bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU630 Improving Diagnostic Precision In Primary Ovarian Insufficiency Using Comprehensive Genetic And Autoantibody Testing
Authors: Vogt Elinor , Bratland Eirik , Berland Siren , Lund Agnethe , Sigridur Bjørnsdottir , Husebye Eystein Sverre , Øksnes Marianne 
Published: October 2023

Abstract
Disclosure: E. Vogt: None. E. Bratland: None. S. Berland: None. A. Lund: None. B. Sigridur: None. E.S. Husebye: None.
Context: Primary ovarian insufficiency (POI) affects approximately 1% of women and has life-changing consequences due to infertility and increased risk of complications related to premature estrogen deficiency. Clinical presentations and pathogenic mechanisms of POI are heterogeneous, but the underlying etiology remains unknown in the majority of cases. Improved diagnostic precision will be an important step towards tailoring future treatments in women with POI. Objective: To evaluate phenotypes and distribution of underlying etiologies in women with newly diagnosed POI. Methods: Prospective cross-sectional study of 100 women with newly diagnosed POI of unknown cause. Standard recommended diagnostic investigations were performed, including screening for chromosomal anomalies and premutations in the fragile X mental retardation 1 gene (FMR1). In addition, we used a two-tiered next generation sequencing (NGS)-based strategy, and assays of autoantibodies against steroid cell autoantigens. Results: We identified chromosomal aberrations in 8%, FMR1 premutations in 3%, genetic variants related to POI in 16%, and autoimmune POI in 3%. A homozygous pathogenic variant in the ZSWIM7 gene (NM_001042697.2) was found in two women, corroborating this as a novel cause of monogenic POI. No associations between phenotypes and genotypes were found. Conclusion: By adding an NGS-based POI-related gene panel, clinical whole exome sequencing, and specific immunoprecipitating autoantibody assays to the recommended diagnostic workup, we were able to determine a likely etiology in one third of the patients.
Presentation: Thursday, June 15, 2023
THU633 Atonal BHLH Transcription Factor 8 (ATOH8) Functions In Decidualization
Authors: Thapa Rupak , Bany Brent 
Published: October 2023

Abstract
Disclosure: R. Thapa: None. B. Bany: None.
ATOH8 is a member of the vast basic helix-loop-helix (bHLH) protein family that is widely known to play a role in various physiological and pathological processes. However, the functional significance of ATOH8 expression in the endometrium during implantation and in the first trimester of pregnancy in women is still lacking. In the mid to late secretory phase of the menstrual cycle, elongated fibroblast-like mesenchymal cells in the uterine endometrium begin to trans-differentiate into polygonal epithelioid-like (decidual) cells. During pregnancy, this process continues more broadly and supports successful embryo implantation and early placental development. We employed an established in vitro model using uterine fibroblast (HuF) cells derived from the decidua parietalis of term patients to investigate the function of ATOH8 during in vitro decidualization. All experiments were carried out using cells isolated from at least six independent patients (N=6). We measured the expression of classical decidualization marker genes and the characteristic shape change from small fibroblast-like cells to large epitheloid-like decidual cells to assess decidualization. Treating cells with steroids plus a membrane-permeable cAMP analog (EPC) for 48h caused in vitro decidualization of these cells, while treatment with vehicle alone had no effect. We discovered that ATOH8 expression was dramatically upregulated during this decidualization at both the mRNA and protein levels, with the protein primarily localized to the nucleus. The functional role of ATOH8 during decidualization was investigated using lentivirus-mediated shRNA knockdown or overexpression of ATOH8. When ATOH8 expression was silenced, we discovered that the ability of the cells to undergo decidualization was greatly and significantly diminished. On the other hand, overexpression of ATOH8 enhanced some aspects of decidualization. The addition of recombinant BMP2 alone had little effect on ATOH8 expression. However, in the presence of EPC it significantly enhanced ATOH8 expression. This effect of BMP2 on ATOH8 expression was inhibited by preincubating the cells with 500 nM DMH-1 (an ALK2/3 inhibitor) for one hr prior to inducing decidualization. Steroids alone did not affect ATOH8 or BMP2 expression. However, the addition of cAMP alone represented the major effect of EPC on ATOH8 expression while having a slight impact on BMP2 expression. A robust increase in BMP2 expression required the presence of both steroids and cAMP together. Our results indicate that ATOH8 plays a crucial role in human endometrial stromal cell decidualization. Further, our results suggest that ALK2/3 receptors are most likely involved in mediating the effect of BMP2 on increasing ATOH8 expression.
