It Mattered Later: A Patient Turned Doctor's Perspective on Fertility Loss

Listen to ASCO's Journal of Clinical Oncology essay, "It Mattered Later: A Patient Turned Doctor's Perspective on Fertility Loss" by Dr. Margaret Cupit-Link, who will be a clinical oncologist at Cardinal Glennon Children's Hospital in St. Louis, MO. The essay is followed by an interview with Cupit-Link and host Dr. Lidia Schapira. Dr Cupit-Link shares her personal experience with childhood cancer and the importance of educating patients on the known and unknown consequences of their therapies so they can, when possible, participate in fertility preservation.

TRANSCRIPT

Narrator: It Mattered Later: A Patient-Turned-Doctor's Perspective on Fertility Loss, by Margaret Cupit-Link, MD

I was 19 years old when I had to make one of the most important decisions of my life. The problem was, at 19 years, it was not important to me—yet.

With piercing clarity, I recall the very first time I heard the word sarcoma. My leg had been hurting, and I had just undergone magnetic resonance imaging. The doctor spoke of abnormal tissue. As a pre-med student, I blurted out the words, "it's cancer, isn't it," and waited for him to reassure me. He did not—he could not—reassure me.

The days and weeks that followed are still a blur. There was more diagnostic imaging, a biopsy of my tibia, and placement of a subcutaneous port in my chest. When we learned that the Ewing sarcoma growing in my leg was not metastatic, my family celebrated; meanwhile, I struggled to eat, sleep, and breathe, unable to accept the reality that I was no longer a healthy college student. I was a patient with cancer.

Before my chemotherapy would begin, my mom and I had to give legal consent. Technically, I had to give consent—as if I would choose to say, "no thanks," to the only treatment that could give me a fighting chance to keep living. With each potential side effect that was mentioned, I felt a piece of my morale slip away. Was I going to die? Maybe. Regardless, I would lose my hair, my appetite, my immune system, and my independence. Should I be lucky enough to live through it, I would be susceptible to a host of late effects from chemotherapy, one of which was infertility. Infertility, I felt, was the least of my worries; it paled in comparison with heart failure, secondary malignancies, and death.

As a 19-year-old, I did not want children. My career goals were my priority, and I had yet to be in a serious romantic relationship. Starting a family was not on my agenda. So, on the worst day of my life, when all I cared about was staying alive, I was told I could choose to undergo ovarian stimulation to harvest follicles in a somewhat experimental process that would delay the start of my chemotherapy by several weeks. Without hesitation, I said no. At the time, I did not realize I was lucky to have had time for such a conversation. My diagnosis and presentation allowed for a small delay before treatment; I would later learn that many patients do not get that luxury.

A little over a year after completing therapy and returning to college, I developed hot flashes, night sweats, and mood swings. On the basis of the levels of luteinizing hormone, follicular stimulating hormone, and anti-Mullerian hormone in my blood and an ultrasound showing ovaries without follicles, I was diagnosed with premature ovarian insufficiency and told it was unlikely my ovaries would recover. I was not heartbroken or even disappointed; I was still so thankful to be alive. I did worry, however, what this would mean for my boyfriend, the person I wanted to marry. To this day I am amazed that he, as a 20-year-old man, was completely accepting of me and my infertility and that never changed, even after he became my husband.

Near the end of my pediatrics residency, I came to understand the term baby fever. My coresidents were getting pregnant, my sister was having a baby, and my husband and I were settled down in our very first home. I visited a reproductive endocrinologist. It had been 9 years since I had completed chemotherapy, and I learned my ovaries were not functioning at all. I was told to plan on adoption—of an embryo or a baby—as I was not a good candidate for fertility treatments.

At first, I did not allow myself to react to this news. How could I mourn something like fertility when I was a 10-year survivor of childhood cancer, had exceeded my career goals, and was married to a wonderful person? Most of the time, and on the outside, I was unphased. I spoke about my desire to adopt with enthusiasm. I was honest about my ovarian failure and made jokes about being in menopause. I celebrated my friends' pregnancies and came to love my nephew as if he were my own.

I considered the many ways in which I could become a parent, each with its own barriers. Because I had not undergone oocyte or embryo cryopreservation before chemotherapy, having a genetic child was simply not an option for me. I could adopt a baby in need through the foster care system, which would not require monetary payment.

