Determinants of Decision Regret Regarding Fertility Preservation in Adolescent and Young Adult Cancer Survivors: A Systematic Review.

Given recent advances in cancer therapeutics, there is a growing population of adolescent and young adult (AYA) cancer survivors navigating the physical and psychological consequences of cancer treatment. Fertility preservation (FP) conversations are of increasing importance for these survivors. Decision regret (DR) is a measure of distress or remorse following a health care decision, and it is a useful tool to evaluate the impact of a treatment on quality of life. The aim of this systematic review is to culminate existing literature focused on determinants of FP DR among AYA cancer survivors and to propose future interventions to reduce DR among AYA cancer survivors. An electronic database search was performed using PubMed, Web of Science, and APA PsycINFO for articles published before December 2023 using the following search criteria: PubMed: "Fertility Preservation"[Mesh] AND decision regret, APA PsycINFO and Web of Science: Fertility Preservation AND decision regret. Articles were organized into five categories that emerged after initial review. Nineteen articles that focused on DR and FP in AYA cancer survivors aged ≤40 and ≥12 years were included. Article results were categorized into five categories pertaining to determinants of FP DR: Unmet Informational and Emotional Needs, Need for Developmentally Appropriate Conversations, Insufficiency of Provider Training, Quality and Timeliness of Fertility Preservation Discussions, and Societal Barriers. These results highlight the need for improved patient and provider education on FP, such as future longitudinal studies focused on standardization of FP-related protocols and the impact of their implementation on DR, especially for AYA cancer survivors.

Recognizing racial and ethnic disparities in women's reproductive health is not enough.

This Views and Reviews is a compilation of reports summarizing the published literature describing racial and ethnic disparities in polycystic ovary syndrome, fibroids, endometriosis, assisted reproductive technology, and disorders of mental health in women. The disparities are unique for each of these conditions and encompass disease prevalence and severity, access to care, and the outcomes of treatment.

Elevated hCG Concentration in a Patient after an Unsuccessful in vitro Fertilization.

A patient had a positive serum human chorionic gonadotropin (hCG) 22 days after a failed in vitro fertilization (IVF). The result was confirmed by repeating the test using quantitative and qualitative assays after 48 hours, but the quantitative result did not double compared to the previous concentration. Heterophilic antibody interference was ruled out. The above results indicated true-positive hCG, but inconsistent with normal pregnancy. Medical history excluded hCG produced by pituitary gland, malignancy and exogenous hCG use. Ectopic pregnancy (EP) was suspected and methotrexate was initiated. Ultrasound showed periadnexal fluid suggesting separation phenomenon on the right adnexal EP and hCG was decreased one weeks after the treatment. Two weeks later, hCG became negative. The above data suggest that the elevated hCG was most likely due to EP following IVF.

Racial disparities in frozen embryo transfer success.

PURPOSE: To compare pregnancy and birth outcomes after frozen embryo transfers (FETs) among White, Black, and Asian women and evaluate the effect of patient, protocol, and cycle characteristics on success. METHODS: A retrospective chart review identified women who underwent an autologous FET at an academic fertility center between January 2013 and March 2020. RESULTS: White, Black, and Asian women completed 1,181 (71.7%), 230 (14.0%), and 235 (14.3%) cycles, respectively. Black women were significantly less likely to achieve a positive hCG level (AOR 0.66, 95% CI 0.49-0.90), clinical pregnancy (AOR 0.71, 95% CI 0.53-0.97), and live birth (AOR 0.65, 95% CI 0.47-0.89) compared to White women after adjusting for possible confounders. There were no differences in the aforementioned outcomes when looking at cycles completed by Asian versus White women. When comparing outcomes by endometrial preparation protocol, significant differences were seen amongst the three groups for live birth rates following natural cycle FETs (52.36%, 25.81%, and 44.19% for White, Black, and Asian women, respectively, p = 0.02), a difference not appreciated after programmed FETs. CONCLUSION: Black race is associated with significantly worse pregnancy and live birth rates following FET when compared to White race. Additionally, significant differences in live birth rates among White, Black, and Asian women exist following natural cycle FET versus programmed FET. These disparities in success are not only important for patient counseling, but also when determining management strategies to improve fertility rates among minority women.