Keywords: ATOH8, Decidualization, Embryo Implantation
Presentation: Thursday, June 15, 2023
THU638 Comparison Of Body Composition Changes In Response To A Hypocaloric Dietary Intervention In Women With And Without Polycystic Ovary Syndrome
Authors: Zhang Jie , Carter Faith , Jarrett Brittany Y , Drewes Bailey , Brink Heidi Vanden , Lujan Marla Elaine 
Published: October 2023

Abstract
Disclosure: J. Zhang: None. F. Carter: None. B.Y. Jarrett: None. B. Drewes: None. H. Vanden Brink: None. M.E. Lujan: None.
Lifestyle intervention aimed at weight loss is recommended for women with polycystic ovary syndrome (PCOS) and concurrent obesity to improve reproductive, metabolic, and psychological health and well-being. However, we and others have shown that women with PCOS have perceptions of reduced success of weight loss interventions, and futility related to adoption of healthy lifestyle practices which can affect motivation and adherence to lifestyle change. Empirical data to support reduced success of weight loss interventions in PCOS is lacking. The objective of this study was to contrast the effectiveness of a hypocaloric dietary intervention on weight loss and body composition in women with and without PCOS. Thirty-eight reproductive age females (body mass index ≥25) with (N=22) or without (N=16) PCOS partook in a 4-week baseline assessment (pre-intervention), followed by a 12-week (3MO, N=17) or 24-week (6MO, N=21) commercial hypocaloric dietary intervention. Serial weight assessments were conducted at least twice per week and dual x-ray absorptiometry (DEXA) measured body composition pre- and post-intervention. Random coefficient models were used to compare changes in weight during the intervention. Differences in body composition pre- and post-intervention and across groups were compared using linear regression and analysis of variance. Participants lost an average of 7.8±3.2% and 9.0±5.0% total body weight with the 3MO and 6MO interventions, respectively. Waist circumference (107.1 ± 14.0 vs. 96.9 ± 12.6cm, P&lt;0.001), total lean mass (55.2 ± 7.2 vs. 51.8 ± 6.4cm, P&lt;0.05), total fat mass (43.2 ± 9.7 vs. 38.8 ± 8.9cm, P&lt;0.01) and trunk lean (27.1 ± 3.7 vs. 25.5 ± 3.6kg, P&lt;0.05) and fat mass ((21.7 ± 5.7 vs. 19.6 ± 5.6kg, P&lt;0.05) were decreased post-3MO intervention in women with PCOS, whereas only total (46.3 ± 8.2 vs. 39.4 ± 9.7kg, P&lt;0.05) and trunk fat mass (23.3 ± 5.2 vs. 20.1 ± 6.0kg, P&lt;0.05) were decreased post-6MO intervention in women with PCOS compared to their pre-intervention values. Percent changes in the aforementioned parameters were similar across groups with either the 3MO or 6MO intervention (P&gt;0.05), as was the rate of weight loss (P&gt;0.05). Women with PCOS demonstrated clinically meaningful changes in body composition in response to hypocaloric dietary interventions aimed at weight loss. Similar changes in body compositions and rate of weight loss between women with and without PCOS support comparable effectiveness of short-term hypocaloric dietary interventions in women with and without PCOS. Knowledge of comparable effectiveness to lifestyle change may aid in adoption and adherence to lifestyle interventions in women with PCOS.
Presentation: Thursday, June 15, 2023
THU643 Hyperandrogenism Caused By A Steroid Cell Tumor Of The Ovary In A Postmenopausal Woman
Authors: Mon Myint Myat Su , Pinero-Pilona Antonio 
Published: October 2023

Abstract
Disclosure: M.S. Myint: None. A. Pinero-Pilona: None.
