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. Author manuscript; available in PMC: 2024 Nov 1.
Published in final edited form as: Curr Opin Pulm Med. 2023 Sep 1;29(6):595–602. doi: 10.1097/MCP.0000000000001009

The modern landscape of fertility, pregnancy, and parenthood in people with cystic fibrosis

Raksha Jain 1, Traci M Kazmerski 2,3, Jennifer L Taylor-Cousar 4,5
PMCID: PMC10629848  NIHMSID: NIHMS1926774  PMID: 37789771

Abstract

Purpose of the review:

With improved long-term survival and the expanding availability of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies that treat the underlying genetic defect in CF, more people are interested in parenthood. CF care centers and people with CF need more information to guide decisions related to parenting.

Recent findings:

Here we present currently available data on fertility, pregnancy and parenthood in the modern era of CF care. Fertility may be improving in females with CF with the use of CFTR modulator therapies and there is an associated increase in annual pregnancies. Infertility in males with CF remains approximately 97%–98% and is unchanged with CFTR modulators in those already born with CF. As more females with CF experience pregnancy, questions remain about the impact of pregnancy on their health and that of their child. Fortunately, there are multiple routes to becoming a parent; however, more work is needed to understand the impact of pregnancy and parenthood in the context of CF as some previous data suggests potential challenges to the health of parents with CF.

Summary:

We encourage CF care teams to have knowledge and resources available to support the reproductive goals of all individuals with CF.

Keywords: Cystic fibrosis, parenthood, fertility, pregnancy, in vitro fertilization, assisted reproductive technology

Introduction:

Improved general health and survival, particularly for those on cystic fibrosis transmembrane conductance regulator (CFTR) modulators, are affording many more people with CF the opportunity to consider parenthood. As is the case for people without CF, there are many different paths to parenthood available to those with CF. However, historically higher rates of subfertility or infertility in some females with CF and the presence of infertility in the majority of males with CF leads more to seek alternative pathways to parenthood. Importantly, however, pregnancy and parenthood may adversely impact short-term health outcomes; thus, research is needed to identify the cause and appropriate interventions to optimize outcomes.

Fertility

Female sex assigned at birth

The reported incidence of infertility or subfertility in females with CF is higher than the general population (estimated at 30–40% in previous reports), however, much of these data predated widespread use of highly effective CFTR modulator therapy.(1, 2) The reproductive anatomy of females with CF is not different than females without CF (Figure 1); the causes of infertility in females are incompletely understood. Possible etiologies include thick cervical mucus secondary to high expression of dysfunctional CFTR in cervical epithelium, delayed puberty and ovulation, poor nutritional status, abnormal uterine bicarbonate levels, low ovarian reserve and the presence of dysfunctional CFTR in areas of the brain involved in reproductive functions including hormone levels.(3–9) In the cervix, because CFTR modulators treat the underlying protein abnormality, both cervical mucous viscosity and pH likely improve and consequently increase fertility.(10–12) This phenomenon is highlighted by a number of reports of unintended pregnancy in females with CF who were thought to be infertile prior to initiation of CFTR modulators.(13) Therefore, contraception is recommended to avoid unplanned pregnancies. In a recent multi-center study of pregnancies from 2010–2021 in the U.S., 40% of pregnancies were reported as unplanned and those with unplanned pregnancies experienced a higher rate of pulmonary exacerbations post-pregnancy than those with planned pregnancies.(14)

Figure 1. Male and female anatomy in cystic fibrosis [74].

Figure 1.

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Male anatomy demonstrating typical absence of the vas deferens. Female anatomy is similar to that of the general population.

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Male sex assigned at birth

The majority of males with CF have congenital bilateral absence of the vas deferens (CBAVD) (Figure 1). Subsequently, 97–98% of males born with CF make sperm, but those sperm are absent in the semen secondary to lack of the anatomical duct through which sperm pass from the testis to the urethra.(15) This absence is thought to be driven by the sensitivity to CFTR dysfunction on the development of the vas deferens in utero to either underdevelopment or atrophy from obstruction.(16, 17) Whereas fertility in females is hypothesized to improve secondary to both direct CFTR effects and extra-pulmonary benefits of CFTR modulators, fertility in males already born with CF is not expected to change. There are reports in G551D homozygous animal models exposed to ivacaftor in utero and a case report of a human male baby exposed to elexacaftor/tezacaftor/ivacaftor in utero (both highly effective CFTR modulators) that resulted in rescue of the vas deferens.(18, 19) It is possible, therefore, for highly effective CFTR modulators to rescue male infertility via in utero exposure. Fertility screening in adolescent and adult males with CF can be done by palpitating for the vas deferens, performing an ultrasound or magnetic resonance imaging and should include a semen analysis to assess presence or absence of sperm.

