Skip to main content
SpringerLink
Log in

Uptake of Preimplantation Genetic Diagnosis in Female BRCA1 and BRCA2 Mutation Carriers

  • Original Research
  • Published:
Journal of Genetic Counseling

Abstract

Women with a germline pathogenic variant in the BReast CAncer susceptibility genes (BRCA1 or BRCA2) have an increased risk of early-onset breast and ovarian cancer. In addition to weighing cancer screening and risk-reduction options, healthy BRCA mutation carriers of childbearing age may choose to preclude passing the mutation to the next generation. In the current study, we report on preimplantation genetic diagnosis (PGD) practices in BRCA-positive Israeli women who were offered PGD at no cost. Methods: we measured PGD uptake, decision satisfaction or regret, and predictors of uptake. Of the 70 participant female carriers, only 25.7% chose to use PGD to prevent transmission of the mutation, and were not predicted by age or religious affiliation. For those who chose IVF/PGD, satisfaction with the decision regarding IVF and PGD was significantly higher than those who did not have IVF and PGD (p < 0.04). Experiencing previous infertility was the only significant predictor of uptake of IVF/PGD (p < 0.001), which may suggest that BRCA status is secondary to infertility in the decision-making process for PGD in women with a BRCA mutation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Allum, N., Sibley, E., Sturgis, P., & Stoneman, P. (2013). Religious beliefs, knowledge about science and attitudes towards medical genetics. Public Understanding of Science, 23(7), 833–849.

    Article  PubMed  Google Scholar 

  • American Cancer Society. (2016). breast cancer risk factors. Retrieved September 12, 2016, from http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-risk-factors

  • Anderson, R. R. (2009). Religious traditions and prenatal genetic counseling. In American journal of medical genetics part C: Seminars in medical genetics (pp. 52–61). Wiley Subscription Services: A Wiley Company, 151C.

    Article  Google Scholar 

  • Antoniou, A., Pharoah, P., & Narod, S. (2003). Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. American Journal of Human Genetics, 72, 1117–1130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baruch, S., Kaufman, D., & Hudson, K. L. (2008). Genetic testing of embryos: practices and perspectives of US in vitro fertilization clinics. Fertility and sterility, 89(5), 1053–1058.

    Article  PubMed  Google Scholar 

  • Ben-Naji, J., Serhal, P., SenGupta, S., Doye, K., & Wells, D. (2016). Preimplantation genetic diagnosis: an overview and recent advances. The Obstetrician and Gynecologist, 18(2), 99–106.

    Article  Google Scholar 

  • Brehaut, J., O'Connor, A., Wood, T., Hack, T., Siminoff, L., Gordon, E., & Feldman-Stewart, D. (2003). Validation of a decision regret scale. Medical Decision Making, 23(4), 281–292.

    Article  PubMed  Google Scholar 

  • Campeau, P., Foulkes, W., & Tischkowitz, M. (2008). Hereditary breast cancer: new genetic developments, new therapeutic avenues. Human Genetics, 124, 31–42.

    Article  CAS  PubMed  Google Scholar 

  • Center for Disease Control. (2015). Birth and natality. Retrieved May 7, 2017, from https://www.cdc.gov/nchs/fastats/births.htm

  • Central Intelligence Agency. (2017). World Factbook. Retrieved May 13, 2017, from Central Intelligence Agency: https://www.cia.gov/library/publications/the-world-factbook/index.html

  • Chan, J., Johnson, L., Sammel, M., DiGiovanni, L., Voong, C., Domchek, S., & Gracia, C. (2017). Reproductive decision-making in women with BRCA1/2 mutations. Journal of Genetic Counseling, 26(3), 594–603.

    Article  PubMed  Google Scholar 

  • Cunningham, J., Goldsmith, L., & Skirton, H. (2015). The evidence base regarding the experiences of and attitudes to preimplantation genetic diagnosis in prospective clients. Midwifery, 31, 288–296.

    Article  PubMed  Google Scholar 

  • Dagan, E., Birenbaum-Carmeli, D., Friedman, E., & Feldman, B. (2017). Performing and declining PGD: Accounts of Jewish Israeli women who carry a BRCA1/2 mutation or partners of male mutation carriers. Journal of Genetic Counseling, 26, 1070–1079.

    Article  PubMed  Google Scholar 

  • Dean, M., & Rauscher, E. (2017). It was an emotional baby: previvors’ family planning decision making styles about hereditary breast and ovarian cancer risk. Journal of Genetic Counseling, 1–13.

  • Derks-Smeets, I., de Die-Smulders, C., Mackens, S., van Golde, R., Paulussen, A., Dreesen, J., et al. (2014a). Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors. Breast Cancer Research and Treatment, 145(3), 673–681.

    Article  PubMed  Google Scholar 

  • Derks-Smeets, I., Gietel-Habets, J., Tibben, A., Tjan-Heignen, V., Meijer-Hoogeveen, M., Geraedts, J., & de Die-Smulders, C. (2014b). Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with heriditary breast and ovarian cancer. Human Reproduction, 29(5), 1103–1112.

