Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the critical role of ovarian fibrosis in maintaining the normal physiological function of the mammalian ovaries, research on this condition has been greatly underestimated, which leads to a lack of clinical treatment options for ovarian dysfunction caused by fibrosis. This review synthesizes recent research on the molecular mechanisms of ovarian fibrosis, encompassing TGF-β, extracellular matrix, inflammation, and other profibrotic factors contributing to abnormal ovarian fibrosis. Additionally, we summarize current treatment approaches for ovarian dysfunction targeting ovarian fibrosis, including antifibrotic drugs, stem cell transplantation, and exosomal therapies. The purpose of this review is to summarize the research progress on ovarian fibrosis and to propose potential therapeutic strategies targeting ovarian fibrosis for the treatment of ovarian dysfunction.

BACKGROUND: Ovarian enlargement is one of several findings of pathology, including ovarian torsion. With increasing use of MRI for acute abdominal pain in children, data for normal ovary size and appearance are needed.
OBJECTIVE: To provide preliminary data on normal sizes of ovaries on MRI in pediatric patients.
METHODS: This retrospective IRB-approved study included girls (5 to 17 years of age) with MRI examinations performed for indications not related to the ovaries from 2018 to 2022. For each MRI, coronal T2-weighted single shot fast spin echo and axial T2-weighted fat-saturated images were independently reviewed by three pediatric radiologists who recorded ovary visualization and ovarian linear measurements (3 planes). Ovarian volumes were calculated from linear measurements. Agreement among observers was calculated using kappa statistics and intraclass correlation coefficients.
RESULTS: A total of 181 MRIs were reviewed. The left ovary was visualized in 166-176 (92-97%) cases (R1-R3) and the right ovary was visualized in 165-174 (91-96%) cases with excellent agreement among reviewers (left: K = 0.89 [0.84-0.94], right: K = 0.85 [0.79-0.91]). Interrater class coefficient (ICC) for largest single dimension of the ovary was left: 0.83 (CI 0.79-0.87) and right: 0.85 (CI 0.81-0.89). There were significant moderate to strong correlations between ovarian volume and age (left: 0.67 [0.58-0.75], right: 0.66 [0.57-0.74]).
CONCLUSIONS: The ovaries can be adequately visualized and measured on MRI with excellent inter-reader agreement. This study serves as the foundation for developing normative values for ovarian volumes by age on MRI.

BACKGROUND: In the realm of in vitro fertilization (IVF), artificial intelligence (AI) models serve as invaluable tools for clinicians, offering predictive insights into ovarian stimulation outcomes. Predicting and understanding a patient\'s response to ovarian stimulation can help in personalizing doses of drugs, preventing adverse outcomes (eg, hyperstimulation), and improving the likelihood of successful fertilization and pregnancy. Given the pivotal role of accurate predictions in IVF procedures, it becomes important to investigate the landscape of AI models that are being used to predict the outcomes of ovarian stimulation.
OBJECTIVE: The objective of this review is to comprehensively examine the literature to explore the characteristics of AI models used for predicting ovarian stimulation outcomes in the context of IVF.
METHODS: A total of 6 electronic databases were searched for peer-reviewed literature published before August 2023, using the concepts of IVF and AI, along with their related terms. Records were independently screened by 2 reviewers against the eligibility criteria. The extracted data were then consolidated and presented through narrative synthesis.
RESULTS: Upon reviewing 1348 articles, 30 met the predetermined inclusion criteria. The literature primarily focused on the number of oocytes retrieved as the main predicted outcome. Microscopy images stood out as the primary ground truth reference. The reviewed studies also highlighted that the most frequently adopted stimulation protocol was the gonadotropin-releasing hormone (GnRH) antagonist. In terms of using trigger medication, human chorionic gonadotropin (hCG) was the most commonly selected option. Among the machine learning techniques, the favored choice was the support vector machine. As for the validation of AI algorithms, the hold-out cross-validation method was the most prevalent. The area under the curve was highlighted as the primary evaluation metric. The literature exhibited a wide variation in the number of features used for AI algorithm development, ranging from 2 to 28,054 features. Data were mostly sourced from patient demographics, followed by laboratory data, specifically hormonal levels. Notably, the vast majority of studies were restricted to a single infertility clinic and exclusively relied on nonpublic data sets.
CONCLUSIONS: These insights highlight an urgent need to diversify data sources and explore varied AI techniques for improved prediction accuracy and generalizability of AI models for the prediction of ovarian stimulation outcomes. Future research should prioritize multiclinic collaborations and consider leveraging public data sets, aiming for more precise AI-driven predictions that ultimately boost patient care and IVF success rates.

