Passionate responses came fast and furious from Huntington's disease (HD) facebook communities following publication of articles by Gene Veritas about real-life dilemmas of two HD families who have made difficult reproductive choices at the extreme ends of the choice spectrum. These two courageous and thoughtful reports hit an emotionally charged nerve: Part 1, a couple who chose to abort an expanded-gene fetus that was subsequently donated to research, and Part 2, an 18 year old woman with juvenile-onset disease who with the support of her family has chosen to continue her pregnancy, which if positive for the expanded gene, her child will likely have juvenile onset disease as well.
No question that HD families face hard reproductive choices. What is known about how families make these decisions?
In an study published in 2007 Drs. R. Klitzman, Karen Marder and collaborators investigated the factors involved in reproductive decision-making in 21 individuals at risk for Huntington's disease [Klitzman R 2007]. Based on data obtained from individual 2-hour focused interviews, they identified that decisions occur over time in a series of dilemmas well known to HD families: whether to allow intimate relationships, whether to marry, whether to have at risk children, whether to undergo preimplantation genetic diagnosis (PGD), and if not PGD whether to test the fetus, and whether to abort a fetus positive for the mutant HD gene, or whether to adopt. Authors then put the many competing factors they identified to influence reproductive decisions into the following crisp categories:
- Ones own interests (not further defined)
- Others' sense of one's responsibilities
- Input from family members and health care professionals
- Broader moral, religious, or societal obligations
Or -- three out of five of these categories have to do with the opinions of others.
No escape from the opinions of others: Adding to the distress in HD families is the inevitable opinions from those who aren't at risk. A study of Swiss law and medical students showed that 94% favored systematic (routine) genetic testing of HD in at risk couples presenting with pregnancy [Elger B 2003]. Another study performed among Mexican neurologists, psychologists and psychiatrists showed that 38% thought that gene expanded individuals "should not" have children [Alonso Vilatela ME 1999]. Another study in three European countries found that most geneticists, obstetricians, lay individuals and pregnant women say they would choose abortion of a fetus with the HD mutation [Drake H 1996].
However, if decision-making is for real: It is clearly a different story if you are the couple at risk. In a French study of couples who were pregnant at the time of genetic testing, most (73%) of those who tested positive for the HD mutation chose to continue the pregnancy [Lesca G 2002]. Only 9% opted to test the fetus. Other studies show that completed pregnancy rates among those couples who have tested positive for the HD mutation are similar [Taylor SD 2005] in some countries, and lower [Goizet C 2002] in others, when compared to couples with no genetic risk.
How "real" is the PGD option? Decisions for those who plan pregnancy and wish an HD-free biologic child would be easier if all at risk couples knew about and accessed PGD procedures that resulted in pregnancy. But how practical is PGD? And why is utilization of this procedure low -- even in countries where national insurance pays for PGD? A recent study that combined results from 4 European PGD centers located in France, Belgium and the Netherlands in the years between 1995 and 2008 showed that only 1 in 5 oocyte retrieval cycles resulted in successful pregnancies [Van Rij MC 2012]. The majority of couples stopped PGD if they failed 2 cycles. Even though direct cost of PGD was covered by health insurance, relatively few couples of those estimated to be at risk accessed this service: in France (6%), Belgium (8.5%), the Netherlands (5.8%). Why so few? Lack of awareness, the requirement for gene testing of the parent prior to PGD, or geographic distance from centers, or stress associated with the procedures, or stigma factors from medical providers, etc.? In another study, couples who had a previous abortion would choose PGD over another abortion, however they rated the combined stress factors of undergoing PGD nearly as high as that of abortion [Lavery SA 2002].
There is no reported data from the U.S. where PGD with non-disclosure is more frequently allowed; the at risk couple is not required to gene test prior to the procedure. However in the U.S., costs of PGD are more often not covered by medical insurance. Even in developed countries in Europe and North America, PGD as presently practiced is not an easy or practical alternative for most couples.
What's stigma got to do with it? Those who are affected by identifiable genetic disease like HD suffer not just from societal and intra-family stigma -- but also from internalized stigma that we have "learned" from others, and incorporated into self. Often internalized stigma has great negative impact on HD individuals and families. Unfortunately there have been no studies how much HD stigma influences life decisions, including reproductive ones in HD. How many decisions are made because we hate aspects of ourselves -- not just the disease.
The goal is to make life worth living: No one should answer for another whether life was, is, or will be worth living because HD gets bad for a long time at the end. Instead all of us, our HD institutions, our organizations. and our families should put more energy into improving treatment and care for those with HD, so that lives become more worth living. And we should work to identify, describe, and decrease HD stigma -- which adds so much burden for all in HD families. And in regard to helping with reproductive decisions we should work to provide non-discriminatory support, and easier voluntary access to PGD with attention to supporting the emotional and financial costs involved in this procedure.
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. PubMed abstract
Elger B, Harding T. Huntington's disease: do future physicians and lawyers think eugenically?. Clin Genet. 2003 Oct;64(4):327-38. PubMed abstract
Alonso Vilatela ME, Ochoa Morales A, García de la Cadena C, Ruiz López I, Martínez Aranda C, Villa A. Predictive and prenatal diagnosis of Huntington's disease: attitudes of Mexican neurologists, psychiatrists, and psychologists. Arch Med Res. 1999 Jul-Aug;30(4):320-4. PubMed abstract
Drake H, Reid M, Marteau T. Attitudes towards termination for fetal abnormality: comparisons in three European countries. Clin Genet. 1996 Mar;49(3):134-40. PubMed abstract
Lesca G, Goizet C, Dürr A. Predictive testing in the context of pregnancy: experience in Huntington's disease and autosomal dominant cerebellar ataxia. J Med Genet. 2002 Jul;39(7):522-5. PubMed abstract
Taylor SD. Predictive genetic test decisions for Huntington's disease: elucidating the test/no-test dichotomy. J Health Psychol. 2005 Jul;10(4):597-612. PubMed abstract
Goizet C, Lesca G, Dürr A; French Group for Presymptomatic Testing in Neurogenetic Disorders. Presymptomatic testing in Huntington's disease and autosomal dominant cerebellar ataxias. Neurology. 2002 Nov 12;59(9):1330-6. PubMed abstract
Van Rij MC, De Rademaeker M, Moutou C, Dreesen JC, De Rycke M, Liebaers I, Geraedts JP, De Die-Smulders CE, Viville S; BruMaStra PGD working group. Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres. Eur J Hum Genet. 2012 Apr;20(4):368-75. doi: 10.1038/ejhg.2011.202. Epub 2011 Nov 9. PubMed abstract
Lavery SA, Aurell R, Turner C, Castello C, Veiga A, Barri PN, Winston RM. Preimplantation genetic diagnosis: patients' experiences and attitudes. Hum Reprod. 2002 Sep;17(9):2464-7. PubMed abstract