However, I knew then and now that the goal of the foster care system is to eventually reunite children with their families; although I was strong, I could not risk falling in love with a child and losing them to reunification. Private adoption was another option. While it felt unethical to pay a large sum of money in exchange for someone else's baby,

I would one day have the luxury of being able afford the price tag (at least $20K US dollars [USD] to $100K USD in the United States, depending on the state and organization). Then, there were the options offered by modern medicine—embryo adoption or in vitro fertilization using a donated oocyte and my husband's sperm. In these cases, even if my body was unable to sustain an embryo, I could use a gestational carrier (surrogate mother). While I knew that having a baby the old-fashioned way was not without its own costs and risks, it was undoubtedly easier than any of my options.

I did not admit—until now—that it hurt to know I would never experience the miracle of pregnancy. It hurt to know that I would never have a child that was half of me and half of my husband. It hurt to know that, even now, my cancer had taken something from me that I could never get back.

My experience with infertility has made me thoughtful about how infertility may affect my patients. As a pediatric oncologist, I am painfully aware that many of my patients who lose their fertility from the drugs I prescribe them will travel the same road of grief I have traveled. I am even more aware, however, that most of my teenage patients are not ready to make decisions about fertility—even when they are forced to do so. In my desire to counsel my patients on this topic, I have tried to imagine a scenario in which the advice of a doctor might have prompted me to prioritize fertility preservation. Perhaps I should have been told that delaying cancer-directed therapy by several weeks would be unlikely to affect my disease outcome. Perhaps I would have benefitted from knowing the complexities of the foster care and private adoption systems. Perhaps fertility preservation should not have been a choice at all, but a standard of care, as it is now.1 What I think I needed to hear, above all, was that I did not understand the gravity of my decision. I did not and could not understand the desire to become a parent that would one day overcome me. If I could go back in time and speak to my 19-year-old self, I would say, "it might not matter to you now, but it will matter to you later."

Just days before I originally planned to submit this article, after 12 years of menopause, I experienced the unexpected. Seven positive urine pregnancy tests later, my doctor sent me for an urgent ultrasound, and it was confirmed: I was 6 weeks pregnant. At first, I felt I was no longer worthy of writing this article: how could I speak up about infertility from cancer therapy after having miraculously conceived a child? However, I eventually realized my pregnancy was yet another reason I should write on this topic.

Only now, as I hold my daughter in my arms, do I fully understand how much my fertility would come to matter to me.

Dr. Lidia Schapira: Hello, and welcome to JCO's Cancer Stories: The Art of Oncology, which features essays and personal reflections from authors exploring their experience in the field of oncology. I'm your host, Dr. Lidia Schapira, Professor of Medicine at Stanford University. Today we are joined by Dr. Maggie Cupit-Link, a third year Pediatric Hematology Oncology Fellow at St. Jude Children's Research Hospital, Maggie will graduate from fellowship and receive her Master's in Clinical Investigations in June. She will then begin a position as a clinical oncologist at Cardinal Glennon Children's Hospital in St. Louis, Missouri.

In this episode, we'll be discussing her Art of Oncology article, "It Mattered Later: A Patient Turned Doctor's Perspective on Fertility Loss."

Our guest disclosures will be linked in the transcript.

Maggie, welcome to our podcast and thank you for joining us.

Dr. Maggie Cupit-Link: Thank you so much for having me. It's an honor to be here.

Dr. Lidia Schapira: It's lovely to have you. I'd love to start just by asking a little bit about your motivation to write and share this piece. It's such an important piece and you really have shown us what was deep in your heart. And then there's this sort of unexpected resolution. Tell us a little bit about what led you to finally finish the piece and share it with the world.

Dr. Maggie Cupit-Link: So I've been writing for a lot of my life as a way to express myself and cope with emotions. And I had cancer when I was 19 and 20, Ewing sarcoma. And during my treatment, I found writing was very therapeutic for me and very healing. So that's when I got really into writing about my personal experience and actually published a book after I finished treatment. But then writing more recently, I was writing about my infertility, which I had from chemotherapy. And I would write about it and journal about it here and there because it was really challenging. And for a long time, I suppressed a lot of those emotions because I didn't think they were helpful. And I felt, I guess, ashamed and embarrassed to feel so upset about infertility as a cancer survivor who has so much in life. So many parts of my life are so normal and full and even more full than the average person so I felt like I wasn't really allowed to grieve my fertility.

