Patricia and Michael Lingerfelt at their 13-week ultrasound.
Patricia and Michael Lingerfelt at their 13-week ultrasound.
Terri Woodard, M.D., a reproductive endocrinologist with joint appointments at MD Anderson and Baylor College of Medicine.
Terri Woodard, M.D., a reproductive endocrinologist with joint appointments at MD Anderson and Baylor College of Medicine.
Khalied Kaskar, embryologist and laboratory manager at Texas Children’s Hospital Family Fertility Center, uses a pipette to move an egg in a drop of culture media.
Khalied Kaskar, embryologist and laboratory manager at Texas Children’s Hospital Family Fertility Center, uses a pipette to move an egg in a drop of culture media.
A five-day-old embryo, or blastocyst, contains two types of cells—the inner cell mass, which will develop into the fetus, and the trophectoderm cells, which will develop into the placenta.
A five-day-old embryo, or blastocyst, contains two types of cells—the inner cell mass, which will develop into the fetus, and the trophectoderm cells, which will develop into the placenta.
Jennifer Litton, M.D., associate professor in the Department of Breast Medical Oncology at MD Anderson.
Jennifer Litton, M.D., associate professor in the Department of Breast Medical Oncology at MD Anderson.
Clinical

Conceiving After Cancer

By integrating a desire to have children into care plans, MD Anderson and Texas Children’s are ensuring dreams of building a family are not dashed by cancer

Conceiving After Cancer

11 Minute Read

An ultrasound screen lights a small room at Texas Children’s Pavilion for Women. Patricia and Michael Lingerfelt watch with bated breath as the image of a 13-week-old fetus flickers onto the screen—their first child, a girl. It’s a sight that, at times, the Lingerfelts thought they might never see.

In 2014, after years of trying to have a child, the couple was dealt an additional blow: a routine annual exam and mammogram showed Patricia had breast cancer. The call came a week before they were scheduled to see an IVF specialist. The cancer diagnosis was frightening enough in itself, but for the couple, already in their 40s, it presented another setback to starting a family that they never expected.

“The very first doctor who gave me the diagnosis told me I would not be able to have kids, that I could just kiss that goodbye,” Patricia said. “At that point, I’m already devastated. One, I have cancer, and two, the doctor is saying I will not be able to have kids ever. When I got to MD Anderson, finding out that there was still a possibility changed everything.”

During a pre-surgery appointment at The University of Texas MD Anderson Cancer Center, Patricia happened across a pamphlet about preserving fertility before, and building a family after, cancer treatment. For a couple whose hopes for a family had so recently been dashed, it felt like fate. That was their first introduction to Terri Woodard, M.D., a reproductive endocrinologist who holds joint appointments in MD Anderson’s Department of Gynecologic Oncology and Reproductive Medicine and Baylor College of Medicine’s Division of Reproductive Endocrinology and Infertility.

The American Cancer Society estimates over 800,000 women are diagnosed with cancer in the United States each year. A cancer diagnosis brings numerous questions and fears—“What stage is it? Will I need surgery, radiation or chemotherapy? What is my long-term prognosis?” With so many immediate concerns, thoughts like, “How will this affect my future fertility?” can easily fall by the wayside. A close relationship between MD Anderson and Texas Children’s Hospital seeks to ask that question before it’s too late, and to make its answer a part of treatment plans.

Patricia and Michael had their first meeting with Woodard before Patricia’s surgery. Luckily, her cancer was stage one and would not require chemotherapy. The plan was for her to undergo a lumpectomy surgery, followed by six weeks of radiation treatment. Through close teamwork between Woodard and Patricia’s oncology team, the Lingerfelts saw their desire to have children worked into her care plan from the very first step.

“It’s hard for me to put into words how we went from being nervous and scared to just comforted and reassured, feeling like we knew what was going to happen from that very first visit,” Michael said. “We said, ‘We still have this dream and desire of having kids.’ For them to say, ‘We can integrate that into the plan of what we’re going to do and how we proceed forward,’ it gave us total comfort and peace of mind.”

The American Society of Clinical Oncology published its first guidelines for fertility preservation in cancer patients back in 2006, but it’s still a topic that is not routinely discussed among all cancer patients. Furthermore, few cancer centers even of the caliber of MD Anderson have a reproductive expert actually embedded in the center as Woodard is. The spirit of collaboration that is a central part of the Texas Medical Center makes it easier for patients to deal with such a complex issue.

