The decision to have a family comes with a great deal of responsibility, and many important choices. For people with Huntington’s disease (HD), one of the most pressing considerations in their decision to have children relates to the disorder. People with HD have a 50% risk of passing the disease to their offspring each time they conceive, unless they attempt an alternative method that stops HD from being inherited through the generations. Those “at risk” of HD, who have parents or relatives with the disease but do not wish to be tested to see whether they are affected, also have the potential to pass HD on to their children as they might be HD-positive.
This article outlines a number of reproductive options available to couples that know their HD status, and to those who prefer not to know. There is no easy answer, and each couple may come to a different conclusion based on their personal preferences and system of beliefs. This article provides possibilities: the solutions, however, can only be reached by the individuals themselves.
Decide whether to get tested^
The first decision a couple faces is whether or not the person at risk should get tested for HD; the test results might significantly shape the choices a couple makes in planning their family. For more information on genetic testing, click here, and to learn more about how getting tested might affect romantic relationships, click here. Getting tested is not necessary, as people who are at risk have several ways to avoid passing on HD without finding out their own status, but it might be helpful.
Not having children/Adoption^
Upon learning of their HD-positive or at risk status, some people choose to not have children. Many people that make this choice do so to avoid the risk of passing HD on to their children, expressing guilt at the thought of transmitting the disease (Decruyanaere et al., 2007). Other couples worry they won’t be able to fully raise the child before the HD-affected parent’s symptoms set in, and they don’t want the disease to compromise their parenting (Klitzman et al., 2007). On one hand, couples who don’t have children can rest easy knowing that they will never pass HD on to future generations; on the other, some may regret not having children (Decruyanaere et al., 2007).
Couples that don’t want to remain childless sometimes decide to adopt instead. Adoption helps a needy child, and allows a couple to raise children without passing on HD. Prospective parents generally work with adoption agencies to help them through the adoption process, and to help them screen children to find the right match. The decision must be weighed carefully, as prospective parents need to consider whether HD will jeopardize their ability to raise children; some adoption agencies might refuse to let HD-positive people adopt on these grounds (Klitzman et al., 2007). For more information about adoption, click here.
Many couples choose to have children naturally. If one parent is HD-positive, then the child has a 50% chance of having HD. If one parent is at risk (and therefore has a 50% chance of having the disease), their child has a 25% of having HD – though that number increases to 50% if the at risk parent begins to show symptoms. If both parents have HD, then the child has a 75% chance of having the disease.
Parents who accept these risks and have children naturally often say that their desire to have children outweighs their fears about HD. They acknowledge that their child might inherit the disease, but express hope that a cure for HD may be found in their child’s lifetime; they also point out that even if no cure is found, their child will have many disease-free years, as HD rarely sets in before age 40 (Decruyenae et al., 2007).
Sperm or egg donation/Surrogate mother^
Couples also have the option of sperm or egg donation, depending on which partner is affected by HD. If the prospective father is HD-positive, couples might consider sperm donation, in which a donor’s sperm is inserted into the prospective mother’s uterus or vaginal canal using a syringe. For more information on sperm donation, click here. If the prospective mother is HD-positive, couples can have children through egg donation, in which another woman donates her eggs and they are fertilized with the father’s sperm through in-vitro fertilization (IVF). Alternatively, a couple could consider having a child with a surrogate mother, where the father’s sperm is inserted into a surrogate mother. However, while sperm donation is relatively inexpensive at several hundred dollars, both egg donation and surrogacy cost thousands of dollars; couples in which the prospective mother has HD generally choose other reproductive options instead.
Test Tube Babies: Preimplantation Genetic Diagnosis (PGD)^
Pre-implantation Genetic Diagnosis (PGD) screens embryos for genetic diseases, such as HD, before they are implanted in a woman’s body. This exciting new technology, developed in 1998, allows couples to prevent their children from inheriting genetic diseases that run in the family (Decruyenae et al., 2007).
To generate the embryos used in PGD, the couple must first undergo in-vitro fertilization (IVF). In IVF, a woman’s eggs and man’s sperm are combined in a laboratory. First, some of the woman’s eggs are collected. Since women usually only release one egg every month, doctors give the woman fertility medication to cause her to release many eggs at once, a process called “superovulation”. The eggs are monitored using ultrasound imaging. Once they are mature, the doctors perform a minor surgery. The woman is given local anesthetic, which numbs the area the doctor will be working on, and sedatives, which put her to sleep. Then, using ultrasound, the doctor guides a hollow needle to the ovary and removes the eggs.
