BRCA carriers have similar reproductive potential at baseline to noncarriers: comparisons in cancer and cancer-free cohorts undergoing fertility preservation

Fertil Steril. 2019 Feb;111(2):363-371. doi: 10.1016/j.fertnstert.2018.10.014. Epub 2018 Dec 6.

Abstract

Objective: To investigate whether BRCA carriers with and without malignancy have decreased ovarian reserve at baseline compared with BRCA noncarriers.

Design: Retrospective cohort study.

Setting: Academic medical center.

Patient(s): Seven-hundred and ninety-five oocyte cryopreservation patients, comprising BRCA carriers with and without malignancy (n = 57) and BRCA noncarriers (n = 738).

Intervention(s): Fertility preservation with oocyte cryopreservation.

Main outcome measure(s): Antral follicle count (AFC), antimüllerian hormone (AMH) concentration, day-3 follicle-stimulating hormone (FSH) level, number of harvested oocytes, and number of mature/cryopreserved oocytes.

Result(s): In the cancer cohort we compared BRCA-positive breast cancer (n = 38) with BRCA-negative breast cancer (n = 53) and with non-breast-cancer malignancies (n = 85). In the cancer-free cohort we compared BRCA carriers (n = 19) with women undergoing elective egg freezing (n = 600). We also compared the BRCA1 (n = 31) versus the BRCA2 carriers (n = 18). The patients' mean ages were 32.4 ± 3.6 years and 35.5 ± 4.3 years in the BRCA carrier and noncarrier cohorts, respectively. BRCA status was associated with a higher day-3 FSH level in the cancer cohort, but we found no changes in the other outcomes compared with the BRCA-negative cancer groups. BRCA carriers without cancer exhibited a higher AFC and number of mature oocytes compared with the patients undergoing planned egg freezing. Overall (cancer and cancer-free cohorts), the BRCA carriers had an increased AFC (15.5 ± 4.6 vs. 12.6 ± 5.7) and number of mature/cryopreserved oocytes (14.0 ± 7.9 vs. 10.4 ± 6.9) compared with the BRCA noncarriers but had no differences in other outcomes.

Conclusion(s): BRCA carriers with and without malignancy exhibit comparable ovarian reserve and responses to ovarian stimulation compared with women with BRCA-negative cancers and cancer-free controls.

Keywords: BRCA carriers; BRCA-positive breast cancer; diminished ovarian reserve; fertility preservation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics
  • Biomarkers / blood
  • Cryopreservation*
  • Databases, Factual
  • Female
  • Fertility Preservation / methods*
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • In Vitro Oocyte Maturation Techniques
  • Mutation*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Oocyte Retrieval
  • Oocytes*
  • Ovarian Reserve / genetics*
  • Ovulation Induction
  • Phenotype
  • Primary Ovarian Insufficiency / blood
  • Primary Ovarian Insufficiency / genetics*
  • Primary Ovarian Insufficiency / physiopathology
  • Retrospective Studies

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers
  • Anti-Mullerian Hormone