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A Case Report of Pregnancy During Use of Targeted Therapeutics for Cystic Fibrosis
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A Case Report of Pregnancy During Use of Targeted Therapeutics for Cystic Fibrosis Sigrid Ladores, Traci M. Kazmerski, and Steven M. Rowe
Correspondence Sigrid Ladores, PhD, RN, PNP, CNE, University of Alabama School of Nursing, 1720 2nd Ave. South, NB 304, Birmingham, AL 35294. [email protected]
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.
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Keywords cystic fibrosis fertility ivacaftor lumacaftor/ivacaftor sexual and reproductive health
Sigrid Ladores, PhD, RN, PNP, CNE, is an assistant professor in the School of Nursing, University of Alabama, Birmingham, AL. Traci M. Kazmerski, MD, MS, is a research fellow in the Division of Respiratory Diseases, Boston Children’s Hospital, Boston, MA. Steven M. Rowe, MD, MSPH, is a professor and Director of the Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
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Accepted August 2016
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ystic fibrosis (CF) is the most common genetic disorder among White people. More than 10 million people, 1 out of every 31 Americans, carries the defective gene, and 30,000 people are affected by this autosomal recessive disease (Cystic Fibrosis Foundation [CFF], 2016). The median predicted survival age for people with CF has steadily climbed since the disorder was first described in the 1930s, from 14 years in 1969 (FitzSimmons, 1993) to slightly more than 40 years currently (CFF, 2016). With significant advances in therapeutics and management, more than half of people currently living with CF are older than 18 years (CFF, 2016).
approved by the U.S. Food and Drug Administration in 2012 for use in those with 10 specific CFTR genetic mutations. It has been shown to significantly improve lung function and weight and reduce hospital admissions through potentiation of CFTR function (Rowe et al., 2014). Ivacaftor enhances mucociliary clearance, presumably because of improved airway hydration and changes in mucus viscosity (Birket et al., in press; Rowe et al., 2014). It has also been associated with substantial improvement in perceived symptoms (Ramsey et al., 2011; Rowe et al., 2014). The drug combination lumacaftor/ivacaftor was recently approved for the treatment of people homozygous for the F508del CFTR mutation. Approximately half of people with CF are homozygous for F508del CFTR (CFF, n.d.). Lumacaftor/ivacaftor combination treatment yielded positive effects on lung function, CF exacerbations, and weight gain (Wainwright et al., 2015). This combination drug’s ability to improve mucociliary clearance is currently being investigated in large multisite studies.
Steven Rowe serves as investigator for Vertex Pharmaceuticals on research contracts conducted at the University of Alabama at Birmingham that include the CFTR potentiator ivacaftor. The other authors report no conflicts of interest or relevant financial relationships.
CF and Targeted Therapeutics
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ª 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.
The underlying genetic cause of CF is a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), a membrane protein responsible for regulating the flow of ions into and out of cells. These gating abnormalities have profound effects on respiratory and gastrointestinal function for this multisystem disease.
Fertility and Pregnancy in CF New therapeutics targeting specific CFTR mutations have been developed. Ivacaftor was
Improved life expectancy and health outcomes have led to an increased number of women with CF
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Because of improved health outcomes, women with cystic fibrosis now face reproductive health decisions, including whether or not to have a child.
who face sexual and reproductive health decisions, including whether or not to have a child. Unfortunately, little is known about the effect of CF on fertility in women with the disease. Many mechanisms may limit the ability for a woman with CF to conceive (Edenborough, 2001; McArdle, 2011). Thicker cervical mucus may inhibit the motility of sperm in the female reproductive tract. Increased cervical mucus viscosity and reduced fertility have been shown in CF mouse models; however, this connection has not been substantiated in women with CF (Hodges, Palmert, & Drumm, 2008). Additionally, the increased adhesion of mucus in CF may be associated with altered bicarbonate transport (Birket et al., 2014; Hoegger et al., 2014). Because a bicarbonate-rich, or alkaline, pH is critical for optimal sperm motility and capacitation (Chan, Ruan, et al., 2009; Chan, Shi, et al., 2006; McArdle, 2011; Muchekehu & Quinton, 2010), the change in the pH of cervical mucus may also lead to impaired fertility. Other factors that may contribute to reduced fertility in women with severe CF disease include malnutrition and poor lung function (Edenborough, 2001; Lyon & Bilton, 2002; McArdle, 2011). Improved survival and overall health have led to major changes in pregnancy outcomes in women with CF (Chan, Ruan, et al., 2009). According to Lyon and Bilton (2002), the CF Foundation Patient Registry indicated that the number of women with CF who became pregnant had doubled in the last 20 years (116 pregnancies in 1992; 249 pregnancies in 2012; CFF, 2013). In the modern era, women with CF who become pregnant have been found to have similar changes in their respiratory function over time compared with nonpregnant women with CF; however, they require increased care compared with their nonpregnant CF maintenance (McMullen et al., 2006; Tonelli & Aitken, 2007). Long-term survival is not negatively affected by pregnancy, and outcomes for pregnant women with CF are improved compared with age-matched women with CF who do not become pregnant (Goss, Rubenfeld, Otto, & Aitken, 2003).