Assisted Reproductive Technology

The majority of males and some females with CF will need to consider ART as an option to have children that are biologically their own. These techniques include in vitro fertilization (IVF) and intrauterine insemination (IUI), but there are other potential options. For males with CF, the first step involves surgical sperm retrieval or testicular sperm aspiration (also known as percutaneous epididymal sperm extraction [PESA], testicular sperm extraction [TESA], microsurgical epididymal sperm aspiration [MESA] or testicular sperm extraction [TESE]). These procedures are office-based and typically performed using local anesthesia. The same procedure can be used for partners of subfertile females with CF to harvest sperm for IUI or IVF versus collecting sperm via ejaculate. Although ART success rates are lower for males with CF compared to males in the general population or those with CBAVD alone, live birth rates of 44–53% have been achieved.(20–22)

In IUI, sperm is inserted directly into the uterus overcoming cervical mucus challenges. (23) In IVF, on the other hand, the egg and sperm are combined in a laboratory dish and transferred in the form of an embryo into the uterus. Both are reasonable options in females with CF. In IUI, the sperm is implanted in the uterus past the thickened cervical mucus using a catheter. No adjuvant hormonal supplementation is typically required. Rarely, the procedure can be associated with infection. For IVF hormone stimulation is required, but also allows for embryos to be stored for later use and for pre-implantation genetic testing. (2, 24) Success rates for pregnancies using IUI are estimated to be 5–25% whereas IVF success rates are typically 20–40%.(25) IVF can also be utilized for males and females if considering surrogacy. See Figure 2 for additional paths to parenthood.

Figure 2. Multiple potential paths to parenthood [74].

Figure 2.

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Multiple parenting options for all genders with CF are similar to those for the general population.

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Pregnancy

Based on low historical survival rates in CF combined with data suggesting poor pregnancy outcomes for people with CF and their infants, pregnancy was often discouraged. As comprehensive clinical care and therapeutic development advanced, US CF Patient Registry (CFFPR) data from the early 2000s suggested no adverse impact on survival in females with CF who became pregnant compared to matched controls.(26) However, subsequent work demonstrated that compared to females with CF who did not become pregnant, those who became pregnant had increased morbidity with more need for illness-related care, intravenous antibiotics and decreased quality of life.(27) Furthermore compared to females without CF, people with CF experience more pregnancy complications (e.g. pre-eclampsia and need for assisted delivery) as do their infants (e.g. increased pre-term birth, congenital anomalies and hyperbilirubinemia.(28) However, it is important to note that the majority of studies describing pregnancy outcomes in CF were retrospective, single site and done in the era prior to the introduction of CFTR modulators.(29–35)

Currently, in contrast to decreasing pregnancy rates in the general US population, pregnancy rates have more than doubled since the introduction of highly effective modulator therapy for the majority of people with CF (Figure 1).(36–38) While it is clear from large randomized trials that CFTR modulators improve health and quality of life,(39, 40) much less is known about the safety of their use during pregnancy and partner conception. Data from individual testing of each modulator (ivacaftor, lumacaftor, tezacaftor and elexacaftor) in animal reproductive models demonstrated no teratogenicity at standard human doses.(29, 41–44) However, the occurrence of cataracts in juvenile rats which were directly administered ivacaftor led to label guidance for cataract assessment in people with CF <18 years of age receiving ivacaftor-or ivacaftor-containing products.(41) To date, published data regarding the use of CFTR modulators during pregnancy is limited to case reports and case series.(11, 45–52) Two international/national retrospective surveys described outcomes of pregnant people with CF and their infants following maternal modulator use.(53, 54) In people with CF who continued modulators during pregnancy, miscarriage rates were consistent with those reported in the general population, and only four adverse outcomes in mothers were rated by treating physicians as related to modulator use. On the other hand, of those who chose to discontinue modulators during pregnancy, 36% experienced health decline leading to re-initiation of therapy.