OBJECTIVE: We present an Egyptian study on pediatric ovarian immature teratomas (ITs), aiming to clarify our treatment strategy selection.
METHODS: A retrospective review of all children with pure ovarian ITs who were treated at our institution between 2008 and 2023. The analysis included clinical characteristics, tumor staging according to Children\'s Oncology Group (COG), grading based on the Norris system, management, and outcomes.
RESULTS: Thirty-two patients were included, with a median age of 9 years. All patients underwent primary surgery. Unilateral salpingo-oophorectomy was performed in 31 patients. Surgical staging was completed in all patients. Based on COG staging, there were 28 patients (87.5%) stage I, 1 (3%) stage II, and 3 (9.5%) stage III. According to Norris classification, 16 patients (50%) were classified as grade I, 9 (28%) grade II, and 7 (22%) grade III. All patients in stage I were treated using surgery-alone approach, whereas the remaining four (12.5%) received adjuvant chemotherapy. Five patients in stage I had gliomatosis peritonei (GP), and none of them underwent extensive surgery. At a median follow-up of 86 months, two patients had events. The first patient (stage III/grade I) developed IT relapse on the operative bed, and the second (stage I/grade I) had a metachronous IT on the contralateral ovary. Both patients were successfully managed with surgery followed by second-line chemotherapy. Five-year overall survival and event-free survival for all patients were 100% and 93.4%, respectively.
CONCLUSIONS: Surgery-alone strategy with close follow-up achieves excellent outcomes for localized ovarian ITs in children, irrespective of the Norris grading or the presence of GP. However, adjuvant chemotherapy is questionable for patients with incompletely resected or locally advanced tumors, and its role requires further evaluation through prospective multicentric studies with a larger sample size.

Studies find long-lived proteins are prevalent in the organs.

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by abnormal steroid hormone levels in peripheral blood and poor-quality oocytes. In the ovary, androgen is produced by theca cells, and estrogen is produced by granulosa cells. Androgen is converted to estrogen in granulosa cells, with cytochrome P450 aromatase as the limiting enzyme during this process. Estrogen receptors (ER) include ER alpha, ER beta, and membrane receptor GPR30. Studies have demonstrated that the abnormal functions of estrogen and its receptors and estradiol synthesis-related enzymes are closely related to PCOS. In recent years, some estrogen-related drugs have made significant progress in clinical application for subfertility with PCOS, such as letrozole and clomiphene. This article will elaborate on the recent advances in PCOS caused by abnormal expression of estrogen and its receptors and the application of related targeted small molecule drugs in clinical research and treatment.

Betamethasone has been extensively used in medicine in recent years and poses potential hazards to aquatic organisms. This study investigated the reproductive toxic effects of betamethasone exposure in fish, employing female Japanese medaka (Oryzias latipes) as a model. Betamethasone exposure at environmentally relevant concentrations (0, 20, 200, and 2000 ng/L) for a period of 15 weeks resulted in its high accumulation in the ovary, leading to abnormal oogenesis in female Japanese medaka. The production of gonadotropins (LH and FSH) in the pituitary gland was inhibited, and sex steroid biosynthesis in the ovary was significantly influenced at the transcriptional level. The imbalance of androgens and estrogens resulted in a decrease in the E2/T ratio and hepatic VTG synthesis, and the suppression of estrogen receptor signaling was also induced. Furthermore, betamethasone exposure delayed spawning and reduced fertility in the F0 generation, and had detrimental effects on the fertilization rate and hatchability of the F1 generation. Our results showed that environmental betamethasone had the potential to adversely affect female fertility and steroid hormone dynamics in fish.

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464.

BACKGROUND: Adiposity profoundly impacts reproductive health in both humans and animals. However, the precise subpopulations contributing to infertility under obese conditions remain elusive.
RESULTS: In this study, we established an obese mouse model through an eighteen-week high-fat diet regimen in adult female mice. Employing single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive single-cell atlas of ovarian tissues from these mice to scrutinize the impact of obesity on the ovarian microenvironment. ScRNA-seq revealed notable alterations in the microenvironment of ovarian tissues in obese mice. Granulosa cells, stromal cells, T cells, and macrophages exhibited functional imbalances compared to the control group. We observed heightened interaction strength in the SPP1-CD44 pairing within lgfbp7+ granulosa cell subtypes and Il1bhigh monocyte subtypes in the ovarian tissues of obese mice. Moreover, the interaction strength between Il1bhigh monocyte subtypes and Pdgfrb+ stromal cell subtypes in the form of TNF - TNFrsf1α interaction was also enhanced subsequently to obesity, potentially contributing to ovarian fibrosis pathogenesis.
CONCLUSIONS: We propose a model wherein granulosa cells secrete SPP1 to activate monocytes, subsequently triggering TNF-α secretion by monocytes, thereby activating stromal cells and ultimately leading to the development of ovarian fibrosis. Intervening in this process may represent a promising avenue for improving clinical outcomes in fertility treatments for obese women.

Ovaries play a crucial role in the regulation of numerous essential processes that occur within the intricate framework of female physiology. They are entrusted with the responsibility of both generating a new life and orchestrating a delicate hormonal symphony. Understanding their functioning is crucial for gaining insight into the complexities of reproduction, health, and fertility. In addition, ovaries secrete hormones that are crucial for both secondary sexual characteristics and the maintenance of overall health. A three-dimensional (3D) prosthetic ovary has the potential to restore ovarian function and preserve fertility in younger females who have undergone ovariectomies or are afflicted with ovarian malfunction. Clinical studies have not yet commenced, and the production of 3D ovarian tissue for human implantation is still in the research phase. The main challenges faced while creating a 3D ovary for in vivo implantation include sustenance of ovarian follicles, achieving vascular infiltration into the host tissue, and restoring hormone circulation. The complex ovarian microenvironment that is compartmentalized and rigid makes the biomimicking of the 3D ovary challenging in terms of biomaterial selection and bioink composition. The successful restoration of these properties in animal models has led to expectations for the development of human ovaries for implantation. This review article summarizes and evaluates the optimal 3D models of ovarian structures and their safety and efficacy concerns to provide concrete suggestions for future research.