And I started to write a piece because I'm part of a working group, a group of physicians working together to learn more about fertility and pediatric cancer survivors, particularly those who have received immunotherapy, because there are a lot of new agents that we don't know as much about when it comes to fertility. And as I was working with this group, I started writing this piece on my own. And then I was about to submit the piece just to the group to show them my personal reflection when I took a pregnancy test and it was positive. So then I took seven–

Dr. Lidia Schapira: -other ones

Dr. Maggie Cupit-Link: I was not, I didn't believe any of them. Then finally I called my sister, and she told me that I was not acting like a doctor, that it was very obvious I was pregnant. And so then I went to see my doctor, but I found out I was six weeks pregnant right at the time of finishing this piece. And at first I thought, "Well, I can't write this piece anymore." But the more I thought about it, the more I thought, "Well, either way, it shows that us oncologists really need to learn more about fertility." And I'm very blessed and lucky to have this ending in my story, but it shows that there's a lot of missing information out there.

Dr. Lidia Schapira: That was an amazing answer, and I have about five different topics now that I want to discuss with you. But let's start with the end. And that is your baby. How old is your baby now?

Dr. Maggie Cupit-Link: So her name is Lila Jude. Two days from now, she'll be seven months on June 12. Her name comes from the family name Carlisle. That's where we got Lila. And then Jude comes from the Patron Saint of Hopeless Causes, St. Jude, but also the hospital that treated me and where I've trained, St. Jude Children's Hospital. So that name was very significant for us.

Dr. Lidia Schapira: So I'm getting goosebumps and teary just to hear you tell the story. Let's start a little bit with some of the themes that you touched on. The first is when you've said that you've always used writing as a way of processing emotionally complex situations as a patient, now, perhaps as an oncologist. Tell us a little bit about the book that you wrote about your experience.

Dr. Maggie Cupit-Link: Sure. When I was in treatment, I wrote a lot of entries in my journal, and it was just a way for me to process things. I think sometimes, for me, I don't know exactly what I feel until I write it down and make myself reflect on it, because I'm a busy body. I'm constantly going and doing. And so during chemo, I couldn't really do it. I had a lot of time to sit, and so I needed to write. And my grandfather is a retired Professor of Christian Philosophy. And during my year of cancer therapy, he and I started writing letters to each other because I had a lot of questions, understandably, about God. So the title of the book is actually "Why God?: Suffering Through Cancer into Faith." And it's a lot about doubt and my anger towards God and what I would see in the hospital around me, the children who were dying from cancer, who even had it worse than me. It felt very impactful to my faith.

But ultimately, through my conversations with my grandfather, he taught me a lot about another way to understand God, another way to understand faith in spite of horrible suffering, which I think is a thing for a lot of people because a lot of people in this world suffer. And so eventually we published a book. During medical school we published it, and it was a compilation of my journal entries intersected with his letters. And so part of it was really personal and raw and journal entry, and part of it was Christian philosophy. So it was an interesting combination.

Dr. Lidia Schapira: Well, Maggie, I will definitely now have to get your book and it'll be on my list for summer reading. So you touch on some of the fundamental, sort of ethical, moral principles of our profession, which is suffering and how we deal with suffering. And you've had a lot of time to reflect and philosophize and also experience this, as well as loss. Can you tell us a little bit about how your experience of loss has evolved over the decade of survivorship?

Dr. Maggie Cupit-Link: I think initially, loss, for me, meant a lot of different things than it does now. I felt like I lost a lot when I was sick because I had to give up a year of college. I lost my tibia and knee bones. I have a prosthetic knee and tibia now, internal, and they function very well, but I don't have a real leg. I lost, of course, in chemo, you lose your hair. I lost a lot of tooth enamel. I lost a lot of friends because I was a teenager, and teenagers don't handle illness very well. People were afraid to talk to me. And then, of course, I lost my ovarian function. For a while, I think I focused on that a little bit more than what I had gained. But over time, it became very obvious to me that despite all the loss that I had during my year of cancer therapy, I gained a lot more. I gained a lot of perspective and a lot of emotional depth. And then ultimately, what directed me to my career decision. I knew I was wanting to be a doctor before I had cancer, but then after that year, I knew exactly what kind I would be if I got through the year.

