Elexacafator/tezacaftor/ivacaftor resolves subfertility in females with CF: A two center case series

O’Connor, Kate; Goodwin, Dana L.; NeSmith, Andrew; Garcia, Bryan; Mingora, Christina; Ladores, Sigrid; Rowe, Steven M.; Krick, Stefanie; Solomon, George M.

doi:10.1016/j.jcf.2020.12.011

Cited by 52 publications

(39 citation statements)

References 11 publications

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“…Based on the presence of CFTR channels in the uterus and cervix, it was hypothesized that fertility for women with CF will improve with the availability of CFTR modulators and, specifically, highly effective CFTR modulators (IVA and ETI). Case reports of unplanned pregnancies suggest that fertility is improved with use of IVA [32][33][34][35]. Additionally, there is a recent case series from the United States supporting this theory [34].…”

Section: Unexpected Pregnancies and Improved Fertility With Modulatorsmentioning

confidence: 96%

“…Case reports of unplanned pregnancies suggest that fertility is improved with use of IVA [32][33][34][35]. Additionally, there is a recent case series from the United States supporting this theory [34]. Two CF care centers reported that 14 women with CF conceived after initiation of ETI, 7 of which were unplanned and 4 of which occurred in women who had been previously deemed infertile following clinical evaluation.…”

Section: Unexpected Pregnancies and Improved Fertility With Modulatorsmentioning

confidence: 97%

“…The exact effect of CFTR modulators on fertility is not yet known, but they are thought to decrease viscosity and increase pH in cervical mucous secretions, promoting a more fertile environment. While exact numbers are not yet available, reports of unexpected pregnancies have occurred on ETI [34,35].…”

Section: Unexpected Pregnancies and Improved Fertility With Modulatorsmentioning

confidence: 99%

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Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era

Jain

Taylor‐Cousar

2021

JPM

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder impacting approximately 80,000 people of all races and ethnicities world-wide. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which encodes a protein of the same name. Protein dysfunction results in abnormal chloride and bicarbonate transport in mucus membranes, including those in the respiratory, gastrointestinal and reproductive tracts. Abnormal anion transport causes viscous secretions at the site of involvement. The majority of people with CF succumb to respiratory failure following recurrent cycles of infection and inflammation in the airways. Historically, providers treated the signs and symptoms of CF, but since 2012, have been able to impact the basic defect for the subset of people with CF who have mutations that respond to the new class of drugs, CFTR protein modulators. With the improved health and longevity afforded by CFTR modulators, more women are interested in parenthood and are becoming pregnant. Furthermore, this class of drugs likely increases fertility in women with CF. However, the safety of CFTR modulators in pregnancy and lactation is only beginning to be established. We summarize available data on the impact of CFTR modulators on fertility, pregnancy and lactation in women with CF.

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Section: Unexpected Pregnancies and Improved Fertility With Modulatorsmentioning

confidence: 96%

Section: Unexpected Pregnancies and Improved Fertility With Modulatorsmentioning

confidence: 97%

Section: Unexpected Pregnancies and Improved Fertility With Modulatorsmentioning

confidence: 99%

See 1 more Smart Citation

Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era

Jain

Taylor‐Cousar

2021

JPM

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“…Remarkably, the triple therapy is particularly well-tolerated. Liver enzyme monitoring is recommended as with ivacaftor, and there have been reports of biliary colic and transient testicular pain, as well as increased fertility in women [89][90][91]. Delayed drug interaction between azithromycin and the TEZ/IVA combination manifested by first degree heart block has also been reported [92].…”

Section: Tezacaftor-ivacaftormentioning

confidence: 99%

New Therapies to Correct the Cystic Fibrosis Basic Defect

Bergeron

Cantin

2021

IJMS

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Rare diseases affect 400 million individuals worldwide and cause significant morbidity and mortality. Finding solutions for rare diseases can be very challenging for physicians and researchers. Cystic fibrosis (CF), a genetic, autosomal recessive, multisystemic, life-limiting disease does not escape this sad reality. Despite phenomenal progress in our understanding of this disease, treatment remains difficult. Until recently, therapies for CF individuals were focused on symptom management. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and its product, a protein present at the apical surface of epithelial cells regulating ion transport, allowed the scientific community to learn about the basic defect in CF and to study potential therapies targeting the dysfunctional protein. In the past few years, promising therapies with the goal to restore CFTR function became available and changed the lives of several CF patients. These medications, called CFTR modulators, aim to correct, potentialize, stabilize or amplify CFTR function. Furthermore, research is ongoing to develop other targeted therapies that could be more efficient and benefit a larger proportion of the CF community. The purpose of this review is to summarize our current knowledge of CF genetics and therapies restoring CFTR function, particularly CFTR modulators and gene therapy.

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“…As it is known, CFTR is expressed in the cervical and endometrial epithelium, causing decreased fertility in many females with cystic fibrosis; thus, it is logical that the use of a CFTR modulator can result in the increased incidence of pregnancy, which has also been described for ELE/TEZ/IVA in a case series [ 31 ]. This is, however, important to discuss before the start of treatment, because in the past with ivacaftor, this has resulted in unexpected and sometimes unwanted pregnancies.…”

Section: Questions To Addressmentioning

confidence: 99%

Management of Individual Patient Expectations When Starting with Highly Effective CFTR Modulators

Aalbers

Bronsveld

Hofland

et al. 2021

JPM

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Highly effective CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ELE/TEZ/IVA will become available for an increasing number of people with cystic fibrosis (pwCF) in the near future. Before the start of this therapy, many questions may arise concerning the expected effects. We assembled the currently available data from the literature about ELE/TEZ/IVA that focused on commonly asked questions from patients. Overall, the literature so far presents a very hopeful prospect of effects, not only on lung function, but also on nutritional status, sinonasal symptoms and quality of life. The effects in patients with pwCF with severe lung damage are also favorable. Treatment is generally well tolerated. In some cases, patient-derived cell models can help in predicting the effects for individual patients.

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Elexacafator/tezacaftor/ivacaftor resolves subfertility in females with CF: A two center case series

Cited by 52 publications

References 11 publications

Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era

Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era

New Therapies to Correct the Cystic Fibrosis Basic Defect

Management of Individual Patient Expectations When Starting with Highly Effective CFTR Modulators

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