Ethical and moral perspectives of individuals who considered/used preimplantation (embryo) genetic testing.

This study examined perspectives on the ethical implications of preimplantation genetic testing (PGT) among individuals who actually (not hypothetically) used or considered using PGT. Most of the prior patient-centered research on PGT ethics used qualitative designs (9 out of the 11 articles) and focused only on single gene testing. This cross-sectional study used an anonymous online questionnaire; 15 items assessed potential ethical concerns involved in PGT decision-making, including clinical indications for PGT, the greater implications of PGT for society, and unused embryo disposition. N = 207 individuals (mean female/male age 35.7/38.9 years, 21% Hispanic or non-White) who had recently used or considered using PGT for single gene (60%) or for chromosomal testing (40%) completed the questionnaire. Most respondents supported PGT screening for disease conditions with childhood or adult onset that are untreatable (64%-85% across items); most opposed PGT for trait selection (76%-81%). Most respondents agreed that PGT aids in parental decision-making (66%-67%), although some expressed concern over potential unforeseen consequences (25%-30%). Regarding disposition of embryos without known genetic abnormalities, most respondents favored freezing indefinitely (86%) or donating to another family (69%), while for embryos with genetic abnormalities, most respondents favored donating to research (78%) or destroying them (62%). Stratification by religious affiliation revealed several differences, such as less acceptance of PGT for diseases that occur in adulthood and have no treatment options among Protestants (p = .015) and greater willingness to donate surplus embryos to research among participants without a religious affiliation (p < .001). These results are limited by the relatively homogeneous sample of participants (mostly White, married, and predominantly college-educated). In summary, participants who considered/used PGT found PGT acceptable overall for screening for disease conditions; most opposed using PGT for trait selection. Our novel questionnaire provides a structured tool for assessing the ethical perspectives surrounding the use of PGT.

Initial psychometric analysis of novel instruments to assess decisional distress and decisional uncertainty in women who have considered using preimplantation genetic testing.

OBJECTIVE: To analyze psychometric properties of two novel instruments assessing decisional distress and uncertainty experienced by individuals considering preimplantation genetic testing (PGT). METHODS: The new PGT Decisional Distress instrument (22 items) assesses negative/positive emotions. The new PGT Decisional Uncertainty instrument assesses Clarity about test benefits/disadvantages (5 items) and Certainty of having adequate information/support to make a good decision (7 items). Scales ranged from 0 to 4. Psychometrics (central tendencies, internal consistency reliability, and discriminant validity) were evaluated. Stratified analysis by decision stage was conducted. All participants had considered or used PGT in the previous 6 months. RESULTS: N = 106 females (mean age 36.5 ± 4.8 years; 16% non-Caucasian; 9% Hispanic) across 16 US states completed an online anonymous questionnaire. On average, respondents reported minimal distress (mean 0.96), high clarity (mean 3.26), and high certainty (mean 3.06), particularly those who had already decided compared to undecided women (P ≤ .02). Instruments had excellent internal consistency (Cronbach's α's 0.92-0.94) and displayed sufficient inter-individual variability (SD's 0.75-0.89). Correlations confirmed expected patterns of association between instruments (P's < .01), indicating discriminant validity. CONCLUSION: We document initial reliability and validity of new instruments to measure emotional distress and uncertainty in female patients who have recently considered PGT for single-gene or chromosomal disorders.

Navigating the body of literature assessing BRCA1/2 mutations and markers of ovarian function: a systematic review and meta-analysis.

