hours. We get the referrals through Epic, which is our electronic health record, by email or by phone. Um, the age range of the patients we see is anywhere from 14 years old to 49 years old. The most common referrals come from gynecology, breast lymphoma and G. I. Um, we do. There is a pediatric nurse practitioner or family nurse practitioner in the pediatrics hospital that does counseling for early adolescents and Children. And she is very proficient, very talented in her counseling. And then she'll refer people to us if they want to go ahead with something. The conversation matters because when comparing survivors to their siblings, cancer survivors to their siblings, survivors had a decreased likelihood of following a pregnancy or conceiving a pregnancy versus their siblings. And they had to reduce chance of having a live birth versus their siblings. And this was based on the dose of calculating agents they received and the age they got their treatment. And then at the age they conceived or tried to father a child. And these are This is just a list of fertility risk resources that you can use to talk to your patients. Um, probably the most common is the cyclophosphamide equivalent dose chart. We don't actually use this because we know that high dose calculating agents and high dose platinum agents are the most damaging fertility and even people getting lower doses than those high doses. You know, we can have two women with the same diagnosis, getting the same treatment, being the same age, and it will affect them very differently. Um, so we use a lot of different things when we're assessing risk. The Uncle Fertility Consortium is at Northwestern University, and they were the first ones to establish an uncle fertility program. And have they have a great website, which, uh, I have a list of websites at the end of my talk. Um, save my fertility does have an online risk calculator for patients, but we use live strong. Um, this is the link that will take you to some risk and fertility preservation charts that I'm going to show you in a couple of slides. So number four is actually number one for us. Um, And when we talk about risk fertility, you know people get a lot of different kinds of cancer treatment. Sometimes it's a combination of things. Sometimes it's just one thing, but we know with chemotherapy that seems to be the most common treatment that patients get. And it can go cause some pretty, um, severe damage to cells, as I tell patients is great for getting rid of cancer. And it acts in all different ways. It can poison parts of the cells that can fuse DNA together. It can break it and maintain the breakage. So there's lots of ways chemotherapy works, Um, and depending on the dose and your age at the time of getting your cancer treatment, it can have different effects, just like it can affect normal tissues like bone marrow and hair follicles. It can also affect eggs and sperm. And then there's our newer therapies, Um, more of the targeted and immune therapies that Dr Weirdo was talking about earlier. That may be more specific to the cancer with less effect on normal tissues, but it can stimulate the immune system sometimes or suppress it. And it can often have side effects on other organs, like the thyroid gland or the hypothalamus or pituitary gland, that can indirectly impact fertility. And we don't really know what the impact of these drugs are on human reproduction. Um, you know, humans aren't dogs or rats, which are what are commonly quoted in a lot of the studies, so we just don't really know what the long term effect is going to be on human reproduction. We will tell people not to try to conceive for sure on these drugs because you don't want these kind of drugs in your body with the developing fetus, and usually the manufacturers will recommend the length of time to be off. Hm. Although sometimes with our high level of caution wanting people to have a healthy baby we will double or triple that just to be on the safe side. Um, surgeries are a little more obvious. Sometimes. Obviously, having your reproductive organs removed is a great threat. Fertility. And unfortunately, the department I work in is responsible for a lot of that. So obviously having your uterus removed means you can't carry a baby. Doesn't mean you can't have a child. Um, but you won't be able to carry that baby Having both of your ovaries removed or both testicles removed with anarchy Ectomy is pretty obvious to, but if you're left with one over here, one testicle that actually can function very well and take the place of two organs bond. That's probably why we have to having your fallopian tubes removed in a self inject. A. Me does not. It impacts your ability to naturally conceive, but you can still have a baby. You still have your ovaries. You still have your uterus. You can carry pregnancy and have a baby baby, but you have to do IVF and then surgeries that hat that are involved. Retro peritoneal lymph node dissection in men can cause something called retrograde ejaculation because of the effects on the nearby structures or the nerves. What happens is when a man ejaculated it can reflux into the bladder. He still make sperm and semen, but it reflexes into the bladder rather than being ejaculated out the the Penis. And usually they have to go to urologist to have treatment. Thio Fix that. Or we can do fertility procedures to try to retrieve the sperm from the bladder. And then brain surgery that involves the hypothalamus or the pituitary can also be an issue with hormone production because it's really the pituitary gland, hypothalamus and pituitary gland to tell the ovaries to make an egg toa ovulate or tell the test is to make sperm radiation to the pelvis, abdomen and brain could be very damaging to fertility. Um, women and men who get total body irradiation, 80% of them will be sterile afterwards. The lethal dose of radiation that will kill 50% of eggs is 2 to 4 gray and men will be completely without sperm with four gray of radiation to the test ease, so it takes very little radiation. Thes eggs and sperm are very sensitive to low doses of radiation. Women who have cervical