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.

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.

Success of the two-dose methotrexate protocol for treatment of ectopic pregnancy in women with a history of prior ectopic pregnancy.

OBJECTIVE: Women with prior ectopic pregnancy (EP) have an increased failure rate when treated with single-dose methotrexate (MTX) for subsequent EP. We sought to determine whether previous EP remained a risk factor for failure when using the two-dose MTX protocol. STUDY DESIGN: Retrospective cohort study of women managed with two-dose MTX. Risk factors for MTX failure were evaluated in univariable analysis and multivariable regression modeling. RESULTS: A total of 234 women with EP between 1999 and 2009 were studied. Of those, 37 (15.8%) had a prior EP. In univariable analysis, prior EP was associated with a greater than twofold increased risk of MTX failure (RR 2.67, 95% CI 1.20-3.77). Higher hCG levels and ultrasound visualization of EP also increased the risk of MTX failure. In multivariable analysis hCG level remained associated with MTX failure, while prior EP did not (adjusted RR 0.97, 95% CI 0.33-2.82). CONCLUSION: Prior EP is not independently associated with MTX failure in women receiving two-dose MTX therapy after controlling for known risk factors.

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.

Health disparities of African Americans in reproductive medicine.

The first paper describing an association between African American race, infertility prevalence, and outcomes of fertility treatments was published more than 20 years ago, calling initial attention to differences in how infertility is experienced, diagnosed, and managed in African Americans. Since that initial publication, multiple other studies have explored African American race and its association with elements of the fertility spectrum-disparities that have been durable over time. The goal of this review is to provide an overview of the evolution of aspects of this research focusing on the outcomes of infertility treatments and barriers to access. A consideration of the system-based practice issues that interface with timely fertility evaluation and treatment in ways that challenge reproductive health equity will be presented.

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.

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.

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.

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.

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.

What are some potential reproductive hazards in the hospital environment?

The Occupational Medicine Forum is prepared by the ACOEM Occupational and Environmental Medical Practice Committee and does not necessarily represent an official ACOEM position. The Forum is intended for health professionals and is not intended to provide medical or legal advice, including illness prevention, diagnosis or treatment, or regulatory compliance. Such advice should be obtained directly from a physician and/or attorney.

Assisted hatching and intracytoplasmic sperm injection are not associated with improved outcomes in assisted reproduction cycles for diminished ovarian reserve: an analysis of cycles in the United States from 2004 to 2011.

OBJECTIVE: To investigate the impact of intracytoplasmic sperm injection (ICSI) and assisted hatching (AH) on assisted reproductive technology (ART) outcomes in initial cycles with diminished ovarian reserve (DOR) as the primary diagnosis. DESIGN: Retrospective cohort study of cycles from the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System database. SETTING: Not applicable. PATIENT(S): A total of 422,949 fresh, nondonor, initial ART cycles of which 8,597 were diagnosed with only elevated FSH and 38,926 were diagnosed with only DOR according to the SART DOR categorization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth and clinical pregnancy rates. RESULT(S): ICSI and AH were associated with diminished odds of live birth in SART DOR-only cycles (adjusted odds ratio [AOR] 0.88, 95% confidence interval [CI] 0.81-0.96 for ICSI; AOR 0.77, 95% CI 0.71-0.84 for AH). No association between odds of live birth and either ICSI or AH in elevated FSH-only cycles was observed. The combination of ICSI and AH was associated with significantly lower odds of live birth in SART DOR-only cycles but not in elevated FSH-only cycles. CONCLUSION(S): In initial ART cycles for which the only indication relates to a diagnosis of DOR, AH and ICSI are not associated with improved live birth rates.

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.

Diagnosis and treatment of diminished ovarian reserve in assisted reproductive technology cycles of women up to age 40 years: the role of insurance mandates.

OBJECTIVE: To explore correlates of diminished ovarian reserve (DOR) and predictors of assisted reproductive technologies (ART) treatment outcome in DOR cycles using the Society for Assisted Reproductive Technologies-Clinical Outcomes Reporting System (SART-CORS) database; we hypothesized that mandated state insurance coverage for ART is associated with the prevalence of DOR diagnosis in ART cycles and with treatment outcomes in DOR cycles. DESIGN: Cross-sectional study using ART cycles between 2004 and 2007. SETTING: Not applicable. PATIENT(S): A total of 182,779 fresh, nondonor, initial ART cycles in women up to age 40 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of DOR and elevated FSH, odds ratio of DOR and elevated FSH in ART mandated vs. nonmandated states, live birth rates. RESULT(S): Compared with cycles performed in states with mandated ART coverage, cycles in states with no ART mandate were more likely to have DOR (adjusted odds ratio 1.43, 95% confidence interval 1.37-1.5) or elevated FSH (adjusted odds ratio 1.69, 95% confidence interval 1.56-1.85) as the sole reason for treatment. Lack of mandated ART coverage was associated with increased live birth rates in cycles diagnosed as DOR, but not in cycles characterized only by an elevated FSH. CONCLUSION(S): A significant association was observed between lack of mandated insurance for ART and the proportion of cycles treating DOR or elevated FSH. The presence or absence of state-mandated ART coverage could impact access to care and the mix of patients that pursue and initiate ART cycles in ways that influence these proportions. Additional studies are needed that consider the coalescence of insurance mandates, patient and provider factors, and state-level variables on the odds of specific infertility diagnoses and treatment prognosis.