PURPOSE: Twelve percent of women in the USA will develop invasive breast cancer in their lifetime, and that risk increases to 80% if they carry a BRCA1 or BRCA2 mutation. BRCA1/2 mutations are thought to potentially affect ovarian reserve and/or fertility. METHODS: PubMed and PubMed Central were searched for publications on ovarian reserve-related outcomes (i.e., AMH and response to controlled ovarian hyperstimulation (COH) protocols) that were reported in relation to BRCA1 and/or BRCA2 mutations from 1950 through May 2019. A meta-analysis was conducted to create forest plots and summary effect measures using Review Manager 5.3. RESULTS: This article reviews the 16 qualifying publications. There were several fundamental methodological differences in the study designs and outcome details reported in AMH studies. Summary statistics found no difference in AMH levels between BRCA1/2+ women as compared with controls (Z overall test effects p ≥ 0.45). Regarding responses to COH, there were overall non-significantly fewer total and mature numbers of oocytes retrieved in BRCA1/2+ cases as compared with controls (meta-analysis Z overall test effects p ≥ 0.40). CONCLUSIONS: While the summary measures indicate no significant differences in AMH levels between BRCA1/2+ cases and controls, readers should be aware that there are significant methodological differences in the AMH reports. Additionally, the response to COH protocols does not seem to be significantly lower in BRCA1/2 mutation carriers in the existing literature. Continued research on both of these clinical parameters would be beneficial for patient counseling.

Does theFMR1 gene affect IVF success?

FMR1 CGG trinucleotide repeat expansions are associated with Fragile X syndrome (full mutations) and primary ovarian insufficiency (premutation range); the effect of FMR1 on the success of fertility treatment is unclear. The effect of FMR1 CGG repeat lengths on IVF outcomes after ovarian stimulation was reviewed. PubMed was searched for studies on IVF-related outcomes reported by FMR1 trinucleotide repeat length published between 2002 and December 2017. For women with CGG repeats in the normal (<45 CGG), intermediate range (45-54 CGG), or both, research supports a minimal effect on IVF outcomes, including pregnancy rates; although one study reported lower oocyte yields after IVF stimulation in women with lower CGG repeat lengths and normal ovarian reserve. Meta-analysis revealed no association within subcategories of normal repeat length (<45 CGG) and IVF pregnancy rates (summary OR 1.0, 95% CI 0.87 to 1.15). Premutation carriers (CGG 55-200) may have reduced success with IVF treatment (lower oocyte yield) than women with a normal CGG repeat length or a full mutation, although findings are inconsistent. Direct implications of the repeat length on inheritance and the risk of Fragile X syndrome have been observed. Patients may require clinical and psychological counselling, and further preimplantation genetic testing options should be considered. Thus, there are clinical and psychological counseling implications for patients and potential further patient decisions regarding preimplantation genetic testing options.

Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR.

There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms.

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 < 0.0003). When asked at T1 to "describe your feelings when you consider that you are potentially a carrier" of a FXP, 10% had negative feelings, 50% felt ambivalent, and 40% had positive feelings. At T2, feelings about not being a carrier were significantly more favorable (p < 0.0001): negative (0%), ambivalent (6.5%), positive (93%). Corroborating prior reports, few women had a negative view of FXP, perhaps anticipating that carrying the FXP explains their infertility. Perception of the seriousness of FXP increased after learning they did not carry the FXP, which would be predicted by health belief models.

Longitudinal interviews of couples diagnosed with diminished ovarian reserve undergoing fragile X premutation testing.

About 10 % of infertile/subfertile women are diagnosed with diminished ovarian reserve (DOR), of which < 5 % will become pregnant spontaneously. Fragile X (FMR1) genetic testing may provide a reason for her early ovarian aging and/or have reproductive implications. Seven women with DOR (genetic study subset) and the male partners of six of these women were separately interviewed about the experience of being asked to undergo this unanticipated genetic test. Three interviews were conducted (before, within 1 week after, and 3 months after learning the test results). None of the participants carried the FMR1 premutation (largest FMR1 allele 27-50 CGG repeats). For women, their pregnancy-seeking journey was long and exhausting. Women understood the reproductive implications of carrying the FMR1 premutation, and hoped for a negative result. Being offered a genetic test caused women to pause and re-think their future reproductive plans. Husbands viewed the infertility journey as filled with unknowns, of which the genetic test results would be one more puzzle piece. The expense of fertility testing/treatment was mentioned by both spouses, though more notably by husbands. The introduction of a possible genetic cause of infertility, with additional potential health consequences for future biological children, caused women to re-think their quest for pregnancy. In contrast, the genetic test was viewed as an additional source of information for their husbands as opposed to raising concern regarding potential reproductive ramifications.

A checklist for timeout on labor and delivery: a pilot study to improve communication and safety.