Trainee Sex and Accreditation Council for Graduate Medical Education Milestone Assessments During General Surgery Residency.

Importance: In evaluating the effectiveness of general surgery (GS) training, an unbiased assessment of the progression of residents with attention to individual learner factors is imperative. Objective: To evaluate the role of trainee sex in milestone achievement over the course of GS residency using national data from the Accreditation Council for Graduate Medical Education (ACGME). Design, Setting, and Participants: This cross-sectional study evaluated female and male GS residents enrolled in ACGME-accredited programs in the US from 2014 to 2018 with reported variation in milestones performance across years in training and representation. Data were analyzed from November 2019 to June 2021. Main Outcomes and Measures: Mean reported milestone score at initial and final assessment, and predicted time-to-attainment of equivalent performance by sex. Results: Among 4476 GS residents from 250 programs who had milestone assessments at any point in their clinical training, 1735 were female (38.8%). Initially, female and male residents received similar mean (SD) milestone scores (1.95 [0.50] vs 1.94 [0.50]; P = .69). At the final assessment, female trainees received overall lower mean milestone scores than male trainees (4.25 vs 4.31; P < .001). Significantly lower mean milestone scores were reported for female residents at the final assessment for several subcompetencies in both univariate and multivariate analyses, with only medical knowledge 1 (pathophysiology, diagnosis, and initial management) common to both. Multilevel mixed-effects linear modeling demonstrated that female trainees had significantly lower rates of monthly milestone attainment in the subcompetency of medical knowledge 1, which was associated with a significant difference in training time of approximately 1.8 months. Conclusions and Relevance: Both female and male GS trainees achieved the competency scores necessary to transition to independence after residency as measured by the milestones assessment system. Initially, there were no sex differences in milestone score. By graduation, there were differences in the measured assessment of female and male trainees across several subcompetencies. Careful monitoring for sex bias in the evaluation of trainees and scrutiny of the training process is needed to ensure that surgical residency programs support the educational needs of both female and male trainees.

Knowledge of PCOS in physicians-in-training: identifying gaps and educational opportunities.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. A recent study found that many obstetrics and gynecology (ObGyn) practicing physicians are unaware of the Rotterdam criteria recommended for diagnosis. Our objective was to identify gaps in trainee knowledge of PCOS diagnostic criteria and management. An online survey was sent out to US ObGyn physicians-in-training in 2018. The primary outcomes were identification of at least one component of each Rotterdam criteria (Rot-3): (1) oligomenorrhea/amenorrhea, (2) clinical or biochemical hyperandrogenism, and (3) ovarian volume or antral follicle count, and identification of all five components (Rot-5). Secondary outcomes were identification of comorbidities and management of PCOS. Multivariable logistic regression was used controlling for gender, seniority (PGY) status, program type, completion of an REI rotation, and number of PCOS patients seen. 85.4% of 347 trainees completing the survey reported using Rotterdam criteria to diagnose PCOS. However, only 55% identified Rot-3 and less than 10% identified Rot-5. Seniority (PGY4 OR 2.2; 95% CI: 1.2-4.1; p = .01) and completion of REI rotation (OR 1.8 95% CI: 1.2, 1.8; p = .006) were associated with identifying Rot-3. Similar findings were noted with identifying Rot-5. Our study identified significant gaps in knowledge regarding PCOS, suggesting an urgent need for improving strategies for trainee education to increase patient satisfaction and provide comprehensive care.

Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort.

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography-tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1-2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1-2% lower estrogen (E1, E2, E3) levels, but 1-2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4-18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1-2% higher (no difference in estrogens). Androgen concentrations were 18-30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

Vitamin D Deficiency Is Associated With Poor Ovarian Stimulation Outcome in PCOS but Not Unexplained Infertility.

