Research shows that 97% to 98% of males with cystic fibrosis (CF) are infertile. Though the genetic disease impacts the reproductive organs in various ways, it is still possible to have biological children with the help of assisted reproductive technology (ART). This article will discuss what causes cystic fibrosis, how cystic fibrosis can affect fertility, and the different treatment options available for conceiving with cystic fibrosis.
What is cystic fibrosis?
Cystic fibrosis is an inherited disease that affects the body’s cells, tissues, and glands, causing damage to the lungs, digestive system, and other organs in the body.
Targeting the cells that produce mucus, sweat, and digestive fluids, the progressive disease thickens secretions in the body. This causes long-lasting lung infections, inflammation, persistent coughing, and shortness of breath. It can also affect a person’s growth and slow weight gain.
According to the Cystic Fibrosis Foundation, there are approximately 40,000 children and adults living with cystic fibrosis in the United States. The disease can affect people of any gender or racial/ethnic group.
Though people with cystic fibrosis require daily care, improvements in treatment have made it possible for those with CF to attend school, explore careers, have children, and lead fulfilling lives well into adulthood.
What causes cystic fibrosis?
Cystic fibrosis is a genetic disorder caused by mutations in a gene known as the “cystic fibrosis transmembrane conductance regulator” gene (CFTR gene). The CFTR gene is located on chromosome 7. These mutations change the way the body moves salt in and out of cells, resulting in thick, sticky mucus in the respiratory, digestive, and reproductive systems, as well as excess salt in sweat.
How is cystic fibrosis inherited?
In order to have cystic fibrosis, a person must have inherited two defective CFTR genes, one from each parent. If a person had inherited only one defective CFTR gene, they are considered a carrier of the disease. Carriers can pass the gene mutations on to their children. The chance of inheriting the CFTR gene or developing cystic fibrosis is as follows:
- If one parent has cystic fibrosis and the other parent is a carrier, there is a 50% chance their child will have cystic fibrosis.
- If both parents carry one copy of the mutated CFTR gene, there is a 25% chance that the child will have cystic fibrosis and a 50% chance the child will be a carrier.
- If only one parent is a carrier of a defective CFTR gene, the child will not have cystic fibrosis, but there is a 50% chance that the child will be a carrier.
Risk factors for cystic fibrosis
The biggest risk factor for cystic fibrosis is family history. Although the inherited disease occurs in all races and ethnic groups, data shows that cystic fibrosis is more common in white people of Northern European ancestry.
How cystic fibrosis affects fertility
Though most men with cystic fibrosis are diagnosed with infertility, they are typically not sterile, because their body can produce sperm. In fact, 90% of people with cystic fibrosis have normal sperm production in the testes. Infertility related to cystic fibrosis stems from a missing sperm duct, called the vas deferens.
Congenital absence of the vas deferens in cystic fibrosis
This condition is called congenital bilateral absence of the vas deferens, or CBAVD. “Congenital” means the person was born with the condition, and “bilateral” means the vas deferens is missing on both testes.
The vas deferens is the duct that transports sperm from the testicles, where they’re produced, to ejaculatory ducts, where sperm combine with semen before ejaculation. Without vas deferens, sperm can’t get to the semen. This makes it impossible for sperm to reach and fertilize an egg through intercourse.
Most people with cystic fibrosis have normal sexual desire and sexual function, but a semen analysis will typically find azoospermia, or a lack of sperm in the semen. The absence of sperm can also contribute to men with cystic fibrosis having low semen volume and thin ejaculate.
Other genitourinary abnormalities associated with cystic fibrosis
Research shows that males with cystic fibrosis may also have other abnormalities, such as:
- Hydrocele. Hydrocele is a swelling of the scrotum due to fluid buildup around the testes. This condition could affect fertility in cases where the hydrocele is infected.
- Inguinal hernia. This type of hernia happens in the groin, and is typically surgically repaired. If there are complications during this surgical repair, risk of infertility is even higher.
Infertility in cystic fibrosis carriers
Even if a person doesn’t have cystic fibrosis, carrying a mutated CFTR gene is associated with an increased risk of infertility. Research has shown that men with azoospermia were more than twice as likely to be CF carriers, compared to fertile men. Some men who carry just one copy of the CFTR gene may also have CBAVD.
Therefore, it’s recommended that all patients with azoospermia be screened with genetic testing to determine whether or not they carry CFTR gene mutations. This can also help couples take steps to prevent passing cystic fibrosis on to their children, if they so choose.
If you’re a cystic fibrosis carrier or you have a history of cystic fibrosis in your family, it’s a good idea to check your fertility health with a semen analysis, and explore cystic fibrosis testing options.
Fertility treatments for males with cystic fibrosis and CBAVD
With the help of assisted reproductive technology (ART), it is usually possible for a person with cystic fibrosis to conceive a child. Sperm retrieval directly from the testes can side-step the missing vas deferens; the sperm can then be injected directly into an egg to facilitate fertilization. Let’s explore the most common fertility treatments for males with cystic fibrosis.
Sperm extraction or aspiration for men with cystic fibrosis
Sperm extraction or aspiration is a process by which sperm is removed surgically from the testicles. So long as a person with cystic fibrosis is producing healthy sperm, a sperm extraction can provide an option for conceiving a genetic child. Sperm extraction procedures include:
- Microsurgical epididymal sperm aspiration (MESA). MESA is a surgical approach for extracting sperm from the epididymis, the structure in the testes in which sperm is stored. During this procedure, the patient is under general anesthesia. The surgeon makes an incision in the scrotal skin to expose the testes and epididymis, and then uses a surgical microscope to retrieve as much sperm as possible.
