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

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Abstract

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.

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Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology & Infertility, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Christina N. Cordeiro Mitchell, William G. Kearns, Mindy S. Christianson & James Segars

  2. New York University, Winthrop Hospital, Mineola, NY, USA

    Bailey McGuinness

  3. School of Medicine, Stony Brook Medicine, Stony Brook, NY, USA

    Eliana Fine

  4. AdvaGenix, Rockville, MD, USA

    William G. Kearns

  5. OB/GYN and Reproductive Medicine Department, Stony Brook Medicine, Stony Brook, NY, USA

    Lisa M. Pastore

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  1. Christina N. Cordeiro Mitchell
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Correspondence to Christina N. Cordeiro Mitchell.

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Cordeiro Mitchell, C.N., McGuinness, B., Fine, E. et al. Navigating the body of literature assessing BRCA1/2 mutations and markers of ovarian function: a systematic review and meta-analysis. J Assist Reprod Genet 37, 1037–1055 (2020). https://doi.org/10.1007/s10815-020-01745-2

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  • DOI: https://doi.org/10.1007/s10815-020-01745-2

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