Once human embryos are created, embryo biopsy can be performed and one or several cells from the embryo can be removed and used for genetic testing. Embryos can be tested for the number of chromosomes (aneuploidy), specific chromosomal re-arrangements (translocation, deletions, inversion, etc), as well as single-gene genetic disorders. Different technologies available for genetic testing are rapidly developing and becoming available for clinical use.
Huntington’s disease is an adult-onset degenerative, fatal genetic disease. Most carriers of the disease are healthy at birth and during early adulthood, but begin to develop symptoms in their 40’s. It is an autosomal dominant condition, meaning that one copy of the gene is all that is needed to develop the disease. Furthermore, there is a 50% chance of passing the gene along to offspring, who will in turn develop the disease as well. Sufferers experience a variety of symptoms including dementia, motor issues, difficulty swallowing and difficulty speaking prior to the loss of being able to care for oneself and/or interact with others. Most victims of the disease succumb to it in early middle age (40-60 years old). It is the slow loss of function as well as the early loss of life that make Huntington’s Disease a terrifying prospect.
Perhaps one of the more confounding aspects of the disease is that those affected may not know that they are carriers until after they have children of their own. Even if a parent has died of Huntington’s, without genetic testing, the adult child only knows of the 50/50 odds of carrying the gene him or herself. And while Medicine does not have a treatment or cure for Huntington’s, there is an opportunity to prevent passing along the gene to the offsprings through Preimplantation Genetic Diagnosis (PGD) and Invitro Fertilization (IVF).
Although most people think of IVF as a procedure for those having difficulty conceiving a child, coupled with modern genetic testing, IVF can help ‘bring home’ a healthy child in the face of predisposing genetic illnesses, whether it be Huntington’s Disease, Cystic Fibrosis or certain forms of Cancer.
We recently treated a couple in just this situation. The potential Father had seen his own Mother die of Huntington’s Disease but declined to be tested himself, knowing that if he indeed was a carrier, there was nothing he could do to prevent the disease in himself and little to lessen its impact. However, he and his wife did realize that there was something they could do to conceive children free of this disease.
Prior to commencing treatment, the couple would be seen by a Genetic Counselor to discuss their options. Upon discharge to the Reproductive Endocrinologist, the wife would undergo an Infertility workup including blood work and ultrasound. Measured would be the woman’s Follicle Stimulating Hormone (FSH), Estradiol, Antimullerian Hormone Level (AMH) and Antral Follicle Count. Crucial to successful IVF with PGD, it is important to determine the ‘fertility potential’ of the couple. The tests given can help create a clearer picture as to the woman’s likely response to hormones necessary for producing and maturing the greatest number of eggs in a single cycle. The AMH level also tells the Reproductive Endocrinologist more about the number of eggs the woman might have remaining, a number that diminishes over time, as well as the quality of the eggs as well. The woman’s uterus would also be imaged in order to confirm normal anatomy. The husband would also undergo a semen analysis to measure the quantity and quality of sperm. Following the testing, the couple would then be counseled as to the likelihood of success based on the results. As with most Infertility issues, those that often affect the female partner (age, hormone levels etc.) are more complicated to treat in order to produce the best results while ‘male factor’ can often be circumvented through the use of laboratory techniques including Intracytoplasmic Sperm Injection (ICSI).
When PGD for single gene disorder is planned, another very important part of the work-up includes genetic set-up. Usually, the prospective parents as well as several other family members have their DNA tested for specific mutation and several other regions of the specific chromosomes to make sure that in the future the testing can be performed with high accuracy and specificity on a limited number of cells, or a single cell, removed from the each embryo. In case of Hungtington’s disease, as well as some other genetic conditions, non-disclosure testing is possible – meaning that genetically normal embryos can be created without knowing if one of the parents is actually a carrier of this disease and will develop symptoms in the future.
After the initial evaluation of the couple by reproductive endocrinologist as well as genetic counseling and genetic set-up is complete, the couple moves forward with an IVF/PGD cycle.
The key to success is a combination of the reproductive endocrinology physician, embryology lab as well as genetic lab working together and coordinating efforts.
The role of the reproductive endocrinologist is to optimize of IVF stimulation and choose just the right amount of hormones needed for ovarian stimulation, careful monitoring, and performing oocyte retrieval and embryo transfer procedures efficiently.
The embryology lab has to be very skilled in micromanipulations, including ICSI, embryo biopsy at every stage of development (polar bodies, blastomere on day 3 of embryo development, as well as blastocyst biopsy), and has to be able to culture embryo until blastocyst stage( day 5-6 embryo culture), and have efficient embryo vitrification program (freezing ).
The top notch genetic facility will also be able to testing for specific genetic mutation as well as to perform Linkage Analysis as well as experience with a variety of different techniques including FISH, PCR, Microarray or array CGH.
Then begins the ‘Numbers Game’. The more embryos are created, the better chance of some of the embryos that are developing well in culture to be free of Huntington’s disease and suitable for embryo transfer.
If the Father does not want to know if he indeed has the gene and consequently will develop the Huntington’s disease itself, the genetic testing is based not on identifying the mutation responsible for the Huntington’s disease, but on linkage analysis – the study of small polymorphic regions of the specific chromosomes that can potentially exclude the embryos carrying the chromosome received from affected grand-parent.
And the results? After going through this complicated process and working closely with the physician, embryology lab, and the team of geneticist, the couple conceived a Huntington’s disease free twin gestation and was discharge to an Obstetrician to monitor what we hope to be a continued healthy and happy pregnancy!
Our job is done here…Sleep well children!