Ovarian Volume Research Articles

Ring Finger Protein 217 Inhibits Ovarian Cancer Progression by Down‐Regulating HAX1 Expression

AbstractRing finger protein 217 (RNF217) has been found to interact with the antiapoptotic protein HS‐1‐associated protein X‐1 (HAX‐1) in myeloid leukemia cells. However, the understanding of RNF217 in ovarian cancer progression remains limited. The relative expression of RNF217 is screened in ovarian cancer using the GEPIA database and calculated its correlation with MKI67, CCNB1, and CDK4. OVCAR‐3 and SK‐OV‐3 cells are transfected with RNF217‐overexpression plasmids. Cell‐counting kit‐8 assay is utilized to assess proliferation. Immunoprecipitation is performed to reveal the interaction between RNF217 and HAX‐1, and a cycloheximide chase assay is performed to analyze HAX‐1 degradation. The GEPIA database indicated down‐regulated expression of RNF217 in ovarian cancer, negatively correlated with MKI67 (R = ‐0.26, P = 1.8e‐09), CCNB1 (R = ‐0.37, P = 3.2e‐18), and CDK4 expression (R = ‐0.24, P = 3.4e‐08). RNF217 overexpression down‐regulated the relative expression of MKI67, CCNB1, and CDK4 in OVCAR‐3 and SK‐OV‐3 cells, resulting in diminished proliferation. In vivo studies using OVCAR‐3 and SK‐OV‐3 cell line‐derived xenograft models also showed that RNF217 overexpression reduced ovarian cancer volume and weight. Furthermore, RNF217 overexpression in SK‐OV‐3 cells inhibited the protein expression of HAX1 by reducing its stability. In conclusion, RNF217 inhibits ovarian cancer progression by down‐regulating HS‐1‐associated protein X‐1 expression.

Safety and efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial

Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. A total of 35 patients received 6×107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No.20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

Minipuberty in Daughters of Women with Hypothyroidism during Pregnancy.

Minipuberty is a term describing transient postnatal activation of the hypothalamic-pituitary-gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring.

Ultrasonographic threshold of ovarian structure in premenopausal women of different ethnicity

The polycystic ovarian morphology (PCOM) is a generally accepted ultrasound marker for ovulatory dysfunction, is one of the criteria for polycystic ovary syndrome (PCOS) and is established based on the assessment of ovarian volume (OV) and the follicle number per ovary (FNPO), taking into account the upper normal values determined in healthy premenopausal women. However, there is a necessity for regular revision of the PCOM characteristics depending on ethnic and age characteristics.The aim. To develop differentiated standards for assessing the ultrasonographic ovary structure in premenopausal women of various ethnicity.Materials and methods. From March 2016 to December 2019, a multicenter cross-sectional prospective study was conducted in Eastern Siberia (Irkutsk region) and in the neighboring Republic of Buryatia. The study included 1134 participants: 715 women of Caucasian origin, 312 Asian women, 107 women of mixed ethnic subpopulation.Results. It has been established that for Caucasians, it is advisable to diagnose PCOM when the ovarian volume is 9 cm3 and/or FNPO ≥ 12; for women of the Asian population – when the ovarian volume is 7 cm3 and/or FNPO ≥ 11; for women of mixed ethnicity – when the ovarian volume is 8 cm3 and/or FNPO ≥ 9. An important advantage of our study is that all participants were recruited from a non-selective multi-ethnic population of women with comparable socio-demographic characteristics living in the same geographical conditions.Conclusion. Differentiated approach for identifying the polycystic ovarian morphology in premenopausal women of different ethnic groups requires using ethnically differentiated normative readings

Development of a Machine Learning-Based Model for Accurate Detection and Classification of Polycystic Ovary Syndrome on Pelvic Ultrasound.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that disrupts reproductive function and hormonal balance. It primarily affects reproductive-aged women and leads to physical, metabolic, and emotional challenges affecting the quality of life.In this study, we develop a machine learning-based model to accurately identify PCOS pelvic ultrasound images from normal pelvic ultrasound images. By leveraging 1,932 pelvic ultrasound images from the Kaggle online platform (Google LLC, Mountain View, CA), we were able to create a model that accurately detected multiple small follicles in the ovaries and an increase in ovarian volume for PCOS pelvic ultrasound images from normal pelvic ultrasound images. Our developed model demonstrated a promising performance, achieving a precision value of82.6% and a recall value of 100%, including a sensitivity and specificity of 100% each. The value of the overall accuracy proved to be 100% and the F1 score was calculated to be 0.905. As the results garnered from our study are promising, further validation studies are necessary to generalize the model's capabilities and incorporate other diagnostic factors of PCOS such as physical exams and lab values.

The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status.

Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic-pituitary-gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit.

The Role of Neutrophyl-to-Lymphocyte Ratio as a Predictor of Ovarian Torsion in Children: Results of a Multicentric Study.

