A Case Report of Pregnancy During Use of Targeted Therapeutics for Cystic Fibrosis

Abstract

New therapeutics, such as ivacaftor, and the combination drug lumacaftor/ivacaftor that target the underlying genetic cause of cystic fibrosis are being hailed as game-changers in this era of personalized medicine. Although these drugs improve lung function, their effects on female fertility have not been studied. In this case report we describe one woman's experience with ivacaftor and her unanticipated pregnancy. Implications related to comprehensive sexual and reproductive health care for women with cystic fibrosis are presented.

Outcomes of pregnancy in women with cystic fibrosis (CF) taking CFTR modulators – an international survey

“…We present the first and largest case series of the outcomes of pregnancy in women with CF taking CFTR modulators throughout part or the entirety of their pregnancy. We are aware of 5 previously published case reports of pregnancies in women with CF taking CFTR modulators [17][18][19][20][21] . In the first case, a 25-year old woman with G551D/3272-26A > G CF and normal lung function conceived while taking IVA and therapy was continued throughout pregnancy [18] .…”

“…IVA was not continued during breast feeding in this case due to personal reasons. In the second case, a 20-year old woman with G551D/c.1585-2A > G CF became pregnant having taken IVA for 5 months prior to conception, however the patient stopped IVA after her positive pregnancy test and did not restart it [19] . There was no evidence of adverse effects on mother or infant and the woman chose to restart IVA 5 weeks post-delivery.…”

“…The small number of individual case reports currently published for women who chose to continue or discontinue CFTR modulators during pregnancy [17][18][19][20][21] makes it difficult for health care providers and for women with CF to make evidence-based decisions when making the important choice to continue or interrupt therapy with CFTR modulators for pregnancy. In order to provide further evidence on the safety of CFTR modulators, we conducted a survey of CF clinicians in the USA, UK, Europe, Israel and Australia in order to identify and describe pregnancy outcomes for women with CF who became pregnant while taking CFTR modulators.…”

Perinatal Outcomes in Cystic Fibrosis Women: Data From the Italian Cystic Fibrosis Registry.

“…Our study refers to a period preceding the availability of CFTR modulators in Italy, whereas a number of cases of successfully completed pregnancies in women receiving these drugs have recently been reported [20]. It is therefore realistic to believe that the innovative treatments of precision medicine will improve the clinical status and fertility of many CF women, thus making it easier for them to become mothers.…”

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 ].…”