    Article  CAS  PubMed  Google Scholar 

  • Donnelly, L., Watson, M., Moynihan, C., Bancroft, E., Evans, D., Eeles, R., et al. (2013). Reproductive decision-making in young female carriers of a BRCA mutation. Human Reproduction, 28(4), 1006–1012.

    Article  CAS  PubMed  Google Scholar 

  • Drazba, K., Kelley, M., & Hershberger, P. (2014). A qualitative inquiry of the financial concerns of couples opting to use preimplantation genetic diagnosis to prevent the transmission of known genetic disorders. Journal of Genetic Counseling, 23(2), 202–211.

    Article  PubMed  Google Scholar 

  • Ethics Committe of the American Society for Reproductive Medicine. (2013). Use of preimplantation genetic diagnosis for serious adult onset conditions: a committee opinion. Fertility and Sterility, 100(1), 54–57.

    Article  Google Scholar 

  • Fortuny, D., Balmana, J., Grana, B., Torres, A., Cajal, T., Darder, E., et al. (2009). Opinion about reproductive decision making among individuals undergoing BRCA1/2 genetic testing in a multicentre Spanish cohort. Human Reproduction, 24(4), 1000–1006.

    Article  PubMed  Google Scholar 

  • Gabai-Kapara, E. L.-K., Lahad, A., Kaufman, B., Friedman, E., Segev, S., Renbaum, P., & Beeri, R. (2014). Population based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proceedings of the National Academy of Sciences of the United States of America, 111(39), 14205–14210.

    Article  CAS  Google Scholar 

  • Hamilton, R., & Hurley, K. (2010). Conditions and consequences of a BRCA mutation in young, single women of childbearing age. Oncology Nursing Forum, 37(5), 627–634.

    Article  PubMed  Google Scholar 

  • Haude, K., McCarthy Veach, P., LeRoy, B., & Zierhut, H. (2016). Factors influencing the decision-making process and long-term interpersonal outcomes for parents who undergo preimplantation genetic diagnosis for Fanconi Anemia: A qualitative investigation. Journal of Genetic Counseling, 26, 640–655.

    Article  PubMed  Google Scholar 

  • Homes-Rovner, M., Kroll, J., Schmitt, N., Rovner, D., Breer, M., Rothert, M., & Talarczyk, G. (1996). Patient satisfaction with health care decisions: the satisfaction with decision scale. Medical Decision Making, 16(1), 58–64.

    Article  Google Scholar 

  • Hurley, K., Rubin, L., Werner-Lin, A., Sagi, M., Kemel, K., & Stern, R. P. (2012). Incorporating information regarding preimplantation genetic diagnosis into discussions concerning testing and risk management for BRCA1/2 mutations. Cancer, 118(24), 6270–6277.

    Article  PubMed  Google Scholar 

  • Insogna, I. G., Ginsburg, E. S., & Partridge, A. H. (2017). Fertility preservation in BRCA carriers: special considerations. In Managing BRCA mutation carriers (pp. 171–187). New Haven: Springer International Publishing.

    Chapter  Google Scholar 

  • Israel Central Bureau of Statistics. (2012). Average age at first birth according to population type and mother's religion 1994-2012. Retrieved May 26, 2017, from www.cbs.gov.il/www/publications/lidot/lidot_table2_12.pdf

  • Järvholm, S., Thurin-Kjellberg, A., & Broberg, M. (2017). Experiences of pre-implantation genetic diagnosis (PGD). Journal of Genetic Counseling, 26, 1008–1016.

    Article  PubMed  PubMed Central  Google Scholar 

  • King, M., Marks, J., & Mandell, J. (2003). Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science, 302, 643–646.

    Article  CAS  PubMed  Google Scholar 

  • Levy-Lahad, E., Catane, R., Eisenberg, S., Kaufman, B., Hornreich, G., Lishinsky, E., et al. (1997). Founder BRCA1 and BRCA2 mutations in Ashekenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. American Journal of Human Genetics, 60(5), 1059–1067.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mazza, E. (2015). Angelina Jolie undergoes surgery to remove ovaries, fallopian tubes to avoid cancer. Retrieved from Huffington post: https://www.huffingtonpost.com/2015/03/24/angelina-jolie-ovaries-surgery_n_6928748.html

  • Menon, U., Harper, J., Sharma, A., Fraswer, L., Burnell, M., ElMasry, K., et al. (2007). Views of BRCA gene mutation carriers on preimplantation genetic diagnosis as a reproductive option for hereditary breast and ovarian cancer. Human Reproduction, 22(6), 1573–1577.

    Article  CAS  PubMed  Google Scholar 

  • Moyer, V. (2014). Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. Annals of Internal Medicine, 160(4), 271–281.

    Article  PubMed  Google Scholar 

  • Muller, C., & Cameron, L. D. (2016). It’s complicated—factors predicting decisional conflict in prenatal diagnostic testing. Health Expectations, 19(2), 388–402.