cancer who have toe have chemo radiation um, very often are. Don't have any ovarian function afterwards, and the uterus is damaged by the radiation. The muscle is damaged, the endometrium is damaged and the blood supply is damaged. And they there have been no reported pregnancies after that kind of treatment. And for women who are able to get pregnant after total body irradiation of just something as little as 12 grade have a marked increased risk of miscarriage, preterm birth and fetal mount position. So fertility risk factors for women. Age is highlighted here, and I am going to flog this during the whole conversation because that's a huge thing for women. Not so much for men, but it is huge for women, their cancer type and stage of cancer. What kind of chemotherapy? They might get radiation to the reproductive and pelvic organs, brain kind of surgery they're gonna have their fertility status at the time of their diagnosis often is unknown because they haven't tried to have a baby that they may. For women with estrogen positive estrogen receptor positive cancers such as breast cancer or uterine cancer, some ovarian cancers. They may need 5 to 10 years of Advent hormone suppression that doesn't necessarily impact their fertility directly, but it's the aging that happens during the time they're on that treatment. And were they able to freeze eggs or embryos or ovarian tissue or sperm prior to treatment? Obviously, females aren't here. Try to cry or preserve sperm. So these are the charts from live strong that I was talking about and another hard to see, and it's very, very busy, but I don't know if my mouse will work here. This chart on the left talks about fertility risks for women, and it's ranked from high risk to very low risk or unknown risk. And this is a list of different kinds of cancer treatments for different kinds of cancers. And this column here really deals with the dose of the medical of the chemotherapy, and it's very chemotherapy heavy this whole chart and age. So women getting a certain dose of cyclophosphamide, same dose if they're under 30. Their risk might be down here in the lower risk group, where if they're between 30 and 40 years old, they may have more of an intermediate risk with the same dose of cyclophosphamide, say, where women over 40 will be in a high risk group. This is a chart that talks about family building options and fertility preservation options, including egg and embryo freezing, ovarian suppression. Moving the ovaries surgically out of the field of radiation, and then alternative ways to build families that many people aren't aware of and often may not want to consider when we first talked to them. But we'll see them for follow up a year or two after their treatment, and they're often more open to talking about these options adoption most people are familiar with. But there's the options of using donor eggs or donor embryos, or for women who aren't healthy enough to carry a pregnancy or who have had a his direct me. They can use a gestational carrier, and we have similar charts for men. So that link I gave you a couple slides ago, we'll take you to these charts, and this is a a little public service announcement from the American Society for Reproductive Medicine. It talks about the chance of pregnancy each month. At 30 you have about a 20% chance of getting pregnant every month and at 40 just within 10 years, you're down to a 5% chance of getting pregnant. And this is because women are born with all the eggs they'll ever have. You don't lose just one egg every month, toe ovulation. You lose hundreds of eggs. That is just naturally what happens to the ovaries. But that egg loss and egg quality accelerates once a woman gets into her late thirties and into her forties, so that causes a reduction. This is for a healthy 30 year old in a healthy 40 year old, and when women get chemotherapy or radiation, it caused a premature depletion of their egg supply. Maybe not 100% but it can put them at risk of an earlier menopause. And this is another chart that is a little more graphic that talks about the decline that happens about the mid thirties, when it really starts to accelerate. The pregnancy rate decreases in the live birth rate also decreases, so just to wake you up for a minute because it is late. Women are born with a lifetime supply of eggs. You actually have the most eggs when you're a 20 week fetus in your mom, and you've already lost some of them by the time you're born, and then you keep losing them before you even start a period. You lose hundreds of eggs every month, and there's a faster decline in your thirties and forties, 51 years old in a couple of months, a Z, the average age of menopause in the United States, and so not so much fun. Cancer treatment can adversely impact the number in the quality of the eggs. We cannot accurately predict how cancer treatment will affect an individual patient. We can't promise to preserve fertility even if they freeze eggs or embryos. That is not a guarantee of a pregnancy or of a live birth. Many women will have a depleted supply of eggs that will not be recovered, and they will have what we call a shorter reproductive window a chance to get pregnant in that short period of time, and they might not be ready for it just because we have fertility preservation technology does not mean it's always safe or appropriate to use, and sometimes we just can't do anything at all. So we do some baseline fertility evaluation for women, and this is called evaluation of Ovarian reserve, which is the capacity of the ovary to provide an egg that is capable of fertilization. And we do two things at M. D. Anderson because it's a cancer center. It's not a fertility center. We get a hormone drawn called anti malaria in hormone, and this is a hormone that basically tells us if the egg supply is normal or not. Um, it's a hormone that's made by the cells that support the very immature eggs. The Antrel follicle count is a trans vaginal ultrasound that looks for follicles in the ovaries. So those air little fluid filled areas on the ovary that are like this spot with a little egg and the blue fluid around