Context: The impact of vitamin D deficiency on the success of ovarian stimulation according to underlying infertility diagnosis has not been investigated. Objective: To evaluate the relationship between vitamin D deficiency and reproductive outcomes after ovarian stimulation in women with either polycystic ovary syndrome (PCOS) or unexplained infertility. Design: Retrospective cohort study. Setting: Analysis of randomized controlled trial (RCT) data. Participants: Participants from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) RCT (n = 607); participants from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) RCT of unexplained infertility (n = 647). Interventions: Serum 25(OH)D levels measured in banked sera. Main Outcome Measures: Primary: live birth; secondary: ovulation (PPCOS II), pregnancy, and early pregnancy loss. Results: In PPCOS II, subjects with vitamin D deficiency [25(OH)D < 20 ng/mL or 50 nmol/L] were less likely to ovulate (adjusted OR, 0.82; 95% CI, 0.68 to 0.99; P = 0.04) and experienced a 40% lower chance of live birth (adjusted OR, 0.63; 95% CI, 0.41 to 0.98; P = 0.04) than those not deficient. In AMIGOS, no significant association between vitamin D deficiency and live birth was noted. In pregnant subjects from both studies, vitamin D deficiency was associated with elevated risk of early pregnancy loss (OR, 1.6; 95% CI, 1.0 to 2.6; P = 0.05). Conclusions: In this investigation of women pursuing ovarian stimulation, the association between vitamin D deficiency and diminished live birth relied on carrying the diagnosis of PCOS and was not observed in unexplained infertility. Given the generally modest success of ovarian stimulation, addressing vitamin D deficiency may prove an important treatment adjunct for many infertile women.

Risk factors for sexual dysfunction in BRCA mutation carriers after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The aim of the study was to identify risk factors for sexual dysfunction in BRCA mutation carriers who have undergone risk-reducing salpingo-oophorectomy (RRSO). METHODS: A cross-sectional study was performed. BRCA1/2 mutation carriers with and without RRSO were surveyed to determine sexual function (Female Sex Function Index [FSFI]), demographics, medical history, sleep quality, depression, and anxiety scores. Characteristics of patients with the lowest quartile of FSFI scores (<14 ±â€Š8.8) were analyzed to identify risk factors for the most severe phenotype. RESULTS: In the 804 women surveyed, 764 underwent RRSO. Of the 529 (69%) carriers with completed FSFI questionnaires in the RRSO cohort, sexual dysfunction was reported in 77.3%. Poor sleep (P = 0.002), hot flashes (P = 0.002), lack of current systemic hormone therapy (HT) use (P = 0.002), depression (P < 0.001), and anxiety (P = 0.001) were associated with sexual dysfunction. In adjusted analyses, depression (adjusted odds ratio [aOR] 2.4, 95% CI, 1.4-4.1) and hot flashes (aOR 1.9, 95% CI, 1.2-3.0) remained significantly associated with sexual dysfunction. Depression was also a significant risk factor for the most severe degree of sexual dysfunction (OR 2.1, 95% CI, 1.3-3.5) and had the greatest impact on Arousal and Satisfaction domain scores of the FSFI. Current systemic HT use seemed to decrease the risk for sexual dysfunction (aOR 0.6, 95% CI, 0.4-1.0). CONCLUSIONS: Sexual dysfunction is highly prevalent in BRCA mutation carriers after RRSO. Depression seems to be a significant risk factor for sexual dysfunction in this patient population and may be under-recognized and undertreated. Patient and provider education on sexual side effects after surgery and risk factors for sexual dysfunction is necessary to decrease postoperative sexual distress. HT may be associated with improved sexual function after surgery.

Social determinants of access to minimally invasive hysterectomy: reevaluating the relationship between race and route of hysterectomy for benign disease.

