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.

Barriers to fertility preservation access in transgender and gender diverse adolescents: a narrative review.

Fertility preservation (FP) involves the cryopreservation of gametes, embryos, and/or gonadal tissue oocytes, for future use in family building. FP as part of a comprehensive approach to care of transgender and gender diverse (TGD) individuals is an understudied topic. Current evidence indicates that gender affirming therapies may increase the risk for infertility. As a result, TGD individuals, including adolescents, should receive counseling regarding FP prior to beginning gender affirming treatment. Many barriers exist to TGD adolescents receiving FP counseling and undergoing FP if desired. The objective of this narrative review is to summarize the literature regarding the desire for FP in TGD adolescents, the barriers to TGD adolescents in accessing of FP, and to discuss potential interventions for alleviation of such barriers. A literature search using the following Medical Subject Headings search terms: 'transgender persons' and 'fertility preservation' and 'adolescents' was conducted via searching PubMed. Additional articles were located via reference review. Included articles consist of qualitative and quantitative research and society guidelines. Articles from inception to 1st July 2023 were included. The results of the literature search have been summarized into the format of a narrative review. Key barriers to FP for TGD adolescents include inconsistencies in form and timing of counseling, potential worsening of gender dysphoria with FP treatment, high cost of treatment, limited research on FP outcomes, and legal barriers. Intersectionality between gender identity and other forms of minority status can compound these barriers to FP and healthcare in general. Barriers to TGD adolescents accessing FP are significant. Increased research is needed upon methods to mitigate these barriers. Solutions include increasing uniformity and timing of FP counseling by varying health care providers, advocacy efforts to mitigate legal and financial barriers, increased research efforts in FP outcomes, and increased cultural competency in clinics offering FP care to TGD adolescents.

Barriers to fertility preservation access in transgender and gender diverse adolescents: a narrative review Multiple barriers exist for adolescents identifying as transgender or gender diverse (TGD) in the pursuit of fertility preservation (FP). In this narrative review, we aim to summarize the literature regarding such barriers. Key barriers to FP for TGD adolescents include inconsistencies in the form and timing of counseling on this topic, the treatment process of fertility preservation can worsen gender dysphoria, there is a very high cost of treatment but limited research on FP results, and various legal barriers to surmount. Intersectionality between gender identity and other forms of minority status can also interact, making FP and healthcare in general difficult to access.

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.

Evaluation of Stillbirth Among Pregnant People With Sickle Cell Trait.

Importance: Relative to what is known about pregnancy complications and sickle cell disease (SCD), little is known about the risk of pregnancy complications among those with sickle cell trait (SCT). There is a lack of clinical research among sickle cell carriers largely due to low sample sizes and disparities in research funding. Objective: To evaluate whether there is an association between SCT and a stillbirth outcome. Design, Setting, and Participants: This retrospective cohort study included data on deliveries occurring between January 1, 2010, and August 15, 2017, at 4 quaternary academic medical centers within the Penn Medicine health system in Pennsylvania. The population included a total of 2482 deliveries from 1904 patients with SCT but not SCD, and 215 deliveries from 164 patients with SCD. Data were analyzed from May 3, 2019, to September 16, 2021. Exposures: The primary exposure of interest was SCT, identified using clinical diagnosis codes recorded in the electronic health record. Main Outcomes and Measures: A multivariate logistic regression model was constructed to assess the risk of stillbirth using the following risk factors: SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (as a proxy for parity), prior cesarean delivery, multiple gestation, patient age, marital status, race and ethnicity, ABO blood type, Rhesus (Rh) factor, and year of delivery. Results: This cohort study included 50 560 patients (63 334 deliveries), most of whom were aged 25 to 34 years (29 387 of 50 560 [58.1%]; mean [SD] age, 29.5 [6.1] years), were single at the time of delivery (28 186 [55.8%]), were Black or African American (23 777 [47.0%]), had ABO blood type O (22 879 [45.2%]), and were Rhesus factor positive (44 000 [87.0%]). From this general population, 2068 patients (4.1%) with a sickle cell gene variation were identified: 1904 patients (92.1%) with SCT (2482 deliveries) and 164 patients (7.9%) with SCD (215 deliveries). In the fully adjusted model, SCT was associated with an increased risk of stillbirth (adjusted odds ratio [aOR], 8.94; 95% CI, 1.05-75.79; P = .045) while adjusting for the risk factors of SCD (aOR, 26.40; 95% CI, 2.48-280.90; P = .007) and multiple gestation (aOR, 4.68; 95% CI, 3.48-6.29; P < .001). Conclusions and Relevance: The results of this large, retrospective cohort study indicate an increased risk of stillbirth among pregnant people with SCT. These findings underscore the need for additional risk assessment during pregnancy for sickle cell carriers.