Acupuncture--help, harm, or placebo?

The most recent meta-analysis appearing in Fertility and Sterility on acupuncture was reevaluated in view of the marked heterogeneity of interventions, controls, data analysis, and timing of interventions in the trials that were included. After removing some of the trials and data based on more rigorous standards for a high quality meta-analysis, a significant benefit of the intervention could no longer be shown. When studies with and without placebo controls were analyzed separately, a placebo effect was suggested. Individual trials with a confidence limit below unity emphasized the potential for a detrimental impact on outcomes, which should be considered both in using acupuncture clinically as an adjunct for IVF and in design of future trials. Much more data that includes a placebo control will be required before a conclusion can be made that acupuncture has a true treatment effect on IVF outcomes. However, unless the timing and method of the acupuncture are standardized, practitioners will still have difficulty being sure that their particular method will help beyond the apparent benefit provided by a placebo.

Predicting the decline in human chorionic gonadotropin in a resolving pregnancy of unknown location.

OBJECTIVES: To characterize the curve derived from serial human chorionic gonadotropin (hCG) values in women with spontaneous resolution of pregnancy of unknown location and to assess factors that modify the decline. METHODS: Data from three sites were extracted from a clinical database of women with a symptomatic pregnancy of unknown location that required follow-up with serial hCG levels. A nonlinear mixed-effects regression model was used to generate hCG elimination curves. RESULTS: Four hundred forty-three women presenting with a pregnancy of unknown location that resolved without intervention were studied between September 2007 and May 2009. Women older than 35 years had a slower hCG decline (P=.001) and those with pain had a steeper decline (P=.006), but these changes did not alter the curve in a clinically meaningful way. The decline in hCG is faster for those with a higher level at presentation. The average decline of hCG in women with spontaneous resolution is slower than previously reported. However, the minimal decline in hCG for women with spontaneous resolution of a pregnancy of unknown location ranged from 35% to 50% at 2 days of follow-up and from 66% to 87% at 7 days, which is more rapid than previously reported. CONCLUSION: In a diverse population, using updated statistical methods, it was observed that the minimal decline in hCG for women with spontaneous resolution is more rapid than previously reported. A decline slower than these thresholds may indicate the presence of retained trophoblastic tissue or ectopic pregnancy. LEVEL OF EVIDENCE: III.

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.

Racial and ethnic differences in reproductive potential across the life cycle.

OBJECTIVE: To review variations in specific reproductive health outcomes by race and ethnicity. A growing number of reports have explored potential gaps in the quality of reproductive health and healthcare across racial and ethnic groups. Diverse results from numerous investigations have made it challenging for practitioners to confirm the significance of these disparities. METHOD(S): Three specific areas of the reproductive life cycle were examined: pubertal onset, outcomes from treatment with assisted reproductive technologies (ART), and the menopausal transition. These areas were selected as they encompass a continuum of events across the reproductive life span of women. Outcomes were compared in black, white, Asian, and Hispanic women. Medline searches querying on keywords puberty, IVF, ART, menopause, menopausal symptoms, racial disparity, race, Asian, Japanese, Chinese, African American, black, Hispanic, and Latino were performed to isolate relevant publications for review. RESULT(S): Differences across race and ethnicity were noted in each clinical endpoint. The most notable findings included earlier puberty in blacks and Hispanics compared with whites, significantly lower live birth rates after ART in all racial and ethnic groups compared with whites, and differences in perimenopausal symptomatology and possibly timing in various racial/ethnic groups compared with whites. Additional research is needed to completely unravel the full significance and basic underpinnings of these disparities. Some of the limitations of the current state of the literature in drawing conclusions about the independent effect of race/ethnicity on reproductive disparities include small samples sizes in some studies, inconsistencies in the characterization of racial/ethnic groups, and incomplete control of potential confounding. CONCLUSION(S): Race and ethnicity appear to be important correlates of outcomes from the initiation of reproduction functioning through to its conclusion. The ultimate goal of identifying racial disparities in reproduction is to isolate the basic determinants of disparities and formulate strategies to improve outcomes for women at risk. The differences demonstrated in this review of the literature could represent environmental, sociocultural, and/or genetic correlates of race that influence these important milestones.

Race, socioeconomic status, and response to methotrexate treatment of ectopic pregnancy in an urban population.

On the basis of the documented racial disparities in ectopic pregnancy incidence and mortality we hypothesized that African-American women with ectopic pregnancy would be more likely than white women to have treatment failure with methotrexate. In this retrospective cohort study, a racial disparity in methotrexate effectiveness was not found, but a significant relationship between low socioeconomic status and methotrexate failure was demonstrated.