OBJECTIVE: To assess the impact on staff communication of a standardized checklist for timeout for patients undergoing a trial of labor after cesarean section and/or elective induction at term. STUDY DESIGN: A comparison of presurvey and postsurvey questionnaire results for labor and delivery personnel assessing communication before and after checklist implementation. RESULTS: From October 2011 through March 2012, 52.9% (N=37) of 70 eligible patients had the standardized checklist for timeout performed. Prior to implementation of the checklist, 66% of respondents (48.8% of nurses, 100% of residents, 90% of attendings) slightly or strongly agreed that their opinions were heard versus 83% of respondents during the study period (73.7% of nurses, 100% of residents, 100% of attendings). Following the intervention, nurses reported that they were more likely to feel as though their opinions were heard (p = 0.05). CONCLUSION: Implementation of a formalized obstetric timeout improved the subjective perception of communication among obstetric staff. This tool has the potential to improve patient safety in labor and delivery.

AMH in women with diminished ovarian reserve: potential differences by FMR1 CGG repeat level.

PURPOSE: We explored whether AMH, as a surrogate for oocyte supply, varies by FMR1 genotype in women diagnosed with diminished ovarian reserve (DOR), a subset of the Primary Ovarian Insufficiency phenotype. Research is inconsistent on the relationship between AMH and FMR1 repeat length, controlling for age. METHOD: Seventy-nine cycling women diagnosed with DOR, and without a family history of fragile X syndrome, provided blood for FMR1 and AMH testing. DOR was defined as elevated FSH and/or low AMH and/or low antral follicle count, with regular menses. FMR1 CGG repeats were stratified by the larger allele <35 repeats (n = 70) v. ≥35 repeats (n = 9). Quadratic and linear models were fit to predict log (AMH) controlling for age. The AMH sample used as the outcome variable was drawn at a later date than the diagnostic AMH. RESULTS: Serum AMH concentration median was 0.30 ng/mL; Ages ranged from 26-43 years. A quadratic model (including age(2)) did not show a relationship with FMR1 CGG level (p-value = 0.25). A linear model of log (AMH), corresponding to an exponential decline of AMH with increasing age, was significantly different, and had a steeper slope, for women with ≥ 35 CGG repeats than women with < 35 repeats (p = 0.035). CONCLUSION: Findings suggest a greater rate of follicular loss that starts at later ages in women with DOR and ≥ 35 CGG repeats.

Sexual function in women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrinologic disorder. Little is known about the effects of PCOS on overall sexual functioning, phases of the sexual response cycle, and sexual satisfaction. AIM: To compare the differences in sexual function between women with PCOS and controls, and to assess the relationship of serum testosterone, body mass index (BMI), hirsutism, and acne with sexual function scores in women with PCOS. METHODS: A cross-sectional analysis in which women who met the National Institute of Child Health and Human Development criteria for PCOS were compared with a group of healthy volunteers. MAIN OUTCOME MEASURES: Results from the validated Changes in Sexual Functioning Questionnaire (CSFQ) were used to assess sexual function. In women with PCOS, serum testosterone levels, BMI, self-reported hirsutism, and acne were assessed as independent variables. RESULTS: Ninety-two women with PCOS and 82 controls were studied. Based on total CSFQ scores, sexual dysfunction was present in 27.2% of cases vs. 24.4% of controls (not signifcant). Women with PCOS had a significantly lower orgasm/completion score compared with women in the control group (P < 0.001). Women with PCOS whose testosterone levels were >1 standard deviation above the mean had significantly better sexual functioning vs. those within 1 SD (P = 0.015) and those >1 SD below the mean (P = 0.033). In women with PCOS, increasing BMI was associated with a significant reduction in the orgasm/completion subdomain, but no significant associations were found in regard to acne or hirsutism. CONCLUSIONS: Women with PCOS have similar sexual functioning scores compared with controls except in regard to orgasm/completion. The subpopulation of women with PCOS whose serum testosterone levels are in the normal reproductive range are at increased risk for sexual dysfunction.

Longitudinal anti-müllerian hormone in women with polycystic ovary syndrome: an acupuncture randomized clinical trial.