Pediatric ovarian torsion (OT) is an emergency condition that remains challenging to diagnose because of its overall unspecific clinical presentation. The aim of this study was to determine the diagnostic value of clinical, ultrasound, and inflammatory laboratory markers in pediatric OT. We performed a retrospective multicentric case-control study in patients with clinical and ultrasound suspicion of OT, in whom surgical examination was performed between 2016-2022 in seven pediatric hospitals. Patients were divided into two groups according to intraoperative findings: OT group (ovarian torsion), defined as torsion of the ovarian axis at least 360°, and non-OT group (no torsion). Demographics, clinical, ultrasound, and laboratory features at admission were analyzed. The diagnostic yield analysis was performed using logistic regression models, and the results were represented by ROC curves. We included a total of 110 patients (75 in OT group; 35 in non-OT group), with no demographic or clinical differences between them. OT-group patients had shorter time from symptom onset (8 vs. 12 h; p = 0.023), higher ultrasound median ovarian volume (63 vs. 51 mL; p = 0.013), and a significant increase in inflammatory markers (leukocytes, neutrophils, neutrophil-to-lymphocyte ratio, C-reactive protein) when compared to the non-OT group. In the ROC curve analysis, the neutrophil-to-lymphocyte ratio (NLR) presented the highest AUC (0.918), with maximum sensitivity (92.4%) and specificity (90.1%) at the cut-off point NLR = 2.57. NLR can be considered as a useful predictor of pediatric OT in cases with clinical and ultrasound suspicion. Values above 2.57 may help to anticipate urgent surgical treatment in these patients.

Study of Sonographic Indicators of Ovarian Reserves in Women With WHO-Defined Anovulatory Disorders.

Depending on the age of the wife or female partner, infertility is defined as the inability of a couple to achieve conception after 12 months if the age is ≤35 years and six months if the age is ≥35 years. About half of female infertility is attributed to ovulatory dysfunction, and the rest is either due to tubal and pelvic pathology or problems such as thyroid disease or anatomic abnormalities. Ovulatory disorders are one of the major factors for infertility problems in couples. Ultrasound monitoring of ovarian follicle growth plays a pivotal role in infertility treatment. The total number of small antral follicles in both ovaries is an important predictive parameter of the ovarian induction cycle, whereas ovarian volume is the parameter most easily assessed by ultrasound. The purpose of this study is to analyze the sonographic indicators of infertility (antral follicle count and ovarian volume) in four World Health Organization (WHO)-defined anovulatory groups and compare the same with that of healthy fertile women.

PSYCHOTIC DISORDER INDUCED BY CLOMIPHENE CITRATE IN A MAN: A RARE CASE REPORT

The clomiphene citrate is one of the selective estrogen receptor modulators and its function is to indirectly induce ovulation, stimulating the secretion of pituitary gonadotropins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)), subsequently increasing testosterone circulation levels. Its main adverse effects include increased ovarian volume, vasomotor symptoms, pelvic discomfort, and hepatic dysfunction. However, some reactions to this medication may be unknown or poorly reported in the scientific literature. Hormonal effects may be responsible for the unfavorable psychotic outcomes in conjunction with the antiestrogenic activity of clomiphene. The appearance of psychotic symptoms, especially in women with a pre-existing psychiatric history, has been previously studied [1,4]. The effects were attributed to an enhanced testosterone-androgen receptor interaction in the brain, subsequently leading to alteration of emotional conditions. Proposed neurobiological targets include catecholaminergic cells in the hypothalamus and other limbic regions of the brain.). Nevertheless, the occurrence of such symptoms has not been reported in the literature in males. This letter aims to report the case of a 36-year-old male patient who presented an adverse reaction that is not clear in the literature on Clomiphene Citrate, since the majority of reported cases are in the female population with some previous psychiatric comorbidity. The patient had a previous diagnosis of fibromyalgia. Approximately 20 days after the introduction of the medication, he presented his first psychotic episode with manifest characteristics, with increased energy, hypersexualization, low need for sleep, grandiose delusions, impulsive and inappropriate behavior lasting an average of 4 days. The patient's family reported that he had never exhibited similar behavior. The second psychotic episode occurred approximately 20 days after the first. In the latter, the patient presented with persecutory delusions, risky behavior, paranoid behavior, risk of self- and hetero-aggression, and was taken to his first psychiatric hospitalization. It was reported that he used clomiphene citrate up to 15 days before psychiatric hospitalization. The use of other psychoactive substances was also ruled out (a toxicological test with a negative result) and admission and neuroimaging exams (magnetic resonance imaging of the skull) were carried out, with all results within normal limits. The patient was admitted to our service being introduced to valproic acid 1000mg/day, risperidone 2mg/day, quetiapine 100mg/day and gabapentin 900mg/day (already being used to treat chronic pain) and clomiphene was suspended. He presented rapid remission of delusions in two days with criticism present in the first week of hospitalization. Due to the absence of psychiatric history, as well as other possible causes for the appearance of symptoms, the psychotic condition described was therefore attributed to the use of clomiphene. Thus, the possibility of this medication inducing the appearance of symptoms should be considered, especially in patients experiencing their first psychotic episode [2,3].

