Email this article Incidence of premature ovarian failure and early menopause in carriers of BRCA1 pathogenic variants
- Authors: Rshtuni S.D.1, Chernukha G.E.1, Donnikov A.E.1, Tabeeva G.I.1, Burmenskaya O.V.1, Marchenko L.A.1
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Affiliations:
- Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
- Issue: Vol 24, No 5 (2022)
- Pages: 374-379
- Section: ORIGINAL ARTICLE
- URL: https://journals.rcsi.science/2079-5831/article/view/100836
- DOI: https://doi.org/10.26442/20795696.2022.5.201688
- ID: 100836
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Abstract
Aim. To determine the incidence of premature ovarian failure (POF) and early menopause with regard to reproductive status in carriers of the pathogenic variant of the BRCA1 gene.
Materials and methods. According to the inclusion and exclusion criteria, out of 90 carriers of pathogenic variants of the BRCA1 gene, 38 females were included in the study group, and 110 females without these pathogenic variants were included in the control group. The reproductive status, age of menopause onset, history of pelvic surgeries, and palliative care were evaluated in the study groups.
Results. The incidence of POF in the group of carriers of pathogenic variants of the BRCA1 gene was significantly higher compared to the control group (p<0.004), while the incidence of early menopause showed no significant differences in the studied groups (13.2% vs. 4.5%, respectively; p<0,069). No significant differences were found in the analysis of reproductive status.
Conclusions. Females with and without pathogenic variants of the BRCA1 gene did not differ significantly by the main indices of reproductive status. Carriers of pathogenic BRCA1 gene variants have a significantly higher incidence of POF vs. controls. Adverse effects of pathogenic BRCA gene variants on women's ovarian reserve and reproductive potential cannot be excluded. Healthy carriers of pathogenic variants of the BRCA1/2 gene are recommended to plan pregnancy in the early reproductive period.
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##article.viewOnOriginalSite##About the authors
Sandra D. Rshtuni
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
Author for correspondence.
Email: rshtunisandra@gmail.com
Graduate Student
Russian Federation, MoscowGalina E. Chernukha
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
Email: g_chernukha@oparina4.ru
D. Sci. (Med.), Prof.
Russian Federation, MoscowAndrew E. Donnikov
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
Email: a_donnikov@oparina4.ru
Cand. Sci. (Med.)
Russian Federation, MoscowGyuzyal I. Tabeeva
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
Email: doctor.gtab@gmail.com
Senior Res. Officer
Russian Federation, MoscowOlga V. Burmenskaya
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
Email: o_bourmenskaya@oparina4.ru
D. Sci. (Biol.)
Russian Federation, MoscowLarisa A. Marchenko
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
Email: l_marchenko@yandex.ru
D. Sci. (Med.), Prof.
Russian Federation, MoscowReferences
- European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI; Webber L, Davies M, Anderson R, et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926-37. doi: 10.1093/humrep/dew027
- Аменорея и олигоменорея. Клинические рекомендации. 2021 г. [Amenoreia i oligomenoreia. Klinicheskie rekomendatsii. 2021 g. (in Russian)].
- Golezar S, Ramezani Tehrani F, Khazaei S, et al. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric. 2019;22(4):403-11.
- Менопауза и климактерическое состояние у женщины. Клинические рекомендации. 2021 г. [Menopauza i klimaktericheskoe sostoianie u zhenshchiny. Klinicheskie rekomendatsii. 2021 g. (in Russian)].
- Goswami D, Conway GS. Premature ovarian failure. Horm Res. 2007;68(4):196-202.
- Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med. 2006;12(9):440-50. doi: 10.1016/j.molmed.2006.07.007
- Cohen IS, Bar C, Paz-Elizur T, et al. DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes. Nucleic Acids Res. 2015;43(3):1637-45. doi: 10.1093/nar/gku1398
- Stolz A, Ertych N, Kienitz A, et al. The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells. Nat Cell Biol. 2010;12:492-9.