it. And on an ultrasound that looks like a black area, um, and the radiologist will count the follicles that measure between two and 10 millimeters. These air the follicles that would respond to fertility medicines. This testing doesn't tell us that someone will or won't get pregnant. It tells us how they would respond to fertility medicine if they're going to do fertility treatment to try toe freeze eggs or embryos. And we like to do this test as a baseline before they start cancer treatment. And we'll do it again a year or two after they finish treatment. So standard fertility preservation options, egg and embryo freezing are the gold standard for fertility preservation. There's also fertility sparing gynecologic surgery, where early ovarian cancers, that gynecologic oncologist might take just part of the ovary out or one ovary and leave the other one in there, um, moving the ovaries or transposing them out of the field of radiation or freezing some of arian tissue to use in the future and ovarian tissue. Prior preservation. If you look at some fertility preservation charts or literature, you might see that this was an investigational option. Um, it's really the only option for pre puberty girls, but it got, um, it is now a standard option for fertility preservation as of December 2019, I think, is when the American Society for Reproductive Medicine, um, decided there was enough evidence that this was probably a good thing to do. It does require surgery, a laparoscopy that could be done and a piggybacked onto other surgeries. It is still really should be done is part of a research protocol. There is a huge loss of eggs at the time of surgery and again when the tissue was thought and transplanted back into the body. So it really isn't suitable for women who are in their forties, and there's a questionable risk of re implanting cancer cells. So, um, some programs will still use this tissue from women who have leukemia. We I'm not sure whether you can put this back and not give people back their disease and then ovarian cancer when the ovary could be affected by micro metastases. That's another time that we don't want Thio, uh, put ovarian tissue back into a person. And there have been over 170 babies born after women have had this ovarian tissue thought and put back into their bodies. This is another busy chart. A couple things I want to point out to you, though, is an egg and embryo freezing. So this takes 2 to 4 weeks to Dio, and some women don't have the time or don't want to take the time to do it, So that could be one factor that can one roadblock for patients. Um, it does delay their treatment because they can't start chemotherapy until this has been completed. They have to be referred out to a fertility practice. They have thio be taught how to do their injections and for fertility medicines, and they have to get to the egg retrieval and have the eggs frozen. But we've had people who go from the egg retrieval sweet to the hospital to start their chemotherapy so they could start pretty quickly afterwards. And then there's the cost. It's expensive. And, you know, a lot of 18 year olds don't have $8000 sitting around to freeze eggs or embryos. And there are only 10 states in the whole United States that have mandated fertility preservation coverage and a lot of insurance companies if they have fertility coverage for patients. If it's a fertility preservation situation, sometimes they'll declined to pay for it, so it can be very expensive. Live strong can help. If contracts with different fertility clinics around the United States to offer reduced prices, there's actually no money that changes hands, but the clinics will agree. Thio offer reduce price for Egger Embryo freezing and most clinics will do that even if patients don't qualify for live strong assistance. There is no guarantee of pregnancy if they do this. For women who don't have a partner, um, they could just freeze eggs. Nobody can tell them what to do with their eggs. We tell them they only belong to them on Git does provide what we call reproductive autonomy for women who have a partner or who want to freeze embryos and are willing to use a sperm donor. They can use that Teoh fertilize the eggs and freeze embryos. This talks about moving the ovaries out of the field of radiation so it does. It does require a surgery. It's a laparoscopy. And if it can't be piggybacked onto another procedure than the patient is in most likelihood gonna have to pay for that surgery herself, it may or may not be covered by insurance. And then conservative treatment for gynecologic cancers can be, you know, just conservative surgery, only taking one over instead of both ovaries for borderline ovarian tumors or using something like a marina. You did that has progesterone for early endometrial cancers. That's so IVF for eager embryo freezing. I've already talked about a lot of these things. That's an outpatient procedures. So are very ill. Women with leukemia really are usually not candidates for these procedures. Um, it's done at a fertility clinic, so they have to be discharged from the hospital, be able to do this and have to delay their chemotherapy, which most patients don't want to do. And neither do there physicians it takes at least two weeks from when they start their IVF medication. It requires daily injections of follicle stimulating hormone and lutin izing hormone with close ovarian monitoring. So they get ultrasounds every couple of days. They get blood drawn to check their hormone levels, and this could be maybe three every two or three days at the beginning, and then it could be three or four days in a row towards the end of the two weeks. For women with estrogen sensitive tumors, we could give them a drug called letrozole orally during IVF stimulation to keep the estrogen levels down to a more physiologic level. Um, freezing eggs and embryos is not a guarantee of pregnancy or live birth, even for women who don't have cancer and most fertility clinics. If you just go in and you need to do IVF when you finally get through all the work up and you're ready to start, they usually time it with the onset of