The possible short-term of Nigella sativa – L in the management of adolescent polycystic ovarian syndrome: results of a randomized controlled trial

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effective in improving gonadotropins and sex hormones. The current study was designed to investigate the effect of Nigella sativa supplementation on PCOS symptoms and their severity in adolescents.MethodsThe current randomized clinical trial was conducted on 114 adolescents with PCOS who were referred to gynecologist offices and clinics in Gonabad, Iran from March 2022 to March 2023. Participants were randomly allocated to the intervention (Nigella sativa 1000 mg/day) and control (10 mg/day medroxyprogesterone from the 14th day of the cycle for 10 nights) groups. The study duration was 16 weeks. Ovarian volume (measured by ultrasound), anthropometric and blood pressure; serum testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), hirsutism severity (Ferriman–Gallwey score) levels were evaluated before and after the study.ResultsData from 103 participants (control group = 53, intervention group = 50) were analyzed. The mean age of participants was 17.0 (Interquartile range [IQR]:2.0). The mean difference in hirsutism score changes (p < 0.001), right (p = 0.002), and left (p = 0.010) ovarian volume, serum LH (p < 0.001) and testosterone (p = 0.001) were significantly higher in the intervention group compared to the control group. The frequency of oligomenorrhea, menometrorrhagia, and amenorrhea, were significantly reduced after the study in the intervention group compared to the control group (ps < 0.001).ConclusionsShort-term Nigella sativa supplementation may be effective in reducing ovarian volume and improving hormonal balance, and menstrual irregularities in adolescents with PCOS. Further research and long-term studies are warranted to validate the potential therapeutic effects of Nigella sativa in adolescents with PCOS.IRCT registration numberIRCT20221017056209N1 Registration date: 2022-11-22.

P-590 Should the ovarian ultrasound markers for the diagnosis of PCOS be revised?

Abstract Study question Should the cut-off values for follicle number and ovarian volume in PCOS be revised, and should they be adjusted based on age or BMI? Summary answer The cut-off for follicle number per ovary can be maintained (age specific, not BMI adjusted), while for ovarian volume, it should be lowered or omitted. What is known already The 2023 International Guideline for PCOS concluded that the quality of evidence for recommendations regarding the ultrasound diagnosis of PCOS (FNPO ≥ 20 and/or ovarian volume (OV) ≥10 mL, in one or both ovaries) is low. It advises to regularly revise thresholds with advancing ultrasound technology and to investigate the impact of age on diagnostic accuracy. Consideration of other biological factors such as BMI is also warranted. Study design, size, duration Retrospective cross-sectional study, including data from 2001-2023, obtained through standardized endocrinological screening at the Department of Reproductive Endocrinology in the Erasmus Medical Center (Rotterdam, The Netherlands). Women diagnosed with PCOS during the screening were eligible for inclusion in the PCOS group. Women who underwent the same screening, had regular menstrual cycles, exhibited normal hormonal values, and showed no endocrinological pathology were eligible for inclusion as controls. Participants/materials, setting, methods A total of 2492 women (15-50 years) with PCOS and 152 controls were included. PCOS was diagnosed according to the 2003 Rotterdam criteria and the 2018 International Guideline. Exclusion criteria included: age &amp;lt; 15 or &amp;gt; 50 years, presence of any cysts (&amp;gt;10 mm) in one/both ovaries, use of oral contraceptives, and missing ultrasound data. The ovarian ultrasound markers were stratified by age in 5-year intervals. Receiver Operating Characteristic (ROC) analyses were performed for optimal cut-offs. Main results and the role of chance In our cohort, most women with PCOS up to age 35 exhibit a TFC ≥ 20, followed by a decline in FNPO above the age of 35. In a subgroup of women aged 35-40 (n = 24 PCOS, n = 24 controls, matched by age, assessed with ultrasound &amp;gt; 8 MHz), we found optimal cut-offs of 14.5 follicles (Left FNPO) and 14 follicles (Right FNPO), with AUC values of 0.94 and 0.93. Median OV in every age group was below the 10 mL cut-off. In women aged 20-35 (n = 75 PCOS, 75 controls, ultrasound &amp;gt; 8 MHz), optimal cut-offs were 6.5 mL (Left OV) and 7.4 mL (Right OV), with AUC values of 0.70 and 0.78. For 35-40 years, cut-offs were 8.0 mL (Left OV) and 7.2 mL (Right OV), including 24 women PCOS and 24 age-matched controls, with AUC values of 0.68 and 0.62. In our cohort 19/2413 women with PCOS (0.8%) would not have received the diagnosis PCOS if OV was not considered as a marker for PCOM. No clinically significant correlation between BMI and FNPO or OV was observed. Limitations, reasons for caution The optimal cut-off values should be interpreted with caution due to the small sample sizes in the ROC analyses. The control group includes women with isolated PCOM. There is an ongoing debate about whether they should be excluded in such analyses. Wider implications of the findings We suggest lowering or omitting the OV cut-off for PCOM detection and establishing age-specific FNPO cut-offs. Future research on ovarian markers in PCOS, should prioritize women with isolated ovulatory dysfunction or hyperandrogenism, aligning with the 2023 International PCOS Guideline recommendation to exclusively investigate PCOM in this subgroup. Trial registration number not applicable

