Attitudes Towards Potentially Carrying the FMR1 Premutation: Before vs After Testing of Non-Carrier Females with Diminished Ovarian Reserve

Diminished ovarian reserve (DOR) and premature ovarian failure are associated with elevated FMR1 CGG repeat alleles. We assessed pretest attitudes about potentially carrying the FMR1 premutation (FXP) (>55 CGG repeats) among reproductive age women compared with attitudes after learning their non-carrier status. Ninety-two women with DOR, regular menses and no family history of Fragile X Syndrome underwent FMR1 testing and completed attitudinal questionnaires before (T1) and 3 months after learning the test results (T2). The analysis utilized signed rank tests and α?=?0.05. Very few women thought they were likely to have a FXP (6.6 %). More participants thought FMR1 premutations were “serious” at T2 (62.9 %) than at T1 (46.1 %, p?p?相似文献   

Improving Health Education for Women Who Carry an <Emphasis Type="Italic">FMR1</Emphasis> Premutation

Women who carry an FMR1 (i.e., fragile X) premutation have specific health risks over their lifetime. However, little is known about their experience understanding these risks and navigating their health needs. The aim of this study was to use qualitative analysis to uncover both barriers and facilitators to personal healthcare using a framework of the Health Belief Model. Five focus groups were conducted with a total of 20 women who carry the FMR1 premutation using a semi-structured discussion guide. All sessions were transcribed verbatim and independently coded by two researchers. The coders used a deductive – inductive approach to determine the prominent themes related to the participants’ experiences seeking healthcare for premutation-related conditions. Salient barriers to personal healthcare included difficult clinical translation of research findings, lack of knowledge among healthcare providers and among the women themselves, different priorities, and shortage of premutation-specific support and targeted educational materials. Facilitators included family members, national and community support organizations, research studies, compassionate physicians, and other premutation carriers. Addressing barriers to personal healthcare through up-to-date educational materials can help diminish misperceptions regarding health risks. Targeted educational materials will aid in information sharing and awareness for women who carry the FMR1 premutation and their physicians.     

Emotional Reaction to Fragile X Premutation Carrier Tests Among Infertile Women

Female fragile X premutation carriers are at ∼10-fold increased risk of premature ovarian failure (follicle stimulating hormone >40 mIU/mL, amenorrhea, age <40). A milder degree of premature ovarian aging (diminished ovarian reserve, where follicle stimulating hormone levels are typically 10–20 mIU/mL) results in infertility. Approximately 10% of fertility clinic patients have this diagnosis. A cohort of 20 women diagnosed with diminished ovarian reserve provided a blood specimen (confidential results), and completed structured questionnaires that assessed emotional reactions to potentially being a premutation carrier (pretest questionnaire, n = 20) and the posttest known carrier status (3 month follow-up questionnaire, n = 18 non-carriers). Responses were measured using 9-point scales, and analyzed with Fisher exact and Wilcoxon exact tests. While most participants did not view fragile X premutations as a serious medical condition, perceptions of seriousness were positively correlated with anger and regret about not knowing sooner of the potential association of these premutations with infertility. Overall, when women (pretest) imagined themselves as carriers, their self-esteem and Health Orientation Scale responses were unchanged with the exception of feeling more afraid (p = 0.004). Despite strongly wishing for negative test results, they were glad to know there might be a medical explanation for their infertility. Financial Support: This work was financially supported by a University of Virginia School of Medicine Research & Development Award.     

Reproductive‐age women are overrepresented among perpetrators of husband killing

When a woman kills her husband, it is almost always an unplanned action of self‐defense against a battering husband or a last‐ditch attempt to survive a batterer's tyranny. Younger, reproductive‐age women are battered and killed by husbands at higher rates than are older, postreproductive‐age women. Because husband killing occurs in the context of self‐defense or as a last‐ditch effort to survive, reproductive‐age women should kill their husbands at higher rates than do postreproductive‐age women. I used a sample of 8,077 husband killings to test this hypothesis. Results support the hypothesis and document that (1) the highest rates of husband killing are for the youngest women, (2) the youngest husbands are at greatest risk of being killed by their wives, (3) women married to older men kill their husbands at higher rates than do women married to same‐age men and women married to younger men, and (4) reproductive‐age women kill their husbands at higher rates than do postreproductive‐age women across two groups: women married to younger men and women married to older men. Discussion suggests directions for future work that can improve the identification of women at greatest risk for husband killing. Aggr. Behav. 26:309–317, 2000. © 2000 Wiley‐Liss, Inc.     

