How IVF and Genetic Testing Can Help Prevent Sickle Cell Anemia

Sickle cell disease is a relatively common genetic disorder affecting approximately 100,000 Americans. Luckily, with the help of IVF treatment and genetic testing, carriers of the trait can now prevent passing it on - leading to healthier babies. 

In this article:

• What is sickle cell disease?
• Sickle Cell Trait vs Sickle Cell Disease
• Does sickle cell disease affect fertility?
• How is sickle cell disease inherited?
• The Role of IVF & Genetic Testing
• What causes sickle cell disease?
• Symptoms of Sickle Cell Disease
• How long do people with sickle cell disease live?
• Treatment for Sickle Cell Disease

What is sickle cell disease?

Sickle cell disease (SCD) refers to a group of inherited disorders that cause red blood cells to become misshapen and break down. With sickle cell disease, red blood cells contort into a sickle shape (instead of the normal circular shape). 

This blood disorder also affects hemoglobin, the essential protein that carries oxygen throughout the body. As a result, those with SCD become anemic. While certain treatments can help manage the effects of the disease, it is an incurable, lifelong medical challenge. 

What medical problems are caused by sickle cell disease?

Sickle cell disease can lead to life-altering side effects. The blockage of blood flow caused by sickled cells leads to many medical complications, including chronic pain, recurring infections, lung tissue damage, blindness, kidney disease, and stroke.

Sickle Cell Trait vs Sickle Cell Disease

If you have sickle cell trait, this means you have inherited the gene for sickle cell disease.

There are about 2.5 million people in the United States with sickle cell trait. However, sickle cell trait does not always turn into sickle cell disease. If a woman and her male partner both carry sickle cell trait, they may produce a child with sickle cell disease. 

Who is most at risk for sickle cell disease?

According to the Centers for Disease Control & Prevention (CDC), around 1 in 13 Black or African-American babies is born with sickle cell trait (SCT). Other groups can carry the sickle cell trait as well, including those of Hispanic, Caribbean, South American, and Central American origin, and people from certain parts of Europe, including Italy and Greece.

Let's put that into perspective. In the United States:

• SCD occurs among about 1 out of every 365 Black or African-American births
• SCD occurs among about 1 out of every 16,300 Hispanic-American births

Does sickle cell disease affect fertility?

While people who carry the sickle cell trait are statistically no more likely to be infertile than the rest of the population, those affected by the disease can see an impact on fertility.

For men with sickle cell disease, there is a higher chance of sperm issues, including lower sperm counts and testicular dysfunction. For women with the condition, their ability to conceive may be reduced as well.

Potential Complications During Pregnancy

Some people with SCD conceive successfully and have no significant changes in their health during pregnancy, while others may have higher rates of complications. The chance for maternal infections, gallbladder issues, heart enlargement, and miscarriage can be increased.  

Sickle Cell Disease & Pregnancy

For those with sickle cell disease, concerns include anemia in the fetus, reduced fetal growth, preterm birth, and lower birth weights. As a result, pregnant people with SCD are often referred to a high-risk obstetrician for prenatal healthcare.

In some cases, those with SCD may opt to have a gestational surrogate carry the pregnancy to minimize potential complications.

Some patients with sickle cell disease are treated with a medication called hydroxyurea. Because it can affect the developing fetus, discontinuing this medication before attempting pregnancy is strongly recommended. 

Want to learn more? Explore CDC fact sheets on sickle cell disease and pregnancy.

How is sickle cell disease inherited?

For a child to be affected with sickle cell disease, both parents must be carriers. Symptoms of the condition would usually begin to appear in early childhood if the child inherits SCD.

The condition is inherited in an autosomal recessive pattern, which sounds complicated, but essentially means that there are four possible outcomes, each carrying a 25% (or 1 in 4) chance of occurring.

These possible outcomes include:

• A 25% chance the child would have two normal copies of the gene
• A 25% chance the child would have sickle cell trait from the mother and a normal copy from the father
• A 25% chance the child would have sickle cell trait from the father and a normal copy from the mother
• A 25% chance that the child would have two copies of the sickle cell trait; which would mean the child is then affected with sickle cell disease

Can carriers of sickle cell trait have a healthy child?

If a couple knows they will have a 25% chance of having a child with sickle cell disease, they can pursue a few different options. Some hopeful parents choose to accept this 25% chance and try to conceive on their own.

For these couples, there is still the option to pursue diagnostic testing during pregnancy to see if sickle cell disease is present in the fetus.

Prenatal Testing for Sickle Cell Disease

A chorionic villus sampling (or amniocentesis) may be performed, which would analyze cells from the fetus and determine if the fetus is affected with the condition. However, these procedures do carry some associated risks, including miscarriage, and some couples are not comfortable pursuing them.

Note: If prenatal testing is not performed, sickle cell disease is looked for in newborn screening panels. This would allow for early diagnosis so that prompt treatment could be initiated.

Get the FAQs on Genetics

A genetic counselor answers common questions about preimplantation genetic testing (PGT) and explores how the information it provides can help families.

The Role of IVF & Genetic Testing

In addition to working with patients who carry sickle cell trait, fertility clinics can also work with patients directly affected by sickle cell disease. Thanks to advancements in the field of fertility treatment and genetic testing, those who carry sickle cell trait or have the disease are now able to avoid passing on the condition to their children.

Couples can minimize the risk of sickle cell before pregnancy by pursuing in vitro fertilization (IVF) with preimplantation genetic testing (PGT). Here's how it all works.