In the retrospective surveys, no infants experienced adverse outcomes that were felt to be definitively related to modulator use during pregnancy or lactation. Of note, few infants underwent evaluation for cataracts. In a recent 2-site study in which all infants exposed to modulators during pregnancy and lactation underwent ophthalmologic examination, 3 of 23 infants had small, clinically insignificant cataracts. The rate of cataracts in infants born to mothers with CF not exposed to modulators is unknown; further research is needed. Because modulators have been shown to cross the placenta and are present in breast milk,(48, 50) breast-fed infants will continue to experience modulator exposure, albeit at much lower levels than while in utero. Pediatricians caring for such exposed infants should recommend ophthalmologic screening and consider liver function test monitoring. Importantly, infants with CF who are exposed to modulators in utero are likely to have false negative newborn screens and lower than expected sweat chloride levels.(50–52) Thus, genetic testing for CF for infants born to mothers on modulators is critical to correctly diagnose the infants and ensure the early treatment intended by the institution of universal newborn screening.

As the number of pregnancies in people with CF continues to occur at much higher rates than it has in the past (Figure 3), it is critical to understand the impact of pregnancy and early parenthood on maternal health was well as infant health in people with CF in the modern era. The Maternal and Fetal Outcomes in the Era of Modulators (MAYFLOWERS) study is primarily designed to understand the impact of pregnancy on lung health, but will also assess the pharmacokinetics of modulators during pregnancy and lactation and glucose excursion during pregnancy (NCT04828382).(55) With consideration of t CF community input, MAYFLOWERS will also assess the impact of pregnancy on mental health. While the CF community awaits this data, recommendations for pregnancy management based on our knowledge to date have been recently reviewed.(56) (57)

Figure 3. Annual pregnancies reported in the U.S. in females ages 14–45 [38].

Figure 3.

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Annual number of pregnancies per year and median predicted survival (years) based on data from the U.S. CF Foundation patient registry over the past 15 years.

Parenthood

A variety of interwoven considerations play into the decision regarding if and when to become a parent which becomes especially complex when one has CF. People with CF highlight that their chronic health condition is a key factor in family-building decisions.(58) Qualitative studies conducted before the widespread use of highly effective modulator therapy (HEMT) suggest that people with CF have concerns related to their ability to balance the care of their children and their disease self-management, fears related to parenting with a limited life expectancy, and struggles related to the complex prioritization of their own health and the needs of their children.(59) Parents with CF also cite worries related to communicating with their children about CF and its impact on their health and survival. Despite this, a systematic review showed that most parents with CF have a positive outlook on parenthood.(60, 61)

More recent qualitative evaluations into the lived experience of parents with CF have been conducted in the era of HEMT. A PhotoVoice exploration sought to understand how parents with CF cope with and balance the competing aspects of parenthood and CF.(62) Using photography to generate discussion, participants shared the importance to pay attention to the joyful aspects of parenting, balance personal health needs with those of children using creative and flexible strategies, and finding ways to deal with the uncertainty of parenthood with CF with known competing priorities and expectations. An interview study of 37 mothers and fathers with CF explored their parenting strategies and support needs from their CF team.(63) Participants shared the importance of multitasking to complete CF care, delegating tasks to partners and other family members, and use of precautions to mitigate risk from children’s infections. They highlighted that the CF team should provide support and resources for parents and potential parents with CF and also desired connections with other parents with CF with whom they could share experiences and strategies for success.

Little is known about the impact of parenthood on the physical and mental health of people with CF. As summarized above, Goss et al found that females with CF who had a pregnancy reported in the US CFFPR) had no survival disadvantage compared to those who did not.(26) A more recent study of French fathers with CF uncovered a trend toward increase outpatient visits in the first 3 years of parenthood with no worsening lung function or body mass index (BMI).(64) However, a study of fathers with CF from the United Kingdom (UK) showed a significant decline in weight and a trend toward lung function decline in the first year of parenthood.(65) Most recently, a study of UK registry data of 296 female and male parents with CF demonstrated a significant decrease in lung function and BMI and an increase in pulmonary exacerbations (PEx) in the first year of parenthood compared to the year prior.(66) Importantly, CFTR modulator use mitigated the impact of parenthood on lung function, but not on BMI or PEx. Despite these findings, there are numerous limitations to prior work, including the lack of focus on paths to parenthood aside from pregnancy, lack of long-term health outcomes, and lack of robust data surrounding the impact of HEMT. Additionally, no prior studies have focused on the impact of parenthood on the mental health of those with CF.

A large, multicenter study describing the impact of parenthood on CF health in the era of CFTR modulators called “Health Outcomes of Parents with CF” (HOPeCF) is currently ongoing in the US(NCT05829694). To provide relatively immediate evidence on parenthood’s effect on pulmonary health and the influence of CFTR modulators, a retrospective longitudinal cohort study will link CFFPR data with cross-sectional surveys of female and male parents and nonparents between 2012–2022. The study team will also conduct a prospective observational study of new parents with CF and include both physical health outcomes and key mental health and psychosocial measures to gain a comprehensive picture of the interplay between parenthood and CF.

