Fertility preservation in women harboring deleterious BRCA mutations: Ready for prime time?

F.A. Peccatori, G. Mangili, A. Bergamini, F. Filippi, F. Martinelli, F. Ferrari, S. Noli, E. Rabaiotti, M. Candiani, E. Somigliana

Research output: Contribution to journalArticle

Abstract

Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The procedure could be considered at a young age and in an elective setting, when ovarian stimulation may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis (PGD) could be considered in BRCA mutations carriers, particularly when good quality oocytes have been stored at a young age. Based on the current knowledge, a univocal approach cannot be recommended; in depth patient counseling is warranted. © The Author 2017.
Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalHuman Reproduction
Volume33
Issue number2
DOIs
Publication statusPublished - 2018

Fingerprint

Fertility Preservation
Mutation
Oocytes
Cryopreservation
Counseling
Preimplantation Diagnosis
Aptitude
Ovulation Induction
Ovariectomy
Fertility
Pregnancy

Keywords

  • BRCA
  • Cancer
  • Fertility preservation
  • Oocytes
  • PGD
  • oral contraceptive agent
  • tamoxifen
  • age
  • Article
  • breast cancer
  • cancer prevention
  • cancer risk
  • cryopreservation
  • female
  • fertility preservation
  • gene mutation
  • health care policy
  • heterozygote
  • human
  • oncogene
  • oocyte
  • ovarian reserve
  • ovary cancer
  • ovary hyperstimulation
  • patient counseling
  • preimplantation genetic diagnosis
  • prophylactic surgical procedure
  • risk reduction
  • salpingooophorectomy
  • adult
  • breast tumor
  • fertility
  • genetic counseling
  • genetics
  • mutation
  • ovary tumor
  • ovulation induction
  • pathophysiology
  • physiology
  • pregnancy
  • procedures
  • trends
  • tumor suppressor gene
  • Adult
  • Breast Neoplasms
  • Cryopreservation
  • Female
  • Fertility
  • Fertility Preservation
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Counseling
  • Humans
  • Mutation
  • Ovarian Neoplasms
  • Ovarian Reserve
  • Ovulation Induction
  • Pregnancy
  • Preimplantation Diagnosis
  • Risk Reduction Behavior

Cite this

Fertility preservation in women harboring deleterious BRCA mutations: Ready for prime time? / Peccatori, F.A.; Mangili, G.; Bergamini, A.; Filippi, F.; Martinelli, F.; Ferrari, F.; Noli, S.; Rabaiotti, E.; Candiani, M.; Somigliana, E.

In: Human Reproduction, Vol. 33, No. 2, 2018, p. 181-187.

Research output: Contribution to journalArticle

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note = "Cited By :4 Export Date: 5 February 2019 CODEN: HUREE Correspondence Address: Mangili, G.; Department of Obstetrics and Gynecology, San Raffaele Scientific Institute, Via Olgettina 60, Italy; email: mangili.giorgia@hsr.it Chemicals/CAS: tamoxifen, 10540-29-1 References: Averette, H.E., Mirhashemi, R., Moffat, F.L., Pregnancy after breast carcinoma: The ultimate medical challenge (1999) Cancer, 85, pp. 2301-2304; Jr, A.H.A., Kroman, N., Paesmans, M., Gelber, S., Rotmensz, N., Ameye, L., De Mattos-Arruda, L., Jensen, M.B., Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: A multicenter retrospective study (2013) J Clin Oncol, 31, pp. 73-79; Birrer, N., Chinchilla, C., Del Carmen, M., Dizon, D.S., Is hormone replacement therapy safe in women with a BRCA mutation? A systematic review of the contemporary literature (2016) Am J Clin Oncol, , Epub ahead of print; Bolton, K.L., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S.J., Karlan, B.Y., Lambrechts, D., McGuffog, L., Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer (2012) JAMA, 307, pp. 382-390; Broer, S.L., Van Disseldorp, J., Broeze, K.A., Dolleman, M., Opmeer, B.C., Bossuyt, P., Eijkemans, M.J., Broekmans, F.J., Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: An individual patient data approach (2013) Hum Reprod Update, 19, pp. 26-36; Callahan, M.J., Crum, C.P., Medeiros, F., Kindelberger, D.W., Elvin, J.A., Garber, J.E., Feltmate, C.M., Muto, M.G., Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction (2007) J Clin Oncol, 25, pp. 3985-3990; Chan, J.L., Johnson, L.N.C., Sammel, M.D., Di Giovanni, L., Voong, C., Domchek, S.M., Gracia, C.R., Reproductive decision-making in women with BRCA 1-2 mutations (2017) J Genet Couns, 26, pp. 594-603; Chai, X., Susan Domchek, S., Noah Kauff, N., Timothy Rebbeck, T., Jinbo Chen, J., Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: Revisiting the evidence for risk reduction (2015) J Natl Cancer Inst, 107, pp. 1-9; Chen, S., Parmigiani, G., Meta-analysis of BRCA1 and BRCA2 penetrance (2007) J Clin Oncol, 25, pp. 1329-1333; Cobo, A., Garc{\'i}a-Velasco, J.A., Coello, A., Domingo, J., Pellicer, A., Remoh{\'i}, J., Oocyte vitrification as an efficient option for elective fertility preservation (2016) Fertil Steril, 105, pp. 755-764; Collins, I.M.I., Milne, R.L., McLachlan, S.A., Friedlander, M., Hickey, M., Weideman, P.C., Birch, K.E., Phillips, K.A., Do BRCA1 and BRCA2 mutation carriers have earlier natural menopause than their noncarrier relatives? 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year = "2018",
doi = "10.1093/humrep/dex356",
language = "English",
volume = "33",
pages = "181--187",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Fertility preservation in women harboring deleterious BRCA mutations: Ready for prime time?