O-220 Ovarify: a deep learning model for automatic calculation of ovarian morphological features in pelvic ultrasonography

Abstract Study question Can a deep learning model accurately characterize ovarian features on pelvic ultrasounds? Summary answer We developed a deep learning model, Ovarify, that can accurately classify and segment ovarian features on pelvic ultrasounds. What is known already Ovarian morphology, as detected using pelvic ultrasonography, is used widely in the assessment of gynecological health. Morphological metrics such as ovarian volume and antral follicle count have known diagnostic and prognostic value for a variety of gynecological outcomes, ranging from risk for ovulatory disorders to likelihood of response to assisted reproductive technologies. However, a lack of standardization in the interpretation of ovarian features, and the time-intensive nature of validated image analysis techniques (such as 2D grid analysis), limits their utility in clinical practice. Deep learning provides an opportunity to overcome these limitations. Study design, size, duration The training dataset for the model comprised 426 3D pelvic ultrasounds obtained using the GE Voluson ultrasound platform, yielding 56,538 individual frames with potential ovarian content. In addition, a similarly collected validation dataset consisted of 95 ultrasounds, yielding 11,304 frames. The held-out test set comprised 107 ultrasounds with 14,767 frames. All frames were manually labeled with the associated 2D ovarian contour, and 163 of the ultrasounds had an associated ovarian volume label. Participants/materials, setting, methods Ovarify consists of two stages: 1) a lightweight classifier that labels ultrasound frames as either positive or negative (having or not having ovarian content) and 2) a subsequent U-Net-inspired segmentation module with an Xception backbone and attention-based decoder that segments the ovary and antral follicles in all frames previously classified as positive. Classification performance was evaluated using F1-score and area under the receiver operating characteristic curve (AUROC). Segmentation performance was evaluated using the Jaccard index. Main results and the role of chance For the classification stage, Ovarify achieved an AUROC of 0.980±0.002 and 0.976±0.004 on the training and validation sets, respectively. On the held-out test set, the model achieved an AUROC of 0.971±0.005. In addition, the model achieved an F1-score of 0.825±0.006, 0.810±0.013, and 0.784±0.014 on the training, validation, and held-out testing sets, respectively. The high AUROC and F1-scores across both seen and unseen datasets support a high-performing classifier. In the segmentation stage, Ovarify reached a median Jaccard index of 0.815±0.004 on the unseen test set when tasked with segmenting the ovary, and a median Jaccard index of 0.657±0.018 on the unseen test set when segmenting antral follicles. High agreement between the ground truth ovary and follicle labels and the predicted segmented regions increases confidence in the downstream morphological analysis. For example, the Pearson correlation coefficient between the Ovarify-calculated ovarian volume and manually-validated ovarian volume was 0.813, indicating that an automatic ovarian volume calculation highly aligns with the ground truth. Ovarify was able to provide predictions in under one minute for the entirety of the held-out test set. Limitations, reasons for caution Ovarify was trained on images generated by the GE Voluson platform and has not been evaluated for generalizability across ultrasound images generated using machines whose output does not match the DICOM format standard. Wider implications of the findings The model developed is relevant for automatically calculating ovarian morphological features from pelvic ultrasounds. This approach has implications in removing user-specific bias and error when calculating biomarkers associated with female reproductive health, including but not limited to ovulatory disorders such as polycystic ovary syndrome (PCOS). Trial registration number not applicable

P-601 Monitoring reproductive hormones during ovarian stimulation: performance and usability of a self-operated at-home urine test

