Moving toward Narrowing the United States Gap in Assisted Reproductive Technology (ART) Racial and Ethnic Disparities in the Next Decade.

The Disparities in Assisted Reproductive Technology (DART) hypothesis, initially described in 2013 and further modified in 2022, is a conceptual framework to examine the scope and depth of underlying contributing factors to the differences in access and treatment outcomes for racial and ethnic minorities undergoing ART in the United States. In 2009, the World Health Organization defined infertility as a disease of the reproductive system, thus recognizing it as a medical problem warranting treatment. Now, infertility care is largely recognized as a human right. However, disparities in Reproductive Endocrinology and Infertility (REI) care in the US persist today. While several studies and review articles have suggested possible solutions to racial and ethnic disparities in access and outcomes in ART, few have accounted for and addressed the multiple complex factors contributing to these disparities on a systemic level. This review aims to acknowledge and address the myriad of contributing factors through the DART hypothesis which converge in racial/ethnic disparities in ART and considers possible solutions to effect large scale societal change by narrowing these gaps within the next decade.

Associations of anti-Müllerian hormone levels among women in their mid-30s with menopausal symptoms ~14 years later.

OBJECTIVE: The aim of this study was to examine associations of anti-Müllerian hormone (AMH) levels in gravid women in their mid-30s with menopausal symptoms ~14 years later and age at natural menopause. METHODS: In this prospective analysis, 474 participants in Project Viva, a longitudinal cohort, were enrolled during pregnancy between 1999 and 2002. AMH levels were determined using plasma samples collected 3 years postpartum. Participants completed the Menopause Rating Scale (MRS) and self-reported age at and reason for menopause at the 17 years postpartum visit (Mid-Life Visit). Primary outcomes were individual MRS item responses and total MRS score. To examine associations between AMH levels and menopausal outcomes, we performed linear and logistic regressions, and survival analyses, adjusting for confounding variables. RESULTS: Mean (SD) AMH level was 2.80 (2.74) ng/mL, measured at 38.2 (3.9) years. At the Mid-Life Visit, mean (SD) age was 52.3 (3.9) years and total MRS score was 8.0 (5.7). During follow-up, 50% had experienced natural menopause, and self-reported mean (SD) age at natural menopause was 50.4 (3.6) years. AMH in the lowest tertile (mean [SD]: 0.47 [0.32] ng/mL) was associated with higher odds of moderate to severe vaginal dryness (adjusted odds ratio: 2.58; 95% CI: 1.16 to 5.73), a lower MRS psychological subscale (adjusted ß: -0.71; 95% CI: -1.35 to -0.07), and earlier attainment of natural menopause (adjusted hazards ratio: 7.1; 95% CI: 4.6 to 11.0) compared with AMH in the highest tertile (mean [SD]: 6.01 [2.37] ng/mL). CONCLUSIONS: Lower AMH in the mid-30s was associated with earlier menopause and increased odds of vaginal dryness but fewer psychological symptoms ~14 years later.

Racial disparities in access to reproductive health and fertility care in the United States.

PURPOSE OF REVIEW: To examine the status of racial and ethnic inequalities in fertility care in the United States (U.S.) at inception of 2022. This review highlights addressable underpinnings for the prevalent differentials in access to and utilization of infertility treatments and underscores gaps in preventive care as key contributors to racial and ethnic disparities in risk burden for subfertility and infertility. RECENT FINDINGS: Significant gaps in access to and utilization of fertility care are consistently reported among racial and ethnic minorities, particularly Black and Hispanic women. Access to and utilization of contraceptives, human papilloma virus vaccination rates, preexposure prophylaxis use, and differentials in treatment of common gynecologic disorders are relevant to the prevalent racial and ethnic disparities in reproductive health. The spectrum of differential in reproductive wellness and the magnitude of reproductive health burden afflicting racial minorities in the U.S. raise concerns regarding systemic and structural racism as plausible contributors to the prevalent state of affairs. SUMMARY: Despite efforts to reform unequal reproductive health practices and policies, racial and ethnic disparities in fertility care are pervasive and persistent. In addition to measures aimed at reducing barriers to care, societal efforts must prioritize health disparity research to systematically examine underpinnings, and addressing structural racism and interpersonal biases, to correct the prevalent racial inequities and mitigate disparities.

Increasing medical student confidence in gender and sexual health through a student-initiated lecture series.

INTRODUCTION: Medical students self-report insufficient training in topics of gender and sexuality in medicine, which may ultimately lead to negative health outcomes in patients for whom they will provide care. This study aims to identify whether a student-initiated lecture series on topics related to gender and sexual health leads to greater student comfort with discussing topics related to diverse sexual content. METHODS: Medical students matriculated during two consecutive academic years were invited to participate in the lecture series. Investigators administered anonymous pre- and post-series surveys (n=152 and 105 respondents, respectively) using google forms. Respondents rated their comfort levels discussing relevant topics and provided narrative feedback concerning strengths and areas for improvement of the lecture series. Overlaps between the 95% confidence intervals around pre- and post-series percentage of students comfortable/very comfortable discussing each topic were examined to compare pre- vs post-series comfort ratings. Narrative comments were reviewed for thematic feedback. RESULTS: 105 medical students completed the lecture series, with 80% identifying as female. Self-assessed comfort levels across all seminar topics were greater in post- versus pre-lecture series surveys with the following topics showing the biggest differences (percentage of students "somewhat" or "very" comfortable [95% confidence intervals]: discussing sexuality with gender (68%[59-77] vs. 29%[22-36]) and sexual minority patients (84%[77-91] vs. 49%[41-57]), HIV prevention counseling (70%[61-78] vs. 20% [20-34]), identifying female genital cutting (44% [34-53] vs. 11%[6-16]), and discussing intimate partner violence (65%[55-74] vs. 33%[25-40]). Qualitative analysis indicated respondents found the lectures to be effective and believed they should be integrated into the required medical school curriculum. CONCLUSION: Our student-initiated lecture series was associated with greater student comfort discussing topics related to gender and sexuality with patients. This framework represents a useful method to address gaps in medical education and has the potential to improve health outcomes in multiple populations.

