How IVF and Genetic Testing Can Help Prevent Sickle Cell Anemia
September is National Sickle Cell Awareness Month. Sickle cell disease is a relatively common genetic disorder – around one in 10 African-Americans is a carrier for the sickle cell trait. Other groups can carry sickle cell trait as well, including Hispanics, Caribbean, South Americans, Central Americans, and those from certain parts of Europe, including Italy and Greece. In addition to working with patients who carry the sickle cell trait, fertility clinics can also work with patients who have sickle cell disease. It’s also important to note that advancements in the field of genetic testing have made it possible for sickle cell carriers to avoid passing on the condition to their children.
What is Sickle Cell Disease?
Sickle Cell Anemia results from a change at a certain point in the beta-globin gene. Red blood cells are usually round, but with this condition, they can be distorted into a sickle, or crescent shape. When the blood cells are sickled, they break down earlier than typical, which leads to anemia.
For a more complete understanding of sickle cell disease and associated symptoms, scroll to the end of this article.
How Does Sickle Cell Disease Affect Fertility?
While parents with sickle cell trait are statistically no more likely to be infertile than the rest of the population, men and women who have the disease can see an impact on fertility. For males with sickle cell disease, there are higher chances for sperm issues, including lower sperm counts and testicular dysfunction. For females with the condition, their ability to conceive may be reduced as well. For people with Sickle Cell disease, fertility treatment can make it possible to achieve pregnancy. For females who do conceive, some have no significant changes in their health during pregnancy, while others may have higher rates of complications. The chance for infections, gallbladder issues, heart enlargement, and miscarriage could be increased.
Also, bone marrow stem cell transplants have 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.
Sickle Cell Disease and Pregnancy Considerations
For those with sickle cell disease, pregnancy-related issues can include anemia in the fetus, reduced growth, preterm birth, and lower birth weight. Therefore, it is often recommended that a high-risk obstetrician follows these patients. In some cases involving sickle cell disease, a gestational surrogate may be used to carry the pregnancy, to minimize complications. Some patients with sickle cell disease are treated with the medication Hydroxyurea. As this may have some effects on a developing fetus, it is recommended that women discontinue this before attempting pregnancy.
What is the Likelihood of Having a Child with Sickle cell Disease When Both Parents are Carriers?
For a child to be affected with sickle cell disease, both parents must be carriers. The condition is inherited in an autosomal recessive pattern, which sounds complicated, but essentially means there are four possible outcomes, each carrying a 1 in 4 chance (or 25%) of occurring. These possible outcomes include a 1 in 4 chance the child would have two normal copies; a 1 in 4 chance the child would have sickle cell trait from the mother and a normal copy from the father; a 1 in 4 chance the child would have sickle cell trait from the father and a normal copy from the mother; and a 1 in 4 chance that the child would have two copies of the sickle cell trait; which would mean the child is affected with sickle cell disease. Symptoms of the condition would usually begin in early childhood.
How IVF and Genetic Testing Can Help Prevent Sickle Cell Anemia
Couples with the sickle cell trait can minimize the risk before pregnancy by pursuing in vitro fertilization, or IVF, with preimplantation genetic testing. IVF involves a woman taking medications to stimulate her eggs. The eggs are retrieved and fertilized with the partner’s sperm. The embryos grow in the laboratory until the blastocyst stage, which is typically day five or day six. At this time, embryo testing occurs, which involves taking a small sampling of cells from the embryo and sending it for analysis. The analysis of the embryo is known as Preimplantation Genetic Diagnosis (PGD) or 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 labs 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 probes, as well as looking at some other gene markers in the embryos, can be used to see if 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 (PGS or PGT-A).
The results report would state which embryos have chromosome issues and are affected with sickle cell, which embryos were carriers, and which did not carry the gene. The couple and their doctor could then make a decision regarding which embryo to transfer.
Can a Carriers of the Sickle Cell Trait Have a Healthy Child?
If a couple is known to have a 25% chance to have a child with sickle cell disease, they can pursue different options. Some couples will accept this 25% chance and try to conceive naturally. For these couples, there is still the option to pursue diagnostic tests during the pregnancy to see if sickle cell disease is present.
A chorionic villi sampling or amniocentesis could be performed which would analyze cells from the fetus and determine if the fetus was affected with the condition. However, these procedures have some associated risks, including miscarriage, and some couples are not comfortable pursuing them. If prenatal testing is not done, sickle cell disease is looked for in newborn screening panels. This would allow for early diagnosis so that prompt treatments could be initiated.
Screening for Sickle Cell Disease Can Prevent the Complications Caused by the Disorder
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 are the Symptoms of 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 usually is made of alpha-globin and beta-globin. As mentioned above, sickle cell results from a change in the beta-globin gene, which causes blood cells to break down earlier than usual.
In addition to anemia, associated issues include recurrent infections, shortness of breath, excess fatigue, and jaundice (yellowing of skin or eyes). The sickled cells can also get stuck in small blood vessels. This symptom can be painful (known as a “pain-crisis”) and can cause 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.
Children usually take antibiotics as a preventive measure, since recurrent infections are a common problem. In some cases, a bone marrow transplant can be done, but this procedure can be risky, and some of the medications needed for this type of treatment can have adverse side effects. Life expectancy is reduced for people with sickle cell disease, but our ability to treat the condition has improved over time, and more people with the condition are living longer lives.
Genetic screening for the Sickle cell trait is crucial in some populations because not all people know they are carriers.
While some people have a family history of sickle cell disease, and others have been tested previously, many people of reproductive age are not aware that they are carriers. Since most people carrying the sickle cell trait have no health issues, it is common for this to go unnoticed. The ideal timing for genetic screening is before pregnancy so that all available reproductive options can be considered.
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About Jamie Speer
James Speer, M.S., a certified genetic counselor, has over 10 years of experience in the fertility field. As the medical field’s understanding of genetic conditions expands and testing becomes more comprehensive, there is a growing need from fertility patients to work with a specialist to understand and consider their options.