Search Results (269)

Background: Asprosin is a relatively recently discovered glucogenic adipokine secreted during fasting that plays an important role in various biochemical processes in the body, including those connected with obesity and insulin resistance. The aim of this exploratory study was to investigate the associations between selected hormonal, anthropometric, and lifestyle-related parameters and serum asprosin concentration. As studies concerning fertility and asprosin have so far been limited to men or women with PCOS, its role in the general female population remains largely unexplored. The direction of this exploration was thus pointed toward possible connections with female fertility. Methods: The case-control study group included 56 women of reproductive age (25–42 years), who were patients of the Reproductive Health Clinic and the Clinic of Endocrinology, Diabetology, and Internal Medicine of the Medical University of Białystok, Poland. The levels of selected hormones, including anti-Müllerian hormone (AMH), estradiol, sex hormone-binding globulin (SHBG), and testosterone, body composition parameters, and a lifestyle parameter—night fasting duration—were assessed to test their associations with serum asprosin concentration. Results: A weak negative correlation was found between AMH level and serum asprosin concentration, suggesting a potential link between asprosin and ovarian reserve. Furthermore, a moderate positive correlation was found between the percentage of total body water (TBW) and serum asprosin concentration. No significant associations were observed between the levels of the other tested hormones and serum asprosin concentration, or between body composition parameters or night fasting duration and serum asprosin concentration. The multivariate model designed in the study shows that AMH, TBW, and night fasting duration explain 23.4% of asprosin variability. Conclusions: Although the nature of the study is exploratory, the findings indicate that the role of asprosin in the female population—particularly its role in fertility—requires further research. Not only is the number of available studies on asprosin insufficient, but the results of this study partly contradict what is known about the hormone from previous studies, which were largely performed with male cohorts. In addition, the results of this study suggest that asprosin may indeed be involved in mechanisms related to female fertility, particularly those connected with ovarian reserve. Nevertheless, studies performed in larger, more homogeneous populations are necessary to confirm the role of asprosin in women, including its association with female fertility. Full article

Organ functions generally decline with age, but the ovary is a prototypical organ that undergoes functional loss over time. Autophagy plays a crucial role in maintaining organ homeostasis, and age-related upregulation of the autophagy inhibitor protein, Rubicon, has been linked to cellular and tissue dysfunction. This review describes how granulosa cell autophagy supports follicular growth and oocyte selection and maturation by regulating cellular energy metabolism and protein quality control. We then introduce the role of selective autophagy, including mitophagy or lipophagy, in steroidogenesis and cellular remodeling during luteinization. In aged ovaries, Rubicon accumulation suppresses autophagic flux, leading to diminished oxidative-stress resilience and enhanced DNA damage. Moreover, impaired autophagy drives the accumulation of ATP citrate lyase, which correlates with poor oocyte quality and reduced ovarian reserve. Following fertilization, oocytes further upregulate autophagy to provide the energy required for blastocyst transition. Conversely, in infertility-related disorders, such as premature ovarian insufficiency, endometriosis, and polycystic ovary syndrome, either deficient or excessive autophagy contributes to disease pathogenesis. Both autophagy inhibitors (e.g., Rubicon) and activators (e.g., Beclin1) could be emerging as promising biomarkers for assessing ovarian autophagy status. Therapeutically, Rubicon inhibition by trehalose in aged ovaries and autophagy suppression by agents such as hydroxychloroquine in polycystic ovary syndrome and endometriosis hold potential. Establishing robust methods to evaluate ovarian autophagy will be essential for translating these insights into targeted treatments. Full article

