Infertility’s Impact on Women’s Lives

Many women express the desire to procreate. Those with CF are no exception. However, some women might find that embarking on that journey might be a little bit more complicated. For women with or without CF, infertility can be unsettling. As with any significant loss, individuals who learn they are infertile often experience a range of emotions, including shock, grief, depression, anger, frustration, a loss of self-esteem or self-confidence, and a sense of having no control over one’s destiny [1].

Adding to this picture, however, is that patients with CF are 2-3 times more likely than the general population to report depression and anxiety, with or without infertility; a subset of this group experiences anxiety specific to medical procedures [2]. Fertility treatment adds new high-stakes, medical procedures and encounters for patients with CF. When females with CF undergo fertility treatment, there is the added burden of additional doctor’s appointments, blood draws, and invasive testing. Appointments are usually first thing in the early morning so that medications can be tweaked for the day, if needed. These early appointments mean that women with CF may face additional pressures to get their treatments done early, eat breakfast, take medications, and get out the door to get to the fertility clinic on time. A patient’s ability to adhere to CF medical regimens may be compromised while undergoing fertility treatments; CF providers should acknowledge and support their patients to maximize their ability to fulfill their CF treatments.

Typical Steps for Diagnosing Infertility

Infertility is customarily defined as the inability to conceive after 1 year of regular unprotected intercourse. Women typically seek an infertility evaluation by a fertility specialist after this initial year if they cannot conceive. In some cases, a physician may tell a woman to get evaluated for infertility after they cannot conceive after 6 months, but this is primarily done on a case-by-case basis. In couples where the female with CF is over the age of 35, however, most practitioners initiate a diagnostic evaluation after a couple cannot conceive after 6 months [7]. 

There are several recommended steps involved for a basic infertility evaluation, detailed in the graphic. A reproductive endocrinologist typically orders or performs this evaluation, although some OB/GYNs may order some testing on their own. For women in partnered relationships, it is helpful for both partners to attend the initial appointments at the fertility clinic. Both partners will likely need to undergo testing to try to determine the cause of infertility and to assess both partners’ reproductive health. Though rarely needed, a fertility provider may also order a laparoscopy so they can visually examine  the patient’s pelvic anatomy and identify possible endometriosis or pelvic adhesions [7]. 

If testing reveals there is a fertility issue, or if the couple has been unable to conceive for a minimum of 6-12 months, then the provider will typically offer any available treatment options to enable them to pursue pregnancy. Fertility specialists may also recommend genetic testing to determine if both partners are CF carriers at the time of the initial evaluation or before any fertility treatment commences, particularly if the non-CF partner has not completed genetic testing prior to this time. 

What Treatments are Available

Special Fertility Treatment Considerations for Women with CF

• • Even with the presence of thick cervical mucus, the physician should still be able to transfer the embryo in an IVF procedure [13]. Some reproductive endocrinologists will choose to perform a “mock transfer” ahead of the real procedure, to enable a clear path to the woman’s uterus. 
  • Achieving pregnancy through IVF poses additional hazards for women with CF or patients who have a transplant. For one, the medications doctors give to stimulate the ovaries to produce eggs may result in ovarian hyperstimulation syndrome, which can, in turn, cause severe respiratory compromise. To prevent this possibility, physicians can prescribe a gentle stimulation regimen, closely monitor the woman’s treatment cycle, and establish a low threshold for cancelling that cycle. Second, since multiple pregnancy is associated with increased maternal complications, it should ideally be avoided if the patient has CF. A multiple pregnancy (with twins, triplets, or more) increases the size of the uterus which can lead to respiratory compromise for the carrier. If a multiple pregnancy does arise, the woman may need to seriously consider selective reduction (termination) to carry only one baby in the pregnancy. The fertility specialist, the obstetrics care provider, the CF physician, and the patient should communicate regularly to ensure that these issues are addressed [14,15].   

• Many women with CF wonder if pursuing infertility treatment might affect their pulmonary and overall health status but there is no research that explores these concerns. 

• To learn what to expect while pregnant with CF, read the Pregnancy chapter in this guide.

Surrogacy 

Surrogacy is an option for women with CF, and for many women, the same IVF process described above can be used to create embryos for surrogacy. A woman with CF may want to consider surrogacy if she has the ability to create embryos through IVF, but does not want to or is not physically healthy enough to carry a pregnancy [see the Family Building chapter for CF-specific considerations for surrogacy]. When considering this option, it is important that the woman understand her state’s surrogacy laws before she starts. A woman with CF might first ask her fertility doctor for recommendations on how to secure a surrogate. She may also reach out to family and close friends to find a volunteer surrogate prior to looking into surrogate agencies. If a surrogate is located nearby, attending appointments and arranging to be at the hospital for delivery might be much easier. Further, a surrogacy lawyer is required both for the intended parents and the surrogate to complete the process; hiring a lawyer avoids legal issues between the prospective parent(s) and the surrogate. The prospective parent(s) and surrogate can decide, before entering into such a contract, whether either party can post on social media, how much the prospective parents will pay for necessities and pampering, and whether medical costs will be covered through an insurance plan or out of pocket. 