Introduction Steroid cell tumor-not otherwise specified (SCT-NOS) is a subtype of steroid cell tumors which, in turn, is a subtype of sex cord-stroma tumors of the ovary. SCTs are exceedingly rare, account for less than 0.1% of all ovarian tumors, can secrete androstenedione, α-hydroxyprogesterone, and testosterone, and cause hyperandrogenism. We present a case of SCT-NOS, which was revealed postoperatively and was associated with breast cancer. Clinical Case A 74-year-old postmenopausal woman presented approximately a year after the onset of hirsutism, frontal alopecia and an elevated serum total testosterone (TTST) 341 ng/dl (reference range 3 to 41 ng/dL) and free testosterone (FRTST) 10.5 pg/mL (reference range 0.0 to 4.2 pg/mL). She has no clitoromegaly, acne, striae, or changes in voice and no history of infertility or PCOS. Physical examination was significant for cushingoid appearance, frontal alopecia, and hirsutism on the face. Her estradiol level was 213 pg/mL (reference range 0 to 30 pg/mL), FSH and LH levels were in the postmenopausal range, 17-hydroxyprogesterone, DHEA-sulfate, androstenedione, and morning cortisol were normal. Pelvic ultrasonography and CT of the abdomen and pelvis did not reveal an adrenal or ovarian abnormality. We suspected an ovarian source and thus recommended bilateral oophorectomy due to the markedly elevated testosterone level and postmenopausal status. We also started spironolactone. Before setting up for surgery, she was diagnosed with invasive lobular left breast cancer and underwent surgery and radiotherapy. Then, she had bilateral salpingo-oophorectomy. After surgery, TTST dropped to 4 ng/dL and FRTST to 2 pg/mL. Her hyperandrogenic symptoms significantly subsided. Pathology revealed a 1.5 cm red-brown nodule within the left ovary. The nodule contains polygonal cells with vacuolated cytoplasm arranged in nests, cords, and sheets. Cells were positive in calretinin and inhibin and negative in Reinke crystal. A steroid cell tumor, NOS was confirmed. Pathologic features associated with aggressive clinical behavior were not present. Conclusion The incidence of SCT-NOS is highest in women of childbearing age but rare in postmenopausal women. There were only a few case reports of SCT-NOS, most of which are relatively larger and revealed on imaging. In our case, the imaging did not localize the tumor. Sex cord-stromal tumors are often not visualized on imaging. Failure to identify a tumor on imaging does not rule out the presence of a tumor. One should always rule out androgen-secreting tumors in cases of significantly high testosterone. When imaging fails to reveal a tumor, bilateral oophorectomy should be considered in postmenopausal women and an ovarian and adrenal venous sampling in women of childbearing age. It is worth doing so because hyperandrogenism is associated with an increased risk of endometrial and breast cancer.
Presentation: Thursday, June 15, 2023
THU645 Comparison Of LC-MS/MS Testosterone Assays Towards Standardization Of Lower Testosterone Ranges
Authors: Cree Melanie G , Ottey Sasha , Sherif Katherine Devine , Sugahara Otoe , Pokuah Fidelia , Lyle Alicia N , Hubert Vesper 
Published: October 2023

Abstract
Disclosure: M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Eli-Lilly, Amino Co. S. Ottey: None. K.D. Sherif: None. O. Sugahara: None. F. Pokuah: None. A.N. Lyle: None. V. Hubert: None.
Objective: Polycystic ovary syndrome (PCOS) is a common disorder in women. The diagnosis of PCOS often includes elevated concentrations of serum testosterone. Previous work has harmonized the higher range of the testosterone assay and normative cut-offs for low and high testosterone concentrations for the male gender. However, similar work is needed to better align existing Liquid Chromatography Tandem Mass Spectroscopy (LC-MS/MS) methods in the lower range of testosterone and determine upper limits of normal for females. Methods: This is a secondary analysis of a pooled cohort of 60 obese adolescents with and without PCOS, enrolled in 1 of three studies (NCT02157974; NCT03041129; NCT03717935) at the University of Colorado, Anschutz. None of the participants were taking hormonal medication to treat PCOS. Frozen plasma samples collected between 6-7 AM were analyzed by Esoterix hormone branch of LabCorp (Agoura Hills, CA) and by the Centers for Disease Control (CDC) Clinical Standardization Programs with LC-MS/MS. Samples were selected from the available participants to encompass the full range of testosterone concentrations available within the cohort. Results: Within the entire cohort (N=60, Age = 15.8, SD: ± 1.7 years, BMI 35.4, SD: ± 5.5 kg/m2), the means between the assays were statistically, but not clinically different (CDC 48.4 SD: ±24.4 ng/dL vs OL 45.4 SD: ±22.1, p=0.013).Deming regression indicated that the assays were not different with an intercept of 2.05 (-3.69 to 7.79, 95% confidence interval) and slope of 0.895 (0.753 to 1.04, 95% confidence interval). The two assays were highly correlated via linear regression (R2=0.859, p&lt;0.001) and with a Bland-Altman comparison, the CDC assay only had a slight positive bias of 3.04, SD: ± 9.18 ng/dL relative to Esoterix. When divided by PCOS status (PCOS N=52, Hirsutism score 6.5±5.9, Control N=8, Hirsutism score 2.1±4.5), the CDC assay ROC demonstrated discrimination of PCOS status with an AUC of 0.903 (0.800-1.00), p&lt;0.001 and the Youden index was &lt;27.1 ng/dL with a sensitivity of 87.5% and a specificity of 86.5%. However, when the sensitivity was at 100%, the specificity was 57.7% and the cut-off &lt;43.0 ng/dL. Conclusions: The Esoterix, a major commercial lab, assay is very similar to that of CDC LC-MS/MS, and able to discriminate PCOS status at 43.0 ng/dL. Future work is needed to 1) align more clinical assays to the CDC standard and 2) define a common cut-off to describe hyperandrogenism in females across the weight and age spectrum.