Recommendations from Multi-disciplinary Focus Groups on Cascade Testing and Genetic Counseling for Fragile X-associated Disorders

The purpose of this paper is to report the outcome of a collaborative project between the Fragile X Research and Treatment Center at the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute at the University of California at Davis, the National Fragile X Foundation (NFXF), and the Centers for Disease Control and Prevention (CDC). The objective of this collaboration was to develop and disseminate protocols for genetic counseling and cascade testing for the multiple disorders associated with the fragile X mental retardation 1 (FMR1) mutation. Over the last several years, there has been increasing insight into the phenotypic range associated with both the premutation and the full mutation of the FMR1 gene. To help develop recommendations related to screening for fragile X-associated disorders, four, two day advisory focus group meetings were conducted, each with a different theme. The four themes were: (1) fragile X-associated tremor/ataxia syndrome (FXTAS); (2) premature ovarian failure (POF) and reproductive endocrinology; (3) psychiatric, behavioral and psychological issues; and (4) population screening and related ethical issues.     

Genetic Risk Assessment for Women with Epithelial Ovarian Cancer: Referral Patterns and Outcomes in a University Gynecologic Oncology Clinic

Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer patients seen in a university gynecologic oncology clinic (1/04–8/06). Electronic medical records (EMR) were used to document genetic service referral, time from diagnosis-to-referral, point-in-treatment at referral, personal/family cancer history, demographics, and genetic test results. Groups were compared using chi-squared and Fisher’s exact test for categorical variables and t-tests for continuous variables. The study population consisted of 376 women with ovarian cancer, 72 (19 %) of who were referred for genetic counseling/testing, primarily during surveillance. Of those referred, 42 (58 %) had personal or family genetic counseling and 34 (47 %) were ultimately tested or identified due to known family mutation. Family history and prior cancer were associated with referral. Family history, living in a larger community, higher-stage disease, and serous histology were associated with undergoing genetic counseling. Risk assessment identified 20 BRCA1/2 (5.3 %) and 1 HNPCC (0.3 %) mutation carriers. Based on recent estimates that 11.7–16.6 % of women with ovarian cancer are BRCA carriers and 2 % are HNPCC carriers, results suggest under-identification of carriers and under-utilization of genetic services by providers and patients. Interventions to increase medical providers’ referrals, even in a specialized oncology clinic, are necessary and may include innovations in educating these providers using web-based methods. Ease of referral by the introduction of an electronic cancer genetic referral form represents another new direction that may increase genetic risk assessment for high-risk women with ovarian cancer.     

Women’s Attitudes Toward Testing for Fragile X Carrier Status: A Qualitative Analysis

Fragile X syndrome (FXS) is primarily due to a repeat expansion mutation found in the FMR1 X-linked gene. We have conducted a qualitative analysis of responses from women concerning their attitudes toward testing for carrier status of the fragile X mutation among reproductive-age women. We obtained responses from focus groups including women with and without FXS in their families. We found the following themes: (1) mothers of children with FXS have difficulty formulating their opinions on population screening because of their unique experiences surrounding their own carrier diagnosis and their relationship with their children with FXS, (2) the motivation for carrier testing and need for information differ by family history of FXS and parental status, and (3) the timing of carrier testing with respect to a woman’s life stage dictates whether carrier information will be viewed as beneficial or detrimental. There was evidence that non-carrier women from the general population would be wholly unprepared for positive carrier results. These findings have significant implications for genetic counseling as well as for population screening.     

Young adult female fragile X premutation carriers show age- and genetically-modulated cognitive impairments

The high frequency of the fragile X premutation in the general population and its emerging neurocognitive implications highlight the need to investigate the effects of the premutation on lifespan cognitive development. Until recently, cognitive function in fragile X premutation carriers (fXPCs) was presumed to be unaffected by the mutation. Here we show that young adult female fXPCs show subtle, yet significant, age- and FMR1 gene mutation-modulated cognitive impairments as tested by a quantitative magnitude comparison task. Our results begin to define the neurocognitive endophenotype associated with the premutation in adults, who are at risk for developing a neurodegenerative disorder associated with the fragile X premutation. Results from the present study may potentially be applied toward the design of early interventions wherein we might be able to target premutation carriers most at risk for degeneration for preventive treatment.     