your period. So maybe on the first or second day of your period, you're going to start your medications. But when women have cancer, they don't have time to wait a month or a couple weeks, so we can actually now start women at any time in their cycle. It could be right after ovulation or before ovulation anywhere and that and their menstrual cycle, and we could get them started on medications and stimulate the ovaries. So this isn't an ovary on drugs. I tell people these air the follicles that air full of fluid, and this is a stimulated ovary, and these are very nice because they're all around the same size, and they've grown nicely in response to the medications. So the first IVF birth was in England in 1978 with Louise Brown. Everybody thought that baby was going to be a freak There was a huge media Fleury when she was born and she was a completely normal baby and she now has her own child in the US The first IVF birth was Elizabeth Car in 1981 and she also has a child. 1.5% of all births are from IVF and there have been over six million IVF babies born in the world, lots of them. So this, in short, is the fertility preservation procedure. Egg production is stimulated by hormone therapy. Follicle stimulating hormone is normally made by the pituitary gland to tell the over every month to make one egg and infertility treatment. We give people much higher amounts of that fertility. Stimulate our follicle stimulating hormone to get many eggs to develop, but in a very controlled way. So this is an injectable hormone. Um, women doing this will take two or three subcutaneous injections every evening when they go in for ultrasound and blood test the nurses Fertility clinic nurses will contact them after talking to the doctor about what to do next. Tell them what does to take and there could be drugs added in or take it stopped during the fertility treatment cycle. The eggs were retrieved from the ovary with a trans vaginal egg retrieval. This is done under anesthesia. If women are freezing eggs, they're frozen after they're taken out of the ovary. It could be frozen for many years as far as we know. And if they're freezing embryos and the eggs in that sperm are put together in a dish allowed to fertilize, which we know usually by the next day and then any developing embryos are usually allowed to grow in an incubator till day five or day six of development, and then they could be frozen for a future embryo transfer. And this is how the egg retrieval is done with a trans vaginal ultrasound. And a needle is, um, put through a needle guide that's attached to the transducer for the ultrasound, and it goes through the vaginal wall into the ovary. So it's nice to be under anesthesia when this happens, and then this is a close up of the needle. Aspirating the fluid out in the egg goes with it into a test tube. This is the only time a test tube is involved in all of this, and then that test tube is handed over to the embryologist in the IVF lab that's attached to the egg retrieval room. It's all a very special set up, carefully screened for you know, you want to keep toxins out of the room, and even the room is sanitized with special fluids that aren't gonna be toxic to developing embryos. The women, Oftentimes, after the retrieval, the doctor, the nurse will write on their hand how many eggs they got because they don't remember. They'll ask 10 times how many eggs they got after anesthesia and just to put people's minds. It is about fertility drugs and cancer risk, because this does rear its head every so often, based on available data, there does not appear to be a meaningful increased risk of invasive ovarian cancer, breast cancer or endometrial cancer following the use of fertility drugs. So reassuring also is that we know that using frozen eggs is good is using fresh eggs, and people have looked at this and the live birth rate per embryo transfer. So once the frozen eggs are thawed and fertilized and made into embryos, that live birth rate is the same as for people using fresh eggs that are fertilized, and then a fresh embryo is transferred into the uterus. So that's very reassuring. And also there's over nine. There's more than 900 babies. This is a little bit dated. Um, babies air Fine. There's no increased risk of chromosome abnormalities, birth defects or developmental problems. So for women talking about embryos a little bit, um, for women who have a high risk cancer mutation such as a BRC a mutation, or for men who have a mutation like lynch syndrome or for just the mutations that will see, um, often in the population cystic fibrosis, sickle cell muscular dystrophy. When there's a high risk of inherited disease, it is considered ethically acceptable to test embryos and p g t preimplantation genetic testing. M for a mutation can be done on a sample of the cells from an embryo called the trophy acted ERM, and this is a group of cells that turns into the placenta, and those cells can be sampled and tested for that specific mutation. So the lab needs the actual mutation report to be able to build a probe to look in the embryo p g t. A. For an employee is toe performed on embryos to screen for things like Down Syndrome and trisomy 16 and 18 and Turner syndrome. And you can also get the sex of the embryo doing that. And then sex selection could be very useful for sex. Sex linked genetic diseases like muscular dystrophy and fragile X syndrome. And then patients have to consider what embryos air they're going to choose to transfer. And what do you do with leftover embryos? That's the part people don't think about, and we encourage them to think about that Fertility sparing surgery and for this is conservative treatment for early gynecologic cancers or pre cancers. And this is important because 15 to 20% of gynecologic cancers are diagnosed in women under the age of 40. Ovarian transposition We've talked about for women with early pre invasive cervical cancer. The doctor could take a cone shaped piece of tissue out of the cervix, and as long as the margins air clear, they can usually try to get pregnant naturally, some for more advanced cervical cancer, but early still, ah, simple