Targeted Therapeutics and Fertility Novel targeted medications, including ivacaftor and combination lumacaftor/ivacaftor, systematically alter the basic CFTR defect and may lead to positive changes in people with CF through
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improved mucus viscosity (Birket et al., 2014, in press; Rowe et al., 2014). The effects of these medications on female fertility were not studied during clinical trials; however, similar improvements in mucus viscosity may occur in the cervix and thus improve the opportunity for fertilization of the ovum through improved sperm motility (Jones & Walshaw, 2015). Although there is a potential for fertility benefit, the fetal effects of these medications are unknown. Although the effects of targeted therapeutics on female fertility in CF have not been studied, anecdotal reports describe a potential improvement in fertility in this population (Jones & Walshaw, 2015). In the case report that follows, we describe one woman’s experience with ivacaftor and her pregnancy. Implications related to the delivery of comprehensive sexual and reproductive health care to women with CF who are taking or considering ivacaftor or lumacaftor/ ivacaftor are also presented. Nurses who work with women with CF in various health care settings and specialties must be knowledgeable about the potential effects of new therapeutics on sexual and reproductive health to provide anticipatory guidance around pregnancy planning and reproductive decision making.
Case A 20-year-old White woman with pancreaticsufficient CF (G551D/c.1585-2A>G genotype) began to take ivacaftor shortly after it was approved by the U.S. Food and Drug Administration. She had a baseline forced expiratory volume in 1 second of 3.25 L, or 103% predicted, and a body mass index of 25.0 kg/m2. She had no hospitalizations in the previous year. She had a remote history of pancreatitis at age 16 years, which resolved after intravenous fluids and bowel rest. In the 2 years before she initiated ivacaftor, she was sexually active. She used drospirenone and ethinyl estradiol oral contraceptive pills (Yasmin) to prevent pregnancy. The woman discontinued oral contraceptive pills approximately 2 months after she initiated ivacaftor, but her sexual activity remained unchanged. Five months after initiating ivacaftor and approximately 3 months after stopping oral contraceptive pills, she became pregnant. She had not been pregnant in the past and had not intended to become pregnant at this time. After her positive pregnancy test result, she ceased taking ivacaftor. Given her normal body mass
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index and lung function, she did not experience clinical benefit as measured by change in forced expiratory volume in 1 second or weight. She denied any subjective changes in cough or sputum production during her time on the drug. At 15 weeks gestation, the woman was referred to a high-risk obstetrician because of her CF. She was diagnosed with gestational diabetes at 23 weeks gestation and was managed with diet modification and frequent glucose monitoring. She did not require medical intervention. At 34 weeks gestation, she began to experience upper abdominal pain in the setting of increased fatty foods in her diet. Her amylase level was elevated at 1,167 units/L (normal reference range ¼ 23–85 units/L) and her lipase level was 18,195 units/L (normal reference range ¼ 0–160 units/L). She was diagnosed with pancreatitis and was managed with intravenous fluids and bowel rest. Her amylase and lipase levels continued on a downward trend; she was admitted for 2 days, and then she was discharged home in stable condition.