Background: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO₃⁻) and nitrite (NO₂⁻) may indicate real-time follicular function during IVF. Methods: In this prospective study, we included 89 women who underwent controlled ovarian stimulation. The Griess test was used to measure NO₂-NO₃ concentrations in follicular fluid collected on the day of oocyte retrieval. Non-parametric and correlation tests were used to investigate the associations between oocyte yield, maturity (MII), fertilization (2PN), embryo development, and hormone levels. Results: Higher NO₂-NO₃ levels were substantially associated with increased total oocyte count, MII oocytes (p = 0.014), and 2PN embryos (p = 0.029). This suggests a strong relationship between NO bioavailability and oocyte competence. NO₂-NO₃ levels showed a positive correlation with estradiol (p < 0.001) and progesterone (p < 0.001), suggesting a possible function in granulosa cell steroidogenesis. Conclusions: Follicular NO metabolites are candidate functional indicators for oocyte quality evaluation and intrafollicular steroidogenic activity. Their predictive value may improve customized IVF treatment, especially in individuals with complicated ovarian phenotypes such as PCOS or decreased ovarian reserve. Full article

Background: Systemic sclerosis is a systemic autoimmune disease that also impacts women’s health in very different ways. Methods: This review summarises the most important data on sexuality, fertility, pregnancy, and menopause from the last 10 years. Findings: We identified nine articles with data on sexuality and a prevalence of sexual dysfunction varying between 46 and 90%. Fertility was examined in six studies, with evidence for a negative influence at least on ovarian reserve. With regard to menopause, only three studies are mentioned that show an increased risk for premature menopause in SSc women. Although pregnancies are rare in SSc women after disease onset, there is growing evidence that pregnancies are feasible but go along with a higher maternal and foetal risk compared to healthy controls. Interpretation: SSc is dominated by female gender, but aspects of women’s health influenced by the disease are still often ignored. The treating physician should be aware of the mostly negative impact on sexuality, fertility, and pregnancy and address these topics with the patients to adapt treatment and follow-up examinations to the patients’ complaints and life situation. Full article

Urolithin A, which is a natural gut microbial metabolite, exerts multiple beneficial effects upon supplementation, including prolonging lifespan, mitigating diseases, restoring the quality of aged oocytes and alleviating drug toxicity. The study aims to investigate the ovarian protective role of Urolithin A using a neonatal mouse ovarian in vitro culture and chemotherapy model, with a particular focus on its mechanisms for inhibiting primordial follicle activation and mitigating cyclophosphamide (CY) or 4-hydroperoxy (4-HC)-induced follicle apoptosis. The results showed that Urolithin A significantly decreased the number of growing follicles and downregulated the expression of oocyte growth-related genes (Gdf9 and Zp3) and protein (DDX4), as well as Ki-67 and BrdU-positive signals. Further studies revealed that Urolithin A significantly downregulated the levels of phosphorylated Akt and FOXO3a and decreased the percentage of oocytes with FOXO3a nuclear export. Molecular docking showed a strong binding ability between Urolithin A and its downregulated gene Pik3cg. Moreover, Urolithin A significantly decreased CY- and 4-HC-induced increases in cleaved Caspase-3- and PARP1-positive signals. Meanwhile, RNA-seq analysis indicated that Urolithin A significantly downregulated CY-induced expression of DNA damage-related genes (Trp73 and Trim29). In short, Urolithin A inhibits primordial follicle activation by reducing PI3K/Akt signaling reactivity. Furthermore, Urolithin A prevents CY-induced follicle apoptosis. The study provides valuable insights into Urolithin A treatment for chemotherapy-induced infertility. Full article

