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.
Objective: To identify modifying genes that explains the risk of fragile X-associated primary ova... more Objective: To identify modifying genes that explains the risk of fragile X-associated primary ovarian insufficiency (FXPOI). Design: Gene-based, case/control association study, followed by a functional screen of highly ranked genes using a Drosophila model. Setting: Participants were recruited from academic and clinical settings. Patient(s): Women with a premutation (PM) who experienced FXPOI at the age of 35 years or younger (n ¼ 63) and women with a PM who experienced menopause at the age of 50 years or older (n ¼ 51) provided clinical information and a deoxyribonucleic acid sample for whole genome sequencing. The functional screen was on the basis of Drosophila TRiP lines. Intervention(s): Clinical information and a DNA sample were collected for whole genome sequencing. Main Outcome Measures: A polygenic risk score derived from common variants associated with natural age at menopause was calculated and associated with the risk of FXPOI. Genes associated with the risk of FXPOI were identified on the basis of the P-value from gene-based association test and an altered level of fecundity when knocked down in the Drosophila PM model. Results: The polygenic risk score on the basis of common variants associated with natural age at menopause explained approximately 8% of the variance in the risk of FXPOI. Further, SUMO1 and KRR1 were identified as possible modifying genes associated with the risk of FXPOI on the basis of an untargeted gene analysis of rare variants. Conclusions: In addition to the large genetic effect of a PM on ovarian function, the additive effects of common variants associated with natural age at menopause and the effect of rare modifying variants appear to play a role in FXPOI risk. (Fertil Steril Ò 2021;116: 843-54. Ó2021 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.
Objective: To examine the degree to which paternal variables of age, body mass index (BMI), and s... more Objective: To examine the degree to which paternal variables of age, body mass index (BMI), and sperm parameters affect vitrified donor oocyte IVF outcomes. Previous studies examining the impact of male partner characteristics on in-vitro fertilization (IVF) have found conflicting results. Concerns are rising over the potential effects of paternal factors, such as age and obesity, on pregnancy and child health. Frozen donor oocyte IVF offers an ideal model to study these effects. Design: Retrospective chart review. Setting: Private fertility clinic. Patient(s): Nine hundred forty-nine recipients undergoing transfer of blastocyst embryo(s) from a vitrified oocyte donor bank between 2008-2015. Intervention(s): None. Main Outcome Measure(s): Implantation rate, clinical pregnancy rate, live birth rate, rate of low birth weight singleton infants (%2500 g), and preterm deliveries (PTD) of singleton infants (<37 wk). Results: After adjusting for covariates known to affect oocyte donation cycle success, male age, BMI and sperm parameters were not associated with differences in IVF outcomes. There were higher PTD rates for men R51 years and BMI R35 kg/m 2 , however, these were not significant after adjustment. There were no differences in rates of low birth weight infants with men >35 years or BMI >25 kg/m 2. Lastly, there were no differences in rates of PTD or low birth weight infants with abnormal sperm parameters. Conclusions: Neither advancing male age, elevated BMI, nor poor sperm quality were associated with outcomes in frozen donor oocyte IVF cycles in this study. Intracytoplamic sperm injection and ''oocyte quality'' likely mitigate some of the effects of male variables on outcomes following cryopreserved oocyte donation. (Fertil Steril Ò 2018;110:859-69. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.
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.