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The woman gave birth to a healthy, 7 pound 14 ounce (3,570 g) male newborn via spontaneous vaginal birth at 40 and 2/7 weeks gestation. She was discharged home 48 hours after birth in stable condition. She resumed ivacaftor 5 weeks after birth and also resumed oral contraceptive pills (ethinyl estradiol and norgestimate [Ortho Tri-Cyclen]) because of a change in insurance. During her pregnancy, she was seen for routine follow-up in the CF center approximately every 8 to 12 weeks. She did not experience any changes in lung function and had no subjective respiratory symptoms. The woman provided informed consent for this report, and institutional review board approval for her interview responses was attained as part of a larger qualitative project. The woman shared her experience with ivacaftor and fertility/pregnancy in an audiotaped interview at age 23 years. Regarding her pregnancy, she described her perception that ivacaftor improved her fertility and linked it to her ability to become pregnant: “I do think it’s possible [that ivacaftor helped me become pregnant] because I know that along with all the other mucus in your body, your vaginal mucus can be thicker, and I know that [ivacaftor]. helps thin it out, so maybe it could help with the sperm.” The woman reported that she was concerned that women with CF might have impaired fertility and
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In this case report we document the experience of a woman with cystic fibrosis and the use of ivacaftor and perceived improved fertility.
was aware of potentially negative effects related to respiratory function during pregnancy. She clearly expressed the desire for her CF care team to warn her about the potential effect of ivacaftor treatment on her fertility and fetal health during pregnancy. She urged health care providers to start the conversation about fertility and pregnancy “before they start [any new drugs] just because if the girl doesn’t take birth control. then [it] would be something that she would think about. A female patient should be talked to about pregnancy with any medication.”
Discussion In this case report we document the experience of a young woman with CF and the use of ivacaftor and perceived improved fertility. Despite the lack of clear evidence regarding the role of ivacaftor versus the cessation of oral contraceptive pills leading to unintended pregnancy in this case, it highlights the critical need to provide comprehensive care to women of childbearing age with CF, including sensitive and thorough discussion about fertility and sexual and reproductive health in this era of targeted therapeutics. In light of potential effects of novel therapies on fertility and increasing pregnancy rates, this case report highlights several implications for improved care delivery for the expanding population of women with CF of childbearing age.
The Need for Comprehensive Sexual and Reproductive Health Education As more women with CF face childbearing and reproductive health decisions, comprehensive sexual and reproductive health education and care are needed. Women with CF desire routine discussions with their CF providers about disease-specific sexual and reproductive health concerns (Kazmerski, Borrero, et al., 2016). CF is a major factor in pregnancy decision making for women with this disease. Authors of a qualitative study of 18- to 30-year-old women with CF found that, although many believed that CF may make pregnancy difficult, most women desired a sense of “normalcy” around reproductive decisions despite having CF. In that study, women also expressed confusion about the ways in which CF
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Nurses play a vital role in educating women with cystic fibrosis about the potential effects of targeted therapeutics on fertility and unknown teratogenic consequences.
directly affects fertility and pregnancy and were dissatisfied with the lack of communication with the CF team about these topics (Kazmerski, Gmelin, Slocum, Borrero, & Miller, 2016). Given the effect of sexual and reproductive health information on reproductive decisions and the evolving nature of reproductive choices with time, anticipatory guidance related to these issues should be provided around puberty and revisited regularly during clinic visits for women with CF. In addition, preconception counseling and care are crucial in light of the implications of CF during pregnancy and before initiating a new medication with unknown fetal effects. The American College of Obstetricians and Gynecologists (2005) recommended that clinicians encourage all female adolescents and women of childbearing age to formulate reproductive health plans and discuss them at each visit. This discussion can provide opportunities for optimization of a woman’s health and for education about pregnancy. With a chronic disease such as CF, these opportunities are vital. Preconception and general sexual and reproductive health care provision in women with CF may be especially critical, because authors of previous literature have shown increased rates of use of less effective contraceptive methods, such as natural family planning, in this population (Gatiss, Mansour, Doe, & Bourke, 2009; Plant et al., 2008). A recent study found that only 49% of sexually active women with CF ages 18 through 45 years were using contraception compared with 65% of women in the general U.S. population (Roe, Traxler, Hadjiliadis, & Schreiber, 2015). In addition to contraceptive choice, nearly one quarter of pregnancies reported in this study were terminated because of being unintended or secondary to deteriorating maternal health status. With these results in mind, education about fertility and sexual and reproductive health is recommended for women with CF (Edenborough et al., 2008). Nurses and advanced practice nurses who work as part of the CF care team or research team are well-positioned to provide critical education on this important issue. Improved sexual and reproductive health education can allow women to make fully informed
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decisions regarding contraceptive choices that are in line with their own reproductive preferences and goals.
