Navigating the body of literature assessing BRCA1/2 mutations and markers of ovarian function: a systematic review and m
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REVIEW
Navigating the body of literature assessing BRCA1/2 mutations and markers of ovarian function: a systematic review and meta-analysis Christina N. Cordeiro Mitchell 1 & Bailey McGuinness 2 & Eliana Fine 3 & William G. Kearns 1,4 & Mindy S. Christianson 1 & James Segars 1 & Lisa M. Pastore 5 Received: 16 December 2019 / Accepted: 12 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords BRCA1 mutation . BRCA2 mutation . anti mullerian hormone . ovarian reserve . in vitro fertilization . controlled ovarian hyperstimulation
Introduction * Christina N. Cordeiro Mitchell [email protected] 1
Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology & Infertility, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2
New York University, Winthrop Hospital, Mineola, NY, USA
3
School of Medicine, Stony Brook Medicine, Stony Brook, NY, USA
4
AdvaGenix, Rockville, MD, USA
5
OB/GYN and Reproductive Medicine Department, Stony Brook Medicine, Stony Brook, NY, USA
Twelve percent of women in the USA will develop invasive breast cancer in their lifetime; that risk increases to 80% in women carrying a BRCA1 or BRCA2 mutation (i.e., BRCA1/2+ status) [1]. BRCA1/2 mutations account for 5–10% of breast cancers and have a population prevalence of 1.0–2.2% in different ethnic groups [2–5]. The general population prevalence of BRCA1 mutations is e
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