While the number of pwCF interested in pursuing parenthood is increasing, it is critical to recognize that many people have complex feelings or are ambivalent toward parenthood.(67) A framework solely focused on planning fails to consider those who cannot or do not want to plan their reproductive decisions. It is important to use a reproductive justice lens when discussing parenthood and pregnancy with people with CF and remain nonjudgmental about their reproductive choices and desires.(68) Indeed, prior qualitative interviews with females with CF found that many do not share their reproductive plans with CF teams for fear of feeling discouraged or judged.(58)

Interventions to support people with CF achieve their reproductive goals can be focused on patient-facing, provider-facing, or systems-based change. Recently, a novel patient-facing, web-based reproductive decision support tool called MyVoice:CF to assist women with CF consider their reproductive futures and family planning needs was found to be highly acceptable, appropriate, and usable for a CF population.(69, 70) Provider training in relationship-centered communication has also been found to be feasible for CF providers and may be adapted to improve family planning discussions. (71) Existing tools to assess reproductive goals may be adapted for the CF population.(72) Systems-level interventions may include leveraging the electronic health record to nudge providers to address family planning and enhance partnerships with reproductive health providers.(73)

Conclusions

As more people with CF face the future and consider becoming parents, CF teams must universally discuss reproductive health and goals with those with CF and be prepared to provide appropriate resources and guidance to support their choices.

Almost all males with CF will need to plan and consider the use of ART or pursuit of other family-building paths. For females with CF, planning pregnancy can help with needed clinical changes to optimize health, limit teratogenic exposures, obtain genetic testing, and gather support and resources. Furthermore, although CFTR modulators may mitigate some of the short-term adverse health impacts of pregnancy and parenthood, future research, can prospectively confirm these findings and identify appropriate areas for intervention.

Key Points:

More people with cystic fibrosis are seeking parenthood

CFTR modulators have changed the landscape of fertility and pregnancy in females with CF.

CFTR modulators have not changed infertility in males already born with CF.

More work is needed to understand the impact of pregnancy and parenthood on the health of people with CF.

CF care teams should be poised with information and tools to support the reproductive goals of people with CF.

Acknowledgement:

Financial support and sponsorship:

RJ, TMK and JTC receive grant support from the Cystic Fibrosis Foundation (JAIN21Y3, KAZMER21Y3, TAYLOR19Y3) to support the CF Foundation TDN Sexual Health and Reproduction and Gender research working group. RJ and JTC receive grant support from the Cystic Fibrosis Foundation for the Maternal and Fetal Outcomes in the Era of Modulators (MAYFLOWERS) study (MAYFLOWER-TAYLOR21A0, JAIN21A0). TMK receives grant support from the National Institutes of Health (1R01HL161164–01A1) for the Health Outcomes of Parents with Cystic Fibrosis (HOPeCF) study.

Conflicts of Interest:

In the last 36 months, RJ has received grants to her University from the CF Foundation, Vertex Pharmaceutical, 4DMT, Insmed, Sound Pharma, and Armata for clinical trial participation. RJ has also received consulting fees from Boerhinger Ingelheim and Recode for serving on their scientific advisory committee, from Syneos for serving on a DSMB, and from Vertex for serving on their Innovation Awards committee. In the last 36 months, JTC has received grants to her institution from the Cystic Fibrosis Foundation, the National Institutes of Health, Vertex Pharmaceuticals Incorporated, Eloxx, and 4DMT; has received fees from Vertex Pharmaceuticals Incorporated related to consultation on clinical research design, participation on advisory boards, and speaking engagements; and has served on advisory boards and/or provided clinical trial design consultation for Insmed, 4DMT, and AbbVie. JTC served on a DMC for AbbVie. JTC serves as the adult patient care representative to the CFF Board of Trustees, and on the CF Foundation’s Clinical Research Executive Committee, Clinical Research Advisory Board, as immediate past chair of the CF TDN’s Sexual Health, Reproduction and Gender Research Working Group, and as Co-Chair of the Heath Equity Team Science Awards study section. She also serves on the scientific advisory board for Emily’s Entourage, and on the ATS Respiratory Health Awards Working Group and as Chair-Elect of the International Conference Committee. She is an Associate Editor for the Journal of Cystic Fibrosis and a member of the International Advisory Board for the Lancet Respiratory Medicine Journal. JTC serves on the Clinical Trials Review (CTLR) Study section for the National Institutes of Health/National Heart. Blood, Lung Institute.