The Need for Education and Research on the Effects of CF-Targeted Therapeutics on Fertility and the Fetus Through our report detailing a woman’s perception of improved fertility secondary to ivacaftor therapy and her resulting unintended pregnancy, we not only raise the need for general comprehensive sexual and reproductive health education for all women of childbearing age with CF but also highlight the importance of preconception counseling when initiating a new medication with unknown fetal effects. In all women of childbearing age, the risks and benefits related to taking such a medication should be carefully discussed before initiation and routinely reviewed as a woman’s individual reproductive plans change. Because there are also risks associated with pregnancy in women with CF and severe lung disease, women and their CF providers should discuss the clinical benefits of CFTR modulator therapy and weigh them against the potential risks to the fetus. Additionally, future research focused on the sexual and reproductive health and fetal effects of new CF therapeutics is crucial. Studies investigating the viscosity and penetrability to sperm of cervical mucus in response to CFTR modulator therapy may help inform women about the fertility effects. This includes postmarketing research on the extant U.S. Food and Drug Administration– approved medications ivacaftor and lumacaftor/ ivacaftor. This is vital, because many people homozygous for F508del are now beginning combination therapy with lumacaftor/ivacaftor.
The Role of the Nurse Nurses on the CF care team provide important sexual and reproductive health care to women with CF. Registered nurses and advanced practice nurses can play a vital role in educating women with CF about the potential effects of targeted therapeutics on fertility and unknown teratogenic consequences. Nurses can routinely partner with and engage women in discussions around their reproductive wishes and goals. Nurses can be advocates for women who may choose to delay initiation of these new drugs if they have immediate plans to conceive. Nurses
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can act as liaisons between CF physicians and women to promote optimal sexual and reproductive health communication as they collaborate on the best plan of care for each woman with CF.
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transmembrane regulator modulators alter functional microanatomical parameters of the airway epithelium. American Journal
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Additionally, nurses who work with childbearing women (i.e., in obstetric and gynecologic clinics and ante-, intra-, and postpartum hospital units) should be knowledgeable about CF-specific fertility and sexual and reproductive health concerns. Care of women with CF in these specialty settings is complicated because of the multisystem nature of the disease. Nurses should be able to identify and anticipate any potential problems that may arise during preconception, pregnancy, and birth, especially in this era of personalized medicine and targeted therapeutics. Lastly, nurse researchers, as part of a multidisciplinary team, should develop projects to study the effects of new therapeutics on female fertility and fetal outcomes. For new drugs that may be widely used in women of childbearing age, it is critical that data on these two key variables be collected, tracked, and reported.
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Conclusion
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The era of personalized medicine has arrived, and its tremendous effect is seen in genetic diseases like CF. Women with CF are living well into adulthood and are able to successfully integrate their disease into their daily lives. New, targeted therapeutics provide hope for women with CF. However, caution should be exercised because there are no clear data on their effects on fertility or the fetus. In this case report we described how a young woman with CF linked her unintended pregnancy to ivacaftor. Nurses who care for women with CF across various health care settings can anticipate the potential needs of these women and provide comprehensive sexual and reproductive health care and education to achieve healthy outcomes similar to the experience of the woman in this case report.
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A Case Report of Pregnancy During Use of Targeted Therapeutics for Cystic Fibrosis Sigrid Ladores, Traci M. Kazmerski, and Steven M. Rowe
Correspondence Sigrid Ladores, PhD, RN, PNP, CNE, University of Alabama School of Nursing, 1720 2nd Ave. South, NB 304, Birmingham, AL 35294. [email protected]
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.