Abstract Study question How effective and user-friendly is a non-invasive, patient-operated urine test (Kinder) in tracking reproductive hormone levels during ovarian stimulation (OS) treatment in an IVF cycle? Summary answer Urinary E1-3G correlates well with blood E2 levels and ovarian follicle development. Patients found it easy and stress-free to perform the urine test at home. What is known already Monitoring blood reproductive hormone levels during OS is a widely accepted practice to ensure the optimal ovarian response to gonadotropin treatment, timing of oocyte maturation triggering and mitigating hyperstimulation risk. However, conventional blood testing is invasive, necessitating patients to travel to clinics for blood sampling, adding to their overall burden. Previous studies have revealed a robust correlation between blood E2 levels, and its corresponding urinary metabolites E1-3G. Kinder is a portable device designed for quantifying urinary E1-3G, allowing patients to conduct tests in the privacy of their homes, and for many obviating the need to travel substantial distances for monitoring. Study design, size, duration This is a prospective, single-cohort, study of Caucasian patients (28-34 years), conducted at Fertility Specialists of Western Australia in Perth, Australia, where patients may travel vast distances for treatment. Twenty-five patients were enrolled from Aug 2022-Aug 2023, and performed home urine tests utilizing the Kinder device in parallel with clinic scheduled blood (ELISA) and ultrasound tests. The primary end point of the study was the correlation between urinary and blood reproductive hormone concentrations (E1-3G). Participants/materials, setting, methods Spearman and Pearson correlation coefficients (CC) and 95% confidence intervals were calculated for E1-3G and E2, and E1-3G/E2 and follicle development (total volume of ovarian follicles by ultrasound). To assess patient acceptability patient-reported outcomes (PRO) were assessed using the State Trait Anxiety Inventory (STAI) questionnaire. Further, patient-reported experiences (PRE) were evaluated through the System Usability Scale (SUS) questionnaire, along with assessing their likelihood to recommend Kinder to their friends or family undergoing IVF treatment. Main results and the role of chance Upon analysing 100 concurrent urine and blood samples from 25 patients, a robust correlation was found between E1-3G and E2 levels (Spearman CC: 0.818, 95% CI: 0.680-0.904; Pearson CC: 0.847, 95% CI: 0.712-0.939). Additionally, we observed a moderate correlation between E1-3G levels and ovarian volume (Spearman CC: 0.701, 95% CI: 0.556-0.805; Pearson CC: 0.670, 95% CI: 0.519-0.781, n = 72), resembled the correlation between E2 levels and ovarian volume (Spearman CC: 0.874, 95% CI: 0.804-0.920; Pearson CC: 0.849, 95% CI: 0.770-0.902, n = 75). PRE: 22 out of 23 patients who completed the survey confirmed that they would definitely, or probably, recommend Kinder. The mean SUS score (91.4) signified an excellent user experience. PRO: Anxiety levels were not affected by use of Kinder (STAI score below threshold of 42.38) in 18/20 patients who completed three STAI surveys (first one before and second one after the initial Kinder test; third one after the third/fourth Kinder test). Although 2/20 patients reported a STAI score of 49 in the final survey, suggesting increased anxiety, both affirmed in the PRE survey that they “will definitely recommend Kinder”, suggesting that the elevated STAI score can be attributed to the overall IVF treatment rather than the use of Kinder itself. Limitations, reasons for caution The sample size is relatively small, necessitating further multi-centre studies with a larger sample size to validate the findings. Wider implications of the findings The results suggest an acceptable interchangeability between at-home urine E1-3G and at-clinic blood E2 monitoring hormone levels during OS treatment. A digital health approach, combining tele-counselling, remote at-home hormone monitoring, and follicle tracking, could reduce patient burden and save many patients the inconvenience of travelling large distances for cycle monitoring. Trial registration number ACTRN12622000488707

P-649 Unconventional action of Luteinizing Hormone

Abstract Study question Has Luteinizing Hormone (LH) a role in the activation/survival of follicles of the primary ovarian reserve? Summary answer LH promotes survival and perhaps activation/growth of primordial and primary follicles, proliferation of granulosa cells of secondary follicles, reduces follicle atresia at later growing stages. What is known already In the mammalian ovary, Primordial Follicles (PMFs) constitutes the primary ovarian reserve, which declines over time due to physiological events such as atresia, recruitment, and ovulation. While in the adult, the role of LH in steroidogenesis and ovulation is well established, recent work from our laboratory has shown that under chemotherapeutic treatments, LH supports PMFs survival in prepuberal mouse ovary. Study design, size, duration LH effects on follicle dynamics and some activities of pre-granulosa cells were investigated in vitro and in vivo. In vitroexperiments were performed on PD4 GFP/Kit mice ovarian fragments and on PD8 CD1 mice ovarian somatic cells cultured up to six days in continuous presence of 0.2, 0.5, 1IU LH. In vivo experiments were performed on 9 PD4 and 8 PD28 CD1 mice receiving an intra-peritoneal injection for eight consecutive days of 1-5IU LH. Participants/materials, setting, methods Number and diameters of the GFP stained oocyte were counted in the ovarian fragments. Kit-Ligand and LH-R mRNA expression levels were analyzed by qPCR in pre-granulosa cells. For in vivo experiments, ovarian volume was measured by Micro-Ct and follicle counts were performed on histological sections. Estrous cycle phases were monitored by vaginal smear during the 8 days of treatment. Statistics was performed using Student’s t-test. Main results and the role of chance In fragments of PD4 mouse ovaries cultured in vitro for six days, 1IU LH significantly increased the number of oocytes with a diameter &amp;gt;40 mm (CTRL 17.7% vs LH 36.07%, p &amp;lt; 0,05), suggesting activation of PMFs. Moreover, the hormone increased the expression of mRNA for LHR and KL in the somatic ovarian cells and promoted their proliferation in vitro. The effects of 1IU LH on PD4 females can be summarized as follows: 1. Ovary volume increase (CTRL 0.3 mm3 vs LH 0.36 mm3, p = 0.07), 2. higher percent of PMFs (CTRL 68.227% vs LH 78.29%, p &amp;lt; 0,05) associated with lower percent of primary (CTRL 7.2% vs LH 4.05%, p &amp;lt; 0.04) and growing follicles (CTRL 14.18% vs LH 8.56%, p = 0.1), 3. higher number of granulosa cell layers (&amp;gt; three layers) in secondary follicles (CTRL 42.8% vs LH 54.6%), and 4. lower percent of atretic follicles (CTRL 2.64% vs LH 1.72%, p = 0.1). Similar results were obtained on 28 dpp mice. Morever, we observed that corpora lutea were present only in ovaries of LH-treated females and that all such females were in estrus. Limitations, reasons for caution The study was conducted only in mice. Wider implications of the findings These studies have highlighted new possible roles of LH on follicle classes (primordial/primary) whose development is considered gonadotropin independent. The results, if confirmed in humans, imply that LH might be used as a treatment for patients with ovarian disorders involved the survival/dynamics of the ovarian reserve. Trial registration number NA