References:

  • 1.Shteinberg M, Lulu AB, Downey DG, et al. Failure to conceive in women with CF is associated with pancreatic insufficiency and advancing age. J Cyst Fibros. 2019;18(4):525–9. [DOI] [PubMed] [Google Scholar]
  • 2.Ahmad A, Ahmed A, Patrizio P. Cystic fibrosis and fertility. Curr Opin Obstet Gynecol. 2013;25(3):167–72. [DOI] [PubMed] [Google Scholar]
  • 3.Kopito LE, Kosasky HJ, Shwachman H. Water and electrolytes in cervical mucus from patients with cystic fibrosis. Fertil Steril. 1973;24(7):512–6. [PubMed] [Google Scholar]
  • 4.Gervais R, Dumur V, Letombe B, et al. Hypofertility with thick cervical mucus: another mild form of cystic fibrosis? JAMA. 1996;276(20):1638. [PubMed] [Google Scholar]
  • 5.Johannesson M, Landgren BM, Csemiczky G, et al. Female patients with cystic fibrosis suffer from reproductive endocrinological disorders despite good clinical status. Hum Reprod. 1998;13(8):2092–7. [DOI] [PubMed] [Google Scholar]
  • 6.Hodges CA, Palmert MR, Drumm ML. Infertility in females with cystic fibrosis is multifactorial: evidence from mouse models. Endocrinology. 2008;149(6):2790–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Chan HC, Shi QX, Zhou CX, et al. Critical role of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Mol Cell Endocrinol. 2006;250(1–2):106–13. [DOI] [PubMed] [Google Scholar]
  • 8.Leahy T, Gadella BM. Sperm surface changes and physiological consequences induced by sperm handling and storage. Reproduction. 2011;142(6):759–78. [DOI] [PubMed] [Google Scholar]
  • 9.Schram CA, Stephenson AL, Hannam TG, Tullis E. Cystic fibrosis (cf) and ovarian reserve: A cross-sectional study examining serum anti-mullerian hormone (amh) in young women. J Cyst Fibros. 2015;14(3):398–402. [DOI] [PubMed] [Google Scholar]
  • 10.Shteinberg M, Taylor-Cousar JL, Durieu I, Cohen-Cymberknoh M. Fertility and Pregnancy in Cystic Fibrosis. Chest. 2021;160(6):2051–60. [DOI] [PubMed] [Google Scholar]
  • 11.Jones GH, Walshaw MJ. Potential impact on fertility of new systemic therapies for cystic fibrosis. Paediatr Respir Rev. 2015;16 Suppl 1:25–7. [DOI] [PubMed] [Google Scholar]
  • 12.Roe AH, Koelper N, McAllister A, et al. Cervical mucus quality in females with and without cystic fibrosis. J Cyst Fibros. 2023. [DOI] [PubMed]
  • 13.O’Connor KE, Goodwin DL, NeSmith A, et al. Elexacafator/tezacaftor/ivacaftor resolves subfertility in females with CF: A two center case series. J Cyst Fibros. 2021;20(3):399–401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Peng G, Taylor-Cousar JL, Lee M, et al. Association between unplanned pregnancies and maternal exacerbations in cystic fibrosis. J Cyst Fibros. 2023. *Given the limited information about pregnancy in national CF registries, no previous literature evaluated the impact of an unplanned pregnancy on maternal outcomes in CF. In this manuscript, investigators using local data from 11 CF centers in the U.S. including 226 pregnancies and show that females with unplanned pregnancies experience more pulmonary exacerbations than those with planned pregnancies.
  • 15.Kaplan E, Shwachman H, Perlmutter AD, et al. Reproductive failure in males with cystic fibrosis. N Engl J Med. 1968;279(2):65–9. [DOI] [PubMed] [Google Scholar]
  • 16.Yoon JC, Casella JL, Litvin M, Dobs AS. Male reproductive health in cystic fibrosis. J Cyst Fibros. 2019;18 Suppl 2:S105–S10. [DOI] [PubMed] [Google Scholar]
  • 17.Campbell K, Zarli M, Schuppe K, et al. Sexual and Reproductive Health among Men with Cystic Fibrosis. Urology. 2023. [DOI] [PMC free article] [PubMed]
  • 18.Sun X, Yi Y, Yan Z, et al. In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis. Sci Transl Med. 2019;11(485). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Fortner C. Reproductive health and family building in the modern era of CF: The earliest possible CFTR modulation: in utero exposure. North American Cystic Fibrosis Conference2022. [Google Scholar]