tracheal ectomy or radical trey collect me where the cervix, with or without the adjacent tissue, could be removed, and then the vagina and the service and the uterus. Or Souter together. And there's a big thick suitor put in the uterus toe. Hold a subsequent pregnancy in the uterus because that's what the cervix does. It holds pregnancy and ovarian cyst ectomy for early or borderline ovarian cancers. Um, just taking one over into about with that affected ovary or using protestation. Allow agents like Mega City or Omega's or putting in a progesterone secreted i e. D. Which is investigational. We have, ah, an algorithm at M. D. Anderson for fertility, sparing treatment for gynecologic malignancies and pre malignancies. This is actually we're currently updating this right now, and, um, this I just I mentioned before that not everybody is a candidate for fertility preservation. So some of the most difficult counseling we have to do is for women with advanced cervical cancer. And that's what this yellow part represents. Is a cervical cancer that is more than two centimeters large, and if it can involve the whole cervix, it can go into the upper part of the vagina. And when you do this egg retrieval and you're putting that needle through the vaginal wall, you don't know. There's a theoretical risk that you could be seating the pelvis and the ovary, possibly with cancer tissue. So for those large tumors, larger tumors greater than two centimeters? Um, we typically don't like to do these egg retrievals. We don't like Thio, even stimulate the ovaries and thes tumors bleed like crazy even when the ultrasound is put in. So it's just too risky for these women. Investigational methods of Fertility preservation Ovarian suppression with a drug like Depo Lupron or Zoladex, can be very effective for suppressing menstrual cycles during chemotherapy when platelets conf all because people can have life threatening periods when they have thrown beside a pina. So if they can get something like a G N R H agonist, which is a gonadotropin releasing hormone agonist, thio shut off the communication between the pituitary gland and the ovary. Um, they won't have periods, but they will have hot flashes, and they may have vaginal dryness. It just depends on how long they get it. They only need to get the strain chemotherapy, but it is not proven to protect fertility or even ovarian function, and it is a little controversial in the fertility world. Some physicians think that it helps, and others think that it's rubbish. Um, it's not FDA approved for fertility preservation and not even really for menstrual suppression. But that's the code we use to try to get insurance coverage for it, because that's what we're using it for, um, menstrual suppression. And for some patients, it's better than nothing. If they can't do anything at all, they might feel better doing this. And we kind of agree with that. Um, and then in vitro. Maturation of immature eggs is also experimental and off label. This is where very immature eggs that have not had follicle stimulating hormone injections to make them grow. They're taken out of the ovary and potentially matured in the laboratory setting. But we really don't have the technology. It's not quite there yet to mature these eggs. Here's very few pregnancies from this, and it's very experimental procedure. Um, just a word about uterus transplantation, because people will ask us about this. It's the first available treatment for what we call absolute uterine factor in fertility, and some women are born without a uterus. Some people have to have their uterus removed for various reasons not necessarily cancer. The first baby was born in Sweden in 2014, and this was after years and years of research. There's more than 11 berths, probably close to 20 now in the world. Patient has to do IVF and freeze embryos before she has the transplant. She has to be a non smoker. There's a lot of counseling that goes along with us. She has to have six months to a year of immune suppression. There should be after the transplant, not before and then these medications air modified during pregnancy, the uterus can come from a living or deceased owner. There is a risk of organ rejection, so that's why they want to give her a long time on the immune suppression before deciding to go ahead with an embryo transfer. The uterus is not meant to last forever. Hysterectomy is recommended so that they can discontinue the immune suppression drugs. Pregnancy after cancer. Return of menstrual periods does not mean a person has good fertility, and chemotherapy is not birth control. So make sure you discuss contraception with your patients. We recommend that patients wait 2 to 5 years after completion of treatment before considering pregnancy, and we want their oncologists to give them medical clearance. We also know that there is the highest risk of cancer recurrences in that first two years. And we don't want anyone being pregnant and having to deal with more cancer treatment for men. There really is no consensus being very conservative and the fertility world. We advise them to wait 12 to 24 months before attempting to father a pregnancy. And we know that for people who are at least two years out from having treatment two years or longer, that there does not appear to be any higher risk of birth defects than in the general population, which is about a baseline of about 3%. Um, we will refer people to maternal fetal medicine high risk obstetricians because treatment cancer treatments can impact a mother's health during pregnancy and then, um, impact a fetus so Dr Robison can impact cardiac function. Biomedicine can impact pulmonary function, and then, with the new therapies, we really don't know how they might impact of pregnancy. So we'll send them to maternal fetal medicine medicine for counseling to discuss the risks, and for women who've had a trickle ectomy have the cervix removed. There is a very high risk of preterm labor and delivery and stillbirth. We asked them to please follow a generally healthy lifestyle, avoid toxins, and they might have to consider third party reproduction or adoption