O-193 Age-related normograms of AMH in women with polycystic ovary syndrome using three different assays

Abstract Study question To develop an age-specific percentile distribution of anti-Müllerian hormone (AMH) in patients with polycystic ovary syndrome (PCOS) measured by three different assays. Summary answer Our age-related normograms may help to interpret AMH levels in PCOS patients and facilitate the use of AMH as a diagnostic tool across age ranges. What is known already In the last years, AMH assessment has gained widespread use in the clinical settings of several conditions. However, several challenges still exist to adopt the AMH as a marker of polycystic ovary morphology (PCOM), as included in the recently updated international guideline. Although different evaluations of age- and assay-specific reference ranges have been published in the last years, these studies have mainly been conducted in normo-ovulatory or infertile women and little is known about the higher range of AMH levels, especially in women with PCOS. Study design, size, duration Retrospective single-center cross-sectional study, including 2,725 women with PCOS who consulted the Reproductive Endocrinology and Infertility Clinic of the Erasmus University Medical Center, Rotterdam, The Netherlands. Participants/materials, setting, methods A total of 2,725 women aged 20 to 40 years with PCOS were included. PCOS was diagnosed according to the Rotterdam Criteria. Serum AMH levels were measured using the following AMH assays: (1) Gen II AMH ELISA, 2) picoAMH assay, and 3) Elecsys AMH plus assay. Age-specific centile curves were constructed using the LMS method. The correlations between AMH with clinical, endocrine, and ultrasound features were also evaluated. Main results and the role of chance To our knowledge, this is the first study with real-world data reporting AMH age-specific percentile nomograms in a large population of PCOS women using three different assays. The 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were calculated according to a population/based approach per age (years) for the Gen II, the picoAMH, and the Elecsys assays. We also considered the age-percentile values of AMH in PCOS patients for the Gen II, the picoAMH and the Elecsys assays according to the cut-offs previously proposed in literature for each specific assay. Interestingly, in our population, a high percentage of women with polycystic ovarian morphology (PCOM) showed AMH levels lower than the cut-offs proposed. Serum AMH levels were significantly higher in patients with phenotype A compared to all other phenotypes for all three assays. For all three assays, we found a statistically significant positive correlation between AMH levels and LH, LH/FSH ratio, testosterone, androstenedione, FAI, mean follicular number, and mean ovarian volume. In contrast, AMH levels were negatively correlated with BMI in all groups. Limitations, reasons for caution This is a retrospective cross-sectional study. Longitudinal studies with a large cohort of women that could be followed for many years are needed to validate our nomogram. Wider implications of the findings AMH threshold levels can be influenced by several variables, making it difficult to identify a general cut-off to diagnose PCOM. Further research should overcome the concept of a single cut-off value. The results of the present study may help clinicians interpret AMH levels in PCOS patients across age ranges. Trial registration number In this retrospective cross-sectional study, 2,725 women who consulted the Reproductive Endocrinology and Infertility Clinic of the Erasmus University Medical Center, Rotterdam, The Netherlands, were included. The Medical Ethical Review Board of the Erasmus University Medical Center Rotterdam approved retrospective studies within this patient population, which includes women with ovulatory dysfunction (MEC-2020-0534).

P-698 The ULTRA trial: transvaginal ULTRAsound-guided ovarian ablation using May Health System in women with PCOS-related infertility: clinical and endocrine outcomes of first–in-human feasibility trial