Background: Hashimoto’s thyroiditis (HT), the most prevalent autoimmune thyroid disorder in reproductive-age women, has been linked to diminished ovarian reserve and subfertility. This study aimed to evaluate the relationship between HT and key fertility parameters, including hormonal markers and reproductive outcomes, while also exploring the potential impact of thyroid hormone replacement therapy. Methods: A retrospective observational study was conducted on 86 women undergoing fertility evaluation. Participants were divided into two groups based on anti-thyroid peroxidase antibodies (ATPO): the HT group (n = 49) and the control group (n = 37). Among women with HT, 57% were receiving levothyroxine (Euthyrox^®) at the time of assessment. Variables analyzed included serum levels of anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), insulin resistance index (HOMA-IR), number of oocytes retrieved, blastocysts formed, pregnancies achieved, and live births. Statistical methods included t-tests, Mann–Whitney U tests, Pearson/Spearman correlations, and linear regression models. Results: Women in the HT group had slightly lower AMH levels and oocyte counts compared to controls, though these differences did not reach statistical significance. TSH values were higher in the HT group and showed a significant negative correlation with blastocyst formation (p = 0.03). Although TSH also showed negative trends with oocyte count, pregnancies, and live births, these correlations did not reach statistical significance. A post-hoc subgroup analysis revealed that HT patients receiving levothyroxine tended to have higher numbers of oocytes retrieved and blastocysts formed compared to untreated HT patients, suggesting a possible beneficial effect of thyroid hormone replacement, although the differences were not statistically significant. Conclusions: HT is associated with subtle but clinically relevant impairments in ovarian reserve and reproductive potential. Thyroid hormone replacement may offer modest benefits and should be considered in the individualized management of fertility in women with thyroid autoimmunity. Full article

Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED. Full article

Background/Objectives: The anti-Müllerian hormone (AMH) is a key biomarker of the ovarian reserve, correlating with ovarian follicle count, fertility outcomes, and menopause timing. Understanding its genetic determinants has broad implications for female reproductive health. However, prior genome-wide association studies (GWASs) have focused exclusively on women of European ancestry, limiting insights into diverse populations. Methods: We conducted a GWAS to identify genetic loci associated with circulating AMH levels in a sample of 1185 Samoan women from two independently recruited samples. Using a Cox mixed-effects model we accounted for AMH levels below detectable limits and meta-analysed the summary statistics using a fixed-effect model. To prioritize variants and genes, we used FUMA and performed colocalization and transcriptome-wide association analysis (TWAS). We also assessed whether any previously reported loci were replicated in our GWAS. Results: We identified eleven genome-wide suggestive loci, with the strongest signal at ARID3A (19-946163-G-C; p = 2.32 × 10⁻⁷) and replicated rs10093345 near EIF4EBP1. The gene-based testing revealed ARID3A and R3HDM4 as significant genes. Integrating GWAS results with expression quantitative trait loci via TWAS, we detected seven transcriptome-wide significant genes. The lead variant in ARID3A is in high linkage disequilibrium (r² = 0.79) with the known age-at-menopause variant 19-950694-G-A. Nearby KISS1R is a biologically plausible candidate gene that encodes the kisspeptin receptor, a regulator of ovarian follicle development linked to AMH levels. Conclusions: This study expands our understandings of AMH genetics by focusing on Samoan women. While these findings may be particularly relevant to Pacific Islanders, they hold broader implications for reproductive phenotypes such as the ovarian reserve, menopause timing, and polycystic ovary syndrome. Full article

Background/Objectives: As the population of women with endometriosis increases, approximately 10% of those of reproductive age experience symptoms such as pelvic pain, painful menstruation, and infertility. Individuals with endometriosis usually undergo multiple surgeries due to the high recurrence rate of the condition. However, ovarian surgery tends to reduce the ovarian reserve, presenting a dilemma when deciding whether to recommend surgery or medical treatment for women of reproductive age. The impact of endometriomas on the residual volume of ovarian tissue remains controversial, and it is unclear whether endometriosis itself or endometriomas are the primary problem. In this study, we aimed to investigate whether women with endometriosis have lower levels of anti-Müllerian hormone than women with healthy ovaries before treatment initiation. Methods: A total of 298 participants enrolled in the endometriosis cohort at Severance Hospital, Korea, from 1 October 2020 to 1 July 2024 were included in this study. Of these, 63 participants were from a retrospective study, and 235 were from a prospective study. Due to the use of different assay methods between the reference values and anti-Müllerian hormone measurements from Severance Hospital, a correction was applied using the regression equation. The mean anti-Müllerian hormone levels for individuals with endometriosis were corrected with the regression equation and compared to those of the reference group for each age group using a one-sample t-test. Results: Anti-Müllerian hormone levels decreased with age in the endometriosis group. When comparing mean anti-Müllerian hormone concentrations between the endometriosis group and reference values, among 168 participants aged 20–31 years, the corrected mean anti-Müllerian hormone concentration was 5.96 ± 3.22 ng/mL, higher than the reference value of 4.94 ± 0.17 ng/mL (p < 0.01). Among 31 participants aged 35–37 years, the corrected average anti-Müllerian hormone value was 4.33 ± 3.06 ng/mL, compared to the reference anti-Müllerian hormone level of 3.22 ± 0.15 ng/mL (p = 0.05). There were no significant differences in corrected anti-Müllerian hormone levels between the 32–34-, 38–40-, 41–43-, and ≥44 years age groups. Conclusions: Patients with endometriosis, especially those aged 20–31 years, tended to have higher anti-Müllerian hormone levels than did individuals with healthy ovaries. In other age groups, there were no differences. Given that these levels do not differ significantly across age groups, it is difficult to conclude that patients with endometriosis have a reduced ovarian reserve. Full article