BACKGROUND: Racial and socioeconomic disparities exist in access to medical and surgical care. Studies of national databases have demonstrated disparities in route of hysterectomy for benign indications, but have not been able to adjust for patient-level factors that affect surgical decision-making. OBJECTIVE: We sought to determine whether access to minimally invasive hysterectomy for benign indications is differential according to race independent of the effects of relevant subject-level confounding factors. The secondary study objective was to determine the association between socioeconomic status and ethnicity and access to minimally invasive hysterectomy. STUDY DESIGN: A cross-sectional study evaluated factors associated with minimally invasive hysterectomies performed for fibroids and/or abnormal uterine bleeding from 2010 through 2013 at 3 hospitals within an academic university health system in Philadelphia, PA. Univariate tests of association and multivariable logistic regression identified factors significantly associated with minimally invasive hysterectomy compared to the odds of treatment with the referent approach of abdominal hysterectomy. RESULTS: Of 1746 hysterectomies evaluated meeting study inclusion criteria, 861 (49%) were performed abdominally, 248 (14%) vaginally, 310 (18%) laparoscopically, and 327 (19%) with robot assistance. In univariate analysis, African American race (odds ratio, 0.80; 95% confidence interval, 0.65-0.97) and Hispanic ethnicity (odds ratio, 0.63; 95% confidence interval, 0.39-1.00) were associated with lower odds of any minimally invasive hysterectomy relative to abdominal hysterectomy. In analyses adjusted for age, body mass index, income quartile, obstetrical and surgical history, uterine weight, and additional confounding factors, African American race was no longer a risk factor for reduced minimally invasive hysterectomy (odds ratio, 0.82; 95% confidence interval, 0.61-1.10), while Hispanic ethnicity (odds ratio, 0.45; 95% confidence interval, 0.27-0.76) and Medicaid enrollment (odds ratio, 0.59; 95% confidence interval, 0.38-0.90) were associated with significantly lower odds of treatment with any minimally invasive hysterectomy. In adjusted analyses, African American women had nearly half the odds of receiving robot-assisted hysterectomy compared to whites (adjusted odds ratio, 0.57; 95%, confidence interval 0.39-0.82), while no differences were noted with other hysterectomy routes. Medicaid enrollment (compared to private insurance; odds ratio, 0.51; 95% confidence interval, 0.28-0.94) and lowest income quartile (compared to highest income quartile; odds ratio, 0.57; 95% confidence interval, 0.38-0.85) were also associated with diminished odds of robot-assisted hysterectomy. CONCLUSION: When accounting for the effect of numerous pertinent demographic and clinical factors, the odds of undergoing minimally invasive hysterectomy were diminished in women of Hispanic ethnicity and in those enrolled in Medicaid but were not discrepant along racial lines. However, both racial and socioeconomic disparities were observed with respect to access to robot-assisted hysterectomy despite the availability of robotic assistance in all hospitals treating the study population. Strategies to ensure equal access to all minimally invasive routes for all women should be explored to align delivery of care with the evidence supporting the broad implementation of these procedures as safe, cost-effective, and highly acceptable to patients.

Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes.

Context: Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third-trimester di-2-ethyl hexyl phthalate exposure and total testosterone (TT) concentrations. Here, we examine early-pregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes. Design: We examined associations between urinary phthalate metabolite concentrations in early pregnancy and serum free testosterone (FT), TT, estrone (E1), and estradiol (E2) in 591 woman/infant dyads in The Infant Development and Environment Study; we also examined relationships between hormones and newborn genital outcomes using multiple regression models with covariate adjustment. Results: E1 and E2 concentrations were 15% to 30% higher in relation to 1-unit increases in log monoisobutyl phthalate (MiBP), mono-2-ethyl hexyl phthalate, and mono-2-ethyl-5-oxy-hexyl phthalate concentrations, and E2 was 15% higher in relation to increased log monobenzyl phthalate (MBzP). FT concentrations were 12% lower in relation to 1-unit increases in log mono(carboxynonyl) phthalate (MCNP) and mono-2-ethyl-5-carboxypentyl phthalate concentrations. Higher maternal FT was associated with a 25% lower prevalence of having a male genital abnormality at birth. Conclusions: The positive relationships between MiBP, MBzP, and DEHP metabolites and E1/E2 are unique and suggest a positive estrogenic effect in early pregnancy. The inverse relationship between MCNP and DEHP metabolites and serum FT supports previous work examining phthalate/testosterone relationships later in pregnancy. Higher FT in relation to a 25% lower prevalence of male genital abnormalities confirms the importance of testosterone in early fetal development.

Ghrelin is independently associated with anti-mullerian hormone levels in obese but not non-obese women with polycystic ovary syndrome.

