Heather Hipp | Emory University (original) (raw)

Papers by Heather Hipp

Fertility and Sterility, Aug 1, 2019

Journal of Assisted Reproduction and Genetics, Nov 30, 2022

Human Reproduction, Aug 9, 2022

STUDY QUESTION Is reproductive aging in granulosa cells associated with markers of ovarian reserv... more STUDY QUESTION Is reproductive aging in granulosa cells associated with markers of ovarian reserve? SUMMARY ANSWER Age acceleration was associated with anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), oocyte yield and maturity, and the number of successfully fertilized embryos. WHAT IS KNOWN ALREADY The rate of reproductive aging varies among women of the same age. DNA methylation can be used to predict epigenetic age in a variety of tissues. STUDY DESIGN, SIZE, DURATION This was a cross-sectional study of 70 women at the time of oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS The 70 participants were recruited for this study at an academic medical center and they provided follicular fluid samples at the time of oocyte retrieval. Granulosa cells were isolated and assessed on the MethylationEPIC array. Linear regression was used to evaluate the associations between DNA methylation-based age predictions from granulosa cells and chronological age. Age acceleration was calculated as the residual of regressing DNA methylation-based age on chronological age. Linear regressions were used to determine the associations between age acceleration and markers of ovarian reserve and IVF cycle outcomes. MAIN RESULTS AND THE ROLE OF CHANCE Participants were a mean of 36.7 ± 3.9 years old. In regards to race, 54% were white, 19% were African American and 27% were of another background. Age acceleration was normally distributed and not associated with chronological age. Age acceleration was negatively associated with AMH levels (t = −3.1, P = 0.003) and AFC (t = −4.0, P = 0.0001), such that women with a higher age acceleration had a lower ovarian reserve. Age acceleration was also negatively correlated with the total number of oocytes retrieved (t = −3.9, P = 0.0002), the number of mature oocytes (t = −3.8, P = 0.0003) and the number of fertilized oocytes or two-pronuclear oocytes (t = −2.8, P = 0.008) in the main analysis. LIMITATIONS, REASONS FOR CAUTION This study used pooled follicular fluid, which does not allow for the investigation of individual follicles. Infertility patients may also be different from the general population, but, as we used granulosa cells, the participants had to be from an IVF population. WIDER IMPLICATIONS OF THE FINDINGS This study demonstrated that epigenetic age and age acceleration can be calculated from granulosa cells collected at the time of oocyte retrieval. GrimAge most strongly predicted chronological age, and GrimAge acceleration was associated with baseline and cycle characteristics as well as cycle outcomes, which indicates its potential clinical relevance in evaluating both oocyte quantity and quality. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Institutes of Health (UL1TR002378) and the Building Interdisciplinary Research Careers in Women’s Health Program (K12HD085850) to A.K.K. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding source had no role in any aspect of this study. J.B.S. serves as Vice Chair for the American Society for Reproductive Medicine Education Committee, is a Medical Committee Advisor for the Jewish Fertility Foundation and works with Jscreen. J.B.S. has received funding from Georgia Clinical Translational Research Alliance. H.S.H., J.B.S. and A.K.S. have received NIH funding for other projects. A.K.K., S.A.G., S.G., Q.S.K., L.J.M. and W.S. have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Fertility and Sterility, Feb 1, 2023

Fertility and Sterility, Sep 1, 2021

Fertility and Sterility, Oct 1, 2018

Reproductive Sciences, Nov 4, 2021

Ovarian reserve is an important determinant of a woman’s reproductive potential, and women with d... more Ovarian reserve is an important determinant of a woman’s reproductive potential, and women with diminished ovarian reserve (DOR) often seek in vitro fertilization (IVF). The underlying etiology of DOR is unknown, but follicular fluid cytokine concentrations likely play a role in follicular development and maturation. The present study seeks to investigate the expression of cytokines in follicular fluid (FF) of women with DOR undergoing IVF and explore correlated functional pathways. One hundred ninety-four women undergoing ovarian stimulation were recruited at the time of oocyte retrieval. Women were classified as having DOR if they met one or more of the following criteria: AMH < 1 ng/ml, FSH > 10 mIU/ml, and/or AFC < 10. Controls included women undergoing IVF for male factor, tubal factor due to tubal ligation, or planned oocyte cryopreservation (non-oncologic). The concentrations of 480 cytokines and related growth factors in follicular fluid were determined using a multiplex immunoassay. Fifty-nine cytokines had significantly different concentrations (53 higher and 6 lower) in the DOR relative to the control group after adjusting for age and body mass index (BMI) (false discovery rate; FDR < 0.1). Using the most informative 44 biomarkers as indicated by a random forest (RF) model, an area under the curve (AUC) of 0.78 was obtained. Thus, follicular microenvironment differs between women with DOR and normal ovarian reserve. The differentially expressed cytokines belong to diverse processes that are primarily involved in follicular maturation and ovulation. These changes may play an important role in treatment outcomes in women with DOR.