Journal of Genetic Counseling

, Volume 27, Issue 6, pp 1386–1394 | Cite as

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

  • Pnina MorEmail author
  • Sarah Brennenstuhl
  • Kelly A. Metcalfe
Original Research


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.


BRCA mutations Predictors Preimplantation genetic diagnosis (PGD) Psychosocial Legal and ethical Genetic counseling Uptake 



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

Compliance with Ethical Standards

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.


  1. 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.CrossRefGoogle Scholar
  2. American Cancer Society. (2016). breast cancer risk factors. Retrieved September 12, 2016, from
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. Campeau, P., Foulkes, W., & Tischkowitz, M. (2008). Hereditary breast cancer: new genetic developments, new therapeutic avenues. Human Genetics, 124, 31–42.CrossRefGoogle Scholar
  9. Center for Disease Control. (2015). Birth and natality. Retrieved May 7, 2017, from
  10. Central Intelligence Agency. (2017). World Factbook. Retrieved May 13, 2017, from Central Intelligence Agency:
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.Google Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefGoogle Scholar
  27. 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
  28. Järvholm, S., Thurin-Kjellberg, A., & Broberg, M. (2017). Experiences of pre-implantation genetic diagnosis (PGD). Journal of Genetic Counseling, 26, 1008–1016.CrossRefGoogle Scholar
  29. King, M., Marks, J., & Mandell, J. (2003). Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science, 302, 643–646.CrossRefGoogle Scholar
  30. 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.PubMedPubMedCentralGoogle Scholar
  31. Mazza, E. (2015). Angelina Jolie undergoes surgery to remove ovaries, fallopian tubes to avoid cancer. Retrieved from Huffington post:
  32. 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.CrossRefGoogle Scholar
  33. Moyer, V. (2014). Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. Annals of Internal Medicine, 160(4), 271–281.CrossRefGoogle Scholar
  34. Muller, C., & Cameron, L. D. (2016). It’s complicated—factors predicting decisional conflict in prenatal diagnostic testing. Health Expectations, 19(2), 388–402.CrossRefGoogle Scholar
  35. National Comprehensive Cancer Network. (2016). Practice guidelines in oncology: genetic/familial high risk assessment: breast and ovarian. Retrieved September 12, 2016, from
  36. 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.CrossRefGoogle Scholar
  37. 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.CrossRefGoogle Scholar
  38. 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.CrossRefGoogle Scholar
  39. 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.CrossRefGoogle Scholar
  40. 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.CrossRefGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. Seigel, R., Miller, K., & Jemal, A. (2016). Cancer statistics. A Cancer Journal for Clinicians, 66(1), 7–30.CrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. Steinberg, A. (2003). Jewish ethics. In Encyclopedia of Jewish Medical Ethics (p. 380). New York: Feldheim.Google Scholar
  45. Sunstein, C. (2016). Do people like nudges? Administrative Law Review.
  46. 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.Google Scholar
  47. 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.CrossRefGoogle Scholar
  48. 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.CrossRefGoogle Scholar
  49. 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.CrossRefGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2018

Authors and Affiliations

  • Pnina Mor
    • 1
    Email author
  • Sarah Brennenstuhl
    • 2
  • Kelly A. Metcalfe
    • 2
  1. 1.Shaare Zedek Medical CenterJerusalemIsrael
  2. 2.University of TorontoTorontoCanada

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