The eggs are then fertilized using the man’s sperm. This is the step that earned this procedure the name “in vitro fertilization”: “in vitro” is Latin for “in glass”, referring to the fact that the fertilization is performed in test tubes or petri dishes, rather than in the body –which gave rise to the term “test tube babies”. The sperm and egg combine to form a single-celled embryo, which grows and divides. For more information on IVF, click here.
Once the embryo has reached the 8-cell stage, PGD is performed. One of the eight cells of the embryo is removed for testing. This procedure is harmless, as the embryo is still composed of stem cells, and can easily grow to replace the lost cell. Since every cell has a complete copy of the genetic code, any one cell will suffice for genetic testing. At this point, a “genetic diagnosis” is carried out on the cell. However, geneticists can’t use the same test that is used to check adults for the HD allele, as one cell isn’t enough to test for CAG repeats directly (a process described here). Instead, scientists take blood samples from both prospective parents, and from the parents of the at-risk individual. They then look at the genes right next to the HD allele, and choose a “marker” – a unique fingerprint of DNA that differs between the chromosome with the HD allele, and those without. Since genes that are close together are almost always inherited together, the embryos with the HD allele will also have this particular marker. Therefore, an embryo that tests positive for the marker is considered “affected”; it carries the HD allele, and is expected to have HD. Embryos that do not carry the marker are “unaffected”, and are considered for implantation (Sermon et al., 2002).
The doctor will then implant between 1-4 embryos. Usually, more than one embryo is implanted, to increase the chances of a successful pregnancy. If the first implantation process fails, and there are enough unaffected embryos remaining from the egg retrieval process, the doctor can simply perform a second implantation. However, if there aren’t enough unaffected embryos remaining, the woman will have to begin the entire process again, starting from egg retrieval.
To summarize, the woman undergoes egg retrieval in which several eggs are collected. Those eggs are fertilized with the man’s sperm through IVF, and allowed to divide to the 8 cell stage. PGD is performed on one cell of each embryo, and the embryos that are HD-free are selected for implantation. This process, while complicated and expensive, virtually ensures that the children of a PGD-tested couple will be HD-free – the only risk of the child having HD would come from human error, and is extremely small.
PGD comes with a handful of medical risks. As multiple embryos are implanted, some women end up having more than one child. Some may be happy with this result, but others might have a more difficult pregnancy. Another problem – ovarian hyperstimulation syndrome – is caused by an over-reaction to the fertility medication used. The problem, which causes symptoms such as diarrhea, nausea, and dizziness, can be solved by drinking more water. Other complications, such as infections acquired during surgery, are treated with antibiotics. For a full discussion of risks, click here.
An alternative form of PGD exists for those who don’t wish to be tested. As with disclosing PGD, IVF is performed to create embryos, and doctors perform PGD to determine which are affected, and which are HD-free. The difference between disclosing and non-disclosing PGD is that the doctor never reveals the at-risk parent’s status: the parents do not find out how many embryos were affected (if any), and do not know how many embryos were implanted.
Non-disclosing PGD brings up a number of weighty issues. First, the doctor knows the status of the at-risk parent, but must keep it a secret. Even if the news is good – if none of the embryos have HD, the parents are almost certain to be HD-free – the doctor can’t reveal the parent’s status, as this would compromise secrecy for other clients; clients who were not congratulated would know their HD-positive status by default (Braude et al., 1998).
Second, if the parent is a carrier, and all embryos are affected, then a “mock transfer” is carried out; the doctor performs an implantation in which no eggs are implanted. This ensures that the person doesn’t find out his or her HD-positive status. Some countries, such as Holland, consider this an unnecessary medical risk, and therefore require the at-risk individual to be tested before undergoing PGD (Asscher and Koops, 2010).
Third, half of the couples that choose non-disclosing PGD are perfectly healthy, and therefore undergo IVF-PGD when they could simply have a natural pregnancy. Again, this factored into Holland’s decision to force couples to get tested before resorting to PGD, as half of the couples will avoid the cost and medical risks of IVF-PGD. However, the US and most other countries have no such policy, and non-disclosing PGD is accepted and performed (Asscher and Koops 2010). For a discussion of the right not to know, click here.