“One of the big barriers in fertility preservation in general is trying to navigate the system. Having to go out to another practice somewhere and tell your story again,” Woodard said. “Here, I talk with the oncologist every time I see the patient. Everyone is on the same page. When the patient is done getting her eggs harvested, we call the oncologist and say, ‘She’s done. She’s all yours.’ It really makes for streamlined care.

Patients like Patricia come to Woodard in a variety of ways. Some are referred by their primary providers, some come across pamphlets like the one Patricia found, and others are already cancer survivors who never had the opportunity to talk about their fertility before treatment and are curious about their options.

Each consult with Woodard involves several major parts. First, they discuss medical history and determine the patient’s current ovarian status—and whether there is any prior history of infertility.

“Based on that assessment we talk about their risk for infertility based on their testing, their age, their medical history,” Woodard said. “From there, we move into the different options for fertility preservation. We talk about the pros and cons of each of those, the time required, the costs and the side effects.”

Cancer treatment affects fertility in a variety of ways: Chemotherapy drugs can damage or destroy a woman’s eggs, or cause early menopause. The intense energy used in radiation therapy can also damage the eggs. The type of surgery required for certain cancers may remove integral parts of the reproductive system, including ovaries, uterus, cervix and surrounding tissue. Finally, some medications recommended for use after treatment, such as tamoxifen, essentially require the use of birth control because they can cause severe birth defects. While tamoxifen itself does not cause infertility, the now 10 years recommended use can put a woman past childbearing age.

The main options offered to women prior to treatment are egg or embryo cryopreservation, or freezing. For both of these processes, hormone injections stimulate the ovaries to produce multiple eggs. The eggs are then retrieved while the patient is under sedation, and either immediately frozen or fertilized with sperm, in the case of embryo freezing. The embryos are allowed to develop for several days and are typically frozen. For Woodard’s patients, these processes take place at the Family Fertility Center in the Texas Children’s Pavilion for Women.

“Until a few years ago, we didn’t do a very good job of freezing eggs,” Woodard said, noting that the water content in eggs lent itself to the formation of ice crystals, which can damage the eggs to the point of destruction. “Now we’ve become a lot better at it, so that has really expanded the options for women who don’t have a partner at the time of treatment and don’t want to have to pick a sperm donor. Furthermore, it gives women reproductive autonomy; her eggs will always be her eggs.”

Another recent improvement that has made egg and embryo cryopreservation a more viable option for women is the fact that it’s no longer dependent on a woman’s natural cycle. The process used to take up to eight weeks, and many patients simply did not have the time to delay treatment for that long.

“We’ve come a long way in realizing that we can do what’s called a random start. We can start a stimulation at any part of a woman’s cycle,” Woodard said. “I had a patient that the day I met her, she started her stim that night. Twelve days later she had her retrieval, and that night she was getting her chemo. We can do this in less than two weeks now.”

Even with these options available, the discovery that mutations in the BRCA1 and BRCA2 genes can cause an increased risk of breast and ovarian cancer, made some patients hesitant to have biological children, not wanting to pass that gene to future generations. Thanks to the advent of preimplantation genetic diagnosis (PGD), it’s now possible to test embryos for specific genetic conditions, like BRCA mutations, before implantation and then use only those embryos without the condition.

A more experimental option for preserving fertility that is not widely available is ovarian tissue freezing. This involves surgically removing pieces of ovarian tissue. This is the only fertility preservation option for girls who have not gone through puberty yet.

“In that ovarian tissue, there are immature eggs,” Woodard said. “The tissue is frozen and after treatment you can thaw and re-implant it. Almost 70 babies have been born this way.”

Researchers are working on maturing eggs from this tissue in the lab so that one day, they won’t even have to transplant the tissue back into the body. Though this option is not currently offered at MD Anderson, Woodard said they are working on a protocol to get a program up and running in the future.

Another fertility preservation option is ovarian suppression—using injectable medications called gonadotropin-releasing hormone agonists to make the ovaries quiescent during treatment.