AU - Peccatori, F.A.

AU - Mangili, G.

AU - Bergamini, A.

AU - Filippi, F.

AU - Martinelli, F.

AU - Ferrari, F.

AU - Noli, S.

AU - Rabaiotti, E.

AU - Candiani, M.

AU - Somigliana, E.

N1 - Cited By :4 Export Date: 5 February 2019 CODEN: HUREE Correspondence Address: Mangili, G.; Department of Obstetrics and Gynecology, San Raffaele Scientific Institute, Via Olgettina 60, Italy; email: mangili.giorgia@hsr.it Chemicals/CAS: tamoxifen, 10540-29-1 References: Averette, H.E., Mirhashemi, R., Moffat, F.L., Pregnancy after breast carcinoma: The ultimate medical challenge (1999) Cancer, 85, pp. 2301-2304; Jr, A.H.A., Kroman, N., Paesmans, M., Gelber, S., Rotmensz, N., Ameye, L., De Mattos-Arruda, L., Jensen, M.B., Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: A multicenter retrospective study (2013) J Clin Oncol, 31, pp. 73-79; Birrer, N., Chinchilla, C., Del Carmen, M., Dizon, D.S., Is hormone replacement therapy safe in women with a BRCA mutation? A systematic review of the contemporary literature (2016) Am J Clin Oncol, , Epub ahead of print; Bolton, K.L., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S.J., Karlan, B.Y., Lambrechts, D., McGuffog, L., Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer (2012) JAMA, 307, pp. 382-390; Broer, S.L., Van Disseldorp, J., Broeze, K.A., Dolleman, M., Opmeer, B.C., Bossuyt, P., Eijkemans, M.J., Broekmans, F.J., Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: An individual patient data approach (2013) Hum Reprod Update, 19, pp. 26-36; Callahan, M.J., Crum, C.P., Medeiros, F., Kindelberger, D.W., Elvin, J.A., Garber, J.E., Feltmate, C.M., Muto, M.G., Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction (2007) J Clin Oncol, 25, pp. 3985-3990; Chan, J.L., Johnson, L.N.C., Sammel, M.D., Di Giovanni, L., Voong, C., Domchek, S.M., Gracia, C.R., Reproductive decision-making in women with BRCA 1-2 mutations (2017) J Genet Couns, 26, pp. 594-603; Chai, X., Susan Domchek, S., Noah Kauff, N., Timothy Rebbeck, T., Jinbo Chen, J., Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: Revisiting the evidence for risk reduction (2015) J Natl Cancer Inst, 107, pp. 1-9; Chen, S., Parmigiani, G., Meta-analysis of BRCA1 and BRCA2 penetrance (2007) J Clin Oncol, 25, pp. 1329-1333; Cobo, A., García-Velasco, J.A., Coello, A., Domingo, J., Pellicer, A., Remohí, J., Oocyte vitrification as an efficient option for elective fertility preservation (2016) Fertil Steril, 105, pp. 755-764; Collins, I.M.I., Milne, R.L., McLachlan, S.A., Friedlander, M., Hickey, M., Weideman, P.C., Birch, K.E., Phillips, K.A., Do BRCA1 and BRCA2 mutation carriers have earlier natural menopause than their noncarrier relatives? 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Heidelberg: Springer International Publishing; Kotsopoulos, J., Librach, C.L., Lubinski, J., Gronwald, J., Kim-Sing, C., Ghadirian, P., Lynch, H.T., Randall, S., Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: A case-control study (2008) Cancer Causes Control, 19, pp. 1111-1119; Kotsopoulos, J., Huzarski, T., Gronwald, J., Singer, C.F., Moller, P., Lynch, H.T., Armel, S., Neuhausen, S.L., Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers (2016) J Natl Cancer Inst, 109, p. 1; Kuang, Y., Chen, Q., Hong, Q., Lyu, Q., Ai, A., Fu, Y., Shoham, Z., Double stimula-tions during the follicular and luteal phases of poor responders in IVF/ ICSI programmes (Shanghai protocol) (2014) Reprod Biomed Online, 29, pp. 684-691; Kuchenbaecker, K.B., Hopper, J.L., Barnes, D.R., Phillips, K.A., Mooij, T.M., Roos-Blom, M.J., Jervis, S., Andrieu, N., Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers (2017) JAMA, 317, pp. 2402-2416; Kwiatkowski, F., Arbre, M., Bidet, Y., Laquet, C., Uhrhammer, N., Bignon, Y.J., BRCA mutations increase fertility in families at hereditary breast/ovarian cancer risk (2015) PLoS One, 10, p. e0127363; Lin, W.T., Beattie, M., Chen, L.M., Oktay, K., Crawford, S.L., Gold, E.B., Cedars, M., Rosen, M., Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non-clinic-based sample of women in northern California (2013) Cancer, 119, pp. 1652-1659; Llort, G., Chirivella, I., Morales, R., Serrano, R., Sanchez, A.B., Teulé, A., Lastra, E., Graña, B., SEOM clinical guidelines in hereditary breast and ovarian cancer (2015) Clin Transl Oncol, 17, pp. 