Ghrelin is an endogenous appetite stimulant that may have a role in ovarian function. Women with polycystic ovary syndrome have anovulation and frequently weight management issues; however the associations between ghrelin and hormonal markers in polycystic ovary syndrome have not been well studied. In order to characterize the association between total ghrelin levels and ovarian function and the possible modification of this relationship by obesity, we examined total ghrelin levels and anti-mullerian hormone, total testosterone, and insulin in obese and non-obese women with and without polycystic ovary syndrome. Total ghrelin levels were lower in obese women with polycystic ovary syndrome (n = 45) compared to obese controls (n = 33) (p = 0.005), but similar in non-obese women with polycystic ovary syndrome (n = 20) compared to non-obese controls (n = 21) (p = NS). In the obese polycystic ovary syndrome group, anti-mullerian hormone was associated with ghrelin levels independent of age, insulin, and total testosterone (p = 0.008). There was no association between total ghrelin and anti-mullerian hormone levels in non-obese women with polycystic ovary syndrome, non-obese controls, or obese controls (p = NS). Our results provide evidence for a potential relationship between ghrelin and ovarian function in obese women with polycystic ovary syndrome that was not observed in non-obese women with polycystic ovary syndrome or controls.

Antimüllerian hormone levels and cardiometabolic risk in young women with polycystic ovary syndrome.

OBJECTIVE: To determine the association between antimüllerian hormone (AMH) levels and metabolic syndrome (MetSyn) in young women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: Academic PCOS center. PATIENT(S): A total of 252 women aged 18-46 years with PCOS. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Association of AMH with markers of cardiometabolic risk and MetSyn. RESULT(S): The median AMH level was 5.1 ng/mL (interquartile range [IQR] 3.0-8.1), and prevalence of MetSyn was 23.8%. AMH levels positively correlated with total T, high-density lipoprotein (HDL) cholesterol, and SHBG and negatively correlated with fasting glucose, homeostasis-model assessment of insulin resistance, body mass index (BMI), and systolic and diastolic blood pressure. A single-unit decrease in AMH was associated with an 11% increase in odds of MetSyn (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03-1.20); the strength of this association was maintained in the multivariate model (OR 1.09, 95% CI 1.01-1.18) adjusting for age and race. Subjects with AMH values in the lowest tertile were twice as likely as those in the highest tertile to have MetSyn (adjusted OR 2.1, 95% CI 1.01-4.3). Total T was not associated with MetSyn or its individual components. CONCLUSION(S): Our findings indicate that in young women with PCOS, low AMH levels predict a greater risk of MetSyn. The role of AMH, an established biomarker of ovarian reserve, in risk stratification of cardiometabolic risk in obese women with PCOS needs to be clarified in longitudinal studies and in the perimenopausal population.

Predictors of pregnancy and live-birth in couples with unexplained infertility after ovarian stimulation-intrauterine insemination.

OBJECTIVE: To identify baseline characteristics of couples that are likely to predict conception, clinical pregnancy, and live birth after up to four cycles of ovarian stimulation with IUI in couples with unexplained infertility. DESIGN: Secondary analyses of data from a prospective, randomized, multicenter clinical trial investigating pregnancy, live birth, and multiple pregnancy rates after ovarian stimulation-IUI with clomiphene citrate, letrozole, or gonadotropins. SETTING: Outpatient clinical units. PATIENT(S): Nine-hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial. INTERVENTION(S): As part of the clinical trial, treatment was randomized equally to one of three arms and continued for up to four cycles or until pregnancy was achieved. MAIN OUTCOME MEASURE(S): Conception, clinical pregnancy, and live-birth rates. RESULT(S): In a multivariable logistic regression analysis, after adjustment for other covariates, age, waist circumference, income level, duration of infertility, and a history of prior pregnancy loss were significantly associated with at least one pregnancy outcome. Other baseline demographic and lifestyle characteristics including smoking, alcohol use, and serum levels of antimüllerian hormone were not significantly associated with pregnancy outcomes. CONCLUSION(S): While age and duration of infertility were significant predictors of all pregnancy outcomes, many other baseline characteristics were not. The identification of level of income as a significant predictor of outcomes independent of race and education may reflect differences in the underlying etiologies of unexplained infertility or could reveal disparities in access to fertility and/or obstetrical care. CLINICAL TRIAL REGISTRATION: NCT01044862.

