Characteristics of patients seeking fertility care in a low-income setting.

OBJECTIVE: Patients face challenges accessing fertility treatment due to barriers such as financial burdens, delayed referral to Reproductive Endocrinologists (REI), low medical literacy, language barriers and numerous other health disparities. Medicaid in New York offers coverage for office visits, blood tests, hysterosalpingograms (HSGs), and pelvic ultrasounds for infertility. The aim of this study is to delineate the characteristics of this underserved population and determine their ability to complete the initial fertility workup. METHODS: This was a retrospective study of all patients seeking fertility care at a single resident/fellow REI clinic in New York from September 2020 - January 2022. RESULTS: During the study period, 87 patients (avg age = 35.2y) sought care at the resident/fellow clinic over 126 appointments. The majority of patients had Medicaid insurance and most primary languages spoken included English (70.1%), Spanish (21.8%), and Bengali (3.4%). Documented Race was comprised of mostly Other (46%), African American (21.8%), Asian (17.2%), and White (11.5%). The majority of patients completed a lab workup (70-80%). Fewer patients underwent a scheduled HSG (59.8%) and patients' partners completed a semen analysis (SA) (27.6%). Overall, there was a significant difference in the ability to complete the initial infertility workup (lab tests vs. HSG vs. SA) across all groups regardless of age, insurance type, primary language spoken, race and ethnicity (p<0.05). CONCLUSIONS: Completing the fertility workup, particularly the male partner workup and imaging studies, can present challenges for underserved patients with infertility. Understanding which patient characteristics and societal factors restrict access to fertility care requires further investigation to improve access to fertility care in underserved communities.

Fumarase Deficiency and Its Effect on Infertility: A Case Series.

Background: Fumarase deficiency is an autosomal recessive condition characterized by severe neurologic abnormalities due to homozygous mutations in the fumarate hydratase (FH) gene. Heterozygous carriers of FH mutations have increased risk of developing uterine fibroids that can be associated with hereditary leiomyomatosis and renal cell cancer (HLRCC). The association between FH mutations and infertility remains uncertain. The objective of our study was to characterize the infertility diagnoses, treatments, and outcomes in women presenting to a fertility center who were found to be carriers of fumarase deficiency based on the presence of heterozygous FH mutations. Case Presentation: A retrospective case series was conducted including 10 women presenting to an academic fertility center who were found to be FH carriers based on genetic carrier screening. Of the 9 women who were engaged in further workup, 2 had imaging results consistent with uterine fibroids. One woman underwent hysteroscopic myomectomy prior to two courses of ovulation induction with timed intercourse (OI/TIC) followed by one successful cycle of IVF. Of the remaining patients, only 1 woman successfully delivered after a cycle of ovulation induction with intrauterine insemination (OI/IUI). Other patients pursuing OI/IUI, OI/TIC, or monitored natural cycles had unsuccessful experiences. Conclusion: Patients with infertility who are offered genetic testing should be screened for FH mutations, as the carriers are at risk of developing HLRCC-associated uterine fibroids, which can influence fertility and pregnancy. Additional research is needed to investigate the impacts of FH mutations on infertility.

Weekday vs. weekend oocyte retrievals: is there a difference?

The purpose of this study was to evaluate whether there is a difference in procedure duration and time spent in the post anaesthesia care unit (PACU) between weekday (WD) and weekend (WE) oocyte retrievals (ORs). This was a retrospective cohort study of patients compared and stratified based on number of oocytes retrieved (1-10, 11-20, and >20). Student's t-test and linear regression models were used to assess the relationship between AMH, BMI, and a number of oocytes retrieved with the duration of procedure and total time spent in the PACU. 664 patients underwent OR of which 578 met inclusion criteria and were analyzed. There were 501 WD OR cases (86%) and 77 (13%) WE ORs. When stratified by number of oocytes retrieved, there was no difference in procedure duration or PACU time between WD vs. WE OR. Longer procedure times were associated with higher BMI (p = 0.04), AMH (p = 0.01) and oocytes retrieved (p < 0.01). Increased PACU times positively correlated with the number of oocytes retrieved (p = 0.04), but not AMH or BMI. While BMI, AMH, and number of oocytes retrieved are associated with longer intra-operative and post-operative recovery times, there is no difference in procedure or recovery time when comparing WD vs. WE procedures.

Assessing burnout among Obstetrics & Gynecology residents during night float versus day float in a large academic hospital.