A Pilot Study of Fragile X Syndrome Screening in Pregnant Women and Women Planning Pregnancy: Implementation,Acceptance, Awareness,and Geographic Factors

We report herein results of a study performed in the Balearic Islands which had the following goals: 1) Determine the proportion of pregnant or non-pregnant women planning pregnancy, who would choose to undergo a screening test for Fragile X Syndrome (FXS), if it is accompanied by the appropriate information; 2) Assess satisfaction and any increase in stress among women who participate in screening; 3) Collect epidemiological information about the incidence of the disease in our population; and 4) Collect demographic and health history data and assess participants’ awareness of the disease. Screening was performed on 3,731 pregnant and non-pregnant women of childbearing age and the results indicate: a very high voluntary rate of participation; a high level of self-reported satisfaction and low levels of stress because of the test; a very high incidence of premutation (1/106) in our population; and a low level of awareness about the existence of FXS (25 %). Additional findings indicate no significant correlation between self-reported health history and premutation detection, and the high premutation incidence does not seem to be specific to the indigenous Balearic population. Based on these results, we discuss the pros and cons of an implementation of preconception and pregnant women screening for FXS within a public health screening program.     

GENDER'S ROLE IN RESPONSES TO INFERTILITY

Infertility is a major life stressor that affects approximately 10% of U.S. married couples. Infertile women and men have reported experiencing depression, helplessness, and marital strain. Given U.S. society's emphasis on women's role as mothers, it has been suggested that women's lives are more disrupted by infertility than those of men. This hypothesis was supported in a survey of 185 infertile couples and 90 presumed fertile couples. Infertile wives, as compared to their husbands, perceived their fertility problem as more stressful, felt more responsible for and in control of their infertility, and engaged in more problem-focused coping. Infertile husbands experienced more home life stress and lower home life performance than did their wives. These differences were not found for presumed fertile couples. Both infertile and presumed fertile wives experienced more depression, more sexual dissatisfaction, and lower self-esteem than did their husbands. Theoretical and counseling implications of these findings are discussed.     

Patient Perceptions of Telephone vs. In-Person <Emphasis Type="Italic">BRCA1/BRCA2</Emphasis> Genetic Counseling

Telephone genetic counseling (TC) for hereditary breast/ovarian cancer risk has been associated with positive outcomes in high risk women. However, little is known about how patients perceive TC. As part of a randomized trial of TC versus usual care (UC; in-person genetic counseling), we compared high risk women’s perceptions of: (1) overall satisfaction with genetic counseling; (2) convenience; (3) attentiveness during the session; (4) counselor effectiveness in providing support; and (5) counselor ability to recognize emotional responses during the session. Among the 554 participants (TC, N?=?272; UC, N?=?282), delivery mode was not associated with self-reported satisfaction. However, TC participants found counseling significantly more convenient than UC participants (OR?=?4.78, 95 % CI?=?3.32, 6.89) while also perceiving lower levels of support (OR?=?0.56, 95 % CI?=?0.40–0.80) and emotional recognition (OR?=?0.53, 95 % CI?=?0.37–0.76). In exploratory analyses, we found that non-Hispanic white participants reported higher counselor support in UC than in TC (69.4 % vs. 52.8 %; OR?=?3.06, 95 % CI?=?1.39–6.74), while minority women perceived less support in UC vs. TC (58.3 % vs. 38.7 %; OR?=?0.80, 95 % CI?=?0.39–1.65). We discuss potential research and practice implications of these findings which may further improve the effectiveness and utilization of TC.     

