Timely Preservation

At Johns Hopkins’ new Fertility Preservation Innovation Center, patients like Alexandra Piselli are finding hope for a fertile future.

Published in Hopkins Medicine - Winter 2022

At the age of 25, Alexandra Piselli felt like her childhood dream of becoming a doctor was finally materializing. It was the summer of 2020, and she was kicking off her third year of medical school at Central Michigan University with an obstetrics rotation.

The grueling workload that left most of her classmates physically and mentally exhausted had the opposite effect on Piselli, who thrived on the excitement in the delivery room. “I was delivering babies and having the time of my life, despite working 14-hour shifts. That’s how I knew I was cut out for this whole medicine thing,” she says.

Then Piselli started itching.

“It felt like there was something under my skin that I couldn’t get out,” she remembers. The itching was relentless, and it became impossible to sleep. She scratched so much that her skin bled.

Doctors ran a battery of tests and discovered a tumor, about the size of a blueberry, blocking the opening where her pancreatic and bile ducts should have been emptying their secretions. With nowhere to go, bile salts had accumulated in Piselli’s skin and caused the intense itching. A biopsy confirmed the tumor was an ampullary pancreaticobiliary adenocarcinoma — a rare form of cancer.

Piselli was on her lunch break when her doctor called to break the news, explaining that she would need to undergo a complex Whipple procedure to remove the tumor, followed by months of chemotherapy and possibly radiation. She hung up the phone, stepped into a hospital restroom to scream, and went back to delivering babies.

It wasn’t until that night, while processing the news with her boyfriend and college sweetheart, that she allowed herself to cry. The tears weren’t out of fear for her life, but from the realization that the chemotherapy she needed to live might kill another childhood dream: becoming a mother.

Working Together to Preserve Fertility

Preserving the fertility of cancer patients like Piselli is one of the goals of the Johns Hopkins Fertility Preservation Innovation Center, which formally launched last spring. The center merged Johns Hopkins’ fertility research and preservation services into one program that offers everything from in vitro fertilization (IVF) and sperm banking to cutting-edge treatments like ovarian tissue freezing and reimplantation.

“We’re connecting a wide range of people to the services they need,” explains Fertility Center Director Mindy Christianson. “We’re helping patients with sickle cell disease who risk losing fertility after bone marrow transplants. We’re helping women who are electively delaying parenthood by freezing their eggs. We’re helping transgender patients who are choosing fertility preservation before having gender-affirming surgery.”

The center is especially attuned to the needs of cancer patients, who run the risk of losing fertility due to chemotherapy, radiation or surgery within the reproductive system. Timely fertility preservation is a must for those diagnosed with aggressive cancers, and few clinics can match the speed of Hopkins’ Fertility Preservation Innovation Center, which is committed to seeing patients within two days.

“We recognize that this is an emergency for women,” says Rebecca Lynn Stone, director of the Kelly Gynecologic Oncology Service and co-director of the new center. “It’s scary, and the patient and the team often want to get moving on a plan as soon as possible. If you don’t have a team with experience overcoming the obstacles — that knows how to make the experience efficient and easy for patients — it can be a no-go.”

The center is one of the few clinics on the East Coast to offer ovarian cryopreservation, which is a game-changer for patients who don’t have weeks to undergo medication treatment to stimulate the ovaries prior to an egg retrieval. The procedure involves removing and storing the egg-producing portion of one ovary prior to cancer treatment. This ovarian cortex tissue can be transplanted in or near the patient’s remaining ovary, or in another location, years later to make pregnancy possible. For prepubertal girls who can’t yet produce mature eggs, freezing ovarian tissue is the only option for preserving fertility.

Prior to 2020, ovarian cryopreservation was still considered experimental. As of 2019, there were approximately 130 live births as a result of this technique reported in medical literature; however, that number is expected to soar as more cancer survivors who froze their tissue as children reach childbearing age.

“At least 50 prepubertal girls have frozen their ovarian tissue at Hopkins over the last decade. Now we’re reaching the next exciting step, which is transplanting the tissue back,” says Christianson, who has harvested ovarian tissue from girls as young as 2. “This will be a huge area of research, because there’s really not an established method for doing those transplants.”

For patients who risk losing fertility due to radiation therapy, the center offers a procedure called ovarian transposition, whereby surgeons move the ovaries out of the pelvis and attach them higher in the abdomen. Even small doses of radiation to the pelvis can destroy eggs, and moving the ovaries out of the targeted area increases the odds that they will continue functioning normally.

Regardless of the fertility treatment, all patients at the center gain access to Hopkins’ team of specialists, including geneticists, oncologists, surgeons and counselors. When patients do become pregnant, those at high risk for complications are connected to expert clinicians at Johns Hopkins’ Division of Maternal–Fetal Medicine to maximize the odds of a healthy birth. The center also works closely with the Division of Minimally Invasive Gynecologic Surgery, the Kelly Gynecologic Oncology Service, The Center for Transgender Health and the Assisted Reproductive Technology Laboratories, which offer genetic testing of embryos.

