Pregnancy and Fertility
Similar to looking at gender differences, investigating the impact of
CFTR modulators on pregnancy and fertility is a relevant topic that
impacts the increasing number of healthier adults with CF. The effects
of CFTR modulators on fertility and pregnancy are beginning to be
reported. 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. In a
2-center retrospective chart review from October 2019 through May 2020,
14 females on ETI became pregnant at a median of 8 weeks (range 1-17
weeks) after starting therapy43. Of these 14 patients,
7 were previously trying to conceive, but had a history of subfertility
or infertility. The other 7 had not been and were not actively trying to
conceive, but only 2 were using condoms and 1 natural family planning,
while 4 were not using any contraception. This study suggests that ETI
may improve fertility in women with CF. ETI was continued in 10 out of
14 women despite the lack of clinical trials during
pregnancy43. In a 2018-2019 international survey of 31
adult CF centers in the US, UK, Australia, Israel and Europe, 64
pregnancies were identified in 61 women on modulators: 31 pregnancies in
28 women on iva, 26 pregnancies on lum/iva, and 7 pregnancies on
tez/iva44. There were numerous maternal complications,
mainly as expected for a patient with CF. However, there were 2 maternal
complications reported by the clinician responding to the survey as due
to modulators (lum/iva): PEx and post-partum acute myelogenous leukemia.
As PEx is common in CF and there have been no associations between
modulators and hematologic malignancies, the authors believe these
complications may not have been related to lum/iva. The pregnancies
resulted in a total of 60 live births, 3 miscarriages (2 on iva, one on
tez/iva) and one termination for maternal health concerns. Although some
infants had complications, none were felt to be due to modulator use and
no infants who were formally examined (6 babies) were found to have
cataracts. No reports of complications during breastfeeding occurred (25
infants were breastfed total)44. 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.