In 1960, a 19-year-old woman with cystic fibrosis (CF) made medical history when she gave birth after only 34 weeks of pregnancy. The patient died three months after delivery.
In 1986, by which time the life expectancy of people with the disease had risen substantially, some 50 women with CF got pregnant. That number nearly tripled to 138 in 1997, rose to 247 by 2007, and reached 273 in 2017 — the last year for which statistics are available.
“This is terrific,” said Raksha Jain, MD, an adult pulmonologist at University of Texas-Southwestern. “We’re going to see more and more of this in our patient population as they feel better and live longer, healthier lives.”
Kathryn McAndrew, an acute care nurse practitioner at Chicago’s Rush University Medical Center, added: “Every year, the median age is going up, and now it’s 46. We anticipate that with the recent approval of Trikafta [Vertex Pharmaceuticals’ triple-combo therapy of elexacaftor, ivacaftor and tezacaftor], life expectancy will continue rising, and the percentage of adult CF patients will increase as well. So we need to be creative and strategic about how we deliver therapies to these patients, and prepare for the impending increase in age.”
Both women spoke at the 2019 North American Cystic Fibrosis Conference in Nashville. Their talks were part of a panel on CF and reproductive issues ranging from contraception and pregnancy to male infertility and in-vitro fertilization (IVF).
Cynthia Brown, MD, director of the Adult CF Program at Indiana University, said: “Once they become pregnant, women with CF are in fear. They wonder, ‘Am I healthy enough? Will my lung function drop? How much weight do I have to gain? Will my baby have CF too?’ In fact, women with CF do have more prenatal complications.”
Patients lack sexual health counseling
For example, Brown said, women with CF have a much harder time gaining weight when pregnant. They’re also 14 times more likely to have diabetes than women without CF, 125 times more likely to die in childbirth, 69 times more likely to have pneumonia, 29 times more likely to have respiratory failure, and 32 times more likely to have mechanical ventilation.
Yet experts say there’s no long-term loss of lung function following pregnancy. According to one study comparing 119 CF patients who gave birth with 1,190 who had never been pregnant, the two groups showed no difference in the rate of decline of either body mass index or average forced expiratory volume in one second (FEV1; a lung function measure).
Unfortunately, said Brown, women with CF are not receiving proper counseling on sexual health and contraception.
“It’s encouraging to see the increasing number of pregnancies in CF patients,” she said. “Most pregnancies do well these days, although not without increased risk. But we’re behind the curve in the way we talk to our patients about sexual reproductive health.”
Only 55% of women with CF have ever used contraception, compared with 74% of healthy women, she said. Likewise, just 26% of women with CF have received either a pap smear or pelvic exam (compared with 44% of healthy women), and only 9% had been given contraceptive counseling (compared with 26% of healthy women).
More to the point, only 32.8% of women with CF understand how their disease affects fertility — even though 78% of such women intend to have children at some point. That’s according to Sigrid Ladores, PhD, of the University of Alabama at Birmingham (UAB) School of Nursing.
“We need to talk about what men and women with CF want to disclose, who they want to share this information with, how and why,” said Ladores. “We need to encourage them to obtain their partner’s family history to determine if there’s a problem or not. If they’re thinking about making a baby, perhaps genetic testing for their partner is important, as well as a discussion if the genetic tests come back positive.”
‘Popsicle Day’ and ‘Squirt Day’
About 98% of men with CF have a congenital bilateral absence of the vas deferens (CBAVD), meaning that they’re born sterile, Ladores said. In contrast, most women with CF have normal reproductive structures — and except for those who are severely malnourished, most experience normal or near-normal menstrual cycles.
“Men with CF have viable sperm within the testes that can be obtained using needle aspiration and cryopreserved for later use,” she said. “Great strides have been made since 1988, when sperm aspiration led to the first biological child born to a man with CF.”
“Assisted reproductive technology such as IVF (in-vitro fertilization) or IUI (intrauterine insemination) can facilitate conception using thawed cryopreserved sperm,” Ladores said. “Unfortunately, the conception rates of men with CF using their own aspirated sperm is unknown and not collected by the CFF Patient Registry.”
It’s a subject Ladores has not only researched, but also one she deals with every day on a personal level: her husband, Andrew, has CF and was not expected to live to see his first birthday.
“Andrew was born with CBAVD in 1973, when treatments were not very good,” she said. “In his late 30s, he enrolled in law school, and today he’s a 46-year-old attorney and more than eight years post-transplant.”
Sigrid and Andrew Ladores have two sons. Asher was born four years before her husband’s lung transplant, and Cooper came into the world four years after the transplant. She uses particularly colorful language to describe the process.
“Testicular sperm aspiration and analysis on Andrew revealed viable sperm but low motility. Five IVF cycles later, we were able to get pregnant from a frozen embryo,” said the researcher. “April 23 is ‘Popsicle Day,’ because that’s when we took Asher out of the freezer. After Andrew had his transplant and his health stabilized, we did eight more fertility cycles using his frozen sperm to create Cooper. We celebrate his ‘Squirt Day’ on March 12.”
CF and pregnancy: Still serious risks
Ladores said she’s currently researching male fertility in CF post-transplant — and among the reasons is a conversation she had with a couple in which both partners expressed regret over their missed chance to conceive a biological child following transplant.
“You could hear the anguish in their voices,” she recalled. “The year after his lung transplant, the man felt good enough to create a family. They went to see a fertility specialist, who said ‘No, you should not use your own sperm. It’s too risky because of your transplant meds.’ He felt like he was punched in the gut. He didn’t see that coming.”
Ladores said her patient was never told that sperm should be aspirated before surgery to preserve the chance at having a biological child. Since then, he and his wife have become vocal advocates for the need to share this information.
Yet no matter how much science has progressed, women with CF still face a much higher risk of complications in pregnancy — especially those who have had lung transplants, said Lisa Zuckerwise, MD, a maternal fetal medicine specialist at Nashville’s Vanderbilt University Medical Center.
Women with CF have a 25%-50% risk of preterm delivery, she said. Pregnancy pushes up the diaphragm by around 4 centimeters, resulting in loss of overall lung volume.
“Healthy women tolerate this really well, but I even had shortness of breath in the second and third trimester,” she said. “These changes are often much more poorly tolerated by patients with CF. Transplant rejection is also a big problem in pregnancy. Women who have had transplants are at significantly higher risk.”
Zuckerwise added: “It’s really important that women with CF know what they’re getting into. Right off the bat, I tell them having babies is hard. It was really hard for me, and I don’t have cystic fibrosis. I also don’t hesitate to scare them into taking care of themselves, because their lives are truly on the line.”
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