956-961; Mavaddat, N., Peock, S., Frost, D., Ellis, S., Platte, R., Fineberg, E., Evans, D.G., Adlard, J., Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of EMBRACE (2013) J Natls Cancer Inst, 105, pp. 812-822; Metcalfe, K.A., Birenbaum-Carmeli, D., Lubinski, J., Gronwald, J., Lynch, H., Moller, P., Ghadirian, P., Friedman, E., International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers (2008) Int J Cancer, 122, pp. 2017-2022; Michaelson-Cohen, R., Mor, P., Srebnik, N., Beller, U., Levy-Lahad, E., Eldar-Geva, T., BRCA mutation carriers do not have compromised ovarian reserve (2014) Int J Gynecol Cancer, 24, pp. 233-237; Moorman, P.G., Havrilesky, L.J., Gierisch, J.M., Coeytaux, R.R., Lowery, W.J., Peragallo Urrutia, R., Dinan, M., Sanders, G.D., Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: A systematic review and meta-analysis (2013) J Clin Oncol, 31, pp. 4188-4198; Oktay, K., Kim, J.Y., Barad, D., Babayev, S.N., Association of BRCA1 mutations with occult primary ovarian insufficiency: A possible explanation for the link between infertility and breast/ovarian cancer risks (2010) J Clin Oncol, 28, pp. 240-244; Pagani, O., Ruggeri, M., Manunta, S., Saunders, C., Peccatori, F., Cardoso, F., Kaufman, B., Gallerani, E., Pregnancy after breast cancer: Are young patients willing to participate in clinical studies? (2015) Breast, 24, pp. 201-207; Pal, T., Keefe, D., Sun, P., Narod, S.A., Fertility in women with BRCA mutations: A case-control study (2010) Fertil Steril, 93, pp. 1805-1808; Peccatori, F.A., Jr, A.H.A., Orecchia, R., Hoekstra, H.J., Pavlidis, N., Kesic, V., Pentheroudakis, G., Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2013) Ann Oncol, 24, pp. 160-170; Perri, T., Lifshitz, D., Sadetzki, S., Oberman, B., Meirow, D., Ben-Baruch, G., Friedman, E., Korach, J., Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers (2015) Fertil Steril, 103, pp. 1305-1312; Powell, C.B., Clinical management of patients at inherited risk for gynecologic cancer (2015) Curr Opin Obstet Gynecol, 27, pp. 14-22; Pravettoni, G., Cutica, I., Righetti, S., Mazzocco, K., Decisions and involvement of cancer patient survivors: A moral imperative (2016) J Healthc Leadersh, 8, pp. 121-125; Quinn, G.P., Pal, T., Murphy, D., Vadaparampil, S.T., Kumar, A., High-risk consumers’ perceptions of preimplantation genetic diagnosis for hereditary cancers: A systematic review and meta-analysis (2012) Genet Med, 14, pp. 191-200; Rebbeck, T.R., Friebel, T., Lynch, H.T., Neuhausen, S.L., Van ‘t Veer, L., Garber, J.E., Evans, G.R., Matloff, E., Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE Study Group (2004) J Clin Oncol, 22, pp. 1055-1062; Rebbeck, T.R., Mitra, N., Domchek, S.M., Wan, F., Chuai, S., Friebel, T.M., Panossian, S., Con Fab, K., Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers (2009) Cancer Res, 69, pp. 5801-5810; Rebbeck, T.R., Kauff, N.D., Domchek, S.M., Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers (2009) J Natl Cancer Inst, 101, pp. 80-87; Ring, K.L., Garcia, C., Thomas, M.H., Modesitt, S.C., Current and future role of genetic screening in gynecologic malignancies (2017) Am J Obstet Gynecol, 217, pp. 512-521. , Epub ahead of print; Rosenberg, L., Thalib, L., Adami, H.O., Hall, P., Childbirth and breast cancer prognosis (2004) Int J Cancer, 111, pp. 772-776; Rzepka-Górska, I., Tarnowski, B., Chudecka-Głaz, A., Górski, B., Zielińska, D., Tołoczko-Grabarek, A., Premature menopause in patients with BRCA1 gene mutation (2006) Breast Cancer Res Treat, 100, pp. 59-63; Sergentanis, T.N., Diamantaras, A.A., Perlepe, C., Kanavidis, P., Skalkidou, A., Petridou, E.T., IVF and breast cancer: A systematic review and meta-analysis (2014) Hum Reprod Update, 20, pp. 106-123; Shapira, M., Raanani, H., Meirow, D., IVF for fertility preservation in breast cancer patients—efficacy and safety issues (2015) J Assist Reprod Genet, 32, pp. 1171-1178; Shapira, M., Raanani, H., Feldman, B., Srebnik, N., Dereck-Haim, S., Manela, D., Brenghausen, M., Levi-Lahad, E., BRCA mutation carriers show normal ovarian response in in vitro fertilization cycles (2015) Fertil Steril, 104, pp. 1162-1167; Shenfield, F., Pennings, G., Devroey, P., Sureau, C., Tarlatzis, B., Cohen, J., ESHRE ethics task force. 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PY - 2018