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Keywords cystic fibrosis fertility ivacaftor lumacaftor/ivacaftor sexual and reproductive health
Sigrid Ladores, PhD, RN, PNP, CNE, is an assistant professor in the School of Nursing, University of Alabama, Birmingham, AL. Traci M. Kazmerski, MD, MS, is a research fellow in the Division of Respiratory Diseases, Boston Children’s Hospital, Boston, MA. Steven M. Rowe, MD, MSPH, is a professor and Director of the Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
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Accepted August 2016
C
ystic fibrosis (CF) is the most common genetic disorder among White people. More than 10 million people, 1 out of every 31 Americans, carries the defective gene, and 30,000 people are affected by this autosomal recessive disease (Cystic Fibrosis Foundation [CFF], 2016). The median predicted survival age for people with CF has steadily climbed since the disorder was first described in the 1930s, from 14 years in 1969 (FitzSimmons, 1993) to slightly more than 40 years currently (CFF, 2016). With significant advances in therapeutics and management, more than half of people currently living with CF are older than 18 years (CFF, 2016).
approved by the U.S. Food and Drug Administration in 2012 for use in those with 10 specific CFTR genetic mutations. It has been shown to significantly improve lung function and weight and reduce hospital admissions through potentiation of CFTR function (Rowe et al., 2014). Ivacaftor enhances mucociliary clearance, presumably because of improved airway hydration and changes in mucus viscosity (Birket et al., in press; Rowe et al., 2014). It has also been associated with substantial improvement in perceived symptoms (Ramsey et al., 2011; Rowe et al., 2014). The drug combination lumacaftor/ivacaftor was recently approved for the treatment of people homozygous for the F508del CFTR mutation. Approximately half of people with CF are homozygous for F508del CFTR (CFF, n.d.). Lumacaftor/ivacaftor combination treatment yielded positive effects on lung function, CF exacerbations, and weight gain (Wainwright et al., 2015). This combination drug’s ability to improve mucociliary clearance is currently being investigated in large multisite studies.
Steven Rowe serves as investigator for Vertex Pharmaceuticals on research contracts conducted at the University of Alabama at Birmingham that include the CFTR potentiator ivacaftor. The other authors report no conflicts of interest or relevant financial relationships.
CF and Targeted Therapeutics
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ª 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.
The underlying genetic cause of CF is a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), a membrane protein responsible for regulating the flow of ions into and out of cells. These gating abnormalities have profound effects on respiratory and gastrointestinal function for this multisystem disease.
Fertility and Pregnancy in CF New therapeutics targeting specific CFTR mutations have been developed. Ivacaftor was
Improved life expectancy and health outcomes have led to an increased number of women with CF
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Because of improved health outcomes, women with cystic fibrosis now face reproductive health decisions, including whether or not to have a child.
who face sexual and reproductive health decisions, including whether or not to have a child. Unfortunately, little is known about the effect of CF on fertility in women with the disease. Many mechanisms may limit the ability for a woman with CF to conceive (Edenborough, 2001; McArdle, 2011). Thicker cervical mucus may inhibit the motility of sperm in the female reproductive tract. Increased cervical mucus viscosity and reduced fertility have been shown in CF mouse models; however, this connection has not been substantiated in women with CF (Hodges, Palmert, & Drumm, 2008). Additionally, the increased adhesion of mucus in CF may be associated with altered bicarbonate transport (Birket et al., 2014; Hoegger et al., 2014). Because a bicarbonate-rich, or alkaline, pH is critical for optimal sperm motility and capacitation (Chan, Ruan, et al., 2009; Chan, Shi, et al., 2006; McArdle, 2011; Muchekehu & Quinton, 2010), the change in the pH of cervical mucus may also lead to impaired fertility. Other factors that may contribute to reduced fertility in women with severe CF disease include malnutrition and poor lung function (Edenborough, 2001; Lyon & Bilton, 2002; McArdle, 2011). Improved survival and overall health have led to major changes in pregnancy outcomes in women with CF (Chan, Ruan, et al., 2009). According to Lyon and Bilton (2002), the CF Foundation Patient Registry indicated that the number of women with CF who became pregnant had doubled in the last 20 years (116 pregnancies in 1992; 249 pregnancies in 2012; CFF, 2013). In the modern era, women with CF who become pregnant have been found to have similar changes in their respiratory function over time compared with nonpregnant women with CF; however, they require increased care compared with their nonpregnant CF maintenance (McMullen et al., 2006; Tonelli & Aitken, 2007). Long-term survival is not negatively affected by pregnancy, and outcomes for pregnant women with CF are improved compared with age-matched women with CF who do not become pregnant (Goss, Rubenfeld, Otto, & Aitken, 2003).