pregnancy After breast cancer. There was a study that looked at tamoxifen use 34% of them of women did not start tamoxifen to keep their estrogen levels down because they wanted to get pregnant, and 25% of them discontinued. Tamoxifin, sometimes without their oncologist knowing about it. So sometimes they'll delay tamoxifen. The oncologist has to be on board with that, though, and we know that pregnancy does not appear to cause a cancer to come back. There's always a risk of cancer recurrence. It doesn't protect against cancer coming back, but it doesn't seem to increase that risk. Post treatment, family building options. People conceive naturally. Ah, lot of the time we don't see them because they haven't had any problems. But if they see a fertility practice, they can have a little assistance with aural medications or injectable medications to help them ovulate. They made a need artificial insemination. If the cervix has been removed. Thio. Get that sperm up into the uterus. Um, there is always IVF, which is our highest technology. Or if they have frozen eggs or embryos, they can use that using frozen eggs. The uterus has to be prepared with estrogen and progesterone. The eggs air warmed, their fertilized and incubated for five or six days, and then the embryos could be transferred into the one embryo could be transferred into the uterus because we really only want one healthy baby at a time that excess embryos could be cryo preserved for the future. So these little black dots in this Petri dish are the eggs. Remember that picture, um, using frozen embryos? Same thing. The uterus is prepared, the embryo is warmed and then it's transferred into the uterus. When the time is appropriate. It's kind of like having a Pap smear. Not like that's any fun, but it's much easier. There's no sedation needed on Ben. We continue the hormones to support the pregnancy through most of the first trimester. These are the cells in the embryo, Aaron in the embryo that turned into the fetus. The cells over here are the trifecta Durham, and that is what turns into the placenta. That is also what have sampled for preimplantation genetic testing. So using frozen ovarian tissue, the tissue is warmed. A laparoscopy is performed as long as the tissue is viable, and then the tissue is transferred under the ovary, ovarian cortex or the outside part of the ovary. Or it could be Sittard together in place, like a blanket onto the ovary. But it could take several months for the tissue to function if it's going to. And people can actually try to get pregnant naturally, because this is a picture of them sewing pieces of tissue under the cortex and you notice how close the edge of the fallopian tube is to the ovary. So if that tissue functions again, women Canova late and get pregnant naturally. Post treatment, family building options there, several of them donor eggs or donated by a known or unknown donor. Sometimes a sister or friend will offer to do that, and sometimes patients think that's weird. They'd rather use an anonymous donor, Um, but they have to. The donor has to go through IVF. Donor sperm could be used, especially if a male doesn't have sperm after, um their cancer treatment, and it could be inseminated with or without using ovulation meds. Donor embryos, air donated from couples who completed IVF because they had fertility problems and they're finished having their Children, and they would rather not discard their excess embryos. They'll donate them to people. So this is a little more like an adoption. A gestational carrier is a woman who carries a pregnancy from what we call an unrelated embryo. So the egg comes from we call this woman the intended parent. They intend mother, and then the intended father provides the sperm. So a gestational carrier is not related to that embryo, as is the case in traditional surrogacy, where the woman uses her own egg and is inseminated with the intended father sperm. That is not legal in a lot of states. Gestational carriers are legal in some states, but every state has its own reproductive laws. And then there's traditional adoption. So I know time is getting a little bit short. I'm gonna kind of go a little faster through this, and we see men, too. Same thing for men. Chemotherapy, surgery and radiation can have a very similar impact on fertility. We could do in vitro fertilization for the male partner for the female with something called interested pleasant sperm injection for men with very low sperm counts. And this compensates for those very low sperm counts. We recommend contraception during treatment and for up to two years after treatment for men and also for women and for men who present a fertility practice with infertility. Sometimes they're sent because they have abnormal sperm counts. They're sent to a urologist for evaluation, and sometimes they pick up testicular cancer, leukemia and lymphoma, which are diseases that can cause men to present with low sperm counts. So again, for men, men make sperm all the time. They're not. They don't have a limited amount of sperm, like women are born with all the eggs they'll ever have and those eggs or not replaceable. But men make sperm all the time so they can actually recover. Sperm counts, maybe not to their baseline, but can recover some sperm. Um, it takes almost three months for sperm to mature, and when we see people for fertility, a third of infertility is related to male factor. A third two female factor in about a third is a combined er, an unknown cause. A cancer treatments can adversely impact sperm producing cells and hormone producing cells. We can accurately protect our predict how cancer treatment will affect male patients either. And it may take several years for sperm production to come back. One man told me it took 17 years until he had enough sperm for his wife to conceive, Um, sperm that are already exposed to chemotherapy when men bank sperm, um, may not be safe to use for future pregnancy. We don't know. We can't tell them that sperm is okay to use. And we don't have good ways to evaluate the sperm for DNA damage, and sometimes we just can't do anything at all. So these