“We all work together,” says Christianson. “One of the amazing things about Hopkins is that we have experts in virtually every field here, and there is a strong spirit of collaboration. This allows us to help patients with very complicated medical conditions.”

‘I Knew I Wanted to Have a Family’

Shortly after her diagnosis in August of 2020, Piselli returned to her home state of Maryland to live with her parents while receiving treatment at Johns Hopkins. The Whipple procedure (pancreaticoduodenectomy) she needed to remove her tumor is a complicated operation that removes the head of the pancreas, the first part of the small intestine (duodenum), the gallbladder and the bile duct.

Multiple studies have shown that the number of Whipple surgeries performed at a hospital in a given year is a strong predictor of patient outcome, with mortality rates as high as 16 percent at low-volume hospitals. Fortunately for Piselli, surgeons at Johns Hopkins have performed over 6,000 Whipple procedures, more than any other institution in the world.

On Labor Day weekend, Piselli traveled to Charleston, South Carolina, to attend a friend’s wedding and spend a final “normal” weekend with her boyfriend, David. During a Saturday morning stroll along the waterfront, David dropped to one knee and asked Piselli to marry him. She said yes.

Her surgery was performed the following Thursday by Kelly Lafaro, an assistant professor of surgery in Hopkins’ School of Medicine and an expert in bile duct cancer and Whipple surgeries. “She’s an absolute rock star. As a medical student myself, I idolize her,” says Piselli. “Her abilities were absolutely amazing to me.”

After nine hours of surgery, Piselli awoke to pain like she had never experienced, which is common for many patients due to the number of organs removed and rearranged during a Whipple procedure. Her parents weren’t allowed to visit because of COVID-19 safety protocols, but she remembers how the nurses and doctors cared for her like family. “Everyone at Johns Hopkins was absolutely amazing. One nurse sat by my bedside for the entire night.”

She describes the weeks after surgery as “a blur of pain.” She had drains coming out of her sides, could barely eat, and was unable to walk on her own. Despite her condition, Piselli was laser focused on preserving her fertility before her chemotherapy treatments began. She was scheduled for a six-month course of Folfirinox, which contains a cocktail of drugs designed to stop the replication of DNA. While these drugs can halt the growth of aggressive tumors, they also pose a risk to rapidly dividing ovarian cells that are critical to maintaining fertility.

“I had just gotten engaged. I knew I wanted to have a family,” she says. “I didn’t want to deprive myself and David of the children we have always wanted together.”

A Growing Need

The need for the specialized services offered at the Fertility Preservation Innovation Center is steadily increasing. The U.S. is home to roughly 17 million cancer survivors, and that number is expected to grow to more than 22 million by 2030, according to figures from the American Cancer Society. Almost 10 percent of patients diagnosed with cancer are under the age of 45, and many of them, like Piselli, hope to have children.

Despite these numbers, national surveys show that less than 50 percent of oncologists routinely refer cancer patients of childbearing age to a fertility specialist. In one study of colon cancer patients under 50, that number was as low as 15 percent. Stone says that her team’s own research shows that women who are single, over 35 or already have one child are also less likely to receive fertility counseling.

Greater numbers of women are also delaying pregnancy to focus on their careers, increasing the odds that they will experience age-related infertility or receive a cancer diagnosis before they are finished having children. Between 1972 and 2019, the average age of first-time mothers in the U.S. jumped from 21 to 27. Most college-educated women aren’t having their first child until their early to mid-30s, which is around the time that fertility begins to decline.

Women in the medical profession are especially at risk of infertility, with many doctors choosing to delay pregnancy until they complete their training and become financially independent. A 2016 survey in the Journal of Women’s Health found that nearly 1 in 4 female physicians had been diagnosed with infertility after struggling to have a baby, compared to 1 in 10 for the general public.

It’s a problem Christianson knows all too well. She delayed having a second child while she completed more than a decade of medical training, only to find herself in need of fertility treatment.

“I definitely think going through my own pregnancy loss and infertility has helped me understand and empathize with my patients,” says Christianson, who eventually gave birth to her son in her 40s with the help of fertility treatment. “I understand how difficult it is to see a negative pregnancy test and experience the emotional rollercoaster of wondering whether you will ever get pregnant.”

Elective oocyte cryopreservation, or egg freezing, is an increasingly popular option for people interested in having children later in life. Egg production and quality diminish as women age, so preserving eggs in advance can significantly improve the odds of a successful pregnancy. According to one IVF cost-effectiveness study, women save an average of $15,000 by freezing their eggs at age 35 and using them at 40, compared to waiting until 40 to attempt pregnancy.

Today, many medical residents come to the fertility center to freeze their eggs, but Christianson says that wasn’t an option when she was training to become a doctor. “Egg freezing was considered experimental before 2012, so it wasn’t widely available like it is now,” she explains. “Women have so many more options today.”