BACKGROUND: The prevalence estimates of burnout among residents vary widely. Resident physicians working overnight have additional stressors and therefore, may be at higher risk of developing burnout. OBJECTIVE: To determine the rates of burnout among residents working night rotations versus day rotations. METHODS: This is a prospective, cross sectional, survey-based assessment of the prevalence of burnout among Obstetrics and Gynecology (OBGYN) residents on nights versus days rotations conducted at a large academic residency program that spans two separate hospitals in New York. All residents in the residency program were asked to complete the Maslach Burnout Inventory - Human Services Survey for Medical Personnel (MBI-HSS (MP)) after the first rotation of the academic year in 2018, 2019, and 2020. The results for each of the three aspects of the MBI-HSS (MP): emotional exhaustion, depersonalization, and personal accomplishment, were then compared for those on nights versus day rotations using students t-test. RESULTS: A total of 76 responses were received, 13 from residents on night rotations and 63 from residents on day rotations with a response rate of 61.8%. Comparing resident responses for a night versus day rotation, the residents averaged a low level of emotional exhaustion (a score of 17 ± 9) on day shift, compared to a moderate level of emotional exhaustion (a score of 18 ± 14) on nights (p = 0.37). Similarly, 55.6% of respondents reports low personal accomplishment on days, compared to 76.9% while on nights. CONCLUSIONS: Emotional exhaustion scores were lower for residents on daytime rotations (mean score 17, SD 9), compared to those on nights rotations (mean 18, SD 14). Although there was no difference in depersonalization when comparing the day and night shift, 45% of the responses indicated high levels of depersonalization regardless of the type of shift. These results highlight the need to continue efforts to minimize burnout in medical training.

Src drives the Warburg effect and therapy resistance by inactivating pyruvate dehydrogenase through tyrosine-289 phosphorylation.

The Warburg effect, which reflects cancer cells' preference for aerobic glycolysis over glucose oxidation, contributes to tumor growth, progression and therapy resistance. The restraint on pyruvate flux into mitochondrial oxidative metabolism in cancer cells is in part attributed to the inhibition of pyruvate dehydrogenase (PDH) complex. Src is a prominent oncogenic non-receptor tyrosine kinase that promotes cancer cell proliferation, invasion, metastasis and resistance to conventional and targeted therapies. However, the potential role of Src in tumor metabolism remained unclear. Here we report that activation of Src attenuated PDH activity and generation of reactive oxygen species (ROS). Conversely, Src inhibitors activated PDH and increased cellular ROS levels. Src inactivated PDH through direct phosphorylation of tyrosine-289 of PDH E1α subunit (PDHA1). Indeed, Src was the main kinase responsible for PDHA1 tyrosine phosphorylation in cancer cells. Expression of a tyrosine-289 non-phosphorable PDHA1 mutant in Src-hyperactivated cancer cells restored PDH activity, increased mitochondrial respiration and oxidative stress, decreased experimental metastasis, and sensitized cancer cells to pro-oxidant treatment. The results suggest that Src contributes to the Warburg phenotype by inactivating PDH through tyrosine phosphorylation, and the metabolic effect of Src is essential for Src-driven malignancy and therapy resistance. Combination therapies consisting of both Src inhibitors and pro-oxidants may improve anticancer efficacy.

FBXO11 promotes ubiquitination of the Snail family of transcription factors in cancer progression and epidermal development.

The Snail family of transcription factors are core inducers of epithelial-to-mesenchymal transition (EMT). Here we show that the F-box protein FBXO11 recognizes and promotes ubiquitin-mediated degradation of multiple Snail family members including Scratch. The association between FBXO11 and Snai1 in vitro is independent of Snai1 phosphorylation. Overexpression of FBXO11 in mesenchymal cells reduces Snail protein abundance and cellular invasiveness. Conversely, depletion of endogenous FBXO11 in epithelial cancer cells causes Snail protein accumulation, EMT, and tumor invasion, as well as loss of estrogen receptor expression in breast cancer cells. Expression of FBXO11 is downregulated by EMT-inducing signals TGFß and nickel. In human cancer, high FBXO11 levels correlate with expression of epithelial markers and favorable prognosis. The results suggest that FBXO11 sustains the epithelial state and inhibits cancer progression. Inactivation of FBXO11 in mice leads to neonatal lethality, epidermal thickening, and increased Snail protein levels in epidermis, validating that FBXO11 is a physiological ubiquitin ligase of Snail. Moreover, in C. elegans, the FBXO11 mutant phenotype is attributed to the Snail factors as it is suppressed by inactivation/depletion of Snail homologs. Collectively, these findings suggest that the FBXO11-Snail regulatory axis is evolutionarily conserved and critically governs carcinoma progression and mammalian epidermal development.