Others have studied acupuncture treatment for polycystic ovary syndrome (PCOS). Anti-müllerian hormone (AMH) is positively correlated with the ovarian follicle pool, thus making it a useful ovarian reserve measure. AMH is elevated in women with PCOS and has been suggested as a diagnostic tool. This study examined the impact of electroacupuncture on AMH concentration in women with PCOS. Seventy-one women with PCOS participated in a randomized, double-blind, sham-controlled clinical trial of acupuncture. Three longitudinal AMH samples over the 5-month protocol were compared with objective ovulation parameters primarily using nonparametric statistics. Results indicated that AMH levels in PCOS were higher than published norms in women without PCOS. There was no difference between the true and sham acupuncture arms in the change in AMH longitudinally. Baseline AMH, but not the change in AMH over time, was inversely correlated with ovulation and menstrual cycle frequencies in both arms combined (P < 0.001). In conclusion, AMH correlated with an increased likelihood of monthly ovulation, as expected from the literature on women without PCOS. The lack of difference by intervention in AMH was consistent with the underlying clinical trial. AMH may be clinically useful to predict which PCOS women are more likely to respond to an intervention.

Psychological measures of patient's decision-making for prenatal genetic testing.

OBJECTIVE: To use a questionnaire to determine the levels of maternal decision-related distress, clarity of the pros and cons, and certainty when considering prenatal genetic diagnostic testing; and to assess the relationship between these constructs and patient characteristics. METHOD: Cross-sectional study. Voluntary, anonymous questionnaires distributed 2017-2019 to women referred for invasive prenatal genetic testing. Excluded: English or Spanish illiterate. Maternal characteristics were collected. Questions evaluated distress, decisional certainty, and decisional clarity on a 5-point Likert scale (range: 0 = low/uncertain/unclear to 4 = high/certain/clear). Analysis: non-parametric Kruskal-Wallis, correlation statistics, and ANOVA. RESULTS: Forty-four female patients completed it. Most were married, white, Catholic, and multiparous. 58% had already made a testing decision. Patients expressed low distress levels (mean 1.18 ± 0.80) and expressed high decisional certainty (mean 3.28 ± 0.76) and clarity (mean 3.30 ± 0.99). Decisional certainty and clarity were positively correlated (r = 0.47, p < .01), whereas distress was negatively correlated with decisional certainty (r = -0.8136, p < .0005) and decisional clarity (r = -0.49, p = .007). No significant differences by religion or parity. Greater distress (p < .05) and less decisional clarity (p = .07) occurred between those still debating testing vs those who had decided. CONCLUSIONS: Higher maternal distress scores were associated with lower decisional certainty and decisional clarity in women considering prenatal genetic testing.

Inter-laboratory validation of the measurement of follicle stimulating hormone (FSH) after various lengths of frozen storage.

BACKGROUND: Serum follicle stimulating hormone (FSH) levels are used clinically to evaluate infertility, pituitary and gonadal disorders. With increased frequency of research collaborations across institutions, it is essential that inter-laboratory validation is addressed. METHODS: An inter-laboratory validation of three commercial FSH immunoassays was performed with human serum samples of varying frozen storage length (2 batches of 15 samples each) at -25 degree C. Percentage differences and Bland-Altman limits of agreement were calculated. RESULTS: The inter- and intra-laboratory consistency of FSH values with the same assay manufacturer was much higher after shorter-term storage (frozen for less than 11 months, mean percentage degradation less than 4%) than after long-term storage (2-3 years, mean percentage degradation = 23%). Comparing assay results from different manufacturers, there was similar overall long term degradation as seen with the same manufacturer (-25%), however the degradation was greater when the original FSH was greater than 20 mIU/mL relative to less than 10 mIU/mL (p < 0.001 trend test). CONCLUSION: The findings suggest that degradation of serum samples stored between 11 months and 2-3 years at -25 degrees C can lead to unstable FSH measurements. Inter-laboratory variability due to frozen storage time and manufacturer differences in assay results should be accounted for when designing and implementing research or clinical quality control activities involving serum FSH at multiple study sites.

Antimullerian Hormone and Impending Menopause in Late Reproductive Age: The Study of Women's Health Across the Nation.

