- The Cystic Fibrosis Foundation issued a position paper on reproductive health in cystic fibrosis patients.
- The paper calls for a discussion about reproductive health at diagnosis and annually thereafter.
- Transmembrane conductance regulator modulator therapies and most other treatments aren’t an obstacle to contraception or pregnancy.
Reproductive health should be addressed from the time of diagnosis of cystic fibrosis and annually thereafter, with a more prominent place in clinical care in the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, according to a Cystic Fibrosis Foundation position paper.
Vast improvements in pulmonary outcomes with CFTR modulator therapies mean the majority of people with cystic fibrosis are now “living into and beyond their reproductive years, with questions including menopause in cystic fibrosis on the horizon,” wrote Raksha Jain, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues in Lancet Respiratory Medicine.
“In an era of CFTR modulators, we know that people with cystic fibrosis are living longer and healthier lives, and part of that is to have a better quality of life as well,” Jain told MedPage Today. “Based on people with cystic fibrosis expressing that they really want to expand their families, that they want to have more normalcy in their lives, we did a deep dive into things such as fertility, contraception, pregnancy, etc.”
CFTR modulators appear to have improved fertility in women but not men, “with reports of both female and male individuals with cystic fibrosis assuming they are infertile when they might not be,” the authors noted.
After approval of the CFTR modulator elexacaftor-tezacaftor-ivacaftor (Trikafta) in 2019, pregnancy rates among cystic fibrosis patients nearly doubled in the U.S. and U.K. by 2024. Unplanned pregnancies rose to as high as half of pregnancies in people with cystic fibrosis, “which isn’t necessarily different than the general population, but for a population that we really used to do a lot of pregnancy planning and discussions [with], we’re fairly surprised at,” Jain said.
However, many people with cystic fibrosis do not have a primary care provider.
“They utilize their cystic fibrosis care team as their primary care physicians, yet not all cystic fibrosis clinicians view themselves as their primary care doctor. So there’s a big gap in who’s taking responsibility for these things, particularly in the reproductive health arena,” Jain emphasized.
Contraception is safe overall without drug-drug interactions with most CFTR modulators other than lumacaftor. But contraceptives are underutilized in cystic fibrosis patients compared with the general population, the authors noted, and a quarter of women with cystic fibrosis directly receive contraceptive prescriptions from their cystic fibrosis provider.
For more than 95% of men with cystic fibrosis, the main reproductive health issue is infertility due to congenital bilateral absence of the vas deferens. CFTR modulators are unlikely to change this when taken after the neonatal period, though they are apparently safe to take during sperm retrieval and partner pregnancy.
The drugs do pass through the placenta and into breast milk, which hasn’t led to any observed long-term infant safety risks, although infant liver function and cataracts are potential concerns. On the other hand, this early exposure to CFTR modulators could potentially benefit infants who have inherited the genetic condition, with some evidence from animal models and case reports supporting an impact on the development of the vas deferens and later fertility outcomes, Jain said. Prevention or even correction of meconium ileus and rescue exocrine pancreatic insufficiency are possible as well.
“After exposure to CFTR modulators in utero, there have been some reports of babies that, for example, are missed on newborn screening because our classic test is actually improved, meaning it wouldn’t detect a baby because their sweat test is normal or their pancreatic function is normal,” she added.
Pregnant women with cystic fibrosis need to be screened more rigorously for diabetes compared with the general obstetric population, and need lung function and nutrition optimization that are unique to their condition as well, the authors noted. Most medications for chronic use, including CFTR modulators, inhaled mucolytics, some inhaled antibiotics, oral macrolides, and pancreatic enzyme replacement therapy, are considered safe or likely safe during pregnancy. Aspirin prophylaxis can also be considered, given the increased eclampsia risk with cystic fibrosis.
“We’re not dictating guidelines,” Jain emphasized. “This is a summary from experts of what we know thus far to raise awareness, but we don’t yet have enough data to say that this is a guideline of what people should or should not do.”