Fragile X-associated primary ovarian insufficiency (FXPOI) occurs in about 20% of women who carry... more Fragile X-associated primary ovarian insufficiency (FXPOI) occurs in about 20% of women who carry a premutation allele (55-200 CGG repeats). These women develop hypergonadotropic hypogonadism and have secondary amenorrhea before age 40. A non-linear association with repeat size and risk for FXPOI has been seen in multiple studies women with a premutation: those with a mid-range of repeats are at highest risk (∼70-100 CGG repeats). Importantly, not all carriers with 70-100 repeats experience FXPOI. We investigated whether AGG interruptions, adjusted for repeat size, impacted age at secondary amenorrhea. We have reproductive history information and AGG interruption data on 262 premutation women: 164 had an established age at amenorrhea (AAA) (for some, age at onset of FXPOI) or menopause, 16 had a surgery involving the reproductive system such as a hysterectomy, and 82 women were still cycling at the last interview. Reproductive status was determined using selfreport reproductive questionnaires and interviews with a reproductive endocrinologist. For each of these 262 women, FMR1 repeat size and number of AGG interruptions were determined. We confirmed the association of repeat size with AAA or menopause among women with a premutation. As expected, both premutation repeat size and the quadratic form of repeat size (i.e., squared term) were significant in a survival analysis model predicting AAA (p < 0.0001 for both variables). When number of AGG interruptions was added to the model, this variable was not significant (p = 0.59). Finally, we used a regression model based on the 164 women with established AAA to estimate the proportion of variance in AAA explained by repeat size and its squared term. Both terms were again highly significant (p < 0.0001 for both), but together only explained 13% of the variation in AAA. The non-linear association between AAA and FMR1 repeat size has been described in several studies. We have determined that AGG interruption pattern does not contribute to this association. Because only 13% of the variation is described using repeat size, it is clear that further research of FXPOI is needed to identify other factors that affect the risk for FXPOI.
Approximately 20-30% of women with an FMR1 premutation experience fragile X-associated primary ov... more Approximately 20-30% of women with an FMR1 premutation experience fragile X-associated primary ovarian insufficiency (FXPOI); however, current risk estimates based on repeat size only identify women with the midrange of repeats to be at the highest risk. METHODS: To better understand the risk by repeat size, we collected self-reported reproductive histories on 1,668 women and divided them into high-resolution repeat size bins of~5 CGG repeats to determine a more accurate risk for FXPOI in relation to CGG repeat length. RESULTS: As previously reported, women with 70-100 CGG repeats were at the highest risk for FXPOI using various statistical models to compare average age at menopause and risk of FXPOI, with women with 85-89 repeats being at the highest risk. Importantly, women with <65 repeats or >120 repeats did not have a significantly increased risk for FXPOI compared to women with <45 repeats. CONCLUSION: Using a large cross-section study on 1,668 women, we have provided more personalized risk assessment for FXPOI using high-resolution repeat size bins. Understanding the variability in risk has important implications for family planning and overall health among women with a premutation.
Clinical pregnancy rate(54.50% vs 63.70%, p<0.001) were significantly higher with frozen embryo t... more Clinical pregnancy rate(54.50% vs 63.70%, p<0.001) were significantly higher with frozen embryo transfer compared to fresh embryo transfer. Variables that were found to be independently associated with clinical pregnancy rate were fresh/frozen embryo transfer, female age and no. of embryo transferred. After adjusting for variables, frozen embryo transfer(0.75 (0.59, 0.95), p¼0.016) was protective factor of clinical pregnancy rate. CONCLUSIONS: Frozen embryo transfer is better than fresh embryo transfer in GnRH antagonist cycle in normo-responders.
Hepatitis B surface antigen, hepatitis C core antibody, syphilis, gonorrhea and chlamydia culture... more Hepatitis B surface antigen, hepatitis C core antibody, syphilis, gonorrhea and chlamydia cultures, CMV IgG and IgM.
Purpose: Emerging evidence indicates that women who carry an FMR1 premutation can experience comp... more Purpose: Emerging evidence indicates that women who carry an FMR1 premutation can experience complex health profiles beyond the two well-established premutation-associated disorders: fragile X-associated primary ovarian insufficiency (FXPOI, affects 20-30% carriers) and fragile X-associated tremor-ataxia syndrome (FXTAS, affects~6-15% carriers). Methods: To better understand premutation-associated health profiles, we collected self-reported medical histories on 355 carrier women. Results: Twenty-two health conditions were reported by at least 10% of women. Anxiety, depression, and headaches were reported by more than 30%. The number of comorbid conditions was significantly associated with body mass index (BMI) and history of smoking, but not age. Survival analysis indicated that women with FXPOI had an earlier age at onset for anxiety and osteoporosis than women without FXPOI. Cluster analysis identified eight clusters of women who reported similar patterns of comorbid conditions. The majority of carriers (63%) fell into three categories primarily defined by the presence of only a few conditions. Interestingly, a single cluster defined women with symptoms of FXTAS, and none of these women had FXPOI. Conclusion: Although some women with a premutation experience complex health outcomes, most carriers report only minimal comorbid conditions. Further, women with symptoms of FXTAS appear to be distinct from women with symptoms of FXPOI.
