VHL & Family Planning: Ethical Considerations & the Importance of Counseling

Andrea S Berkemeier BSE Biomedical Engineering, University of Michigan

MA Bioethics & Society, King’s College London asberkemeier@gmail.com

This presentation is derived from my dissertation research submitted to King’s College London in 2015.

International VHL Medical Symposium Boston, MA Saturday, April 9, 2016

Children of VHL-positive couples

50% chance of inheritance

VHL & Reproductive Physiology

Infertility Tumors of the epididymis may block sperm and consequently cause infertility.

VHL Alliance 2014

Progesterone (P) Tumor Growth Some research suggests that high exposure to P (ie: during pregnancy) or sustained exposure to P (ie: from P-based contraceptives) may be associated with increased VHL tumor manifestation / growth.

Adekola et al. 2013; Franzten et al 2012

VHL & Reproductive Physiology

Infertility Tumors of the epididymis may block sperm and consequently cause infertility.

VHL Alliance 2014

Progesterone (P) Tumor Growth Some research suggests that high exposure to P (ie: during pregnancy) or sustained exposure to P (ie: from P-based contraceptives) may be associated with increased VHL tumor manifestation / growth.

Adekola et al. 2013; Franzten et al 2012

Are there other questions I

should be asking?

Can I have children? SHOULD

I have children?

REPRODUCTIVE CHOICE What are the options? Who gets to choose?

The Alternative Options:

PnGT

IVF (+PGD)

Adoption

Prenatal diagnosis (PnGT) with termination of VHL-positive fetus(es)

Acquiring existing children instead of reproducing (creating new children)

In vitro fertilization (IVF) with pre-implantation genetic diagnosis (PGD), plus selective implantation of VHL-negative embryos

“Transmission Guilt”, “Genetic Responsibility”

“I always hoped to have children one day, but I risk passing on VHL and that [having children] may be both selfish and irresponsible.…

VHL has forced me to take a more pragmatic approach to the whole procreation thing and to plan the best possible future for a child.…

I know my father feels incredibly guilty about passing his illness on, even though it was not in any way his fault. I feel lucky that science and technology have given me the opportunity to at least try to have children without passing on VHL.”

SenGupta et al., 2012, p103

Novas and Rose, 2000 Kasparian et al., 2015

Is this negative eugenics?

Some say NO. These are no longer governmentally mandated but rather individual decisions (Habermas 2003).

Some say YES, but with a revised goal. The “aim is, first and foremost to relieve… all human beings of the burdens of genetic disease” (Buchanan 1996).

PnGT: PRENATAL GENETIC TESTING The original option?

Prenatal Genetic Testing (PnGT)

Two methods:

• Amniocentesis (mid 2nd trimester)

• CVS (late 1st trimester)

Original

Developed later

“To alleviate the “humiliation” that women faced in obtaining post-amniocentesis “therapeutic abortions”.

Cowan 1993, p14

Why test earlier?

Why are women humiliated?

“Earlier diagnosis seemed particularly necessary because of the social and religious attitudes of some ethnic groups at risk. For instance, British Muslims originating from Pakistan are as distressed as anyone else by having children suffering from [a rare genetic disease], but most find mid-trimester diagnosis and abortion unacceptable. However, they expressed a lively interest in the possibility of first trimester diagnosis.”

Cowan 1993, p15 – quoting Modell 1986

Why are women humiliated?

“Earlier diagnosis seemed particularly necessary because of the social and religious attitudes of some ethnic groups at risk. For instance, British Muslims originating from Pakistan are as distressed as anyone else by having children suffering from [a rare genetic disease], but most find mid-trimester diagnosis and abortion unacceptable. However, they expressed a lively interest in the possibility of first trimester diagnosis.”

(Cowan 1993, p15 – quoting Modell 1986)

Social Factors

Ethical Frameworks

Evaluating Reproductive

Options

Is PnGT “appropriate” for VHL?

“Requests for [PnGT] for conditions which (like VHL) do not affect intellect and have some treatment available are not common. Differences in perspective may exist… regarding the use of [PnGT],

particularly if the testing is being considered for the purpose of termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.”

Frantzen et al. 2012, VHL Chapter of Gene Reviews

But knowledge is power, right?

• Most women who are given a positive test result terminate their pregnancy (Press 2008).

• Women who actively choose to continue a pregnancy with a positive test result may be socially shunned (Lippman 1991, p28).