  • 20.McCallum TJ, Milunsky JM, Cunningham DL, et al. Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes. Chest. 2000;118(4):1059–62. [DOI] [PubMed] [Google Scholar]
  • 21.McBride JA, Kohn TP, Mazur DJ, et al. Sperm retrieval and intracytoplasmic sperm injection outcomes in men with cystic fibrosis disease versus congenital bilateral absence of the vas deferens. Asian J Androl. 2021;23(2):140–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Persily JB, Vijay V, Najari BB. How do we counsel men with obstructive azoospermia due to CF mutations?-a review of treatment options and outcomes. Transl Androl Urol. 2021;10(3):1467–78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Kredentser JV, Pokrant C, McCoshen JA. Intrauterine insemination for infertility due to cystic fibrosis. Fertil Steril. 1986;45(3):425–6. [DOI] [PubMed] [Google Scholar]
  • 24.Medical Advisory S. In vitro fertilization and multiple pregnancies: an evidence-based analysis. Ont Health Technol Assess Ser. 2006;6(18):1–63. [PMC free article] [PubMed] [Google Scholar]
  • 25.Nandi A, Raja G, White D, Tarek ET. Intrauterine insemination + controlled ovarian hyperstimulation versus in vitro fertilisation in unexplained infertility: a systematic review and meta-analysis. Arch Gynecol Obstet. 2022;305(4):805–24. [DOI] [PubMed] [Google Scholar]
  • 26.Goss CH, Rubenfeld GD, Otto K, Aitken ML. The effect of pregnancy on survival in women with cystic fibrosis. Chest. 2003;124(4):1460–8. [DOI] [PubMed] [Google Scholar]
  • 27.Schechter MS, Quittner AL, Konstan MW, et al. Long-term effects of pregnancy and motherhood on disease outcomes of women with cystic fibrosis. Ann Am Thorac Soc. 2013;10(3):213–9. [DOI] [PubMed] [Google Scholar]
  • 28.Jelin AC, Sharshiner R, Caughey AB. Maternal co-morbidities and neonatal outcomes associated with cystic fibrosis(). J Matern Fetal Neonatal Med. 2017;30(1):4–7. [DOI] [PubMed] [Google Scholar]
  • 29.Taylor-Cousar JL, Shteinberg M, Cohen-Cymberknoh M, Jain R. The Impact of Highly Effective Cystic Fibrosis Transmembrane Conductance Regulator Modulators on the Health of Female Subjects With Cystic Fibrosis. Clin Ther. 2023;45(3):278–89. [DOI] [PubMed] [Google Scholar]
  • 30.Ashcroft A, Chapman SJ, Mackillop L. The outcome of pregnancy in women with cystic fibrosis: a UK population-based descriptive study. BJOG. 2020;127(13):1696–703. [DOI] [PubMed] [Google Scholar]
  • 31.Ahluwalia M, Hoag JB, Hadeh A, et al. Cystic fibrosis and pregnancy in the modern era: a case control study. J Cyst Fibros. 2014;13(1):69–73. [DOI] [PubMed] [Google Scholar]
  • 32.Gilljam M, Antoniou M, Shin J, et al. Pregnancy in cystic fibrosis. Fetal and maternal outcome. Chest. 2000;118(1):85–91. [DOI] [PubMed] [Google Scholar]
  • 33.McMullen AH, Pasta DJ, Frederick PD, et al. Impact of pregnancy on women with cystic fibrosis. Chest. 2006;129(3):706–11. [DOI] [PubMed] [Google Scholar]
  • 34.Thorpe-Beeston JG, Madge S, Gyi K, et al. The outcome of pregnancies in women with cystic fibrosis--single centre experience 1998–2011. BJOG. 2013;120(3):354–61. [DOI] [PubMed] [Google Scholar]
  • 35.Cohen-Cymberknoh M, Gindi Reiss B, Reiter J, et al. Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression. J Cyst Fibros. 2021;20(3):388–94. [DOI] [PubMed] [Google Scholar]
  • 36.National Center for Health Statistics. Health, United States, 2020–2019: Table Brth. Hyattsville, MD. 2020-2021. Available from: https://www.cdc.gov/nchs/hus/data-finder.htm [ [Google Scholar]
  • 37.Cystic Fibrosis Foundation Patient Registry. 2021. Annual Data Report, Bethesda, Maryland. ©2022 Cystic Fibrosis Foundation.
  • 38.Cystic Fibrosis Foundation Patient Registry. 2023. Highlights Report, Bethesda, Maryland. ©2023 Cystic Fibrosis Foundation.