But I think one thing I've had to learn apart from that is being able to feel loss, even when you have so much. Because I have a lot of gratitude and I have so many good things in my life now with my health and my husband and now my baby and this wonderful career. Even though I have all those wonderful things, I'm still allowed to feel loss sometimes because I will be susceptible to late effects and there will be things in my life that are not quite normal because of going through cancer therapy. And then, of course, the other layer of loss is the people that we lose along the way. If you see behind me in my office, there's a picture of a little boy on the shelf up there. He was my good friend when I was sick. His name is Odie, and he died from hepatocellular carcinoma. When we were sick, he was a good bit younger than me. He was like a little brother to me during therapy.

The loss of his life definitely propelled me forward to try to change more for other kids. And I think one thing I struggle with now as an oncologist and I'm still learning to do, is process the loss of my patients as it happens. I think I'm lucky that when I lose a patient, when a patient loses their life, I still see the beauty in what I was able to provide for them and their family. That's still a gift. I feel that it's important for me to grieve the loss of their lives, and I'm working on finding, like, the best way to do that for me over time.

Dr. Lidia Schapira: You will find a lot of reflections on this topic in the pages of Art of Oncology over the last 20 plus years. I think that is a very, very common theme. I'm really impressed with how well you just understand the importance of this, to stay emotionally healthy and resilient.

My next question addresses that a little bit, and it has to do with processing the early experience of being a cancer survivor. As a young medical student and as a young physician, what was that like for you?

Dr. Maggie Cupit-Link: I think early on, I had a lot of guilt when it came to being a survivor. This concept of survivor guilt, I think you can read about it as well, and I'm sure there are some articles in the Art of Oncology about it. But the idea that, like, 'why me?' and when I encounter patients who go through similar diseases or experiences that won't have good outcomes, 'why? Why me? Why did I get a good outcome and they didn't?' And so early on, I struggled with that more. I felt guilty about it. I think over time, I recognized that the guilt– I mean, I always knew it was illogical. That doesn't mean we don't feel it. I think over time, I've recognized the guilt as unproductive. And so I tried to empathize with myself about it and acknowledge that I feel guilty. But then instead, what can I do with this feeling that's helpful? So where can I put this? What can I do to make things better for somebody with it? And I think that I've been able to do that better as time has gone along.

I also think that early on in my survivorship, I thought that I had even more ability to understand patients' perspectives than I did. And I learned quickly that everybody's experience, even another 19-year-old with Ewing sarcoma who had to leave college, is so different. And so I've been humbled along the way in learning that just because I understand part of their experience does not mean I understand their experience all the way, and that I should never assume that I do. I should always listen and wait to try to understand more about what's different about their perspective.

Dr. Lidia Schapira: I'm surprised a little and maybe delighted to hear the wisdom in your words. You are so young and yet you know so much. Did you have any mentors during medical school and residency who helped you process this? And then playing it forward, how do you imagine now that you're going to be an attending, mentoring others who may be the young Maggie and come under your tutelage?

Dr. Maggie Cupit-Link: I've had a lot of mentors, for sure, in life. I've been in therapy pretty much my whole life. I'm really lucky that my grandmother is a PhD psychologist and she's a clinical counselor. And so from the time I was a child, if there was ever a problem, I would go see a therapist. There was no exception to that, especially when I became sick. And then in the aftermath of that, I've frequently been seeing a therapist, and that really helps me gain wisdom. I think that's been one big source of mentorship.

But there have been other providers that have been big sources of mentorship for me for this. One was actually a good friend of mine. Her name is Beth. She's a physician, a clinical research physician scientist at St. Jude, and she was a fellow when I was a patient. And we became friends back then. And then when I went back to college afterwards and then medical school, I shadowed her a few times. I did an away rotation with her once at St. Jude while I was in medical school, and during that time, I remember meeting a boy with Ewing sarcoma. And I remember walking into the room thinking, "Oh, this is great. I totally get this. I'm going to be so helpful to his mom." And I quickly learned that he had metastatic disease, which meant, really, we had a different disease entirely. And that when I told his mother about me, I almost felt like it made things worse because she knew that my outcome was different than her son's was going to be. And I remember Beth afterwards reflecting with me, saying like, "Yeah, it is true. Everyone will have a different story, even if you understand a lot." I think she told me, "You don't always have to tell people your experience in order to use your experience." And so that was one of the ways that I learned. I don't have to share everything upfront in order to still have so much empathy and compassion.