Presentation: Thursday, June 15, 2023
FRI416 Primary Hyperaldosteronism in Pregnancy
Authors: Seav Susan M , Basina Marina 
Published: October 2023

Abstract
Disclosure: S.M. Seav: None. M. Basina: None.
Background: Primary hyperaldosteronism is extremely rare in pregnancy. Since 1962, only approximately 30 cases have been reported in the literature.1
Clinical Case: A 40-year-old female was referred for work-up of primary hyperaldosteronism (PHA). She was first diagnosed with hypertension (HTN) at age 29 during her first pregnancy. Laboratory work-up was consistent with PHA: serum aldosterone 22.6 ng/dL, renin activity 0.1 ng/mL/hr, aldosterone:renin ratio of 226. Post-saline infusion aldosterone level was 10.7 ng/dL. Adrenal CT scan showed a 6mm left-sided adenoma. Surgery was not recommended because adrenal vein sampling did not show lateralization. She was started on Spironolactone 25 mg/day. Despite the significant pregnancy risks, patient continued to desire conception and was switched to Labetolol. She was lost to follow-up and returned to the emergency room for dizziness at 26 weeks pregnant with twins with BP 180/109 mmHg. She had not been taking any anti-hypertensives and there was evidence of severe fetal growth restriction in both babies. After a goals of care discussion, patient deferred emergent C-section and suffered intrauterine fetal demise on hospital day 9.
Conclusion: PHA in pregnancy is rare and difficult to diagnose and manage. Newer studies estimate that &gt; 5-10% of patients with HTN have PHA.2 Hence, maintaining high vigilance of this disease in pregnant patients is even more imperative, including screening for PHA during pre-conception period in hypertensive women. A systematic review of 38 cases of PHA in pregnancy showed that 19% of cases were diagnosed with HTN prior to pregnancy without PHA screening.1 The average age of women in this study was 29.8 years. Additionally, there is a correlation in women with younger age at diagnosis and having unilateral PHA, in which case adrenalectomy should be performed prior to conception.3 In pregnancy, first line anti-hypertensive therapies include alpha methyl dopa, labetolol, and nifedipine. In PHA, diuretics such as amiloride and mineralocorticoid receptors should also be considered if BP is not at goal. Spironolactone and eplerenone have been safely used in pregnancy with both male and female fetuses.1,4 If surgery is not an option and medical therapy is ineffective, then physicians should have a low threshold to admit patients for close BP monitoring.
1Landau, et al. Primary Aldosteronism and Pregnancy. Annales d’Endocrinologie. 2016;77:148–160 2Funder, et al. Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889–1916 3Akasaka, et al. Sex Difference in the Association Between Subtype Distribution and Age at Diagnosis in Patients With Primary Aldosteronism. Hypertension. 2019;74(2):368-374 4Cabassi, et al. Eplerenone Use in Primary Aldosteronism in Pregnancy. Hypertension. 2012;59:e18-e19
Presentation: Friday, June 16, 2023
FRI443 Optimizing Conditions Of Tubule-like Structures In Testicular Organoids That Will Support Spermatogenesis
Authors: Printy Olivia , Laronda Monica M 
Published: October 2023

Abstract
Disclosure: O. Printy: None.