• Within pediatric medicine, it is widely recommend to wait to perform genetic testing until the patient can consent as a competent adolescent / adult (Borry et al. 2006).

Can I have PnGT even if I don’t want to terminate VHL-positive pregnancies?

“Expressionist Objection”

What do these technologies say about VHL-positive individuals?

1. The lives of individuals with disabilities are not worth living.

2. Only perfect individuals should be brought into the world (and imperfect individuals have no right to exist.)

Buchanan 1996, p28

Buchanan, 1996

PnGT: an undesirable contingency plan

Decision-making within the context of this contingency plan is

“extremely burdensome for both the couple and the professionals involved.”

De Die-Smulders et al. 2003, p309 – citing Hardman 2009

IVF WITH PGD A more ethical option? (Cameron & Williamson 2002)

IVF Counseling Agenda

The “mechanics”

The welfare of the child

“Spare” embryos

Questions?

[Legally] we must consider the welfare of any existing or future child(ren) born as a result of treatment. As part of this initial assessment, we will ask you to complete a questionnaire. If any information given raises concerns, these will be discussed with you and you will be asked to meet with a counsellor. Very occasionally, it may be necessary to delay or cancel your treatment.

National Health Service, 2008, p30

Welfare of the Child

Welfare of the Child

VHL-positive or VHL-negative,

the child will still be

VHL-affected because YOU have VHL.

‘Spare’ embryos

• ‘Spare’ == ‘suboptimal’ or in excess

• ‘Utility’ of the fresh embryo

“Couples should not be approached for the donation of fresh embryos to research… subject to some exceptions [such as PGD-positive embryo s, because]… a couple who has chosen PGD for a serious inheritable condition is unlikely to wish to have an ‘affected’ embryo transferred or frozen and is more likely to consent to such embryos [for research]. “

Scott et al. 2012, p43-45 – emphasis in original

ADOPTION The forgotten option?

External limitations?

Assisted Reproductive Technology (ART) is marketed as enhancing reproductive choice, [but] many feminists counter that ART actually narrows choice by discouraging alternatives like child-free living and adoption.

Jennings 2010, citing: Bartholet 1992, 1993; van Balen and Inhorn 2002;

Becker 2000; Franklin 1998; Rebick 1993; Rothman 1984, 1989/2000.

Internal limitations?

“People who emphasize the importance of genetic background… [and those] who perceive potential genetic problems with adoptees will be less willing to adopt a child.”

(Bausch 2006, p50 , p60 )

Is there anything ELSE

we should consider?

Concluding Thoughts

• NO reproductive option guarantees the genetic outcome of the child.

• An “informed decision” requires understanding of complex ethical considerations.

• Social factors impact the ethical frameworks from which a patient (or counselor) approaches family planning.

• Patients may benefit from comprehensive counseling.

APPENDICES

Acronyms

ART Artificial Reproductive Technology

IVF In-vitro Fertilization

P Progesterone

PGD Pre-implantation Genetic Diagnosis

PnGT Prenatal Genetic Testing

Works Cited (page 1 of 2) Adekola, H., Soto, E., Lam, J., Bronshtein, E., Chaiworapongsa, T. and Sorokin, Y. (2013) ‘von Hippel-Lindau Disease

and Pregnancy: What an Obstetrician Should Know’, Obstetrical and Gynecological Survey, 68(9), pp. 655–662. doi: 10.1097/OGX.0b013e3182a85063

Bausch, R. S. (2006) ‘Predicting Willingness to Adopt a Child: A Consideration of Demographic and Attitudinal Factors’, Sociological Perspectives, 49(1), pp. 47–65. doi: 10.1525/sop.2006.49.1.47.

Borry, P., Stultiens, L., Nys, H., Cassiman, J.-J. and Dierickx, K. (2006) ‘Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers’, Clinical Genetics, 70(5), pp. 374–381. doi: 10.1111/j.1399-0004.2006.00692.x.

Buchanan, A. (1996) ‘Choosing Who Will Be Disabled: Genetic Intervention and the Morality of Inclusion’, Social Philosophy and Policy, 13(02). doi: 10.1017/s0265052500003447.

Cameron, C. and Williamson, R. (2002) ‘Is there an ethical difference between preimplantation genetic diagnosis and abortion?’, Journal of Medical Ethics, 29(2), pp. 90–92. doi: 10.1136/jme.29.2.90.

Cowan, R. S. (1993) ‘Aspects of the History of Prenatal Diagnosis’, Fetal Diagnosis and Therapy, 8(1), pp. 10–17. doi: 10.1159/000263869.