The Opportunity to Be a Mother

Piselli’s surgeon referred her to Christianson, who worked with her Hopkins oncologist, Michael Jon Pishvaian, on a plan to retrieve her eggs before her first day of chemotherapy on November 5, 2020. The first time she visited the Fertility Center in Lutherville–Timonium, just north of Baltimore, it was less than three weeks after her surgery, and she was still struggling to walk.

“I cannot stress enough how self-conscious and terrible I felt about not being able to walk on my own, but Dr. Christianson was just so wonderful. She patiently walked by my side and tried to make me comfortable every step of the way.”

Piselli was prescribed a cocktail of hormones to inject into her belly twice daily for two weeks. The trauma of the surgery had stopped her menstrual cycle, and Christianson wanted to ensure the greatest possible number of mature eggs were ready for retrieval by the end of October. To confirm everything was going according to plan, Piselli returned every two days for transvaginal ultrasounds and bloodwork. Christianson also recommended she take a drug called Zoladex throughout her six months of chemotherapy, which temporarily suspends ovarian activity to reduce the risk of damage to the ovaries.

To Piselli’s dismay, her insurance provider refused to cover the cost of her fertility treatment, classifying it as nonessential. Upon hearing the news, Christianson directed her to Livestrong Fertility — a program that offers financial support to patients with cancer in need of fertility services — and recommended pharmacies that offer discounted fertility medications. “I was so grateful to Dr. Christianson, because she immediately knew what to do. At every single turn, she was trying to make it easier for me,” remembers Piselli.

While one mature egg is normally released per menstrual cycle, with the help of fertility drugs, doctors can capture 10 to 20 mature eggs on average during an egg retrieval procedure. On the day of Piselli’s procedure, Christianson secured a whopping 32 eggs. Between those eggs and the protective effects of the Zoladex, Piselli’s doctors have assured her that, one way or another, she will get the opportunity to be a mother.

The Future of Fertility

The research being done by Christianson, Stone and other clinicians affiliated with the Fertility Preservation Innovation Center has the potential to shape future treatments and expand access to fertility services. They have investigated a variety of topics in recent years, including the benefits of using fresh versus frozen embryos, ovarian reserves in young women being treated for sickle cell anemia, and the impact of ovarian cryopreservation on follicle density in girls with cancer, which is a key predictor of reproductive potential.

James Segars, who co-leads the new center with Christianson and Stone, recently invented a treatment for uterine fibroids, which are noncancerous growths on the inside and outside of the uterus that can cause pain, infertility, and complications during pregnancy and birth. Segars’ treatment uses an enzyme called collagenase to break down the fibroid tissue.

“If we had a better treatment for fibroids, I think the quality of life of many, many millions of women — particularly African American women — would be greatly improved,” says Segars, who also serves as director of the Division of Reproductive Science and Women’s Health Research at Johns Hopkins. An estimated 70 percent of white women and between 80 and 90 percent of African American women will develop fibroids by age 50, according to the National Institutes of Health.

“Our mission is really to educate women, and even providers, about the reproductive tract and what the options are when it comes to assisted reproductive technology,” says Stone, who co-authored a study with Christianson on why more female cancer patients aren’t referred to fertility experts. “We need to increase awareness and access to fertility-preserving services for patients who want to pursue that.”

As fertility research progresses, lesser-known treatments like ovarian cryopreservation will become more commonplace, predicts Christianson. She says some researchers are even exploring ways to retrieve eggs in the lab by thawing ovarian tissue and creating an artificial ovary.

“We’re really just at the beginning of the growth of this field. Perhaps, 20 years from now, people will be freezing pieces of ovarian cortex instead of freezing eggs for fertility preservation,” she says.

Back on Track

For stone, helping patients like Piselli is what makes her job worthwhile.

“People want to know that you did everything you could to help them, even if it’s not the outcome they were hoping for,” Stone says. “The fact that you took the time — you cared about them, and you thought outside of the box — that’s what really matters.”

After her egg retrieval, Piselli completed six months of traditional chemotherapy, followed by a year of oral chemotherapy. So far, all of her cancer scans have been clear, and it feels like her life is finally back on track. Better, even.

To be closer to her parents and doctors, she transferred from Central Michigan University to Georgetown University, where she will resume her third year of medical school this spring. “I have such a hard time saying this has been the worst time of my life, because it has always been my dream to go to Georgetown medical school,” she says, crediting her oncologist, Pishvaian, for encouraging her to apply.

Piselli and David have set their wedding date for March 25, 2023, at a vineyard in Virginia. The idea of postponing motherhood while completing medical training doesn’t appeal to Piselli, who has learned not to delay her dreams, as life doesn’t always go according to plan.

“As soon as I am medically cleared,” she says, “we are going to have children.”

Photo of a Piselli with her fiance
Engaged just a few days before her cancer treatment began, Piselli, left, is now a third-year medical student at Georgetown. She and her fiancé, David, are set to be wed on March 25, 2023. — and they hope to start their family soon after.