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with the endocrine system by mimicking or blocking the action of endogenous hormones such as estrogens, androgens, and thyroid hormones. This systematic review aims to evaluate the current epidemiological evidence linking EDC exposure with adverse reproductive outcomes in males and females of reproductive age. A total of 14 observational studies published between 2014 and 2024 were included following structured searches in PubMed, Scopus, and Google Scholar. The most commonly studied EDCs included bisphenol A (BPA), its analogs (such as bisphenol S, BPS), phthalates, parabens, per- and polyfluoroalkyl substances (PFAS), and persistent organic pollutants (POPs). The review found consistent associations between EDC exposure and multiple reproductive endpoints, such as impaired semen quality, decreased ovarian reserve, infertility, polycystic ovary syndrome (PCOS), altered hormone levels—specifically estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)—and adverse outcomes in assisted reproductive technologies (ART), including in vitro fertilization (IVF). Despite methodological heterogeneity, the findings support the biological plausibility of EDCs in disrupting reproductive function. The review highlights the urgent need for regulatory measures, increased public awareness, and longitudinal studies to assess the cumulative effects of chronic EDC exposure on human fertility. Full article

Ovarian cancer (OC) is the most lethal gynecological cancer globally. Its incidence and mortality consistently rise after menopause. While parity reduces the risk of OC, nulliparity during a woman’s fertile years increases it. Although the association between reproductive history and OC risk is well-established, the long-term impact of pregnancy on the postmenopausal human ovary has received little to no attention. Parity apparently delays the natural decline of the ovarian reserve, but this association also remains unexplored to date. Based on data from cellular, biochemical, and histological markers, as well as epidemiological studies, transcriptomic analyses, and gene knockout mouse models, we review compelling evidence suggesting a critical intraovarian interplay between the residual ovarian reserve and the ovarian surface epithelium (OSE) in the aged ovary. This interaction appears to be a key factor underlying the protective effect of parity on ovarian cancer (OC) risk. We propose that functional FSHR signaling in the remnant follicles of the aged multiparous ovary somehow counteracts the oxidative stress and subsequent chronic inflammation typically observed in the senescent ovary. This mechanism would minimize DNA damage, thereby lowering the probability of neoplastic transformation in the aged mammalian ovary. The precise mechanism by which pregnancy imprints such a long-term follicle–OSE crosstalk warrants further investigation. Full article

Proteases play crucial roles in ovarian folliculogenesis, regulating several processes from primordial follicle activation to ovulation and corpus luteum formation. This review synthesizes the current knowledge on the diverse functions of proteases in ovarian physiology and pathology. We discuss the classification and regulation of proteases, highlighting their importance in extracellular matrix remodeling, cell signaling, and apoptosis during ovarian follicular development. We explore the roles of several proteases including matrix metalloproteinases, tissue inhibitors of metalloproteinases, the plasminogen activator system, and cathepsins, and their roles in the critical functions of ovarian biology including follicle dynamics and senescence. Furthermore, we address the involvement of proteases in ovarian pathologies, including cancer, polycystic ovary syndrome, and primary ovarian insufficiency. By integrating recent findings from clinical genomics and animal models, this review provides a comprehensive overview of protease functions in the ovary, emphasizing their potential use for therapeutic interventions in reproductive medicine. Full article