Implementation and Assessment of a Novel Telehealth Education Curriculum for Undergraduate Medical Students.

INTRODUCTION: Despite its healthcare advantages and expanded use during the COVID-19 pandemic, telehealth is not included in many medical school curricula. METHODS: In this prospective mixed methods study (n=52), we created a novel Telehealth Education Curriculum (TEC) for the third year Obstetrics and Gynecology (Ob/Gyn) rotation at New York Medical College during COVID-19. The TEC included supervised telehealth patient encounters via video conference [and a virtual Objective Structured Clinical Encounter (vOSCE)] designed to simulate a telehealth encounter (Zoom Video Communications, Inc.). We measured student perceptions of the TEC via two 4-point Likert surveys, which included free response questions, administered via SurveyMonkey between April and June 2020. Participation was voluntary and responses were de-identified. We computed means and response distributions across survey questions using SPSS; IBM version 19. RESULTS: The response rate was 92% for both the Telehealth (33/36) and vOSCE (48/52) surveys. Seventy-six percent (25/33) strongly or moderately agreed that telehealth and in-person patient encounters have similar educational value. Eighty-three percent (40/48) strongly or moderately agreed the vOSCE provided a valuable patient interaction. Ninety-seven percent (32/33) strongly or moderately agreed the telehealth encounters should continue during COVID-19 restrictions versus 82% (27/33) agreeing they should be incorporated into the curriculumpost COVID-19. CONCLUSION: Almost all students responded that the TEC should continue during COVID-19 and most agreed it should be incorporated into the Ob/Gyn clerkship permanently, after COVID-19. We found vOSCEs to be an effective method for teaching telehealth to medical students. Key challenges identified by students included adjusting to a virtual format, lack of body language, and communicating empathy virtually. Positive takeaways included practice with telemedicine and an opportunity for continued clinical education during COVID-19.

Association of sugar-sweetened beverage intake with maternal postpartum weight retention.

OBJECTIVE: During the perinatal period, modifiable behaviours contributing to excess weight gain, including sugar-sweetened beverage (SSB) intake, are understudied. We examined the extent to which perinatal SSB intake affects postpartum weight retention (PPWR). DESIGN: We measured SSB intake frequency in the third trimester and 1-month postpartum using the NHANES Dietary Screener Questionnaire. We assessed the association between SSB intake and PPWR (difference between 6-month postpartum and pregravid weight) using multivariable regression adjusted for socio-demographic and anthropometric variables. SETTING: Greater Boston area. PARTICIPANTS: Three hundred forty-eight mother-infant pairs in the Rise and SHINE prospective birth cohort. RESULTS: Mean age was 32·7 (sd 5·0) years; the sample was 47 % white, 32 % Hispanic, 14 % Asian and 7 % Black. Women reported mean daily SSB intake frequencies of 0·9 (sd 1·2) and 0·7 (sd 1·0) times/d in the third trimester and 1-month postpartum, respectively. At 6-month postpartum, average weight retention was 3·4 (sd 5·7) kg; 108 (sd 31 %) women had substantial PPWR, defined as a ≥ 5 kg increase between pregravid and 6-month postpartum weight. Each 1-time/d increment in SSB intake frequency during the third trimester (ß = 0·46 kg (95 % CI, 0·07, 0·86)) and 1-month postpartum (ß = 0·52 kg (95 % CI 0·03, 1·00)) was associated with higher weight retention at 6 months. Increased SSB intake frequency in the third trimester (OR: 1·37; 95 % CI 1·10, 1·75) and 1-month postpartum (OR: 1·17; 95 % CI 0·92, 1·52) resulted in higher odds of substantial PPWR. CONCLUSIONS: SSB consumption during the perinatal period is associated with higher weight retention at 6-month postpartum. Avoiding SSB may reduce the risk of excess weight retention.

Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial.

BACKGROUND: There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. METHODS AND FINDINGS: FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention. CONCLUSIONS: Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02530385.

Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity.

We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1). Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment-related significant adverse event (abdominal pain). Two patients subsequently developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No additional cases of bacteremia occurred. Median follow-up for survivors is 15 months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall survival and progression-free survival after FMT were 85% (95% confidence interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively. There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition and urine 3-indoxyl sulfate concentration indicated improvement in intestinal microbiome diversity after FMT that was associated with expansion of stool-donor taxa. These results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.

Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients.

Immunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.

Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection.

BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up. METHODS: We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8 weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above. RESULTS: Overall, 180 patients aged 7-95 years with a minimal follow-up of 8 weeks were included in the analysis. CDI resolved in 82 % of patients after a single treatment, rising to a 91 % cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed. CONCLUSIONS: We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.