are the same live strong torch charts for men. Um, the left sided one talks about fertility risks and then family building options is on the right hand side. Age is not so much of a factor for men, and again it's cancer type and stage. What kind of chemotherapy are they going to get? High dose calculating agents and platinum agents are the most damaging. Often we don't know what their fertility statuses we do get a semen analysis if they banks firm, and that could be used as their baseline and fertility preservation options. Freezing sperm through ejaculation is the gold standard, but sperm can also be retrieved surgically. The test ease could be shielded from radiation, and they can do IVF with their partner and make embryos to freeze to use in the future. Investigational options for little boys who haven't gone through puberty is to do testicular tissue freezing. There have been no births reported, and this is a very experimental procedure. So we refer men who want to free sperm to sperm banks or to a urologist. They need infectious disease testing the longest. A sperm sample has been stored that actually was used for a pregnancy is 30 years. It's a long time. I'm not sure what the circumstances were in that one. Um, there are procedures that can be done for men with spinal cord injuries or men who have difficulty producing sperm. There is vibrant Ori stimulation or electoral ejaculation, which I won't go into right now, but it does require anesthesia pardon and again, men can have complete absence of sperm with only four gray of radiation, and then If they do decide to do embryos with their partner, they just have to preside. Provide the sperm sample and their partner can do IVF, and they could get embryos. So using the frozen sperm, their partner has to have a thorough fertility evaluation, and she may or may not need medication and monitoring. We try to get the sperm into the uterus right around the time of ovulation so that it's waiting there for the egg to be released. Or she could do IVF and just to try to wrap up a little bit, Um, there is fertility preservation assistance for patients who don't have insurance coverage. Live strong works with Freedom Fertility Pharmacy and one of the fertility drug companies that donates fertility medications. Thousands of dollars of fertility medications if the patient qualifies for the live strong program. If you get a patient, sending you will live strong oncologist form, please complete it. Give it, send it back to live strong. There's a fax number right on the form because live strong won't approve the patient until they have that part of the application back. And that's the thing that I find holds the IVF cycle up the most. This is very time sensitive. There's a heartbeat program through Walgreens Specialty Pharmacy that works with another fertility drug company to donate fertility medicine. So between these two big donations, patients get pretty much all the medication they need thousands of dollars worth for nothing to do IVF. There's a storage fertility called Re Protect that offers a long term storage discount. There's also Fairfax Cryobank that offers storage discounts for patients with cancer. And then there's foundations and groups that patients can apply to for a grant. But that doesn't help them with the immediate cost of fertility preservation. So barriers to fertility preservation, a lack of knowledge about treatment, effects on fertility, lack of knowledge of fertility preservation options. It's not addressed by the oncologist or the oncology team. Patients need a timely referral that gives them many more options. The time needed to do fertility preservation for women in particular, is, um, it's very important cost of it and lack of insurance coverage. I think that's the number one. Number one and two are the time needed to do it in the cost and lack of insurance coverage, and they may not be an appropriate candidate for it. So the role of the nurse and the oncology provider discuss it. Just ask them. Are they interested in future fertility? And then you can refer them. Tow us or to somebody in your community. There are decision aids. There's risk predictors and post treatment option charts. Be an advocate for your patient. Everybody is a candidate for the conversation. Even if they already have Children, they might want more. Um, the conversation really does matter. So this is how you can find a fertility clinic close to you. Go to the Society for Assisted Reproductive Technology website start dot org's. There's a section called Find a Clinic here, and when you click on that, you can put in a zip code and you can find a fertility clinic close to your patient. Um, so I think we met the objectives for this talk. To explain the need for the conversation, reviewed the fertility preservation guidelines, be able to explain the risks for men and women, discuss post treatment family building options, discussed barriers and described the role of the provider in this conversation thes air the websites that are very helpful for you. Um, this is the Uncle Fertility Consortium I mentioned earlier live strong. This is the one that gives you those risk and option charts. And remember that dish full of eggs? This is what they turned into any questions. It looks like we don't have any questions coming in. But I do want to note that you know what's interesting. That is what I've heard, um, during this time is that the percentage of women freezing their eggs has increased significant during co vid. And I assume, because people have more time on their hands and they're not working Azaz much. Um, but I wonder if you have seen higher numbers of these services at M. D. Anderson or with the oncology patients. However, I do assume other factors come into play due to the costs of these procedures and the overall financial impact from cancer treatment. Right? So at M. D. Anderson, you know, we in March and April, when things really closed down, we just weren't seeing patients not even doing video or telephone consoles or anything. And the fertility clinics actually closed down, too, because they didn't know what the impact is