Predicting first trimester pregnancy outcome: derivation of a multiple marker test.

OBJECTIVE: To predict first trimester pregnancy outcome using biomarkers in a multicenter cohort. DESIGN: Case-control study. SETTING: Three academic centers. PATIENT(S): Women with pain and bleeding in early pregnancy. INTERVENTION(S): Sera from women who were 5-12 weeks' gestational age with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage/spontaneous abortion (SAB) was analyzed by ELISA and immunoassay for activin A, inhibin A, P, A Disintegrin And Metalloprotease-12, pregnancy-associated plasma protein A (PAPP-A), pregnancy specific B1-glycoprotein (SP1), placental-like growth factor, vascular endothelial growth factor, glycodelin (Glyc), and hCG. Classification trees were developed to optimize sensitivity/specificity for pregnancy location and viability. MAIN OUTCOME MEASURE(S): Area under receiver operating characteristic curve, sensitivity, specificity, and accuracy of first trimester pregnancy outcome. RESULT(S): In 230 pregnancies, the combination of trees to maximize sensitivity and specificity resulted in 73% specificity (95% confidence interval (CI) 0.65-0.80) and 31% sensitivity (95% CI 0.21-0.43) for viability. Similar methods had 21% sensitivity (95% CI 0.12-0.32) and 33% specificity (95% CI 0.26-0.41) for location. Activin A, Glyc, and A Disintegrin And Metalloprotease-12 definitively classified pregnancy location in 29% of the sample with 100% accuracy for EP. Progesterone and PAPP-A classified the viability in 61% of the sample with 94% accuracy. CONCLUSION(S): Multiple marker panels can distinguish pregnancy location and viability in a subset of women at risk for early pregnancy complications. This strategy of combining markers to maximize sensitivity and specificity results in high accuracy in a subset of subjects. Activin A, ADAM12, and Glyc are the most promising markers for pregnancy location; P and PAPP-A for viability.

Postablation risk factors for pain and subsequent hysterectomy.

OBJECTIVE: To assess patient characteristics associated with pain and hysterectomy after endometrial ablation. METHODS: A retrospective cohort study was performed using data from two large academic medical centers. Three hundred patients who underwent endometrial ablation between January 2006 and May 2013 were identified for study. Data collected included baseline characteristics at the time of ablation, relevant medical history, and ablation technique. Univariate tests of association and logistic regression were used to evaluate risk factors for postablation pain or hysterectomy. RESULTS: Of the 300 women who had endometrial ablation performed during the study period, 270 had follow-up data for analysis. Twenty-three percent developed new or worsening pain after ablation and 19% underwent a hysterectomy. A history of dysmenorrhea gave a 74% higher risk of developing pain (adjusted odds ratio [OR] 1.74, 95% confidence interval [CI] 1.06-2.87) and tubal sterilization conferred more than double the risk (adjusted OR 2.06, 95% CI 1.14-3.70). Women of white race were 45% less likely to develop pain (adjusted OR 0.55, 95% CI 0.34-0.89). For hysterectomy, a history of cesarean delivery more than doubled the risk (adjusted OR 2.33, 95% CI 1.05-5.16), whereas uterine abnormalities on imaging, including leiomyoma, adenomyosis, thickened endometrial strip, and polyps, quadrupled the risk (adjusted OR 3.96, 95% CI 1.25-12.56). A procedure performed in the operating room decreased the risk of hysterectomy by 76% (adjusted OR 0.24, 95% CI 0.07-0.77). Hysterectomies for the indication of pain occurred more than 3 years sooner than for other indications (P<.001). CONCLUSION: Patient characteristics should be considered when counseling patients about the possible outcomes of endometrial ablation. A significant portion of ablations are complicated by postablation pain.

Decreased cholesterol efflux capacity and atherogenic lipid profile in young women with PCOS.