De Die-Smulders, C. E. M., de Wert, G. M. W. R., Liebaers, I., Tibben, A., Evers-Kiebooms, G., de Die-Smulders1, C. E. M., de Wert2, G. M. W. R., Liebaers4, I., Tibben5, A. and and, 6 (2013) ‘Reproductive options for prospective parents in families with Huntington’s disease: clinical, psychological and ethical reflections’, Oxford Journals - Medicine & Health - Human Reproduction Update, 19(3), pp. 304–315. doi: 10.1093/humupd/dms058. Available online at: http://humupd.oxfordjournals.org/content/19/3/304.long [Accessed: 7 June 2015].

Frantzen, C., Links, T. P., and Giles, R. H. (2012a), 'Von Hippel-Lindau Disease'. GeneReviews®. [Internet]. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1463 [Accessed 4 Feb. 2015].

Frantzen, C., Kruizinga, R. C., van Asselt, S. J., Zonnenberg, B. A., Lenders, J. W. M., de Herder, W. W., Walenkamp, A. M. E., Giles, R. H., Hes, F. J., Sluiter, W. J., van Pampus, M. G. and Links, T. P. (2012) ‘Pregnancy-related hemangioblastoma progression and complications in von Hippel-Lindau disease’, Neurology, 79(8), pp. 793–796. doi: 10.1212/wnl.0b013e3182661f3c

Habermas, J. (2003) The future of human nature. Cambridge, UK: Polity Press.

Works Cited (page 2 of 2) Jennings, P. K. (2010) ‘“God Had Something Else in Mind”: Family, Religion, and Infertility’, Journal of Contemporary

Ethnography, 39(2), pp. 215–237. doi: 10.1177/0891241609342432.

Kasparian, N. A., Rutstein, A., Sansom-Daly, U. M., Mireskandari, S., Tyler, J., Duffy, J. and Tucker, K. M. (2014) ‘Through the looking glass: an exploratory study of the lived experiences and unmet needs of families affected by Von Hippel–Lindau disease’, European Journal of Human Genetics, 23(1), pp. 34–40. doi: 10.1038/ejhg.2014.44.

Lippman, A. (1991) ‘Prenatal genetic testing and screening: constructing needs and reinforcing inequities.’, American Journal of Law and Medicine, 17(1-2), pp. 15–50.

NHS - National Health Service (2008) Guy’s and St Thomas' Centre for Preimplantation Genetic Diagnosis. Available at: http://www.guysandstthomas.nhs.uk/resources/our-services/acu/pgd-booklet.pdf [Accessed: 7 June 2015]

Novas, C. and Rose, N. (2000) ‘Genetic risk and the birth of the somatic individual’, Economy and Society, 29(4), pp. 485–513. doi: 10.1080/03085140050174750.

Press, N. (2008) ‘Genetic Testing and Screening’, in Crowley, M. (ed.) From Birth to Death and Bench to Clinic: The Hastings Center Bioethics Briefing Book for Journalists, Policymakers, and Campaigns. Garrison, NY: The Hastings Center, pp. 73–78. Available at: http://www.thehastingscenter.org/Publications/BriefingBook/Detail.aspx?id=2176 [Accessed: 29 March 2015].

Scott, R., Williams, C., Ehrich, K. and Farsides, B. (2012) ‘Donation of “spare” fresh or frozen embryos to research: who decides that an embryo is “spare” and how can we enhance the quality and protect the validity of consent?’, Medical Law Review, 20(3), pp. 255–303. doi: 10.1093/medlaw/fws013.

SenGupta, S. B., Vadaparampil, S. T. and Menon, U. (2011) ‘Preimplantation Genetic Diagnosis for Hereditary Cancers’, inReproductive Health and Cancer in Adolescents and Young Adults. Springer Science + Business Media, pp. 103–113.

VHLA – VHL Alliance (2014). The VHL Handbook: What You Need to Know, A Reference Handbook for people with von Hippel-Lindau, their families, and support personnel. Available online at: http://www.vhl.org/wordpress/patients-caregivers/getting-support/ [Accessed 4 Feb. 2015].

VHLA - VHL Alliance (2015) Childbearing Choices. Available at: http://www.vhl.org/wordpress/patients-caregivers/basic-facts-about-vhl/commonly-occurring-vhl-manifestations/reproductive-organs-and-pregnancy/pregnancy-and-vhl/childbearing-choices/ (Accessed: 18 July 2015)