About 10% of women who are unable to get pregnant are diagnosed with diminished ovarian reserve (DOR). DOR describes a reduction in ovarian function. Few women (<5%) with this diagnosis will become pregnant spontaneously and they do not respond normally to fertility drugs. There are no effective treatments to reverse this condition. Women with DOR may have a premutation alteration of the Fragile X gene (""""""""carriers""""""""). Carriers of this premutation are also at increased risk for premature ovarian failure (POF), which is a greater degree of ovarian dysfunction than DOR. About 5-6% of the women with POF are premutation carriers (14% if she has a family history of premature menopause; 2% otherwise). It is unknown what percentage of women with DOR are premutation carriers. We will extend the current Fragile X research on POF to the DOR population.
Specific aims of this study are: (1) to determine the prevalence of the Fragile X premutation among DOR women; (2) to determine if the prevalence varies with a family history of early menopause and/or infertility; and (3) to determine if there is a relationship between patient age, follicle stimulating hormone level, and the """"""""size"""""""" of the premutation. In this prospective cohort, 65 eligible DOR patients will be enrolled from three academic medical centers (Virginia, North Carolina) and one private practice. The protocol includes pretest genetic counseling, a blood sample for Fragile X testing, and questionnaires. No blood test results will be filed in the medical charts, and women will have the option of learning their Fragile X test results or not. Post test genetic counseling will be provided to all carriers. We are currently pilot-testing this study; among our first 16 participants, one is a carrier and 15 have wanted to learn their test results. The statistical analysis will consist of proportions with binomial testing, logistic regression models, and linear regression models. This research may identify a new phenotype from Fragile X premutations, begin the development of a clinical tool to predict age-at-infertility among carriers, and enhance reproductive planning and decision-making by carriers. The implications of fertility treatment to Fragile X carriers is notable in terms of transmitting Fragile X Syndrome to the children born via fertility treatment; therefore, this research also has applications to the greater issue of the impact on society and individuals from unanticipated genetic testing. ? ? ?

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Small Research Grants (R03)
Project #
Application #
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Urv, Tiina K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Virginia
Obstetrics & Gynecology
Schools of Medicine
United States
Zip Code
Pastore, Lisa M; Antero, Maria; Ventura, Karen et al. (2014) Attitudes towards potentially carrying the FMR1 premutation: before vs after testing of non-carrier females with diminished ovarian reserve. J Genet Couns 23:968-75
Pastore, Lisa M; Karns, Logan B; Ventura, Karen et al. (2014) Longitudinal interviews of couples diagnosed with diminished ovarian reserve undergoing fragile X premutation testing. J Genet Couns 23:97-107
Cizmeli, Ceylan; Lobel, Marci; Franasiak, Jason et al. (2013) Levels and associations among self-esteem, fertility distress, coping, and reaction to potentially being a genetic carrier in women with diminished ovarian reserve. Fertil Steril 99:2037-44.e3
Pastore, Lisa M; Young, Steven L; Baker, Valerie L et al. (2012) Elevated prevalence of 35-44 FMR1 trinucleotide repeats in women with diminished ovarian reserve. Reprod Sci 19:1226-31
Scriver, Jessica; Baker, Valerie L; Young, Steven L et al. (2010) Inter-laboratory validation of the measurement of follicle stimulating hormone (FSH) after various lengths of frozen storage. Reprod Biol Endocrinol 8:145