Attitudes Toward Fragile X Mutation Carrier Testing from Women Identified in a General Population Survey

Fragile X syndrome is primarily due to a CGG repeat expansion found in the FMR1 X-linked gene. In a previous study, we conducted focus groups with women to assess their attitudes towards fragile X carrier screening. In this follow-up study, we conducted in-depth interviews of general population reproductive-age women who were identified as carriers. We explored their attitudes toward testing for carrier status of the fragile X mutation. These women underwent screening primarily to participate in a research project rather than in search of a diagnosis for specific symptoms. As such, these women were wholly unprepared for positive carrier results. Their responses about their results and carrier screening, in many cases, were being worked out over the course of the interview itself. The most salient finding of this work is the apparent lack of relevance of carrier status to these women. Many expressed that although the information could be relevant in the future, it is not relevant at this stage of their lives in terms of family planning (either with respect to having unaffected offspring or to premature ovarian failure) and personal relationships. Although issues of abortion seemed prominent in the focus groups, we found that carrier status did not have an apparent effect on women’s attitudes about termination. We hypothesize this may be related to the fact that women had not processed their new carrier status and had not related it to previously-formed personal opinions. The findings of this work have significant implications for genetic counseling and population screening. Genetic counselors should be mindful that general population women may not recognize the immediate importance of their carrier status even when literature is provided and discussed prior to providing a sample. As part of comprehensive genetic counseling, counselors should identify the reproductive life stage of the woman receiving the new information and help her identify when this information would be more meaningful in her life. Counselors can assist in setting up a personalized road map with specific types of services that will be more applicable to the woman as her carrier status becomes more relevant.     

Positive affect mediates the relationships between resilience,social support and posttraumatic growth of women with infertility

This study aims to explore the relationship between resilience, social support, positive affect and posttraumatic growth among Chinese women with infertility, and to examine the mediating role of positive affect. A convenience sample of 1733 women diagnosed with infertility was recruited from the infertility outpatient clinics at three reproductive hospitals in Shandong Province of China between May 2015 and April 2016. They completed a background questionnaire, the Posttraumatic Growth Inventory, the Perceived Social Support Questionnaire, the Connor-Davidson Resilience Scale, the Positive and Negative Affect Schedule. Individuals reported high levels of PTG (M = 64.81; SD = 16.20). Perceived social support (β = .11, p < .001), resilience (β = .18, p < .001) and positive affect (β = .46, p < .001) were related to PTG. Positive affect may play a mediating role in the relationships between resilience (.125, .201, p < .001), social support (.055, .121, p < .001) and PTG. This study examines the effects of resilience, social support, and positive affect on PTG among Chinese infertile women. Wherein, positive affect may play a mediating role in the relationships between resilience, social support and PTG.     

Fragile X-associated tremor/ataxia syndrome (FXTAS)

Carriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55-200 repeats) develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction. In excess of one-third of male premutation carriers over 50 years of age develop the fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS also represents a new form of inclusion disease, with eosinophilic intranuclear inclusions found throughout the brain in both neurons and astrocytes. Because FXTAS appears to be relatively specific to male premutation carriers, who are known to possess elevated levels of FMR1 mRNA, the neuropathology may arise as a consequence of a toxic gain-of-function of the mRNA itself, although this proposal requires additional direct testing. One of the critical needs at present is a better estimate for the prevalence of this disorder, because FXTAS is likely to be underdiagnosed in the adult movement disorders clinics.     

Performing and Declining PGD: Accounts of Jewish Israeli Women Who Carry a <Emphasis Type="Italic">BRCA1/2</Emphasis> Mutation or Partners of Male Mutation Carriers

To describe factors associated with preimplantation genetic diagnosis (PGD) decisions among Jewish Israeli BRCA1/2 carriers or spouses of a male carrier, we contacted all women who initiated PGD consultation for embryonic BRCA1/2 mutation detection at Sheba Medical Center, prior to March 2014. Applying a qualitative approach, we asked women to elaborate on the factors they considered in either opting for PGD or discontinuing the screening procedure. Participants were 18 Jewish Israeli women; 14 were carriers of one of the Ashkenazi founder mutations in BRCA1/2, and four were spouses of male mutation carriers, who underwent at least one cycle of PGD. Prior to seeking PGD, ten of the women had no children. At the time of the interview, all but three had at least one child. Three factors emerged as key motivators for PGD: having witnessed the disease in a close relative (n = 12); prior IVF treatment for infertility (n = 12); and having pre-existing frozen embryos (n = 6). Ten women withdrew from the PGD process due to clinical, logistical, and financial reasons. In conclusion, most women decided to withdraw from PGD instead of continuing until a successful conception was achieved. Those who opted for PGD attributed their discontinuation of further screening to the emotional burden that is greatly intensified by practical difficulties.     

