VOLUME 1, ISSUE 1, P1-15, OCTOBER 01, 2020
Carleigh B. Nesbit, D.O., Jia Huang, M.D., Ph.D., Bhuchitra Singh, M.D., M.P.H.,
Jacqueline Y. Maher, M.D., Lisa M. Pastore, Ph.D., James Segars, M.D.
To provide an update on single-gene mutations identified as causative for pathologic diminished ovarian reserve (DOR) to inform clinical screening recommendations.
A systematic review of the literature was performed in accordance with PRISMA guidelines using PubMed and EMBASE databases. Only full-text articles in English were included and articles were excluded that did not relate to single-gene causes of pathologic DOR in humans. The search was supplemented using references of the included articles. Primary outcomes included prevalence ratios (PRs) for 12 genes associated with pathologic DOR.
A total of 550 articles were screened, with 108 articles included for review. Fifteen observational studies had prevalence data available for quantitative analysis. Elevated prevalence ratios were found in women with DOR for the FMR1 premutation and FMR2 mutations as well as single-nucleotide polymorphisms in the BMP15, GDF9, FSHR, and NOBOX genes. Although some studies have suggested an increased prevalence of BRCA1 and BRCA2 mutations in women with DOR, the prevalence in the controls in the included studies was elevated and PRs did not achieve statistical significance.
Women diagnosed with DOR are at an increased risk of carrying mutations in FMR1, FMR2, and variants in BMP15, GDF9, FSHR, and NOBOX genes. Of these, the only gene identified as having the potential to cause significant deleterious effects in offspring is the FMR1 premutation, which supports current national screening guidelines. Further studies of BRCA1 and BRCA2 are needed to determine whether pathologic DOR might be associated with mutations in those genes.