Targeted Therapeutics and Fertility Novel targeted medications, including ivacaftor and combination lumacaftor/ivacaftor, systematically alter the basic CFTR defect and may lead to positive changes in people with CF through
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improved mucus viscosity (Birket et al., 2014, in press; Rowe et al., 2014). The effects of these medications on female fertility were not studied during clinical trials; however, similar improvements in mucus viscosity may occur in the cervix and thus improve the opportunity for fertilization of the ovum through improved sperm motility (Jones & Walshaw, 2015). Although there is a potential for fertility benefit, the fetal effects of these medications are unknown. Although the effects of targeted therapeutics on female fertility in CF have not been studied, anecdotal reports describe a potential improvement in fertility in this population (Jones & Walshaw, 2015). In the case report that follows, we describe one woman’s experience with ivacaftor and her pregnancy. Implications related to the delivery of comprehensive sexual and reproductive health care to women with CF who are taking or considering ivacaftor or lumacaftor/ ivacaftor are also presented. Nurses who work with women with CF in various health care settings and specialties must be knowledgeable about the potential effects of new therapeutics on sexual and reproductive health to provide anticipatory guidance around pregnancy planning and reproductive decision making.
Case A 20-year-old White woman with pancreaticsufficient CF (G551D/c.1585-2A>G genotype) began to take ivacaftor shortly after it was approved by the U.S. Food and Drug Administration. She had a baseline forced expiratory volume in 1 second of 3.25 L, or 103% predicted, and a body mass index of 25.0 kg/m2. She had no hospitalizations in the previous year. She had a remote history of pancreatitis at age 16 years, which resolved after intravenous fluids and bowel rest. In the 2 years before she initiated ivacaftor, she was sexually active. She used drospirenone and ethinyl estradiol oral contraceptive pills (Yasmin) to prevent pregnancy. The woman discontinued oral contraceptive pills approximately 2 months after she initiated ivacaftor, but her sexual activity remained unchanged. Five months after initiating ivacaftor and approximately 3 months after stopping oral contraceptive pills, she became pregnant. She had not been pregnant in the past and had not intended to become pregnant at this time. After her positive pregnancy test result, she ceased taking ivacaftor. Given her normal body mass
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index and lung function, she did not experience clinical benefit as measured by change in forced expiratory volume in 1 second or weight. She denied any subjective changes in cough or sputum production during her time on the drug. At 15 weeks gestation, the woman was referred to a high-risk obstetrician because of her CF. She was diagnosed with gestational diabetes at 23 weeks gestation and was managed with diet modification and frequent glucose monitoring. She did not require medical intervention. At 34 weeks gestation, she began to experience upper abdominal pain in the setting of increased fatty foods in her diet. Her amylase level was elevated at 1,167 units/L (normal reference range ¼ 23–85 units/L) and her lipase level was 18,195 units/L (normal reference range ¼ 0–160 units/L). She was diagnosed with pancreatitis and was managed with intravenous fluids and bowel rest. Her amylase and lipase levels continued on a downward trend; she was admitted for 2 days, and then she was discharged home in stable condition.
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The woman gave birth to a healthy, 7 pound 14 ounce (3,570 g) male newborn via spontaneous vaginal birth at 40 and 2/7 weeks gestation. She was discharged home 48 hours after birth in stable condition. She resumed ivacaftor 5 weeks after birth and also resumed oral contraceptive pills (ethinyl estradiol and norgestimate [Ortho Tri-Cyclen]) because of a change in insurance. During her pregnancy, she was seen for routine follow-up in the CF center approximately every 8 to 12 weeks. She did not experience any changes in lung function and had no subjective respiratory symptoms. The woman provided informed consent for this report, and institutional review board approval for her interview responses was attained as part of a larger qualitative project. The woman shared her experience with ivacaftor and fertility/pregnancy in an audiotaped interview at age 23 years. Regarding her pregnancy, she described her perception that ivacaftor improved her fertility and linked it to her ability to become pregnant: “I do think it’s possible [that ivacaftor helped me become pregnant] because I know that along with all the other mucus in your body, your vaginal mucus can be thicker, and I know that [ivacaftor]. helps thin it out, so maybe it could help with the sperm.” The woman reported that she was concerned that women with CF might have impaired fertility and
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In this case report we document the experience of a woman with cystic fibrosis and the use of ivacaftor and perceived improved fertility.
was aware of potentially negative effects related to respiratory function during pregnancy. She clearly expressed the desire for her CF care team to warn her about the potential effect of ivacaftor treatment on her fertility and fetal health during pregnancy. She urged health care providers to start the conversation about fertility and pregnancy “before they start [any new drugs] just because if the girl doesn’t take birth control. then [it] would be something that she would think about. A female patient should be talked to about pregnancy with any medication.”