Hashimoto’s thyroiditis is the most prevalent autoimmune thyroid disorder, and it disproportionately affects women of reproductive age. Its impact on fertility and assisted reproductive technologies [ART] has become an area of growing clinical interest. Thyroid autoimmunity can influence female reproductive health through multiple interconnected mechanisms, including subtle thyroid hormone imbalances, reduced ovarian reserve, altered endometrial receptivity, and dysregulated immune responses. Subclinical hypothyroidism and the presence of anti-thyroid antibodies have been linked to increased miscarriage risk and reduced success rates in ART, particularly in intracytoplasmic sperm injection (ICSI) cycles. Although levothyroxine supplementation is widely used, its benefits in euthyroid women remain uncertain. Recent studies suggest that gut microbiota may modulate immune function and affect fertility outcomes among women with autoimmune thyroid conditions. This narrative review synthesizes findings from a broad literature base of over 40 peer-reviewed publications published between 2010 and 2025, with 30 of the most relevant and methodologically robust studies selected for detailed analysis. The review integrates clinical, endocrine, immunological, and microbiome-related perspectives. The evidence supports the need for personalized fertility management in women with Hashimoto’s thyroiditis and highlights directions for future research into immune and microbiota-targeted therapies. Full article

Granulosa cell (GC) dysfunction contributes to diminished ovarian reserve (DOR). We collected GC and follicular fluid samples from the patients of normal ovarian reserve (NOR) and DOR. RNA-seq of GCs showed that cholesterol/sterol metabolism and biosynthesis and extracellular matrix organization were enriched in the DOR group. Metabolomics of follicular fluid revealed enrichment in steroid hormone biosynthesis, tryptophan metabolism, and fatty acid β-oxidation in DOR. The apoptosis rate was increased, whereas the proliferative rate was decreased in GCs of DOR. The Prussian blue staining rate was increased whilst GPX4 and SLC7A11 expression were downregulated in GCs of DOR. Mitochondrial morphology displayed the features of ferroptosis in GCs of DOR. FSHR, CYP19A1, NR5A1, and phosphorylated CREB levels were substantially downregulated in GCs, accompanied by increased androgen levels in follicular fluids in DOR. The key factors linked to the mevalonate pathway, HMGCR, SQLE, and SREBF2, were robustly increased in DOR. FSHR and NR5A1 levels were correlated with CYP19A1 levels, whilst CYP19A1 levels were positively correlated with GPX4 and SLC7A11 levels. Our findings indicate ferroptosis and dysregulation of cholesterol/sterol metabolism and biosynthesis occurrence in GCs of DOR, which might be associated with reduced FSHR signaling and decreased conversion of androgen to estrogen. Full article

We investigated whether FMR1 allelic complexity—integrating CGG repeat length with the number and pattern of AGG interspersions—can be used as a predictor of ovarian reserve and in vitro fertilization (IVF) success. This cohort study included 124 females with infertility attributed to female factors undergoing intracytoplasmic sperm injection (ICSI). The total CGG repeat lengths and AGG interspersion patterns of the FMR1 gene were determined by conventional polymerase chain reaction (PCR) and triplet-primed PCR. The allelic complexity (allelic score) was calculated using a previously described formula by combining the allelic scores, allowing for the stratification of samples into equivalent and dissimilar groups. No statistically significant differences were observed in ovarian reserve markers or overall IVF outcomes between the two groups. However, within the dissimilar group, the allelic score of allele 1 was significantly correlated with the number of both injected metaphase II and two-pronuclei oocytes. These findings suggest that FMR1 allelic complexity may contribute to predicting IVF success, particularly in females classified in the dissimilar group, who appear more susceptible to IVF failure than those in the equivalent group. Further research into the predictive utility of FMR1 could provide valuable insights for fertility assessment and enhance assisted reproductive technologies. Full article