Abstract Study question What is the feasibility of transvaginal ULTRAsound (TVUS)-guided ovarian ablation using the May Health System to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related infertility? Summary answer The feasibility of TVUS-guided ovarian ablation to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related anovulatory infertility was demonstrated. A pivotal study is underway. What is known already Laparoscopic ovarian drilling (LOD) is widely accepted as an effective second line treatment in PCOS-related infertility. However, laparoscopy is an invasive procedure that requires general anaesthesia and carries significant risks. Furthermore, there is no standardization of the LOD technique among surgeons. In contrast, the May Health System has been designed to deliver a precisely calculated amount of ovarian ablation via a less invasive route without general anaesthesia. This approach therefore transforms an invasive surgical procedure to an office-based technique similar in ovarian access to the well-established oocyte retrieval. Feasibility and safety results of this trial have previously been reported. Study design, size, duration This study included two feasibility, single-arm clinical trials running in parallel in the EU and US assessing the May Health System in performing TVUS-guided ovarian ablation in anovulatory PCOS women resistant to first-line ovulation induction drugs. Sample size was up to 35 participants with post-procedure follow-up (FU) of 24 months in EU and 12 months in US. Endpoints for this study were technical success, ovulation rates, pregnancy rates, and hormonal changes. Participants/materials, setting, methods Seven fertility centres participated in the trials. Participants were clomiphene/letrozole-resistant PCOS women aged 18-40 years. PCOS was diagnosed according to Rotterdam criteria. Participants underwent TVUS-guided ovarian ablation using the May Health System. The initial five participants underwent laparoscopy concurrent with TVUS-ablation. Post-procedure, serum progesterone was measured weekly until confirmation of ovulation or up to 12 weeks. Women were evaluated at 3 and 6 month, and then telephoned at 9- 12- and 24-month (EU sites only). Main results and the role of chance Thirty-one participants (mean±sd age, 31.9±3.3 years; BMI, 29.84.7kg/m2) underwent May Health TVUS-guided ovarian ablation and 25 completed at least six-months FU, with follow-up ongoing. Fourteen (45.2%) ovulated spontaneously within 3-months. Six more participants (19.3%) ovulated between three and nine months (after restarting CC/LTZ) giving a combined ovulation rate, with and without first-line medication restart, of 64.5% (20/31). Of the 31 participants who underwent the procedure, 10 (32%) have conceived to date, with seven live births, two ongoing, and one miscarriage. In 30 cases (97%), the targeted ablation was achieved successfully, while in one case (3%) the procedure was abandoned for the second ovary due to pain (n = 1). The median (IQR) serum AMH concentrations significantly decreased from baseline 76.1 (32.0, 210.7) to 62.5 (21.2, 253.6) pmol/l at 3-month (p = 0.001) and 56.7 (11.5, 126.8) pmol/l at 6-month (p = 0.001) post-procedure (Figure 2). The magnitude of post-ablation AMH decline was significantly (p = 0.047) greater in those who ovulated (responders) (-23.7% (-36.5, 17.7)) versus non-responders (-7.3% (-25.2, -1.6)). Ovarian volume significantly (p = 0.005) decreased from 13.6±5.1 ml at baseline to 10.1±3.7 ml at 6-month FU. There were no statistically significant changes in mean circulating testosterone, LH, or FAI at 3- or 6-month. Limitations, reasons for caution A limitation of this study is the lack of a comparator treatment / placebo arm. However, this was not necessary for this feasibility trial. It is possible to assume that the post-procedure ovulation and pregnancies could be compared for each participant with pre-procedure lack of ovulation and failure to conceive. Wider implications of the findings These data suggest that the investigational May Health System may offer an effective office-based second line ovulation inducing procedure for PCOS. The observed decline in circulating AMH, which was sustained for at least six months, could be the underlying mechanism of ovarian rebalancing that leads to subsequent resumption of ovulation. Trial registration number NCT03760926

Pelvic ultrasound and pubertal attainment in girls with sexual precocity: the pivotal role of uterine volume in predicting the timing of menarche.

Among girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (TUS-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and TUS-M, in order to identify the most reliable predictor of the timing of menarche. Retrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers. The time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p<0.0001) with LH (r:-0.61), FSH (r:-0.59), estradiol (r:-0.52) and stimulated LH values (r:-0.58). Among pUS parameters, ovarian volume (r:-0.17 left, -0.30 right) and uterine body-to-cervix ratio (r:-0.18) poorly correlated with TUS-M, while uterine diameters (r:-0.61 longitudinal, -0.64 anteroposterior) and volume (r:-0.70) achieved a highly statistical significance (p<0.0001). Uterine volume (UV) showed a negative logarithmic relationship with TUS-M and represented the most reliable predictor of the timing of menarche in uni- and multivariable analyses (p <0.001). ROC analyses identified the UV thresholds that best predict the onset of menarche within 18, 12 and 6 months, respectively: 3.76, 6.02 and 8.80 ml. The logarithm of UV shows the best statistical performance in predicting the timing of menarche in girls assessed for pubertal precocity. Accordingly, we developed a user-friendly online application that provides clinicians with an estimation of the months expected to elapse before menarche, based on the UV recorded upon pUS.