MESA has a high success rate. Research shows that sperm is successfully retrieved in 96–100% of cases, typically yielding 15–95 million sperm.
- Percutaneous epididymal sperm aspiration (PESA). Similar to MESA, PESA is a procedure used to extract sperm from the epididymis. However, instead of using an incision, PESA uses a needle to puncture the skin of the scrotum.
The procedure typically retrieves smaller quantities of sperm (usually thousands to millions of sperm). Though PESA is seen as less reliable than MESA, some individuals choose PESA as it’s simpler, uses local anesthetic instead of general, and costs less.
- Testicular sperm extraction (TESE). TESE is similar to MESA, but tissue is removed from the testicle and examined to extract as much sperm as possible. TESE is typically performed in an operating room under general anesthesia, though it can also be performed in a physician’s office with local anesthesia alone.
The difference between MESA and TESE is that more spermatozoa can be obtained in the former, but the MESA procedure is more time consuming and surgically challenging than TESE.
In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI)
After sperm is collected from one of the procedures above, it can be used for IVF with ICSI. IVF is a procedure in which eggs are then retrieved from the ovaries surgically, mixed with sperm in a controlled vessel for fertilization, and then transferred back to the uterus for pregnancy.
ISCI is an IVF technique. In this technique, instead of mixing millions of sperm with the extracted eggs, a single sperm is injected into an egg to facilitate fertilization. This is valuable for those with low sperm count — as only one sperm is needed for fertilization — or those with poor sperm motility.
Often, sperm retrieved directly from the testes has lower motility and there are fewer sperm to work with, so ICSI is necessary.
Preimplantation genetic testing
If a person with cystic fibrosis wants to have children with someone who’s also a CF carrier, embryo genetic testing is valuable. Embryos that are created with IVF can be tested for specific gene disorders before they are transferred back to the uterus for pregnancy. This allows parents to select healthy embryos that aren’t affected by cystic fibrosis, if they so choose.
Cystic fibrosis carrier screening
Also known as cystic fibrosis genetic testing, cystic fibrosis carrier screening is a test that examines a person’s DNA to determine if they are a carrier of one of the gene mutations that causes cystic fibrosis. The test can help prospective parents determine if they have a chance of having a child born with the genetic disease.
There are over 1,000 mutations in the CFTR gene associated with cystic fibrosis. Cystic fibrosis testing can identify the most common of these. Cystic fibrosis carrier testing is typically done via a blood or saliva sample.
Who should test for the CFTR gene mutations?
Anyone can check if they’re a carrier of the CFTR gene. There are some individuals for which testing is highly recommended including:
- People who have a family history of cystic fibrosis
- Those whose partner has cystic fibrosis, is a carrier, or has a family history of the disease
- People who have a medical condition that may be related to cystic fibrosis, such as male factor infertility
- Those who have received abnormal semen analysis results, such as azoospermia
Cystic fibrosis testing, along with other carrier testing, is also often recommended for couples who are trying to conceive.
What if my cystic fibrosis carrier test results are normal/negative?
If a carrier screening test does not identify a cystic fibrosis-related mutation, you will most likely not have a child with cystic fibrosis. If your partner is a CF carrier, your child may be (though they won’t have cystic fibrosis, since it requires gene mutations from both parents).
A caveat: A routine screening might not detect rare mutations, so there is still a very small possibility that you may be a carrier, especially if you have a family history of the disease.
All newborns are tested for the genetic disorder as part of the newborn screening (NBS) initiative in the US.
I have been diagnosed as a cystic fibrosis carrier. What should I do?
If you test positive as a carrier of the cystic fibrosis-related gene mutations, it doesn’t mean you have cystic fibrosis. However, if your partner is also a carrier, there is a chance that your child could have cystic fibrosis.
If tests show that you are a CF carrier but your partner is not, there is a very slim chance that you will have a child with the disease. However, your child could be a CF carrier.
If you and your partner are both carriers, there is a 25% (1 in 4) chance that your child will have cystic fibrosis. In this case, it is recommended that you consult a fertility specialist or seek genetic counseling before trying to conceive. IVF with embryo genetic testing — as described above — can help you identify healthy embryos that aren’t affected by cystic fibrosis.
If you or your partner are already pregnant and you find out you’re both carriers, prenatal testing of your fetus for cystic fibrosis is available.
Remember, even if you and your partner are both CF carriers, it’s possible (and likely) that you’ll be able to have a healthy baby.
How can I check my own fertility?
Since many individuals do not find out that they are cystic fibrosis carriers until they encounter fertility issues, checking your fertility early is a good first step in family planning.
An at-home sperm testing kit is an easy way to measure key factors of sperm health and take steps to improve your fertility. Legacy’s mail-in semen analysis tests for crucial semen parameters, including volume, count, concentration, motility, and morphology. It is the most scientifically advanced at-home semen test, performed in CLIA-certified labs by a team of experienced scientists and thoroughly received by medical staff.
If you are having trouble conceiving, checking your fertility can help you diagnose or rule out male fertility issues. If you discover that cystic fibrosis gene mutations are at the root of these issues, consider seeing a fertility specialist to help you outline the various treatment options that can help you start a family with success.