  • 39.Heijerman HGM, McKone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394(10212):1940–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Middleton PG, Mall MA, Drevinek P, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381(19):1809–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. https://pi.vrtx.com/files/uspi_ivacaftor.pdf.
  • 42. https://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf.
  • 43. https://pi.vrtx.com/files/uspi_tezacaftor_ivacaftor.pdf.
  • 44. https://pi.vrtx.com/files/uspi_elexacaftor_tezacaftor_ivacaftor.pdf.
  • 45.Kaminski R, Nazareth D. A successful uncomplicated CF pregnancy while remaining on Ivacaftor. J Cyst Fibros. 2016;15(1):133–4. [DOI] [PubMed] [Google Scholar]
  • 46.Ladores S, Kazmerski TM, Rowe SM. A Case Report of Pregnancy During Use of Targeted Therapeutics for Cystic Fibrosis. J Obstet Gynecol Neonatal Nurs. 2017;46(1):72–7. [DOI] [PubMed] [Google Scholar]
  • 47.Vekaria S, Popowicz N, White SW, Mulrennan S. To be or not to be on CFTR modulators during pregnancy: Risks to be considered. J Cyst Fibros. 2020;19(2):e7–e8. [DOI] [PubMed] [Google Scholar]
  • 48.Trimble A, McKinzie C, Terrell M, et al. Measured fetal and neonatal exposure to Lumacaftor and Ivacaftor during pregnancy and while breastfeeding. J Cyst Fibros. 2018;17(6):779–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Mainz JG, Michl RK, Beiersdorf N, et al. Successful Pregnancy of a Patient with Cystic Fibrosis Genotype F508del/ F508del and Progressed Pulmonary Destruction on lumacaftor/ivacaftor. Klin Padiatr. 2019;231(5):271–3. [DOI] [PubMed] [Google Scholar]
  • 50. Collins B, Fortner C, Cotey A, et al. Drug exposure to infants born to mothers taking Elexacaftor, Tezacaftor, and Ivacaftor. J Cyst Fibros. 2022;21(4):725–7. *Limited data is available regarding the pharmacokinetics of CFTR modulators in females with CF who are pregnant. This paper highlights in 3 females with CF that elexacaftor/tezacaftor/ivacaftor passes through the placenta and into breastmilk and thus incites questions about the potential impact of this exposure on babies born to mothers with CF who take CFTR modulators during pregnancy.
  • 51.Gomez-Montes E, Salcedo Lobato E, Galindo A, et al. Prenatal cystic fibrosis transmembrane conductance regulator modulator therapy: A promising way to change the impact of cystic fibrosis. Fetal Diagn Ther. 2023. [DOI] [PubMed]
  • 52.Szentpetery S, Foil K, Hendrix S, et al. A case report of CFTR modulator administration via carrier mother to treat meconium ileus in a F508del homozygous fetus. J Cyst Fibros. 2022;21(4):721–4. [DOI] [PubMed] [Google Scholar]
  • 53.Nash EF, Middleton PG, Taylor-Cousar JL. Outcomes of pregnancy in women with cystic fibrosis (CF) taking CFTR modulators - an international survey. J Cyst Fibros. 2020;19(4):521–6. [DOI] [PubMed] [Google Scholar]
  • 54.Taylor-Cousar JL, Jain R. Maternal and fetal outcomes following elexacaftor-tezacaftor-ivacaftor use during pregnancy and lactation. J Cyst Fibros. 2021;20(3):402–6. [DOI] [PubMed] [Google Scholar]
  • 55.Jain R, Magaret A, Vu PT, et al. Prospectively evaluating maternal and fetal outcomes in the era of CFTR modulators: the MAYFLOWERS observational clinical trial study design. BMJ Open Respir Res. 2022;9(1). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Middleton PG, Gade EJ, Aguilera C, et al. ERS/TSANZ Task Force Statement on the management of reproduction and pregnancy in women with airways diseases. Eur Respir J. 2020;55(2). [DOI] [PubMed] [Google Scholar]
  • 57.Montemayor K, Tullis E, Jain R, Taylor-Cousar JL. Management of pregnancy in cystic fibrosis. Breathe (Sheff). 2022;18(2):220005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Kazmerski TM, Gmelin T, Slocum B, et al. Attitudes and Decision Making Related to Pregnancy Among Young Women with Cystic Fibrosis. Matern Child Health J. 2017;21(4):818–24. [DOI] [PubMed] [Google Scholar]