And then I've also had the honor to work with many doctors who have just role modeled, listening really well and really good bedside manner and compassion. The physician who treated me, Dr. Pappo, still works at St. Jude, and so I've gotten to work with him a little as well, and he role modeled wonderful bedside manner. And then my primary research mentor as well, Dr. Federico has taught me a lot. And just watching her with our shared patients and the way she tells family news and the way she explains things has been really helpful to me, too. So I would say a lot of mentors and a lot of therapy.

Dr. Lidia Schapira: I like that combination. Clearly, it's been very productive and useful for you. Tell us a little bit about choosing to work in this field after your personal experience. I mean, it sounds like you were headed to St. Jude's to a laboratory to do research even before the diagnosis, but one could easily imagine that you would have chosen to become a dermatologist after this, or somebody who was not totally immersed in this culture of cancer and also a lot of grief and suffering, as we've just said before. Tell us a little bit about your research passion and how these two themes in your life, your personal experience of cancer and survivorship and your research, have meshed.

Dr. Maggie Cupit-Link: Well, I think I knew that I was going to do this career in some capacity when I was watching the kids around me during my treatment. And I think this is one of the reasons why it was so important for me to be treated at a pediatric institution. I know that the AYA population is sometimes treated with adults and sometimes children, and I would advocate that being treated with children is helpful because children are miraculous, resilient creatures. And I remember deciding that I was going to have to fix my attitude during chemo because I was very depressed and very angry and deciding that maybe it would help me if I could just play with the kids in the waiting room and try to distract them and make them have a better day. And so I decided I would try to do that for myself, but ultimately they distracted me and made me have a better day. And so the more I was around the kids, the more I knew that they just hold so much optimism and innocence and light that I feel that we lose as adults. And I wanted to be around it. So in a way it was selfish that I would choose this career because I just wanted to be with them, but also knew that if I was going to go through all this nonsense, I better use it. That was very motivating for me.

And I think it has been a gift from my experience and maybe my therapy and who knows what else that I'm able to take the bad and the grief that I experience personally and use it to feel differently about the grief that I feel as a doctor. I think I feel differently about loss than my colleagues. It's still hard when I see patients suffer, when patients lose their lives, it's still hard. But I think it's hard in a different way than it is for some of my colleagues. And for some reason, I think I feel more comfortable in that space. I think I feel comfortable around that.

Dr. Lidia Schapira: Tell me a little bit more by what you mean by saying that it is hard, it has to be hard, but it's hard in a different way because of your lived experience. Tell me a little bit more.

Dr. Maggie Cupit-Link: I think I'm not uncomfortable around suffering and death. I think I feel very comfortable around children who are suffering and children who are dying, doesn't scare me and doesn't make me feel like I need to turn away, because I feel it's familiar in a sense. And I think I also, having been the patient who received so much comfort and support and love from providers, should I have died, I still would have valued all of that support so much that allows me to value the support that I'm giving, even in the face of death.

Dr. Lidia Schapira : Maggie, you're amazing. Tell us a little bit about your research and your plans now that you're going to be finishing your formal training? Where will we find Maggie in a few years? What will you be doing? What will we be reading?

Dr. Maggie Cupit-Link: Well, I have really enjoyed doing clinical research. Back in college, after I finished therapy and went back to school, I did join a couple different St. Jude labs and did a variety of different things. But I was not a natural in bench research. I broke a lot of things. I'm very clumsy. It was not my area. I was not good at it. And that's okay. I've decided to come to terms with that. I love science itself and it's been really wonderful to get this Master's in Clinical Investigations throughout fellowship because I could directly apply a lot of those skills to my research in clinical research. And so I'm really passionate about writing and helping with trials, clinical trials, but specifically would like to help with trials that focus on acute and late effects of toxicities. One of my major research projects has been creating a prospective study to evaluate the early late effects in high risk neuroblastoma survivors. And I chose that population because they receive all the therapies that you can imagine, the kitchen sink, and some novel immunotherapies that we don't really understand fully yet in mechanism of action, and so things like that, as well as evaluating acute toxicities and interventions for those. I distinctly remember every inpatient chemo that I experienced turning to my mom and saying, "There has to be a better way," because my burden of side effects was really high. And I just remember saying, "There has to be a better way." And my mom would say, "Yes, there has to be. You can figure that out one day." So I do, I hope I can make some small changes in the way we give conventional therapy and the way we handle side effects as well as prevention of late effects.

