Two Unanticipated Pregnancies While on Cystic Fibrosis Gene-Specific Drug Therapy

Abstract

Women with cystic fibrosis (CF) desire to become pregnant and accomplish the same life goals as women without CF. The underlying pathology of CF and medications used to treat this genetically transmitted disease can affect women’s reproductive potential. An interview with Ana (pseudonym), who became pregnant twice while taking the medication lumacaftor/ivacaftor (LUMA/IVA), was analyzed using thematic analysis. She described her experiences related to “Fertility and Pregnancy Surrounding LUMA/IVA,” the major theme that emerged from her narrative. While there are anecdotal reports of infants conceived by women on LUMA/IVA and other CF precision medications, pregnancy rates and outcomes are not systematically tracked. Education about risks and benefits of these medications should be provided as part of comprehensive clinical care.

Review of CFTR Modulators 2020

“…In a patient experience interview, a pregnant woman reported that the provider team was neutral or encouraged discontinuation of modulator treatment stating "They [health-care providers] weren't sure at that point if it [lum/iva] was safe or not safe. There wasn't any information on it so they said, 'It's up to you"' 42 . As both infertility and subfertility are common in CF, many have seen an increase in pregnancies with modulator use.…”

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

“…CFTR modulators in animal models showed no adverse impact on fertility when given at normal human doses [ 35 , 36 , 37 , 38 ] ( Table 1 ). In people using CFTR modulators and consequent systemic improvement in their CFTR function (leading to improvements in nutritional status, and possibly improving cervical mucus consistency and pH) [ 30 ], there have been reports of both improved fertility (7/12 women who previously reported infertility became pregnant with an average time to conception, following ivacaftor initiation of 3.2 months [range 1–8.5]) and unplanned pregnancies [ 39 , 40 , 41 ]. In the phase 3 trial of ivacaftor, in which participants agreed to use contraception throughout the trial [ 23 ], approximately 2% of the women became pregnant [ 39 ].…”

“…While ivacaftor, tezacaftor, and elexacaftor, given at maternally toxic doses, caused minor abnormalities (decreased body weight in rats given ivacaftor at 7 times the MRHD, decreased body weight, delayed pinna attachment and eye opening in rabbits given tezacaftor at 1 times the MRHD, and decreased body weight in rats given ≥4 times the MRHD), none of the approved modulators impacted organogenesis at normal human doses [ 35 , 36 , 37 , 38 ] ( Table 1 ). Although this animal data is reassuring, because of the lack of data in pregnant women, caution is advised for use in pregnancy, and some clinicians have advised women to discontinue use of modulators during pregnancy [ 40 , 41 , 43 , 44 , 45 ].…”

“…There are no studies of the use of CFTR modulators in pregnant women with CF; however, several case reports have appeared in the literature that include women who unintentionally and intentionally became pregnant while being treated with ivacaftor and lumacaftor/ivacaftor [ 39 , 40 , 41 , 43 , 44 , 45 , 46 ] ( Table 2 ). Of the six pregnancies reported in five women using ivacaftor, four of the infants were exposed to ivacaftor in all trimesters (the number of trimesters of exposure was not reported in one case, and in one case, a woman discontinued ivacaftor when it was determined that she was pregnant) [ 39 , 40 , 43 , 46 ].…”

“…In a third report of two infants born to the same mother, both infants were exposed to lumacaftor/ivacaftor throughout both pregnancies; no adverse impacts on the infants were reported. [ 41 ] Of the eleven infants exposed to modulators during pregnancy, only four had formal ophthalmologic exams; all were normal. Importantly, three attempts to discontinue CFTR modulators because of unknown safety in pregnancy resulted in pulmonary decline in three women, leading to resumption of therapy [ 43 , 44 , 45 ].…”