- Xiong B, Li S, Ai JS, et al. BRCA1 is required for meiotic spindle assembly and spindle assembly checkpoint activation in mouse oocytes. Biol Reprod. 2008;79:718-26.
- Pal T, Keefe D, Sun P, Narod SA; the Hereditary Breast Cancer Clinical Study Group. Fertility in women with BRCA mutations: a case-control study. Fertil Steril. 2010;93(6):1805-8.
- Oktay K, Kim JY, Barad D, Babayev SN. Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks. J Clin Oncol. 2010;28:240-4.
- Derks-Smeets IAP, van Tilborg TC, van Montfoort A, et al. BRCA1 mutation carriers have a lower number of mature oocytes after ovarian stimulation for IVF/PGD. J Assist Reprod Genet. 2017;34:1475-82. doi: 10.1007/s10815-017-1014-3
- Turan V, Bedoschi G, Emirdar V, et al. Ovarian Stimulation in Patients With Cancer: Impact of Letrozole and BRCA Mutations on Fertility Preservation. Cycle Outcomes Reprod Sci. 2018;25(1):26-32.
- Shapira M, Raanani H, Feldman B, et al. BRCA mutation carriers show normal ovarian response in in vitro fertilization cycles. Fertil Steril. 2015;104(5):1162-7.
- Gunnala V, Fields J, Irani M, et al. BRCA carriers have similar reproductive potential at baseline to noncarriers: comparisons in cancer and cancer-free cohorts undergoing fertility preservation. Fertil Steril. 2019;111:363-71. doi: 10.1016/j.fertnstert.2018.10.014
- Lin W, Titus S, Moy F, et al. Ovarian Aging in Women With BRCA Germline Mutations. J Clin Endocrinol Metab. 2017;102(10):3839-47. doi: 10.1210/jc.2017-00765
- Kępczyński Ł, Połatyńska K, Nykel A, et al. Age of natural menopause onset in BRCA1/2 carriers – systematic review and meta-analysis. Prz Menopauzalny. 2020;19(4):171-3. doi: 10.5114/pm.2020.101946
- Schoenaker DA, Jackson CA, Rowlands JV, Mishra GD. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents. Int J Epidemiol. 2014;43(5):1542-62. doi: 10.1093/ije/dyu094
- Finch A, Valentini A, Greenblatt E, et al. Frequency of premature menopause in women who carry a BRCA1 or BRCA2 mutation. Fertil Steril. 2013;99:1724-8.
- Rzepka-Górska I, Tarnowski B, Chudecka-Głaz A, et al. Premature menopause in patients with BRCA1 gene mutation. Breast Cancer Res Treat. 2006;100: 59-63.
- Lin WT, Beattie M, Chen LM, et al. Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non-clinic-based sample of women in northern California. Cancer. 2013;119:1652-9.
- Collins IM, Milne RL, McLachlan SA, et al. Do BRCA1 and BRCA2 mutation carriers have earlier natural menopause than their noncarrier relatives? Results from the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. J Clin Oncol. 2013;31:3920-5.
- van Tilborg TC, Broekmans FJ, Pijpe A, et al. Do BRCA1/2 mutation carriers have an earlier onset of natural menopause? Menopause. 2016;23:903-10.
- Hofmann ER, Milstein S, Boulton SJ, et al. Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis. Curr Biol. 2002;12:1908-18.
- Уварова Е.В., Буралкина Н.А. Параметры овариального резерва девочек 15–17 лет с гармоничным половым и физическим развитием. Репродуктивное здоровье детей и подростков. 2010;3:20-8 [Uvarova EV, Buralkina NA. Parametry ovarial'nogo rezerva devochek 15–17 let s garmonichnym polovym i fizicheskim razvitiem. Reproduktivnoe zdorov'e detei i podrostkov. 2010;3:20-8 (in Russian)].
- Buonomo B, Massarotti C, Dellino M, et al. Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting. BMC Med. 2021;19(1):205. doi: 10.1186/s12916-021-02081-7
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