Ovary morphology determines ovary-to-grain transition process and final grain weight potential in wheat

The ovary-to-grain transition process is crucial for individual grain weight potential, but the but the physiological regulation of this highly dynamic and complex developmental process remains largely unknown unknown. Here, we performed a high temporal-resolution analysis of the proximal (large) and distal (small) ovaries/grains collected at an interval of 3 days from the booting stage to maturity stage. During grain-filling process, proximal grains always maintained a greater dry matter (0–36 days after anthesis, DAA), water (0–33 DAA), sugar (3–33 DAA), protein (6–36 DAA), and starch (amylose and amylopectin, 18–36 DAA) content, and larger volume (-15–36 DAA) than distal grains, but their partition or concentration did not differ between the proximal and distal grains. This result suggested that the capability of proximal and distal grains to produce water, sugar, protein, and starch within the same volume was similar; thus, grain sink (i.e. volume) was the cause in determinant of grain weight potential. In fact, the proximal ovary had a larger volume and related parameters (length, width and thickness) than the distal ovary before anthesis stage. in addition, the correlation coefficients of length and width with volume are higher than the correlation coefficients of thickness with volume. Clearly, we discovered a dynamic physiological mechanism for high proximal grain weight: the rapid elongation and widening of the proximal ovary improved its size, which passed to the proximal grain a volume advantage in the following ovary-grain transition, which allowed it to took up more sucrose and then converted into more starch and protein, improving dry matter accumulation and increasing proximal grain weight. Our findings provide a precise strategy for breeding and cultivation to increase individual grain weight potential by improving ovary volume.

Role of Ovarian Volume in Fertile and Infertile Women by Sonography at Swabi

Background: The measurement of ovarian volume via sonography is an important parameter in assessing ovarian aging and defining fertility potential in women. In the Swabi region, where advanced medical facilities are limited, measuring ovarian volume could be particularly useful for diagnosing fertility issues. This cross-sectional study investigates the relationship between ovarian size and female fertility among women in Swabi. Objective: To evaluate the role of ovarian volume in distinguishing between fertile and infertile women in the Swabi district using ultrasound. Methods: A cross-sectional study was conducted at the Department of Radiology, Mahaban Medical and Research Hospital, Swabi, Khyber-Pakhtunkhwa, Pakistan. A total of 101 participants were recruited from community health clinics using convenience sampling. Data on demographic characteristics, medical history, and menstrual cycle regularity were collected via standardized questionnaires. Ovarian dimensions were measured by trained personnel using transvaginal sonography (TVUS), which provided accurate and reproducible results. Descriptive statistics, including means, standard deviations, and percentages, were calculated for variables such as age, ovarian measurements, and fertility status. Cross-tabulation was used to classify participants based on fertility status and menstrual cycle regularity. Correlation tables were generated to examine the interrelationship between fertility status and cycle regularity. Data analysis was performed using the Statistical Software for Social Sciences (SPSS version 25.0). Results: The average age of participants was 28.52 years (SD = 5.08). The mean ovarian volumes for the right and left ovaries were 6.66 cm³ (SD = 3.28) and 7.46 cm³ (SD = 4.26), respectively. Among the participants, 62 were fertile, and 39 were infertile. Fertile participants had slightly higher mean ovarian measurements (right ovary: 6.90 cm³, left ovary: 7.19 cm³) compared to infertile participants (right ovary: 6.29 cm³, left ovary: 7.89 cm³). The regularity of menstrual cycles did not significantly differ between fertile and infertile women, with 31 fertile participants having regular cycles and 31 having irregular cycles. Conclusion: The study found that fertile women had slightly higher ovarian volumes compared to infertile women. However, menstrual cycle regularity did not differ significantly between the two groups. These findings suggest that while ovarian volume may be a useful indicator of fertility, menstrual cycle regularity alone is not a reliable predictor of fertility status in this cohort.

An Open Randomised Clinical Study to Evaluate the Combined Effect of Krishna Tila Kashayam and Shatapuspa Choornam in PCOS

PCOS has ovarian dysfunction along with hyperandrogenism and polycystic ovarian morphology. PCOS is a condition where involvement of Kapha dosha is present along with Vata dosha along with Rasa Dhatu, Medo dhatu and Arthava- the Upadhatu of Rasa is affected. Because of having the properties of Ushna virya, Kashaya Tiktha rasa, Arthava janana properties, Krishna Tila Kashayam and Shatapuspa choornam has been mentioned for the treatment of Arthava kshaya (anovulation and oligomenorrhea) in PCOS. The treatment is fully focused on Vata Kapha hara chikitsa and Arthava vardhaka. The drugs selected for the present study can be easily prepared and administered, cost effective. In this study, Tila kashayam along with Anupanam Gudam and Shatapuspa choornam along with Anupanam Madhu has been given and the results have been noted. In the present study, a total of 40 patients suffering from PCOS were selected from OPD and IPD of SJSACH. The thesis is widely focused on increasing the quantity of flow in amenorrhoea or oligomenorrhea cases, to check the size of the ovarian follicle before and after treatment and to check if there is any reduction in hair growth in hirsutism patients. There was a notable change seen in mild to moderate PCOS cases regarding the interval between 2 cycles, duration of flow between 2 cycles and quantity of flow between 2 cycles. There was a notable change seen in reduction of ovarian cyst volume before and after treatment. Hirsutism, BMI and waist circumference - there was no significant changes noted during these 3-month period.