Attitude of Medical School Students in China Towards Genetic Testing and Counseling Issues in FXS

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. However, genetic testing protocols and genetic counseling guidelines for FXS are not yet established in mainland China. In the present study, we conducted a comprehensive analysis using a self-administered questionnaire among students at the Xiangya medical school to investigate their attitude towards genetic testing and counseling issues of FXS. We have gained a general understanding of the attitudes of medical students towards these FXS issues in China. This information is of immense importance to develop appropriate genetic tests and to train counselors for FXS. As the medical school students surveyed are prospective physicians who will be a part of the Chinese health system, our survey was focused on the basic knowledge of FXS, population-based FXS screening, confidentiality and reproductive options for mutation carriers. The study demonstrated that only less than one third of the participants had heard about FXS. 94.6 % of participants were in favor of FXS screening for women in their reproductive age who had a genetic history of FXS. Furthermore, only half of the participants would inform their families about their genetic status in case of positive test results, and more than half of the participants supported natural conception and prenatal diagnosis for FXS mutation carriers. Additional findings and research implications are also discussed. This survey targeting potential doctors provides important information for the development of FXS genetic test and counselor training for the Chinese health system.     

The Influence of Gender-related Factors on HIV Prevention among Chinese Women with Disrupted Marital Relationship

Two-hundred-and-thirty-one Chinese women were individually interviewed on their HIV-prevention behavior and gender-related psychosocial factors. Compared to women with intact marriages, women with marital disruption endorsed more inaccurate information about HIV/AIDS, had less worry about contracting HIV from their husbands, and were less likely to use condoms in current and future sexual activities. Among sexually active Chinese married women, rates of condom use in the past 6 months were 60% for the intact group and 38% for the disrupted group. Factors that discriminated between condom non-users and users among sexually active women in the disrupted group included: conservative gender attitudes toward sexuality and sexual decision-making, negative attitudes toward condom use, and lack of concern about contracting HIV from their husbands.     

The effects of anxiety and depression on in vitro fertilisation outcomes of infertile Chinese women

The object was to assess anxiety and depression during in vitro fertilisation (IVF) treatment and determine IVF-related psychological factors in infertile Chinese women. The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate anxiety and depression among 842 patients, respectively. A univariate analysis was used to compare variables among three SAS groups and three SDS groups. Anxiety and depression were both represented in 21.3% of the cases. Patients <35 years tended to be more anxious. In women <35 years, the SDS scores were higher with lower educational backgrounds and female or couple’s infertility, while the SAS scores were higher in female or couple’s infertility. In older ones, the SDS scores were higher in those with lower educational backgrounds and longer time for infertility, while the SAS scores were higher in those with lower educational backgrounds. In SAS groups 1–3, the embryo availability was 5.0 (3.0–8.0), 5.0 (3.0–8.0), and 3.0 (2.0–4.5) (p = .013); and the fertilisation rate was 91.9, 90.4, and 81.8% (p < .001), respectively. We concluded that infertile women experience anxiety and depression during IVF treatment, especially in women <35 years. Younger women with female infertility would be more anxious and depressive while higher education can protect them from depression. In older ones, they would experience more depressive with longer time for infertility and be less anxious and depressive with higher education. Anxiety affects the fertilisation rate and embryo availability.     

Living With Genetic Vulnerability: a Life Course Perspective

This is the second article of a two part series about utilizing the life course perspective (LCP) in genetic counseling. Secondary data analysis was conducted on a grounded theory, longitudinal study which provided a wide focus on living with hereditary breast and ovarian cancer (HBOC) risk. The aim of this analysis was to explore the longitudinal data for both the temporal and social context of living with BRCA mutation genetic test results. Sixteen women from two previous studies were interviewed on multiple occasions over an 8 year time period. The LCP was used to direct a thematic analysis of the data. Families experience the consequences of knowing they carry a BRCA1 or BRCA2 gene mutation long after the initial diagnosis. These women’s experiences across time reflect the concepts of the LCP and show how life is changed when families know they live with a genetic vulnerability to an adult-onset and potentially life-threatening disease. Different emphases on concepts from the LCP were evident across the different age groups. For example, the group of 40–50 year old women emphasized the concept of linked lives, those in their 30’s focused on human agency and women in their 20’s were more focused on timing of events. This study helps give direction to healthcare providers counseling women living with a BRCA mutation.