BACKGROUND: A test that helps predict the time to the final menstrual period (FMP) has been sought for many years. OBJECTIVE: To assess the ability of antimullerian hormone (AMH) measurements to predictions the time to FMP. DESIGN: Prospective longitudinal cohort study. SETTING: The Study of Women's Health Across the Nation. PARTICIPANTS AND MEASUREMENTS: AMH and FSH were measured in 1537 pre- or early perimenopausal women, mean age 47.5 ±â€…2.6 years at baseline, then serially until 12 months of amenorrhea occurred. AMH was measured using a 2-site ELISA with a detection limit of 1.85 pg/mL. MAIN OUTCOME MEASURE: Areas under the receiver operating curves (AUC) for AMH-based and FSH-based predictions of time to FMP, stratified by age. Probabilities that women would undergo their FMP in the next 12, 24, or 36 months across a range of AMH values were assessed. RESULTS: AUCs for predicting that the FMP will occur within the next 24 months were significantly greater for AMH-based than FSH-based models. The probability that a woman with an AMH <10 pg/mL would undergo her FMP within the next 12 months ranged from 51% at h<48 years of age to 79% at ≥51 years. The probability that a woman with an AMH >100 pg/mL would not undergo her FMP within the next 12 months ranged from 97% in women <48 years old to 90% in women ≥51 years old. CONCLUSIONS: AMH measurement helps estimate when a woman will undergo her FMP, and, in general, does so better than FSH.

Sexual functioning of Latino women seeking outpatient gynecologic care.

INTRODUCTION: A sample of Latino women from an ambulatory obstetrics and gynecology (Ob/Gyn) clinic were queried about their sexual functioning using the Changes in Sexual Functioning Questionnaire (CSFQ-14). AIM: To assess the degree of self-reported sexual complaints in a sample of Latino women living in the United States; to assess if the prevalence of symptoms differs from one study of women living in Spain; and to determine if sexual complaints were associated with demographics, sexual/reproductive history, selected medications, or religious practices. MAIN OUTCOME MEASURES: CSFQ-14 scores and demographic variables. METHODS: CSFQ-14 questionnaire in an out-patient, bilingual Ob/Gyn clinic in Central Virginia. RESULTS: Seventy-one native Spanish-speaking patients (59% born in Mexico) completed the U.S. Spanish version of the CSFQ-14 and a short questionnaire for potential covariates. The mean age was 28.7 years (range 17-60). Birth place was outside of the United States for 95.8% (N = 67). Eighty percent of participants had children and 96% reported being currently sexually active. Low sexual functioning, as defined by a total CSFQ score of < or = 41, was found in 26 (41.3%) participants. Taking medication for depression and/or anxiety was associated with lower sexual functioning (P = 0.03). Women who had children of any age living in the household were less likely to report low sexual functioning (P = 0.05; P = 0.01 when restricted to infants) than women without children living in the household. Thirteen of 68 women (19.1%) reported a history of physical and/or sexual abuse, but this was not associated with low sexual functioning. There was no association between self-reported religious affiliation or church attendance frequency and sexual complaints. Respondents in our sample had lower (i.e., worse sexual function) overall CSFQ scores compared with a sample of college students in Spain (P < 0.01), but higher (i.e., better sexual function) overall scores than workers in Spain (P < 0.04). On the subscales, our Latino population reported greater pleasure and less desire/interest than women who live in Spain. CONCLUSIONS: Self-reported rates of low sexual functioning were common in this cross section of Latino women. Medical treatment of depression and/or anxiety was associated with lower functioning. Direct inquiry about the sexual health of U.S. Latino women presenting for routine health care may assist in the identification of sexual difficulties in this population.

Emotional reaction to fragile X premutation carrier tests among infertile women.

Female fragile X premutation carriers are at approximately 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.

Psychological and emotional concomitants of infertility diagnosis in women with diminished ovarian reserve or anatomical cause of infertility.

