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Assessment of ovarian reserve and reproductive outcomes in BRCA1 or BRCA2 mutation carriers
  1. Jordi Ponce1,
  2. Sergi Fernandez-Gonzalez1,
  3. Iris Calvo1,
  4. Maite Climent1,
  5. Judith Peñafiel2,
  6. Lidia Feliubadaló3,
  7. Alex Teulé3,
  8. Conxi Lázaro3,
  9. Joan Maria Brunet3,4,
  10. Beatriz Candás-Estébanez5 and
  11. Montserrat Durán Retamal6
  1. 1 Gynecology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
  2. 2 Biostatistics Unit, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
  3. 3 Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Barcelona, Spain
  4. 4 Hereditary Cancer Program, Catalan Institute of Oncology, IDIBGI, Girona, Spain
  5. 5 Clinical Laboratory, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
  6. 6 Centre for Reproductive and Genetic Health, London, UK
  1. Correspondence to Dr Sergi Fernandez-Gonzalez, Gynecology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; sergi.sfg{at}


Introduction The clinical impact on fertility in carriers of BRCA1 and BRCA2 mutations remains unclear. The aim of this study was to assess ovarian reserve as measured by anti-mullerian hormone levels in BRCA1 or BRCA2 mutation carriers, as well as to investigate the impact of anti-mullerian hormone levels on reproductive outcomes.

Methods The study involved a cohort of women who tested positive for BRCA1 and BRCA2 screening or were tested for a BRCA1 or BRCA2 family mutation. Blood samples were collected for anti-mullerian hormone analysis and the reproductive outcomes were analyzed after a mean follow-up of 9 years. Participants were classified into BRCA mutation-positive versus BRCA mutation-negative. Controls were healthy relatives who tested negative for the family mutation. All patients were contacted by telephone to collect data on reproductive outcomes. Linear regression was used to predict anti-mullerian hormone levels by BRCA status adjusted for a polynomial form of age.

Results Results of anti-mullerian hormone analysis and reproductive outcomes were available for 135 women (BRCA mutation-negative, n=66; BRCA1 mutation-positive, n=32; BRCA2 mutation-positive, n=37). Anti-mullerian hormone curves according to BRCA status and adjusted by age showed that BRCA2 mutation-positive patients have lower levels of anti-mullerian hormone as compared with BRCA-negative and BRCA1 mutation-positive. Among the women who tried to conceive, infertility was observed in 18.7% of BRCA mutation-negative women, in 22.2% of BRCA1 mutation-positive women, and in 30.8% of BRCA2 mutation-positive women (p=0.499). In the multivariable analysis, there were no factors independently associated with infertility.

Discussion BRCA2 mutation-positive carriers showed more diminished anti-mullerian hormone levels than BRCA1 mutation-positive and BRCA mutation-negative women. However, these differences do not appear to have a negative impact on reproductive outcome. This is important to consider at the time of reproductive counseling in women with BRCA1 or BRCA2 mutations.

  • BCRA1
  • BCRA2
  • anti-Müllerian hormone
  • ovarian reserve
  • fertility
  • reproduction

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  • JP and SF-G are joint first authors.

  • Presented at This study was presented as a poster at the 21st European Congress on Gynaecological Oncology, Athens, 2019.

    Furthermore, it was presented as an oral communication at the 34th National Congress of the Gynaecology Oncology section of the Spanish Society of Gynecology and Obstetrics, Barcelona, 2018.

  • Contributors JP: development, supervision, edition. SF-G: data collection, development, edition, supervision. ICL, e-mail: data collection, development. MTC, e-mail: data collection, development. JPM, e-mail: data collection, statistics analysis. LFE: data collection, patients selection. ATV: data collection, supervision. CL: data collection, supervision. JMBV: edition, supervision. BC-E: AMH analysis, data collection. MDR: edition, supervision.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.