Testicular organoids are increasingly being investigated as a potential means of fertility restoration. These organoids have been shown to self-organize to recapitulate the inner architecture of the native testis, forming tubule-like structures that resemble the seminiferous tubules. However, these tubule-like structures lack dimensionality and do not contain a large, meiotically active germ cell population. We hypothesized that if testicular organoids are cultured under appropriate microenvironmental conditions, we will observe the development of tubule-like structures with diameters that resemble what is seen in vivo, in addition to appropriate somatic cell localization and Sertoli-germ cell interactions. To test this hypothesis, we generated organoids from 5dpp male CD1 mice at three cellular seeding densities: low density (170,000 cells per well), medium density (280,000 cells per well), and high density (310,000 cells per well). The heterogenous testicular cell suspension formed compact organoids at all three seeding densities and organoid diameter increased with increasing cell number. To assess the ability of the organoids to mimic the inner architecture of a testis, we performed immunohistochemistry on 14-day-old organoids: for the major somatic cell types of the testis Leydig cells (HSD3B2), peritubular myoid cells (ACTA1), and Sertoli cells (SOX9). Thus far, only medium density organoids appear to recapitulate the compartmentalization seen in native testes. These organoids tend to contain semi-continuous ring-like structures composed exclusively of ACTA1positive cells; these structures encapsulate a population of SOX9-positive cells, while HSD3B2-expressing cells are located on the periphery of the organoids. To assess the organoids’ ability to fuse to form a larger aggregate, organoids were transferred to 3D printed troughs. However, organoids did not merge and appeared to die. However, when organoids are cultured together in microcentrifuge tubes and alginate structures, they fused to form a larger aggregate. In the future, immunohistochemistry will be used to evaluate whether any extended tubule-like structures formed within the aggregates. Additionally, spermatogonial stem cells will be injected into the aggregates and ELISA assays will be performed to assess the spermatogenic and hormonal functionality of the organoids.
Presentation: Friday, June 16, 2023
FRI448 Mother Versus Daughter Attitudes Toward Breastfeeding In American Indians: Implications For Reproductive Health Education
Authors: Seely Ellen W , Demirci Jill Radtke , Hebert Luciana E , Kelty Estelle , Heydarpour Mahyar , Moore Kelly , Charron-Prochownik Denise 
Published: October 2023

Abstract
Disclosure: E.W. Seely: None. J.R. Demirci: None. L.E. Hebert: None. E. Kelty: None. M. heydarpour: None. K. Moore: Consulting Fee; Self; Novo Nordisk. D. Charron-Prochownik: None.
Background: Breastfeeding has well established health benefits for mothers and their children, being associated with a reduction in incidence of type 2 diabetes and childhood overweight/obesity. Accordingly, the American Academy of Pediatrics recommends 6 months of exclusive breastfeeding, followed by 1-2 years of continued breastfeeding. American Indian and Alaska Native (AIAN) women have among the lowest rates of breastfeeding of all races/ethnicities in the United States. The low rate is striking given the high rates of type 2 diabetes and obese/overweight AIAN children and young adults. To explore the low breastfeeding rates, we examined breastfeeding attitudes among AIAN mother-daughter dyads at 5 sites (Southwest, Northeast, Plains, and Northwest Coast, U.S.) in data from the Stopping GDM randomized controlled trial (NCT02723266). Methods: We used data collected among 149 mother-daughter dyads, who were asked 7 questions from the CDC’s Infant Feeding Practices Survey II focusing on the importance of breastfeeding and its potential health benefits. An additional question was asked: “If a child was breastfed, he/she will be less likely to get diabetes.” We compared mother/daughter attitudes using Chi-square tests. Results: Mean age + standard deviation of mothers was 44.1 + 9.3 and daughters 16.7 + 3.0 years. Eighty percent of both mothers and daughters agreed or strongly agreed that “Infant formula is not as good as breast milk.” However, attitudes that the best way to feed a baby is breastfeeding and that babies should be exclusively breastfed for the first 6 months were both statistically higher in mothers than daughters (74% vs. 59% and 68% vs. 40%, respectively). Mothers also had significantly higher agreement with the statements that breastfeeding was beneficial for prevention of ear infections (66% vs. 18%), respiratory illness (67% vs. 27%), diarrhea (48% vs. 22%), obesity (42% vs. 12%) and diabetes (35% vs. 13%) than daughters. Conclusion: Significant agreement between mothers/daughters exists for the belief that infant formula is not as good as breast milk. However, daughters’ attitudes toward the benefits of breastfeeding differ significantly from mothers with daughters endorsing weaker beliefs in infant health benefits of breastfeeding. This information is important to design early interventions to increase breastfeeding in AI women by increasing awareness of benefits and eliciting maternal support for adolescents and young adult women prior to planning a pregnancy.
Presentation: Friday, June 16, 2023