Phase 1: IVF Treatment

IVF involves taking medications to stimulate the growth of eggs in the ovaries. After the eggs have matured, they are retrieved and fertilized with the patient's designated sperm (either from their partner or a donor).

Phase 2: Embryo Development & Biopsy

Embryos are monitored as they grow in the IVF laboratory until they reach the blastocyst stage, which is typically around Day 5 or Day 6. A small sampling of cells is carefully removed from the embryo(s) and sent to an external genetics laboratory for analysis.

Phase 3: Embryo Testing 

The analysis of the embryo is known as preimplantation genetic testing (PGT) or, more specifically, preimplantation genetic testing for monogenic disorders (PGT-M).

To accomplish this, the lab would need samples from the couple (and usually other family members as well), to help track the chromosome carrying the mutation in the family. The genetics lab will then typically develop 'probes,' which are small stretches of DNA that match the familial mutation.

It can take several weeks to prepare for cases like these. These unique probes, as well as assessing other gene markers in the embryos, help to determine whether the embryos are positive or negative for the condition.

Couples pursuing PGT for sickle cell would typically also have their embryos analyzed for chromosome issues at the same time (PGT-A).

Phase 4: Results & Next Steps

As soon as your fertility clinic receives the results report from the genetics lab, they will know which embryos have chromosome issues, which embryos are affected with sickle cell, which embryos are carriers, and which embryos do not carry the gene.

Your doctor and genetic counselor will then discuss these results with you and your partner to help you make a decision regarding which embryo to transfer. 

Why Screening Both Partners is So Important

Some people with the condition have one copy of sickle cell trait, and a different type of mutation in their other beta-globin gene, such as hemoglobin C trait, or beta-thalassemia trait. So, if one person has sickle cell trait, it is crucial to test a partner for sickle cell trait as well as other possible beta-globin changes.     

What causes sickle cell disease?

Sickle cell disease affects hemoglobin, which is the protein in red blood cells that carries oxygen to different parts of the body. Our adult hemoglobin is usually made of alpha-globin and beta-globin.

Red blood cells are usually round, but with SCD, they can be distorted into a sickle, or crescent shape. When the blood cells are sickled, they break down earlier than normal, leading to anemia.  

Symptoms of Sickle Cell Disease

In addition to anemia, associated issues include recurrent infections, shortness of breath, chronic fatigue, and jaundice (yellowing of skin or eyes). The sickled cells can also get stuck in small blood vessels, leading to extreme pain, and even a loss of oxygen to different parts of the body, including the lungs, kidney, and spleen.

High blood pressure can be seen in blood vessels going to the lungs, which can be a severe complication. Children with sickle cell disease can also have delayed growth and many different complications. People with the condition need a lot of medical care to manage and control all of the related symptoms. 

How long do people with sickle cell disease live?

The average life expectancy of those with sickle cell disease has improved since all children are now screened for the condition. However, life expectancy is still only in the mid-40s. Our ability to treat the condition has improved over time, allowing more people with the condition to live longer lives.

Treatment for Sickle Cell Disease

Like all patients with chronic disease, patients with sickle cell disease are best managed through a comprehensive, multidisciplinary care approach. Here's what you should know.

Early Diagnosis

Health maintenance for patients with sickle cell disease starts with early diagnosis, preferably soon after birth. Treatments include penicillin prophylaxis, vaccination against pneumococcus bacteria, and folic acid supplementation.

General Treatment & Support

Treatments for sickle cell disease complications often include antibiotics, pain management, intravenous fluids, blood transfusion, and surgery. Establishing a strong psychosocial support system is also of the utmost importance.

Helpful resources include the Sickle Cell Disease Association of America, Centers for Disease Control & Prevention, SCDAA Sickle Cell Disease Educational Information Repository, and the American Society of Hematology.

Blood Transfusions

Blood transfusions can help by reducing recurrent pain crises, risk of stroke, and other complications. Because red blood cells contain iron, and there is no natural way for the body to eliminate it, patients who receive repeated blood transfusions can accumulate iron in the body until it reaches toxic levels.

It is important to remove excess iron from the body, because it can gather in the heart, liver, and other organs and may lead to serious organ damage and even death. This is referred to as transfusional iron overload, and requires additional treatment. 

Hydroxyurea

A single randomized clinical trial of 299 patients with SCD demonstrated that compared to placebo, hydroxyurea was associated with lower annual rates of pain crises, painful episodes of acute chest syndrome and need for transfusions. 

Bone Marrow Transplant

Bone marrow stem cell transplants have also been utilized for the treatment of sickle cell disease.  As this procedure can impact future fertility, it is recommended that patients consider fertility preservation, including possible freezing of eggs, sperm, or embryos, before the transplant.  

Treatment Options for Children with Sickle Cell Disease

Children usually take antibiotics as a preventive measure, since recurrent infections are a common problem. In some cases, a bone marrow transplant can be performed, but this procedure can be quite risky, and some of the medications needed for this type of treatment can have adverse side effects.

Be Aware & Proactive 

Genetic screening for the sickle cell trait is crucial. While some people are aware that they have a family history of sickle cell disease, or have been tested previously, many don't even know that they are carriers.

Since many people carrying the sickle cell trait have no apparent health issues, it isn't uncommon for the disease to go unnoticed. If you are Black or Hispanic-American, it is important to undergo genetic screening before pregnancy so all available reproductive options can be considered. 

With awareness, education, and proper screening, carriers of the sickle cell trait can still become parents - without the fear of passing on the disease to their future children.