  • 59.Barker H, Moses J, O’Leary C. ‘I’ve got to prioritise’: being a parent with cystic fibrosis. Psychol Health Med. 2017;22(6):744–52. [DOI] [PubMed] [Google Scholar]
  • 60.Hailey CE, Tan JW, Dellon EP, Park EM. Pursuing parenthood with cystic fibrosis: Reproductive health and parenting concerns in individuals with cystic fibrosis. Pediatr Pulmonol. 2019;54(8):1225–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Jacob A, Journiac J, Fischer L, et al. How do cystic fibrosis patients experience parenthood? A systematic review. J Health Psychol. 2021;26(1):60–81. [DOI] [PubMed] [Google Scholar]
  • 62. Stransky OM, Benipal S, Pam M, et al. “Find ways to work parenting into cystic fibrosis”: A PhotoVoice exploration of being a parent and having CF. Pediatr Pulmonol. 2023;58(5):1527–34. *In order to understand the perspective of becoming a parent as a person with CF, investigators used a qualitative research method, PhotoVoice, to identify common themes experienced by parents with CF. The three methathemes regarding joy, balance and competing priorities can help guide clinician discussion with people with CF as they consider parenthood.
  • 63.Stransky OM, Pam M, Bernard M, Taylor-Cousar JL, and Kazmerski TM 2022.
  • 64.Dugueperoux I, Hubert D, Dominique S, et al. Paternity in men with cystic fibrosis: a retrospective survey in France. J Cyst Fibros. 2006;5(4):215–21. [DOI] [PubMed] [Google Scholar]
  • 65.Bianco B, Horsley A, Brennan A. Implications of fatherhood in cystic fibrosis. Paediatr Respir Rev. 2019;31:18–20. [DOI] [PubMed] [Google Scholar]
  • 66. Kazmerski TM, Jain R, Lee M, Taylor-Cousar JL. Parenthood impacts short-term health outcomes in people with cystic fibrosis. J Cyst Fibros. 2022;21(4):662–8. *Investigators used United KingdomCF registry data to evaluate the impact of being a parent on heath outcomes of males and females with CF. Among 296 people with CF who became paretnts, there was a significant decline in ppFEV and BMI and increase in pulmonary exacerbations one year after becoming a parent. The pulmonary changes were mitigated in the setting of CFTR modualtor use.
  • 67.Borrero S, Nikolajski C, Steinberg JR, et al. “It just happens”: a qualitative study exploring low-income women’s perspectives on pregnancy intention and planning. Contraception. 2015;91(2):150–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Callegari LS, Aiken AR, Dehlendorf C, et al. Addressing potential pitfalls of reproductive life planning with patient-centered counseling. Am J Obstet Gynecol. 2017;216(2):129–34. [DOI] [PubMed] [Google Scholar]
  • 69.Stransky OM, Pam M, Ladores SL, et al. Engaging Stakeholders in the Development of a Reproductive Goals Decision AID for Women with Cystic Fibrosis. J Patient Exp. 2022;9:23743735221077527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Kazmerski TM, Stransky OM, Wright CE, Pilewski J, Talabi MB, Callegari LS, Chang JC, Abebe KZ, Miller E, Deal A, O’Leary R, and Borrero S. Feasibility testing of a web-based reproductive decision support tool for cystic fibrosis. . Oral presentation at the American Thoracic Society Annual Meeting, Washington, DC.; 2023. [DOI] [PubMed] [Google Scholar]
  • 71.George C, Raymond KF, Collins L, et al. Partnership Enhancement Program: Piloting a Communication Training Program for Cystic Fibrosis Care Teams. J Patient Exp. 2021;8:23743735211014049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Stulberg DB, Datta A, White VanGompel E, et al. One Key Question(R) and the Desire to Avoid Pregnancy Scale: A comparison of two approaches to asking about pregnancy preferences. Contraception. 2020;101(4):231–6. [DOI] [PubMed] [Google Scholar]
  • 73.Roe AH, Yapalater S, Hadjiliadis D. Electronic health nudges to improve reproductive health care for women with cystic fibrosis. J Cyst Fibros. 2021;20(3):397–8. [DOI] [PubMed] [Google Scholar]

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