OBJECTIVE: To examine the magnitude and predictors of emotional reactions to an infertility diagnosis in two groups of women: those with diminished ovarian reserve (DOR), and those clinically diagnosed with an anatomical cause of infertility (ACI). DESIGN: Cross-sectional study. SETTING: Academic and private fertility clinics. PATIENT(S): Women diagnosed with DOR (n = 51) and women diagnosed with ACI (n = 51). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Fertility Problem Inventory (infertility distress), Rosenberg Self-Esteem Scale, Health Orientation Scale (emotional reactions to receiving a diagnosis). RESULT(S): Women with DOR had statistically significantly higher infertility distress scores than women with ACI and higher scores on subscales assessing distress from social concerns, sexual concerns, and a need for parenthood. In both groups, higher self-esteem was associated with lower infertility distress. Hierarchical multiple regression analyses revealed that for women with DOR and those with ACI lower infertility distress but not self-esteem predicted a more positive emotional reaction toward receiving a fertility diagnosis. CONCLUSION(S): Women diagnosed with DOR have greater infertility distress but similar self-esteem and emotional reactions to their diagnosis compared with women who have an anatomical cause of infertility. These results suggest that for both groups distress surrounding infertility itself may influence the way women respond to learning the cause of their infertility.

Distribution of the FMR1 gene in females by race/ethnicity: women with diminished ovarian reserve versus women with normal fertility (SWAN study).

OBJECTIVE: To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls and whether associations vary by race/ethnic group. DESIGN: Case-control study. SETTING: Academic and private fertility clinics. PATIENT(S): DOR cases (n = 129; 95 Whites, 22 Asian, 12 other) from five U.S. fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n = 803; 386 Whites, 219 African-Americans, 102 Japanese, 96 Chinese) from the United States-based SWAN Study had one or more menstrual period in the 3 months pre-enrollment, one or more pregnancy, no history of infertility or hormone therapy, and menopause ≥46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): FMR1 CGG repeat lengths. RESULT(S): Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians. White cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls or by race/ethnic group within cases in the longer allele. CONCLUSION(S): This study refutes prior reports of an association between DOR and high normal/intermediate repeats and confirms an association between DOR and low normal repeats in Whites.

Initial chemotherapy followed by surgical cytoreduction for the treatment of stage III/IV epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to evaluate differences in morbidity, progression-free interval, and survival in women with advanced epithelial ovarian cancer treated with initial chemotherapy versus initial surgery. STUDY DESIGN: All women with epithelial ovarian cancer who were treated surgically at our hospital between January 1, 1995, and January 1, 2003, were eligible; the cases of 200 patients met the criteria and underwent retrospective chart review. RESULTS: Ninety-eight patients (49%) had initial chemotherapy, and 102 patients (51%) had initial surgery. Patients who received initial chemotherapy were more likely to have stage IV disease (initial chemotherapy, 27%, vs initial surgery, 8%; P = .042) and grade 3 disease (initial chemotherapy, 73%, vs initial surgery, 61%; P = .025). Optimal cytoreduction was achieved more often in patients who received initial chemotherapy (initial chemotherapy, 86%, vs initial surgery, 54%; P < .001). Only optimal cytoreduction (P = .022), and not treatment choice (P = .089), had an impact on median survival. CONCLUSION: Initial chemotherapy is a reasonable alternative to initial surgery for the treatment of selected patients with advanced epithelial ovarian cancer.

Acceptance of fragile X premutation genetic screening in women with ovarian dysfunction.

OBJECTIVE: The purpose of this study was to assess patient perception of fragile X premutation genetic testing (FRAX). STUDY DESIGN: This was a cross-sectional survey of women with elevated follicle stimulating hormone levels with (premature ovarian failure or early menopause [POF/EM], n = 20) or without (diminished ovarian reserve [DOR], n = 20) amenorrhea. Seventy-five percent participated. RESULTS: Seventy-five percent of the DOR group and 43% of the POF/EM group desired FRAX testing. Eighty-three percent wanted to assist the scientific knowledge of FRAX, even if they did not want to know their own results. POF/EM women were more concerned than DOR women about paying out-of-pocket (P = .001) and maintaining confidentiality insurance-wise (P = .07). Primary motivations for women who wanted testing were the desire to know if they have FRAX, and wanting to determine if FRAX is the cause of their ovarian dysfunction. The primary decision factor for those declining testing was unwillingness to pay out-of-pocket (75%). CONCLUSION: Women with ovarian dysfunction are interested in FRAX testing. Cost, confidentiality, and the implications for relatives are their key concerns.