Part of the lived experience of being at risk for or living with Huntington’s disease (HD) is thinking about the unique challenges involved with planning a family. Although the possibility of HD being inherited can make the decision of having a baby very difficult, various options have been developed for people living with hereditary diseases to reduce this risk. One such option is in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD). IVF is an assisted fertility medical procedure where a donor egg is fertilized by the donor sperm outside of the body, and implanted into the uterus. Preimplantation genetic diagnosis (PGD) is a form of prenatal diagnosis applied to potential parents who are potential or known carriers of a genetic disease, such as Huntington disease. This procedure was developed to address the desire for people with, or at risk for, HD to know if they could have children without passing the disease on to the next generation1. Since the birth of the first “IVF baby” in 1978, more than four million IVF babies have been born worldwide 2.
What is in vitro fertilization (IVF)?
The term “In vitro” means “performed or taking place in a test tube, culture dish, or elsewhere outside a living organism” 3. In vitro is often used to describe studies and procedures performed outside the body and in a glass laboratory dish or container. In vitro fertilization (IVF) is an assisted fertility technique involving a series of procedures performed to combine a man’s sperm and a woman’s eggs outside the woman’s body, and ultimately implant a fertilized egg (an embryo) into the woman’s uterus 4. The IVF process involves the following steps:
1. Ovarian stimulation
This involves the prospective mother taking a series of medications to release more eggs than normal. The IVF cycle (a term commonly used to describe the steps involved until implantation) begins with the mother taking fertility drugs for a span of 8 and 12 days 5. Fertility drugs work by triggering the release of hormones that regulate ovulation. Depending on the patient, a prospective mother’s doctor may recommend starting an IVF cycle by taking birth control for a number of days to prevent ovulation from happening too early in the cycle. After their fertility medication, the prospective mother is administered a a “trigger injection” of human chorionic gonadotropin (HCG), lupron , or both to stimulate their ovaries to produce eggs 6. Human chorionic gonadotropin (HCG) is a hormone released during pregnancy that stimulates the production of other hormones that helps maintain the uterus for pregnancy 7. Lupron is a drug containing synthetically made gonadotropin-releasing hormone analog/agonist (GnRH) intended to shut down the ovaries; then other drugs are used to stimulate egg production and facilitate multiple egg extraction8.
2. Egg retrieval
36 hours after the trigger injection9, the eggs are removed from the body through an egg removal technique, the most common being a transvaginal ultrasound aspiration 10. During this procedure, the prospective mother is first sedated and given pain medication. An “ultrasound probe”, which looks like a long probe with a needle at the tip, is inserted into the vagina, and the needle guide through the vaginal wall and into the follicles. Once the needle is inside a follicle, the eggs are suctioned into the needle’s canal 4. Multiple eggs can be removed in a span of about 20 minutes; an average of 10-15 eggs are retrieved during the process 11. The retrieved eggs are then placed in a nutritive liquid known as “culture medium” and incubated for 4.
3. Sperm retrieval
Sperm can be derived from a semen sample (from a partner or sperm donor) at a lab or a clinic the morning of egg retrieval. Other methods, such as testicular aspiration, which involves the use of a needle or surgical procedure to extract sperm directly from the testicle, could be recommended by a health professional under certain circumstances 3.
Fertilization can be attempted using two common methods. One is conventional insemination, which involves healthy sperm and mature eggs being mixed in a dish and and incubated overnight 4. The other is intracytoplasmic sperm injection (ICSI), where a single healthy sperm is injected directly into each mature egg. ICSI is often used when semen quality or number is a problem or if fertilization attempts during prior IVF cycles failed 4.
5. Preimplantation genetic diagnosis (PGD)
Preimplantation genetic diagnosis (PGD) is a form of prenatal diagnosis recommended to potential parents with known carrier status of a genetic disease, such as HD 12. PGD allows a prospective parent to check if a fertilized egg carries the disease causing gene, even before implantation. During this process, 5-6 days after fertilization 5, the embryo is grown in the laboratory until it has divided to about eight cells; this takes about two to three days. One or two cells are removed from each embryo at this stage to undergo genetic tests for HD. The removal of these cells at this early stage of development does not affect the embryo’s development. After testing, the HD-negative embryos are implanted into the prospective woman’s womb4. When choosing to pursue PGD, there is a “non-disclosure PGD” option that enables an at-risk parent to have HD-free children without finding out their own genetic status. Specifically, at-risk parents remain blind to their own results, the embryo’s genetic test results, how many successful fertilizations occurred, and how many embryos are implanted. Only the health professionals handling the genetic tests of the embryos are aware of the results. If there are no mutation-free embryos, the IVF cycle stops here, and the parents are informed that the process was unsuccessful without being informed specifically why 13. Some risks associated with this test include embryos being damaged when cells are removed, and the HD test being inconclusive due to a lack of DNA. This could result in a healthy embryo outside of the body without an official genetic diagnosis (if they are positive or negative for the genetic disease).