going to be on pregnancy. There's a difference between freezing your eggs for fertility preservation and what we call social egg freezing, where women are freezing their eggs because they're going to delay childbearing. And I think that's where you see people with more time on their hands. Or maybe they have insurance coverage through there health insurance that they could do this and clinics will offer this, I don't know, because we're not a fertility clinic at M. D. Anderson. I know Dr Woodard. Her practice at Texas Children's Hospital is just oncology focused. So they do get women who do. There are other physicians in that practice. To there are women who come in to do, um, social egg freezing, as we call it. But I can honestly tell you, if that's increased, it wouldn't surprise me. Okay, well, thank you so much, Deborah, For your interesting and informative presentation, I'm sure that others can relate with me. But even being within the oncology field for over 10 years now, I have to admit that I don't know that much about Uncle Fertility. So and we we don't learn about this a nursing school, nor are we exposed to it in any other way until the concern comes up with our patients. So fertility is is such a huge concern for patients, regardless of gender or age, and is also an indicator for quality of life. So on dwell, we may not be the experts in this area like you. At least we can invite the patient into this conversation and assess the need and make them feel comfortable to address it in the future of it comes up and refer them to the proper resource is so thank you again, Deborah. Thank you for coming. Appreciate it. And to the attendees out there, I want to thank you all so much for staying through this first day of our symposium. We've had a packed day, but also filled with so many interesting and pertinent topics that will help us in our practice. Um, I would also like to remind you that if you're interested in staying on and learning more, there is a non CE symposium hosted by Jazz pharmaceuticals on, uh, introducing a new treatment option for patients with previously treated metastatic small cell lung cancer. Um, right after this foran hour, Andi, in order to access the link to the offering, just scroll down where you see the conference agenda. Andi, you will see the link for it. And then also tomorrow morning from 6. 30 to 7:30 a.m. Pacific standard time. Um, there will be another non CEO hosted, um, symposium again by jazz pharmaceuticals and this time on vex Eos. It's a case based discussion on improving outcomes and patients with nearly diagnosed a secondary and all. And so the virtual event is going to open. Um, and colleague networking Will will then start at 7:30 a.m. Pacific time, the welcoming and the morning announcements at 7 50. And then we will jump into our first presentation at 8 a.m. Pacific standard time. And as far as regarding obtaining your CE credits and your certificates, there will be an email sent out the week after her next week that you used thio email the email that you used to register for this conference with those instructions on how to get that. So once again, thank you all for participating today, and I look forward to seeing you all tomorrow. Jen, I just wanted to jump in really quickly. We actually did get three questions in the Google sheet. They all came in right after you said we didn't get any questions. E o. Quickly. So there is a question. Is there an option for fertility preservation? For women who have to start chemotherapy quickly for, for example, acute leukemia 2 to 4 weeks would be a long delay in treatment. Okay, so usually there's no options. Well, sometimes talk to them about the option of using a drug called like Depo Lupron. Thio keep their ovaries quiet during chemo because we think quiet ovaries maybe don't get as much chemotherapy delivered to them. But that is one of those investigational options and not guaranteed to protect fertility. They're in a tough position, and there's a lot of grieving that goes on. We do a lot of hand holding, and when we can, we hug. But that was in the before world, right? Right, understand? So our next question is, how long can eggs embryos embryos be kept frozen before they're no longer deemed viable? Well, we've had embryos. We've been doing embryo freezing for a long time, and they can really be frozen for years. Embryos freeze and thaw a little bit better than eggs do eggs are mostly water. Um, so in the way we used to freeze them, they would get more damage from ice crystals when they were thought. Now we do something called vitrification, which is like an instant freezing turns them into a glass like state with liquid nitrogen and egg Freezing has been standard therapy since about 2013, so we've only got about seven years of data, but everything it seems like they could be frozen for at least that long, probably longer. And there's no issues with the Babys. Wow, that's they don't get freezer burn. But the process. And we have one last question. Um, we are this, uh, this person says we're using Lupron injections prior to starting chemo to help preserve a varying function. Is that something that you are seeing success with? It's good. So it depends on the patient's age and what they're getting for their chemotherapy. Um, the breast people actually did a pretty big study that showed for women with triple negative breast cancer that the women who got those injections actually had some preservation of ovarian function, better preservation, and they actually had more pregnancies than women with the same cancer who didn't get the injection. But a lot of those women still got pregnant when they were able to. So again, that's an investigational use of it, even to preserve ovarian function. And it doesn't work for everybody, but again, it maybe it's better than doing nothing. And I think you know there's not many side effects to it, but I think it makes the patients feel better that they're doing something. Thank you for that. Looks like we don't have any more questions. So when I thank you again and thank you everyone for participating in today, we'll see you tomorrow.