Y1 - 2018

N2 - Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The procedure could be considered at a young age and in an elective setting, when ovarian stimulation may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis (PGD) could be considered in BRCA mutations carriers, particularly when good quality oocytes have been stored at a young age. Based on the current knowledge, a univocal approach cannot be recommended; in depth patient counseling is warranted. © The Author 2017.

AB - Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The procedure could be considered at a young age and in an elective setting, when ovarian stimulation may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis (PGD) could be considered in BRCA mutations carriers, particularly when good quality oocytes have been stored at a young age. Based on the current knowledge, a univocal approach cannot be recommended; in depth patient counseling is warranted. © The Author 2017.

KW - BRCA

KW - Cancer

KW - Fertility preservation

KW - Oocytes

KW - PGD

KW - oral contraceptive agent

KW - tamoxifen

KW - age

KW - Article

KW - breast cancer

KW - cancer prevention

KW - cancer risk

KW - cryopreservation

KW - female

KW - fertility preservation

KW - gene mutation

KW - health care policy

KW - heterozygote

KW - human

KW - oncogene

KW - oocyte

KW - ovarian reserve

KW - ovary cancer

KW - ovary hyperstimulation

KW - patient counseling

KW - preimplantation genetic diagnosis

KW - prophylactic surgical procedure

KW - risk reduction

KW - salpingooophorectomy

KW - adult

KW - breast tumor

KW - fertility

KW - genetic counseling

KW - genetics

KW - mutation

KW - ovary tumor

KW - ovulation induction

KW - pathophysiology

KW - physiology

KW - pregnancy

KW - procedures

KW - trends

KW - tumor suppressor gene

KW - Adult

KW - Breast Neoplasms

KW - Cryopreservation

KW - Female

KW - Fertility

KW - Fertility Preservation

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Genetic Counseling

KW - Humans

KW - Mutation

KW - Ovarian Neoplasms

KW - Ovarian Reserve

KW - Ovulation Induction

KW - Pregnancy

KW - Preimplantation Diagnosis

KW - Risk Reduction Behavior

U2 - 10.1093/humrep/dex356

DO - 10.1093/humrep/dex356

M3 - Article

VL - 33

SP - 181

EP - 187

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 2

ER -