Navigating the body of literature assessing BRCA1/2 mutations and markers of ovarian function: a systematic review and meta-analysis

J Assist Reprod Genet. 2020 May;37(5):1037-1055. doi: 10.1007/s10815-020-01745-2. Epub 2020 Mar 24.


Purpose: Twelve percent of women in the USA will develop invasive breast cancer in their lifetime, and that risk increases to 80% if they carry a BRCA1 or BRCA2 mutation. BRCA1/2 mutations are thought to potentially affect ovarian reserve and/or fertility.

Methods: PubMed and PubMed Central were searched for publications on ovarian reserve-related outcomes (i.e., AMH and response to controlled ovarian hyperstimulation (COH) protocols) that were reported in relation to BRCA1 and/or BRCA2 mutations from 1950 through May 2019. A meta-analysis was conducted to create forest plots and summary effect measures using Review Manager 5.3.

Results: This article reviews the 16 qualifying publications. There were several fundamental methodological differences in the study designs and outcome details reported in AMH studies. Summary statistics found no difference in AMH levels between BRCA1/2+ women as compared with controls (Z overall test effects p ≥ 0.45). Regarding responses to COH, there were overall non-significantly fewer total and mature numbers of oocytes retrieved in BRCA1/2+ cases as compared with controls (meta-analysis Z overall test effects p ≥ 0.40).

Conclusions: While the summary measures indicate no significant differences in AMH levels between BRCA1/2+ cases and controls, readers should be aware that there are significant methodological differences in the AMH reports. Additionally, the response to COH protocols does not seem to be significantly lower in BRCA1/2 mutation carriers in the existing literature. Continued research on both of these clinical parameters would be beneficial for patient counseling.

Keywords: BRCA1 mutation; BRCA2 mutation; anti mullerian hormone; controlled ovarian hyperstimulation; in vitro fertilization; ovarian reserve.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anti-Mullerian Hormone / genetics
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Fertility / genetics
  • Humans
  • Mutation / genetics
  • Oocytes / growth & development
  • Oocytes / metabolism
  • Ovarian Reserve / genetics*


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