Discussion In this case report we document the experience of a young woman with CF and the use of ivacaftor and perceived improved fertility. Despite the lack of clear evidence regarding the role of ivacaftor versus the cessation of oral contraceptive pills leading to unintended pregnancy in this case, it highlights the critical need to provide comprehensive care to women of childbearing age with CF, including sensitive and thorough discussion about fertility and sexual and reproductive health in this era of targeted therapeutics. In light of potential effects of novel therapies on fertility and increasing pregnancy rates, this case report highlights several implications for improved care delivery for the expanding population of women with CF of childbearing age.
The Need for Comprehensive Sexual and Reproductive Health Education As more women with CF face childbearing and reproductive health decisions, comprehensive sexual and reproductive health education and care are needed. Women with CF desire routine discussions with their CF providers about disease-specific sexual and reproductive health concerns (Kazmerski, Borrero, et al., 2016). CF is a major factor in pregnancy decision making for women with this disease. Authors of a qualitative study of 18- to 30-year-old women with CF found that, although many believed that CF may make pregnancy difficult, most women desired a sense of “normalcy” around reproductive decisions despite having CF. In that study, women also expressed confusion about the ways in which CF
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Nurses play a vital role in educating women with cystic fibrosis about the potential effects of targeted therapeutics on fertility and unknown teratogenic consequences.
directly affects fertility and pregnancy and were dissatisfied with the lack of communication with the CF team about these topics (Kazmerski, Gmelin, Slocum, Borrero, & Miller, 2016). Given the effect of sexual and reproductive health information on reproductive decisions and the evolving nature of reproductive choices with time, anticipatory guidance related to these issues should be provided around puberty and revisited regularly during clinic visits for women with CF. In addition, preconception counseling and care are crucial in light of the implications of CF during pregnancy and before initiating a new medication with unknown fetal effects. The American College of Obstetricians and Gynecologists (2005) recommended that clinicians encourage all female adolescents and women of childbearing age to formulate reproductive health plans and discuss them at each visit. This discussion can provide opportunities for optimization of a woman’s health and for education about pregnancy. With a chronic disease such as CF, these opportunities are vital. Preconception and general sexual and reproductive health care provision in women with CF may be especially critical, because authors of previous literature have shown increased rates of use of less effective contraceptive methods, such as natural family planning, in this population (Gatiss, Mansour, Doe, & Bourke, 2009; Plant et al., 2008). A recent study found that only 49% of sexually active women with CF ages 18 through 45 years were using contraception compared with 65% of women in the general U.S. population (Roe, Traxler, Hadjiliadis, & Schreiber, 2015). In addition to contraceptive choice, nearly one quarter of pregnancies reported in this study were terminated because of being unintended or secondary to deteriorating maternal health status. With these results in mind, education about fertility and sexual and reproductive health is recommended for women with CF (Edenborough et al., 2008). Nurses and advanced practice nurses who work as part of the CF care team or research team are well-positioned to provide critical education on this important issue. Improved sexual and reproductive health education can allow women to make fully informed
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decisions regarding contraceptive choices that are in line with their own reproductive preferences and goals.
The Need for Education and Research on the Effects of CF-Targeted Therapeutics on Fertility and the Fetus Through our report detailing a woman’s perception of improved fertility secondary to ivacaftor therapy and her resulting unintended pregnancy, we not only raise the need for general comprehensive sexual and reproductive health education for all women of childbearing age with CF but also highlight the importance of preconception counseling when initiating a new medication with unknown fetal effects. In all women of childbearing age, the risks and benefits related to taking such a medication should be carefully discussed before initiation and routinely reviewed as a woman’s individual reproductive plans change. Because there are also risks associated with pregnancy in women with CF and severe lung disease, women and their CF providers should discuss the clinical benefits of CFTR modulator therapy and weigh them against the potential risks to the fetus. Additionally, future research focused on the sexual and reproductive health and fetal effects of new CF therapeutics is crucial. Studies investigating the viscosity and penetrability to sperm of cervical mucus in response to CFTR modulator therapy may help inform women about the fertility effects. This includes postmarketing research on the extant U.S. Food and Drug Administration– approved medications ivacaftor and lumacaftor/ ivacaftor. This is vital, because many people homozygous for F508del are now beginning combination therapy with lumacaftor/ivacaftor.