CONTEXT: Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. OBJECTIVE: The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. DESIGN AND SETTING: A case control study was performed at an academic PCOS center. PATIENTS: Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study. MAIN OUTCOME MEASURES: The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy. RESULTS: Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). CONCLUSIONS: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.

Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers.

OBJECTIVE: This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. METHODS: Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. RESULTS: Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. CONCLUSIONS: Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.

Joint effects of smoking and gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women.

BACKGROUND: Although smoking has a known association with hot flashes, the factors distinguishing smokers at greatest risk for menopausal symptoms have not been well delineated. Recent evidence supports a relationship between menopausal symptoms and variants in several genes encoding enzymes that metabolize substrates such as sex steriods, xenobiotics, and catechols. It is currently not known whether the impact of smoking on hot flashes is modified by the presence of such variants. OBJECTIVE: The objective of the study was to investigate the relationship between smoking and hot flash occurrence as a function of genetic variation in sex steroid-metabolizing enzymes. METHODS: A cross-sectional analysis of data from the Penn Ovarian Aging study, an ongoing population-based cohort of late reproductive-aged women, was performed. Smoking behavior was characterized. Single-nucleotide polymorphisms in five genes were investigated: COMT Val158Met (rs4680), CYP1A2*1F (rs762551), CYP1B1*4 (Asn452Ser, rs1800440), CYP1B1*3 (Leu432Val, rs1056836), and CYP3A4*1B (rs2740574). RESULTS: Compared with nonsmokers, European-American COMT Val158Met double-variant carriers who smoked had increased odds of hot flashes [adjusted odds ratio (AOR) 6.15, 95% confidence interval (CI) 1.32-28.78)]; European-American COMT Val158Met double-variant carriers who smoked heavily had more frequent moderate or severe hot flashes than nonsmokers (AOR 13.7, 95% CI 1.2-154.9). European-American CYP 1B1*3 double-variant carriers who smoked described more frequent moderate or severe hot flashes than nonsmoking (AOR 20.6, 95% CI 1.64-257.93) and never-smoking (AOR 20.59, 95% CI 1.39-304.68) carriers, respectively. African-American single-variant CYP 1A2 carriers who smoked were more likely to report hot flashes than the nonsmoking carriers (AOR 6.16, 95% CI 1.11-33.91). CONCLUSION: This is the first report demonstrating the effects of smoking within the strata of gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women. The identification of individuals with a genetic susceptibility to smoking-related menopausal symptoms could contribute to interventions targeted at reducing reproductive morbidity both in the menopause and across the reproductive life course.

Outcomes following fibroid expulsion after uterine artery embolization.

PURPOSE: To evaluate retrospectively the sequelae of fibroid expulsion (FE) after uterine artery embolization (UAE). MATERIALS AND METHODS: From a population of 759 UAE procedures performed from July 1999 to June 2009, 37 patients were found to have a uterine fibroid communicating with the endometrial cavity resulting in "bulk" FE with the passage of large fragments or an entire tumor or "sloughing" FE with shedding or "melting" of the tumor. Medical records and magnetic resonance images were evaluated for clinical information and tumor characteristics, respectively. RESULTS: The mean age of patients with FE was 43 years ± 5 (SD), with 12 nulliparous and 25 parous. Expulsion took place a mean of 14.8 weeks ± 17.7 after UAE (range, 1.6-105.9 wk). FE was asymptomatic in 5% of cases (n = 2) and symptomatic in 95% (n = 35). Among symptomatic cases, 89% (n = 31) had bulk expulsion and 11% (n = 4) had sloughing expulsion. Forty-nine percent of patients (n = 18) had tumor expulsion at home or had an office/emergency room transvaginal myomectomy (TVM), 27% (n = 10) underwent operative TVM, and 8% (n = 3) had hysteroscopic resection. Urgent and elective hysterectomies were performed in 11% (n = 4) and 5% of cases (n = 2), respectively. Nulliparous women showed a trend toward undergoing hysterectomy compared with parous women (33% vs 8%; P =.07, Fisher exact test). CONCLUSIONS: Most women tolerate FE well, with approximately half needing no operative intervention, but some may need to undergo hysteroscopy, operative TVM, or even hysterectomy. Nulliparous women are potentially at greater risk to require hysterectomy.