Prospective parents will also need to create a birth plan with the surrogate. The intended parents can do a hospital tour to become comfortable with the birth plan; they should tell the hospital staff about the surrogacy arrangement before the birth. The woman with CF might want to share with the hospital staff that she has CF so they know to keep things extra-sanitary. The prospective parent(s) may be able to detail who will be in the room during the birth and can talk to the hospital about potential plans for after the delivery. In addition, before the baby is born, the prospective parent(s) and surrogate may discuss whether or not the surrogate will attempt to pump breast milk.

What Treatments are Available

The Impact of Modulators on Infertility

With modulator therapy, a “modulator baby boom” is underway.18 Modulators have certainly affected female fertility.18 A study by Corcoran, Campbell, and Ladores about providers’ perspectives on fertility and fertility preservation reported that half of their participants had witnessed an increase in pregnancies since their patients started HEMT.[18[ 

These observations are confirmed in the data reported in the CF Foundation’s Patient Registry. In 2019, there were 310 pregnancies, which was an increase attributed to improved medical care; in 2021, after many women began HEMT, the registry reported 675 pregnancies and a rise in unplanned pregnancies.[19,20] To address the knowledge gap about modulators and fertility, the CF Foundation Therapeutics Development Network is undertaking a cohort study to evaluate the impact of CFTR modulators on women’s fertility. [See also Pregnancy chapter in this guide]. 

Kazmerski et al. have noted: “[a] 2005 Australian survey found that 84% of men with CF wanted children, whereas a 2018 survey found that 78% of adolescent and young adult women with CF in the United States intended to become parents.”[21] Given these desires, CF clinics need to integrate comprehensive, age-appropriate discussions about family planning, including contraception and discussions about fertility and infertility, into CF care.[21] 

For men, infertility remains at approximately 98% due to congenital bilateral absence of the vas deferens (CBAVD) and other conditions; these conditions are not affected by HEMT.[20–22] However, men generally have sperm that can be retrieved, and there are several different reproductive technologies available to them that can assist.[20–22] (See Male Health and CF chapter).

Though there is excitement about the effects of modulator therapy on fertility in women, people who do not take modulators because of their side effects or because they do not have the mutations that current modulators can treat may feel left behind. About 10% of people with CF are not eligible for HEMT because of their genotype, and this population is disproportionately Black, Asian, or other minority ethnicities.[20,23] This disparity in access to HEMT may disproportionately affect the fertility of ethnic minorities.

Reworking Clinic Care with Increasing CF Reproductive Needs

Our Patient Task Force (PTF) session on (In)fertility (3.26.2020) revealed that providers who discuss reproductive issues with patients often react to patients’ inquiries, rather than proactively seek out such conversations [17]. Providers typically discuss reproductive issues after an initial discussion with the parents of a recently diagnosed child with CF [14].  Since CF-related concerns often consume the entire clinic visit, providers have infrequent opportunities to address important reproductive issues, like fertility. Sometimes they raise the topic when a woman’s reproductive plans and decisions are less salient in the patient’s life [14]. Our PTF discussions also revealed that women with CF may underestimate the degree to which they are fertile, and so they may not use reliable methods of birth control. Our dialogue confirmed that women with CF need more accurate information about their potential fertility from their providers [2].

Indeed, part of ensuring optimal sexual and reproductive health (SRH) care for females with CF is making sure that they receive adequate education and health care before attempting to become pregnant. However, many studies show that young women with CF, in particular, have lower rates of SRH education, fewer rates of screening for STIs, fewer cervical cancer screenings, and fewer pelvic exams.24 Existing research has found that older adolescent and young adult women with CF prefer to have their healthcare providers begin the discussion about family planning and fertility. Older women with CF, however, prefer to bring up the topic themselves.21 Regardless, females want discussions about fertility and family planning to be tailored to their specific CF needs. Reproductive endocrinologists, high-risk OB/GYNS, and other specialists are generally not part of the CF center care team, leading to fragmented care.21  In addition, healthcare providers outside of the CF center are not likely to have much knowledge of the drugs used by CF patients, including HEMT.21

Mental Health

Though improved therapies and management have lengthened the lives of people with CF and made having children possible, grappling with fertility and infertility can still be a difficult journey. Mental health concerns during this stage of people’s lives, therefore, need special consideration. Kazmerski et al. note that “[i]nfertility or pregnancy loss may result in stress, anxiety, or depression for both men and women.”[21]  For men and women struggling with infertility or other reproductive concerns, the more complicated paths to parenthood can induce feelings of grief and loss, can impact their relationships, and can raise concerns about what to disclose to their families.[21] Adoption with a serious chronic disease, for instance, can be a tremendous source of anxiety.[25]    

Sometimes, the CF clinic itself can be a source of anxiety during the time in which a person with CF negotiates family planning.  Because sexual and reproductive health discussions and care are not yet fully integrated into the CF clinic setting, many patients face additional healthcare appointments with specialists and many efforts to educate them.[26] Kazmerski et al. note that patients sometimes experience disapproval from their CF care team when they express a desire to start a family. This was cited as a source of stress for these patients.[21] To be sure, transgender and gender-diverse CF patients may face additional challenges in getting appropriate support in their fertility journey but deserve the same level of care.[21] 

Currently, there is minimal consensus on the best practices to help CF patients and families cope with such stressors.[21,25]  Equally important, there is not enough research on the psychological needs of  LGBTQIA+ people with CF or people of color with CF and their family-building journeys.[21,23]  In the era of HEMT, it has become evident that patients need psychosocial care and support at every stage of their lives, especially during those years when they are dealing with fertility or infertility concerns and when they become parents.