The Role of the Nurse Nurses on the CF care team provide important sexual and reproductive health care to women with CF. Registered nurses and advanced practice nurses can play a vital role in educating women with CF about the potential effects of targeted therapeutics on fertility and unknown teratogenic consequences. Nurses can routinely partner with and engage women in discussions around their reproductive wishes and goals. Nurses can be advocates for women who may choose to delay initiation of these new drugs if they have immediate plans to conceive. Nurses
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can act as liaisons between CF physicians and women to promote optimal sexual and reproductive health communication as they collaborate on the best plan of care for each woman with CF.
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transmembrane regulator modulators alter functional microanatomical parameters of the airway epithelium. American Journal
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of Physiology–Lung. Chan, H. C., Ruan, Y. C., He, Q., Chen, M. H., Chen, H., Xu, W. M., … Zhou, Z. (2009). The cystic fibrosis transmembrane conductance regulator in reproductive health and disease. Journal of
Additionally, nurses who work with childbearing women (i.e., in obstetric and gynecologic clinics and ante-, intra-, and postpartum hospital units) should be knowledgeable about CF-specific fertility and sexual and reproductive health concerns. Care of women with CF in these specialty settings is complicated because of the multisystem nature of the disease. Nurses should be able to identify and anticipate any potential problems that may arise during preconception, pregnancy, and birth, especially in this era of personalized medicine and targeted therapeutics. Lastly, nurse researchers, as part of a multidisciplinary team, should develop projects to study the effects of new therapeutics on female fertility and fetal outcomes. For new drugs that may be widely used in women of childbearing age, it is critical that data on these two key variables be collected, tracked, and reported.
Physiology, 587(Pt. 10), 2187–2195. http://dx.doi.org/10.1113/ jphysiol.2008.164970 Chan, H. C., Shi, Q. X., Zhou, C. X., Wang, X. F., Xu, W. M., Chen, W. Y., … Yuan, Y. Y. (2006). Critical role of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Molecular and Cellular Endocrinology, 250(1–2), 106–113. http://dx.doi.org/10. 1016/j.mce.2005.12.032 Cystic Fibrosis Foundation. (n.d.). CFTR modulator basics. Retrieved from https://www.cff.org/Living-with-CF/Treatments-and-Therapies/ CFTR-Modulators/CFTR-Modulator-Basics/ Cystic Fibrosis Foundation. (2013). Cystic fibrosis foundation patient registry: 2012 annual data report. Retrieved from http://www. cysticfibrosisdata.org/ReportsUS.html Cystic Fibrosis Foundation. (2016). About cystic fibrosis. Retrieved from https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/ Edenborough, F. (2001). Women with cystic fibrosis and their potential for reproduction. Thorax, 56(8), 649–655. http://doi.org/10. 1136/thorax.56.8.649 Edenborough, F. P., Borgo, G., Knoop, C., Lannefors, L., Mackenzie, W. E., Madge, S., … Johannesson, M. (2008). Guidelines for the management of pregnancy in women with cystic fibrosis. Journal of Cystic Fibrosis, 7(Suppl. 1), S2–S32. http://dx.doi. org/10.1016/j.jcf.2007.10.001 FitzSimmons, S. C. (1993). The changing epidemiology of cystic fibrosis. Journal of Pediatrics, 122(1), 1–9. http://dx.doi.org/10.
Conclusion
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The era of personalized medicine has arrived, and its tremendous effect is seen in genetic diseases like CF. Women with CF are living well into adulthood and are able to successfully integrate their disease into their daily lives. New, targeted therapeutics provide hope for women with CF. However, caution should be exercised because there are no clear data on their effects on fertility or the fetus. In this case report we described how a young woman with CF linked her unintended pregnancy to ivacaftor. Nurses who care for women with CF across various health care settings can anticipate the potential needs of these women and provide comprehensive sexual and reproductive health care and education to achieve healthy outcomes similar to the experience of the woman in this case report.
Gatiss, S., Mansour, D., Doe, S., & Bourke, S. (2009). Provision of contraception services and advice for women with cystic fibrosis. Health
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