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.
Objective: To identify modifying genes that explains the risk of fragile X-associated primary ova... more Objective: To identify modifying genes that explains the risk of fragile X-associated primary ovarian insufficiency (FXPOI). Design: Gene-based, case/control association study, followed by a functional screen of highly ranked genes using a Drosophila model. Setting: Participants were recruited from academic and clinical settings. Patient(s): Women with a premutation (PM) who experienced FXPOI at the age of 35 years or younger (n ¼ 63) and women with a PM who experienced menopause at the age of 50 years or older (n ¼ 51) provided clinical information and a deoxyribonucleic acid sample for whole genome sequencing. The functional screen was on the basis of Drosophila TRiP lines. Intervention(s): Clinical information and a DNA sample were collected for whole genome sequencing. Main Outcome Measures: A polygenic risk score derived from common variants associated with natural age at menopause was calculated and associated with the risk of FXPOI. Genes associated with the risk of FXPOI were identified on the basis of the P-value from gene-based association test and an altered level of fecundity when knocked down in the Drosophila PM model. Results: The polygenic risk score on the basis of common variants associated with natural age at menopause explained approximately 8% of the variance in the risk of FXPOI. Further, SUMO1 and KRR1 were identified as possible modifying genes associated with the risk of FXPOI on the basis of an untargeted gene analysis of rare variants. Conclusions: In addition to the large genetic effect of a PM on ovarian function, the additive effects of common variants associated with natural age at menopause and the effect of rare modifying variants appear to play a role in FXPOI risk. (Fertil Steril Ò 2021;116: 843-54. Ó2021 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.
Objective: To examine the degree to which paternal variables of age, body mass index (BMI), and s... more Objective: To examine the degree to which paternal variables of age, body mass index (BMI), and sperm parameters affect vitrified donor oocyte IVF outcomes. Previous studies examining the impact of male partner characteristics on in-vitro fertilization (IVF) have found conflicting results. Concerns are rising over the potential effects of paternal factors, such as age and obesity, on pregnancy and child health. Frozen donor oocyte IVF offers an ideal model to study these effects. Design: Retrospective chart review. Setting: Private fertility clinic. Patient(s): Nine hundred forty-nine recipients undergoing transfer of blastocyst embryo(s) from a vitrified oocyte donor bank between 2008-2015. Intervention(s): None. Main Outcome Measure(s): Implantation rate, clinical pregnancy rate, live birth rate, rate of low birth weight singleton infants (%2500 g), and preterm deliveries (PTD) of singleton infants (<37 wk). Results: After adjusting for covariates known to affect oocyte donation cycle success, male age, BMI and sperm parameters were not associated with differences in IVF outcomes. There were higher PTD rates for men R51 years and BMI R35 kg/m 2 , however, these were not significant after adjustment. There were no differences in rates of low birth weight infants with men >35 years or BMI >25 kg/m 2. Lastly, there were no differences in rates of PTD or low birth weight infants with abnormal sperm parameters. Conclusions: Neither advancing male age, elevated BMI, nor poor sperm quality were associated with outcomes in frozen donor oocyte IVF cycles in this study. Intracytoplamic sperm injection and ''oocyte quality'' likely mitigate some of the effects of male variables on outcomes following cryopreserved oocyte donation. (Fertil Steril Ò 2018;110:859-69. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.
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.