In short, PGD allows couples to have children that will be HD-free. The procedure, admittedly, is physically and emotionally draining, particularly because the success rate is currently around 20%; a couple may have to undergo multiple rounds of IVF-PGD for a successful pregnancy (Sermon et al., 2002). Furthermore, with a price-tag of $9,000-$18,000, this procedure might be out of reach for some couples, particularly if their health insurance companies refuse to subsidize the cost. However, many HD-positive or at-risk couples have had successful pregnancies through IVF-PGD. For an account of an HD-positive mother who had twins through IVF-PGD, and successfully lobbied her health insurance company to cover most of the expenses, please click here.
Testing the Fetus: Prenatal Diagnosis^
Another option exists for women who are already pregnant: Doctors can perform a prenatal diagnosis, in which the fetus is tested for HD. As with PGD, this procedure can take two forms: HD-positive people undergo a “disclosing” prenatal diagnosis, and people who are at-risk but do not wish to be tested can have “non-disclosing” prenatal diagnosis, in which their fetus is tested for the risk of HD and the parent’s status remains unknown.
Prenatal diagnosis can be performed through chorionic villus sampling (CVS) or amniocentesis. In both, a needle is guided by ultrasound imaging to collect a sample of cells for genetic testing. In CVS, the needle is inserted into the uterus through the vagina, and collects a few cells from the placenta, the organ that develops alongside the fetus and supplies it with oxygen and nutrients from the mother. CVS is usually performed 10-13 weeks after the mother’s last menstrual period. Amniocentesis is performed later, around 14-20 weeks into the pregnancy. In amniocentesis, a needle is inserted through the abdomen into the uterus and takes a sample of amniotic fluid – the fluid surrounding the fetus – for genetic testing. Both CVS and amniocentesis are very safe procedures, though there is a very small increase in risk of miscarriage. For more information on CVS, please click here, and to read more about amniocentesis, please click here.
Once those samples are taken, genetic tests are performed. For a disclosing prenatal diagnosis, doctors determine the number of CAG repeats the fetus has in its Huntington gene, as described here. If the fetus has 35 or fewer CAG repeats, it is considered HD-free; with 40 or more CAG repeats, it is considered HD-positive; with 36-39, the fetus has an uncertain prognosis, and may or may not develop HD in its lifetime.
If the parent is at-risk for HD, but does not wish to know their status, a non-disclosing prenatal diagnosis is performed through “exclusion testing”. In exclusion testing, the CAG repeats are not directly measured; instead, doctors look at “linked markers” to see which parent the fetus inherited its genetic material from, as previously described in the PGD section of this article. In this method, the couple must get in touch with their parents to collect small blood samples for testing. For the HD-positive parent of the “at-risk” person (the “grandparent” of the fetus), the doctors find markers for the Huntington gene. The doctors consider the fetus at risk of developing HD if either of the affected grandparent’s copies of the Huntington gene are present in the fetus; the grandparent’s HD allele, as well as the grandparent’s non-HD allele, both cause the fetus to be deemed “high-risk”. Therefore, there is a 50% chance that the fetus will have HD if it is marked as high-risk.
After a few weeks, the parents obtain their results. If the fetus is HD-free, the parents can rest easy; the child won’t suffer from the disease, and will never pass HD on. Unfortunately, some parents will receive upsetting results from the genetic test, and have a difficult choice to make.
Parents who are informed that their fetus has HD sometimes choose to keep the child, and do so for a number of reasons. Some say their desire for a child outweighs their fears about HD; others point out that the child will have many disease-free years before symptoms begin; still more express the hope that a cure for HD may be found in their child’s lifetime (Decruyenae et al., 2007). Views on abortion also play a large part in many people’s decisions; for some, their opposition to abortion outweighs their desire to prevent HD from being passed on to their children. A handful of parents don’t believe the results of a prenatal diagnosis should be grounds for abortion because they consider this the first step down a slippery slope towards a eugenic society, in which we begin choosing traits for our children (Klitzman et al., 2007).
All of these concerns are valid points, and deserve careful contemplation. However, most couples that learn that their fetus is HD-positive decide to terminate the pregnancy (Decruyenae et al., 2007). These parents often say they would feel unethical bringing an HD-positive fetus to term, as they don’t wish to subject a child to the difficulties they themselves have undergone (Klitzman et al., 2007).