I am currently collaborating with Children's Oncology Group on one of their projects in the late effects of neuroblastoma, and I hope to continue collaborating with that group as well as my career advances. I'll be an attending physician at Cardinal Glennon Children's Hospital, which is a part of St. Louis University. And I have family here in St. Louis. My husband is a dentist here with his dad. They have a practice together, so it was really important for us to be here. And this hospital is a charity hospital as well, which I really think is a wonderful thing. And that makes me feel a little bit tied to St. Jude, since it's a charity hospital as well. And so I hope to be able to continue some of the clinical projects and some collaborations with the COG as I take care of patients. And I do hope to continue writing other stuff as well.

Dr. Lidia Schapira: Maggie, I have to ask you one last question, and that is that in your piece you say you were 19 and fertility didn't matter to you then, and you couldn't have understood then or couldn't make space for the later. Now that you are where you are and you're dealing with young adults who may be your patients in similar situations, tell me a little bit about how you think about involving the parents perhaps in this conversation or sort of making space to attend to some of these very thorny issues that may have so many repercussions on future health.

Dr. Maggie Cupit-Link: I think it depends on the patient of course. Because, as you know, some patients can't have a conversation about fertility based on medical acuity. But when a patient has the luxury of time, I think that that's just not a discussion I rush through. And I agree with you that using the parents perspective would be incredibly helpful. I think, I've had a few older patients that I discuss this with, and they're all different because I even had a 17-year-old patient who told me she wanted to be a mom for sure. And so she was different than me and that she already knew that was important to her. But when people think it's not important, I just encourage them to think about it more and talk to their parents about it and to remember that who they are today is not who they were 10 years ago, and who they're going to be 10 years ago is not who they were today. And that this is something you can't time travel with. This is your chance to make a decision. And really, the fertility preservation methods, generally, they're pretty safe and not traumatizing. And so it's sort of like, why not just go ahead and do it? Especially if the institution you're a part of is offering it. And I think there are a lot of ways to get funding for that, too.

Dr. Lidia Schapira: Well, you are definitely a champion.

Dr. Maggie Cupit-Link: Thank you.

Dr. Lidia Schapira : I know that our readers and our listeners are going to follow your career, and I thank you so much for your thoughtful essay and for agreeing to this conversation. It's been a real pleasure.

Dr. Maggie Cupit-Link: Well, thank you. I have one more thing to tell you before we end.

Dr. Lidia Schapira: Yes, tell me.

Dr. Maggie Cupit-Link: So after I had the baby, my doctor and I decided we would wait to get on birth control until we saw if I was going to go back into menopause or not. We waited, and then I got pregnant again. And so I am 16 weeks pregnant with a baby boy this time. And so I'll have my second child 12 months after the first.

Dr. Lidia Schapira: Oh, my goodness.

Dr. Maggie Cupit-Link: It is a blessing. But after that, I might have to consider birth control to space some- plan, space some people out a little bit. But we're very excited.

Dr. Lidia Schapira: The gift of your survivorship is now in your 30s. You need to have that conversation about family planning that most people and couples have earlier on. So congratulations. Congratulations.

Dr. Maggie Cupit-Link: Thank you so much.

Dr. Lidia Schapira: Beautiful way to end. And to our listeners, until next time. Thank you for listening to JCO's Cancer Stories: The Art of Oncology. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all of the ASCO shows at asco.org/podcasts.

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Guest Bio:

Dr. Maggie Cupit-Link will be a clinical oncologist at Cardinal Glennon Children's Hospital in St. Louis, Missouri.

Additional Reading:Why, God?: Suffering Through Cancer into Faith, by Margaret Carlisle Cupit, et al