Fragile X-associated primary ovarian insufficiency (FXPOI) occurs in about 20% of women who carry... more Fragile X-associated primary ovarian insufficiency (FXPOI) occurs in about 20% of women who carry a premutation allele (55-200 CGG repeats). These women develop hypergonadotropic hypogonadism and have secondary amenorrhea before age 40. A non-linear association with repeat size and risk for FXPOI has been seen in multiple studies women with a premutation: those with a mid-range of repeats are at highest risk (∼70-100 CGG repeats). Importantly, not all carriers with 70-100 repeats experience FXPOI. We investigated whether AGG interruptions, adjusted for repeat size, impacted age at secondary amenorrhea. We have reproductive history information and AGG interruption data on 262 premutation women: 164 had an established age at amenorrhea (AAA) (for some, age at onset of FXPOI) or menopause, 16 had a surgery involving the reproductive system such as a hysterectomy, and 82 women were still cycling at the last interview. Reproductive status was determined using selfreport reproductive questionnaires and interviews with a reproductive endocrinologist. For each of these 262 women, FMR1 repeat size and number of AGG interruptions were determined. We confirmed the association of repeat size with AAA or menopause among women with a premutation. As expected, both premutation repeat size and the quadratic form of repeat size (i.e., squared term) were significant in a survival analysis model predicting AAA (p < 0.0001 for both variables). When number of AGG interruptions was added to the model, this variable was not significant (p = 0.59). Finally, we used a regression model based on the 164 women with established AAA to estimate the proportion of variance in AAA explained by repeat size and its squared term. Both terms were again highly significant (p < 0.0001 for both), but together only explained 13% of the variation in AAA. The non-linear association between AAA and FMR1 repeat size has been described in several studies. We have determined that AGG interruption pattern does not contribute to this association. Because only 13% of the variation is described using repeat size, it is clear that further research of FXPOI is needed to identify other factors that affect the risk for FXPOI.
Approximately 20-30% of women with an FMR1 premutation experience fragile X-associated primary ov... more Approximately 20-30% of women with an FMR1 premutation experience fragile X-associated primary ovarian insufficiency (FXPOI); however, current risk estimates based on repeat size only identify women with the midrange of repeats to be at the highest risk. METHODS: To better understand the risk by repeat size, we collected self-reported reproductive histories on 1,668 women and divided them into high-resolution repeat size bins of~5 CGG repeats to determine a more accurate risk for FXPOI in relation to CGG repeat length. RESULTS: As previously reported, women with 70-100 CGG repeats were at the highest risk for FXPOI using various statistical models to compare average age at menopause and risk of FXPOI, with women with 85-89 repeats being at the highest risk. Importantly, women with <65 repeats or >120 repeats did not have a significantly increased risk for FXPOI compared to women with <45 repeats. CONCLUSION: Using a large cross-section study on 1,668 women, we have provided more personalized risk assessment for FXPOI using high-resolution repeat size bins. Understanding the variability in risk has important implications for family planning and overall health among women with a premutation.
Clinical pregnancy rate(54.50% vs 63.70%, p<0.001) were significantly higher with frozen embryo t... more Clinical pregnancy rate(54.50% vs 63.70%, p<0.001) were significantly higher with frozen embryo transfer compared to fresh embryo transfer. Variables that were found to be independently associated with clinical pregnancy rate were fresh/frozen embryo transfer, female age and no. of embryo transferred. After adjusting for variables, frozen embryo transfer(0.75 (0.59, 0.95), p¼0.016) was protective factor of clinical pregnancy rate. CONCLUSIONS: Frozen embryo transfer is better than fresh embryo transfer in GnRH antagonist cycle in normo-responders.
Hepatitis B surface antigen, hepatitis C core antibody, syphilis, gonorrhea and chlamydia culture... more Hepatitis B surface antigen, hepatitis C core antibody, syphilis, gonorrhea and chlamydia cultures, CMV IgG and IgM.
Purpose: Emerging evidence indicates that women who carry an FMR1 premutation can experience comp... more Purpose: Emerging evidence indicates that women who carry an FMR1 premutation can experience complex health profiles beyond the two well-established premutation-associated disorders: fragile X-associated primary ovarian insufficiency (FXPOI, affects 20-30% carriers) and fragile X-associated tremor-ataxia syndrome (FXTAS, affects~6-15% carriers). Methods: To better understand premutation-associated health profiles, we collected self-reported medical histories on 355 carrier women. Results: Twenty-two health conditions were reported by at least 10% of women. Anxiety, depression, and headaches were reported by more than 30%. The number of comorbid conditions was significantly associated with body mass index (BMI) and history of smoking, but not age. Survival analysis indicated that women with FXPOI had an earlier age at onset for anxiety and osteoporosis than women without FXPOI. Cluster analysis identified eight clusters of women who reported similar patterns of comorbid conditions. The majority of carriers (63%) fell into three categories primarily defined by the presence of only a few conditions. Interestingly, a single cluster defined women with symptoms of FXTAS, and none of these women had FXPOI. Conclusion: Although some women with a premutation experience complex health outcomes, most carriers report only minimal comorbid conditions. Further, women with symptoms of FXTAS appear to be distinct from women with symptoms of FXPOI.
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