CFTR Modulators: Impact on Fertility, Pregnancy, and Lactation in Women with Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is a life-shortening genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. These mutations lead to abnormal ion transport in mucous membranes throughout the body, including in the respiratory and gastrointestinal and reproductive tracts. Improvements in care and therapy have led to substantial increases in the quantity and quality of life for those with CF. Consequently, women with CF are increasingly interested in having families. Although pregnancy was once discouraged for women with CF, at this point, even women with moderately severe lung disease can successfully navigate pregnancy. With the recent approval of a triple combination CFTR modulator therapy that improves lung function, nutritional status, and quality of life for people with a single copy of the most common CFTR mutation, it is expected that the number of women with CF who choose to become pregnant will continue to increase. Although animal reproduction models show no alarming signals for use during pregnancy at normal human doses, there is a paucity of human safety data in pregnancy and lactation. This review summarizes what is currently known about the impact of use of CFTR modulators on fertility, pregnancy, and lactation in women with CF.

Ultrasound findings of pubertal development in girls with cystic fibrosis and their association with clinical outcomes and Tanner staging

“…Delayed puberty and malnutrition can decrease fertility in patients with CF. The use of CFTR modulators is promising in pubertal delay because of their systemic improvements, e.g., cervical mucus changes leading to increased fertility (28).…”

Gynecologic health care for females with cystic fibrosis

“…With the recent advent of CFTR modulator therapy, it is crucial to understand any impact these medications may have on fertility. In animal models, elexacaftor and ivacaftor impair fertility at toxic doses, however have no such effect at normal human dose; tezacaftor and lumacaftor have not been shown to impact fertility at any dose [55] . Clinical data are lacking, but the report that 2% of females enrolled in ivacaftor clinical trials became pregnant, in addition to case reports of unintended pregnancy with use of modulators after an extended period of infertility, have led clinicians to suspect that modulators may actually improve fertility [56] .…”

Review of CFTR Modulators 2020

“…Further research and counseling on possible increased reproductive potential with CFTR modulators is needed. The CF Foundation Therapeutics Development Network established a working group on Women's Health, which through an upcoming observational study of women and pregnancy outcomes (MAYFLOWERS-Maternal and Fetal Outcomes in the Era of Modulators) 45 , will help gain more insights.…”