The decision becomes even more difficult for parents who choose a non-disclosing prenatal diagnosis, and learn that their child is “high-risk”. While the fetus has a 50% chance of being HD-positive, there is still a 50% chance that the fetus is HD-free. For this reason, some countries, such as France, make it very difficult for a woman to have an abortion on the grounds of a non-disclosing prenatal diagnosis (Sermon et al., 2002).
This decision is difficult to make, and parents will have to weigh many personal, moral, and religious considerations; this article only scratches the surface of factors that might take a part in the choice. Some parents choose to avoid prenatal diagnosis entirely, as they don’t wish to risk the psychological and physical burden of abortion (Decruyenae et al., 2007). Ideally, a couple should discuss these issues with a genetic counselor; if possible, counseling should begin before the couple conceives, especially for non-disclosing prenatal diagnosis, as it may take longer than expected for doctors to find useful linked markers for the test.
Despite the difficulties of living with an inheritable disease, prospective parents should not feel limited by their HD-positive or at-risk status; those who wish to have children have many options, many of which prevent the passage of HD. This decision involves difficult choices, where a couple must weigh personal moral, ethical, and religious beliefs, while taking into account the opinions of family members and close friends. The end result, however, is well worth the work.
1. “Amniocentesis : American Pregnancy Association.” Promoting Pregnancy Wellness : American Pregnancy Association. American Pregnancy Association, Apr. 2006. Web. 25 June 2011. <http://www.americanpregnancy.org/prenataltesting/amniocentesis.html>.
This is an easy-to-read website with an in-depth discussion of amniocentesis, going into how the procedure is done, and any risks that might be involved.
2. “Chorionic Villus Sampling: CVS.” Promoting Pregnancy Wellness : American Pregnancy Association. American Pregnancy Association, Apr. 2006. Web. 17 June 2011.
This is an easy-to-read website with an in-depth discussion of CVS, going into how the procedure is done, and any risks that might be involved.
3. Asscher E, Koops BJ. The right not to know and preimplantation genetic diagnosis for Huntington’s disease. J Med Ethics. 2010 Jan;36(1):30-3
This is an easy-to-read paper on the ethics of non-disclosing PGD and non-disclosing prenatal diagnosis
4. Braude PR, De Wert GM, Evers-Kiebooms G, Pettigrew RA, Geraedts JP. Non-disclosure preimplantation genetic diagnosis for Huntington’s disease: practical and ethical dilemmas. Prenat Diagn. 1998 Dec;18(13):1422-6. Review.
This article explores some of the ethical considerations that non-disclosing prenatal diagnosis and non-disclosing PGD bring up, and could be useful for at-risk individuals.
5. Decruyenaere M, Evers-Kiebooms G, Boogaerts A, Philippe K, Demyttenaere K, Dom R, Vandenberghe W, Fryns JP. The complexity of reproductive decision-making in asymptomatic carriers of the Huntington mutation. Eur J Hum Genet. 2007 Apr;15(4):453-62. Epub 2007 Jan 24.
This is an easy-to-read study looking into the reproductive decision-making process of couples who know their HD-positive status.
6. Klitzman R, Thorne D, Williamson J, Chung W, Marder K. Decision-making about reproductive choices among individuals at-risk for Huntington’s disease. J Genet Couns. 2007 Jun;16(3):347-62.
This is an easy-to-read study looking into the reproductive decision-making process of couples that are at-risk, but do now wish to be tested.
7. Sermon K, De Rijcke M, Lissens W, De Vos A, Platteau P, Bonduelle M, Devroey P, Van Steirteghem A, Liebaers I. Preimplantation genetic diagnosis for Huntington’s disease with exclusion testing. Eur J Hum Genet. 2002 Oct;10(10):591-8.
This technical paper describes how PGD is performed.
8. “What Are the Risks of PGD Treatment?” Guy’s and St Thomas’ Centre for Preimplantation Genetic Diagnosis. Centre for Preimplantation Genetic Diagnosis, 18 May 2009. Web. 29 June 2011. <http://www.pgd.org.uk/whatispgd/risks/pgdrisks.aspx>.
This easy-to-read website that discusses the medical risks of PGD.
M. Hedlin, 7.20.11; recorded by B. Tatum, 8/21/12