6. Embryo transfer
If PGD is performed, 5-6 days after fertilization, one to two healthy embryos found not to be carriers of HD are selected to be transfered. If PGD is not performed, a “fresh embryo transfer” is typically performed, where 1-2 days after fertilization, one to two healthy embryos are chosen to be transferred14. During the embryo transfer procedure, the health professional will insert a long, thin, and flexible tube called a catheter into the prospective mother’s vagina. After numbing medication is applied to the cervix, the tube is guided through the cervix and into the uterus, where one or more embryos are placed using a syringe attached to the catheter; if successful, an embryo will implant in the lining of your uterus 3. The mother may be instructed to receive a progesterone supplementation (administered via injection and vaginal suppositories) to maintain a thickened uterine lining 5.
7. Pregnancy Testing
About 12 days to two weeks after egg retrieval, a health professional will test a sample of the mother’s blood to detect whether they are pregnant. At least two pregnancy tests are typically done following the embryo transfer.
Many options are available to people at risk for HD, or who have been diagnosed with HD, who wish to start a family. One of these options includes IVF with PGD. If a prospective parent is at risk but has not received a genetic test, embryonic genetic testing such as non-disclosure PGD can be performed while protecting the at-risk parent from learning of their gene status 12. Research on this topic continues to be underway to reduce the risks associated with the process, and improve the success of the process 15.
The HOPES podcast team is currently working on a podcast focused on the personal experiences of people who have undergone IVF because of their relationship with HD. Stay tuned for its release!
- Lahiri, N. (2011) Making babies: having a family, the HD way. HD BUZZ. https://en.hdbuzz.net/036
- Science News (2018) More than 8 million babies born from IVF since the world’s first in 1978. Science Daily.https://www.sciencedaily.com/releases/2018/07/180703084127.htm
- Mayo Foundation for Medical Education and Research (2020) In vitro fertilization (IVF). Mayo Clinic. https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
- Keck School of Medicine of USC (2020). IVF Cycle Details.USC Fertility. https://uscfertility.org/fertility-treatments/ivf-cycle-details/
- Loma Linda University Center for Fertility & IVF (2020). In Vitro Fertilization (IVF). Loma Linda University. https://lomalindafertility.com/treatments/ivf/
- Betz, D., Fane, K. (2020) Human Chorionic Gonadotropin (HCG). Stat Pearls. https://www.ncbi.nlm.nih.gov/books/NBK532950/
- Flinn, S. (2008) Lupron-What Does It Do To Women’s Health? National Women’s Health Network. https://www.nwhn.org/lupron-what-does-it-do-to-womens-health/
- Coastal Fertility Medical Center (2019) The Importance of the IVF “Trigger” Shot in Egg Quality. https://www.coastalfertility.com/the-importance-of-the-ivf-trigger-shot-in-egg-quality/
- Mayo Foundation for Medical Education and Research (2020) Egg retrieval technique. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/multimedia/egg-retrieval-technique/img-20008644
- Blue Sky Fertility (2020) PGS / PGD. https://www.blueskyfertility.com/pgs-pgd-kansas-city#:~:text=Preimplantation%20Genetic%20Diagnosis%20(PGD),-Pre%2Dimplantation%20genetic&text=Briefly%2C%20the%20ovaries%20are%20stimulated,(and%20sometimes%206)%20days.
- Blancat, J. (2017) Preimplantation genetics and other reproductive options in Huntington disease. Handb Clin Neurol. 2017 ; 144: 107–111. doi:10.1016/B978-0-12-801893-4.00009-2.
- Reproductive Genetic Innovations LCC (n.d.) Preimplantation Genetic Diagnosis (PGD). http://www.rgipgd.com/documents/Non%20disclosure%20testing.pdf
- Johnson, J. (n.d.) What to know about embryo transfers. Medical New Today. https://www.medicalnewstoday.com/articles/314571
- The Fertility Institutes (n.d.) IVF Success Rates Increase Using PGD. https://www.fertility-docs.com/programs-and-services/pgd-screening/pgd-increases-ivf-success-rates.php