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.