    Article  PubMed  Google Scholar 

  • National Comprehensive Cancer Network. (2016). Practice guidelines in oncology: genetic/familial high risk assessment: breast and ovarian. Retrieved September 12, 2016, from http://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf

  • Ormondroyd, E., Donnelly, L., Moynihan, C., Savona, C., Bancroft, E., Evans, D., et al. (2012). Attitudes to reproductive genetic testing in women who had a positive BRCA test before having children: a qualitative analysis. European Journal of Human Genetics, 20(1), 4–1.

    Article  PubMed  Google Scholar 

  • Peate, M., Meiser, B., Cheah, B. C., Saunders, C., Butow, P., Thewes, B., et al. (2012). Making hard choices easier: a prospective, multicentre study to assess the efficacy of a fertility-related decision aid in young women with early-stage breast cancer. British Journal of Cancer, 106(6), 1053–1061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinn, G., Vadaparampil, S., Wilson, C., King, L., Choi, J., Miree, C., & Friedman, S. (2009). Attitudes of high-risk women toward implantation genetic diagnosis. Fertility and Sterility, 91(6), 2361–2368.

    Article  PubMed  Google Scholar 

  • Rich, T., Liu, M., Etzel, C., Bannon, S., Mork, M., & Ready, K. (2014). Comparison of attitudes regarding preimplantation genetic diagnosis among patients with hereditary cancer syndromes. Familial Cancer, 13(2), 291–299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Risch, H., McLaughlin, J., Cole, D., Rosen, B., Bradley, L., Kwan, E., et al. (2001). Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. The American Journal of Human Genetics, 68(3), 700–710.

    Article  CAS  PubMed  Google Scholar 

  • Rubin, L. R., Werner-Lin, A., Sagi, M., Cholst, I., Stern, R., Lilienthal, D., & Hurley, K. (2014). ‘The BRCA clock is ticking!’: negotiating medical concerns and reproductive goals in preimplantation genetic diagnosis. Human Fertility, 17(3), 159–164.

    Article  PubMed  Google Scholar 

  • Seigel, R., Miller, K., & Jemal, A. (2016). Cancer statistics. A Cancer Journal for Clinicians, 66(1), 7–30.

    Article  Google Scholar 

  • Staton, A. D., Kurian, A., Cobb, K., Mills, M., & Ford, J. (2008). Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers. Familial Cancer, 7, 179–186.

    Article  PubMed  Google Scholar 

  • Steinberg, A. (2003). Jewish ethics. In Encyclopedia of Jewish Medical Ethics (p. 380). New York: Feldheim.

    Google Scholar 

  • Sunstein, C. (2016). Do people like nudges? Administrative Law Review. https://dash.harvard.edu/handle/1/16147874.

  • Van Rij, M. C., De Rademaeker, M., Moutou, C., Dreesen, J. C., De Rycke, M., Liebaers, I., et al. (2012). Preimplantation genetic diagnosis (PGD) for Huntington’s disease: the experience of three European centres. European Journal of Human Genetics, 20(4), 368–375.

  • Werner-Lin, A. (2008). Beating the biological clock: the compressed family life cycle of young women with BRCA gene alterations. Social Work in Health Care, 47(4), 416–437.

    Article  PubMed  Google Scholar 

  • Woodson, A. H., Muse, K. I., Lin, H., Jackson, M., Mattair, D., Schover, L., et al. (2014). Breast cancer, BRCA mutations, and attitudes regarding pregnancy and preimplantation genetic diagnosis. The Oncologist, 19(8), 797–804.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zuckerman, S., Zeevi, D. A., Gooldin, S., & Altarescu, G. (2017). Acceptable applications of preimplantation genetic diagnosis (PGD) among Israeli PGD users. European Journal of Human Genetics, 25, 1113–1117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the couples who participated in our study and Aviva Yoselis of Viva Research Institute for her editorial assistance.

Author information

Authors and Affiliations

  1. Shaare Zedek Medical Center, Jerusalem, Israel

    Pnina Mor

  2. University of Toronto, 155 College Street, Toronto, Ontario, M5T 1P8, Canada

    Sarah Brennenstuhl & Kelly A. Metcalfe

Authors
  1. Pnina Mor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah Brennenstuhl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kelly A. Metcalfe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pnina Mor.

Ethics declarations

Conflict of Interest

Pnina Mor, Sarah Brennenstuhl, and Kelly A Metcalfe declare that they have no conflict of interest.

Human Studies and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Animal Studies

This article does not contain any studies with animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mor, P., Brennenstuhl, S. & Metcalfe, K.A. Uptake of Preimplantation Genetic Diagnosis in Female BRCA1 and BRCA2 Mutation Carriers. J Genet Counsel 27, 1386–1394 (2018). https://doi.org/10.1007/s10897-018-0264-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10897-018-0264-2

Keywords

Search

Navigation