“It’s thought that an ovary that is not actively cycling might be more resistant to chemo than one that is,” Woodard said. “However, this is experimental, and the data is mixed about whether it really works or not. But for most women, the risks of using it are low and if a woman is willing to try it, it might be better than nothing.”

In terms of the issue with tamoxifen, some patients will opt to take it for several years, then stop while they try to conceive and restart once again after the child is born. Other patients may opt to delay tamoxifen to try to have a child immediately, or even delay indefinitely.

While there are more options today than even just a few years ago, Woodard said after consulting with patients and oncologists, sometimes the best and safest course of action is to begin treatment immediately. But that doesn’t have to mean the end of the road for cancer patients who want to start a family.

“I never feel like the door is closed,” Woodard said. “Unfortunately a lot of these procedures aren’t covered by insurance, but we want women to know their dreams of motherhood don’t have to be squashed. There are so many ways to build families now, and if they’re open to it, they can still be a parent.”

After discussing with Woodard and the oncology team at MD Anderson, the Lingerfelts made several decisions prior to treatment. First, due in part to their age and desire to try to conceive immediately, they elected to delay tamoxifen indefinitely. Patricia tested positive for a mutation of the BRCA2 gene, putting her at higher risk for developing breast and ovarian cancer, so they have also discussed prophylactic removal of the breast tissue or ovaries within the next five years or so. Finally, they chose to begin IVF very soon after the conclusion of her cancer treatment.

“I finished radiation in January 2015, and two months after that, we started the first cycle of IVF to retrieve eggs,” Patricia said.

Unfortunately, that first round resulted in only one embryo that was not high quality. The couple chose to wait to do another cycle, which they began in October. This time they had four embryos sent to genetic testing and were left with one to implant.

“We transferred the one on Feb. 1, and two weeks later found out we were pregnant on my birthday,” Patricia said.

For the Lingerfelts, this pregnancy is the realization of a dream over a decade in the making—one that quite a few times they thought might be a lost cause. Now, not only are they expecting their first child, but they also have the hope of potentially having a second.

“We’re super excited to see the possibility of that dream becoming a reality,” Michael said. “It’s taken a little while for it to sink in. To see that first ultrasound, when we saw the baby and saw the heartbeat—there was a lot of emotion in that moment.”

Cancer Treatment During Pregnancy

Cancer knows no timeline, and sometimes it can strike in the midst of the joy and possibility of a new pregnancy. In previous years, patients were advised to terminate the pregnancy for their own health. Today, there are treatment options for pregnant cancer patients that are safe for both mom and baby.

Jennifer Litton, M.D., an associate professor in the Department of Breast Medical Oncology at MD Anderson, has treated women diagnosed with breast cancer after becoming pregnant.

“No, you don’t have to terminate a wanted pregnancy,” Litton said. “There’s no data that shows doing that improved outcomes.”

While adjustments need to be made to accommodate pregnancy, treating a pregnant cancer patient is much like treating a non-pregnant patient. Surgery can still be performed, and many chemotherapy drugs are safe after the first trimester, once the organs have developed. Chest X-rays and mammograms can also be done with fetal shielding.

“The steps are what we do for our non-pregnant patients and that’s really key to why patients have done so well here,” Litton said, adding that, unlike many physicians, she also prefers to let patients go into labor naturally.

“I know a lot of doctors take the baby super early, but for me, if I still have treatment to give, I think it’s so much better if they don’t have a NICU baby at 30 weeks,” she said. “There’s no reason because it doesn’t change outcome. Our average birth week was 37 weeks, and I think that’s a big part of why our kids are doing so well, too.”

Treating pregnant patients involves working closely with the patients’ obstetricians, as it involves much more fetal monitoring than an average pregnancy.

“Before chemo, I want them to see their maternal-fetal medicine specialist and have a good ultrasound so they can assess the fetus, the fluid around the fetus, the cord growth,” Litton said. “Then what happens is they show up with a handwritten note
or the doctor calls me and says we’re good to go. They come across the street and we start the chemo that day.”

The same process repeats before every dose of chemotherapy.

“If you give someone the regular therapy you would give a non-pregnant patient, just in the right timing,” Litton said, “we’ve shown in studies here and in Europe that they do just as well as non-pregnant breast cancer patients.”

(Click image to enlarge)

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