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.

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.

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.

Maternal urinary phthalate metabolites in relation to gestational diabetes and glucose intolerance during pregnancy.

BACKGROUND: Phthalates are common plasticizer chemicals that have been linked to glucose intolerance in the general population, but there is only limited research on their association with gestational diabetes (GDM). OBJECTIVE: We evaluated the association between 11 urinary phthalate metabolites and GDM, impaired glucose tolerance (IGT), and continuous blood glucose concentration during pregnancy in The Infant Development and Environment Study (TIDES). Based on prior study results, our primary analyses focused on monoethyl phthalate (MEP) in relation to our outcomes of interest. STUDY DESIGN: We used multi-variable logistic regression to examine the odds of GDM and IGT in relation to an interquartile-range (IQR) increase in natural log (ln)-transformed, specific gravity (SG)-adjusted first trimester (T1) and average of T1 and third trimester (T3) ("T1T3avg") phthalate metabolite concentrations. We fit linear regression models to examine the percent change in blood glucose per IQR increase in ln-transformed, SG-adjusted T1 and T1T3avg phthalates. In sensitivity analyses, we examined interactions between exposure and race. We adjusted for maternal age, maternal body mass index, study center, race/ethnicity, parity, and gestational age at glucose testing. RESULTS: In our sample of 705 pregnant women, we observed 60 cases of GDM, 90 cases of IGT, and an average GLT blood glucose of 113.6 ±â€¯27.7 mg/dL. In our primary analysis, T1T3avg MEP was positively associated with GDM ([OR (95% CI) per IQR increase] T1T3avg MEP: 1.61 (1.10, 2.36)). In secondary analyses, most other phthalates were not found to be related to study outcomes, though some associations were noted. Sensitivity analyses indicated possible strong race-specific associations in Asians, though these results are based on a small sample size (n = 35). CONCLUSION: In alignment with our a priori selection, we documented an association between T1T3avg MEP and GDM. Additional phthalate metabolites were also found to be linked to glucose intolerance, with possible stronger associations in certain racial/ethnic subgroups. Given the prevalence of phthalate exposures and the growing evidence of associations with metabolic outcomes, future studies should continue to examine this question in diverse cohorts of pregnant women, particularly in those who may be at higher risk for GDM and IGT.

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.

ASRM standard embryo transfer protocol template: a committee opinion.

Standardization improves performance and safety. A template for standardizing the embryo transfer procedure is presented here with 12 basic steps supported by published scientific literature and a survey of common practice of SART programs; it can be used by ART practices to model their own standard protocol.

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.

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.

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.

A Molecular Perspective on Procedures and Outcomes with Assisted Reproductive Technologies.

The emerging association of assisted reproductive technologies with adverse perinatal outcomes has prompted the in-depth examination of clinical and laboratory protocols and procedures and their possible effects on epigenetic regulatory mechanism(s). The application of various approaches to study epigenetic regulation to problems in reproductive medicine has the potential to identify relative risk indicators for particular conditions, diagnostic biomarkers of disease state, and prognostic indicators of outcome. Moreover, when applied genome-wide, these techniques are likely to find novel pathways of disease pathogenesis and identify new targets for intervention. The analysis of DNA methylation, histone modifications, transcription factors, enhancer binding and other chromatin proteins, DNase-hypersensitivity and, micro- and other noncoding RNAs all provide overlapping and often complementary snapshots of chromatin structure and resultant "gene activity." In terms of clinical application, the predictive power and utility of epigenetic information will depend on the power of individual techniques to discriminate normal levels of interindividual variation from variation linked to a disease state. At present, quantitative analysis of DNA methylation at multiple loci seems likely to hold the greatest promise for achieving the level of precision, reproducibility, and throughput demanded in a clinical setting.