Search Results (356)

The hallmark feature of empty follicle syndrome (EFS) is failure to retrieve oocytes from apparently mature follicles despite adequate ovarian stimulation and appropriate ovulation triggering. Although considered uncommon, with a reported prevalence ranging from 0.2% to 7%, EFS may have a profound clinical and psychological impact and can recur in assisted reproductive technology (ART) cycles. Modern classification systems divide EFS into genuine and false forms. Genuine EFS is potentially associated with intrinsic abnormalities involving luteinizing hormone/choriogonadotropin receptor (LHCGR) signaling, oocyte competence, and cumulus–oocyte interaction, whereas false EFS is primarily attributed to pharmacokinetic or pharmacodynamic factors resulting in inadequate trigger exposure. Borderline EFS represents a third phenotype characterized by incomplete or partial impairment of final oocyte maturation. This review examines the pharmacodynamics of ovulation-triggering agents, including human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) agonist protocols, and dual-trigger strategies, and their roles in regulating final oocyte maturation. The molecular aspects of periovulatory signal transduction and the mechanisms of LHCGR activation, epidermal growth factor (EGF)-like pathways, and meiotic resumption in relation to EFS etiopathogenesis will be described. The impact of patient-dependent conditions like obesity, poor ovarian reserve, polycystic ovary syndrome (PCOS), and pituitary response on trigger response will be assessed. New approaches like post-trigger monitoring of hormones and rescue treatment with gonadotropins represent a valuable method for avoiding cycle cancellation in patients at risk. Overall, EFS is increasingly regarded not as a single disorder but as a heterogeneous spectrum of periovulatory dysfunction arising from pharmacological, endocrine, and intrinsic ovarian factors that impair completion of final oocyte maturation. Full article

Background/Objectives: Fertility preservation is a key component of cancer care in women of reproductive age, and controlled ovarian stimulation (COS) followed by oocyte/embryo cryopreservation is considered the standard strategy. Although COS protocols are generally standardized, systemic effects related to different malignancies may interfere with ovarian reserve assessment and influence stimulation planning and counselling. This study aimed to evaluate COS outcomes across different malignancy types in women undergoing fertility preservation. Methods: This retrospective study included 331 oncological patients who underwent COS for fertility preservation at a single referral center between May 2008 and May 2025. Patients were stratified into three groups according to malignancy type: breast cancer, hematological malignancies, and other cancers. Ovarian reserve was assessed using serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). COS outcomes, including stimulation duration, total gonadotropin dose, number of retrieved and mature oocytes, follicular output rate (FORT), and follicle-to-oocyte index (FOI), were compared among groups. Results: Patients with hematological malignancies were significantly younger and showed higher AFC values compared with the other groups, whereas AMH levels did not differ significantly. After adjustment for age and AFC, patients with hematological malignancies showed significantly lower AMH levels compared with breast cancer patients (β = −0.94 ng/mL, 95% CI −1.40 to −0.48, p < 0.001), supporting the presence of a relative AMH–AFC discordance. In unadjusted analyses, gonadotropin requirements were higher in breast cancer patients, whereas the number of retrieved and mature oocytes was higher in patients with hematological malignancies. However, after adjustment for age and AFC, malignancy type was not independently associated with retrieved oocytes, mature oocytes, total gonadotropin dose, or stimulation duration. FORT and FOI were comparable among groups. Conclusions: Malignancy type did not appear to independently impair ovarian responsiveness to stimulation. Patients with hematological malignancies showed preserved stimulation outcomes despite AMH values not being proportionally higher than expected based on their younger age and higher AFC. These findings suggest that AMH should be interpreted with caution in systemic malignancies and that AFC may be particularly useful for tailoring fertility preservation counselling and stimulation strategies when AMH and AFC are discordant. Full article

Artificial intelligence (AI) technologies, which are being actively developed in modern medicine today, increase the speed and quality of patient care. This article mainly seeks to demonstrate the use of various options of computer analysis of clinical images to solve practical problems of increasing the efficiency of routine diagnostics using retrospective analysis, as well as show the potential for its widespread implementation (due to the scalability of the architecture) in practical healthcare, exemplified by ultrasound (US) and magnetic resonance imaging (MRI) data analysis. This is an interuniversity study, its research protocol was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the local Ethics Committee of Orel State University named after I. S. Turgenev (Protocol No. 25 dated 16 November 2022). The software was developed using Python 3.7 and open neural network models. Statistical processing included an efficiency assessment for which IBM SPSS Statistics 20.0 was used. Detection errors in the analysis of 550 US cases did not exceed 6–8% and were associated with technical difficulties due to image quality. When studying 1030 MRI studies, only 0.19% of cases failed to obtain reliable image analysis results. The differences in the average values for the dimensional characteristics of the studied vessels were 0.11–0.12 mm. The effectiveness of AI in clinical tasks is presented. The improvement in segmentation accuracy was achieved through the use of step-by-step image optimization during the AI training stage. The evolution of technologies in medicine, aimed at digitalization and personalization, is intended to improve the quality and speed of studying images in practical work. Full article

Background and Objectives: The aim of this study is to evaluate the effects of oridonin on a cisplatin-induced ovarian injury rat model. Materials and Methods: Thirty female rats were divided into three groups. Group 1: control; group 2: cisplatin; group 3: cisplatin plus oridonin group. In groups 2 and 3, the rats were injected with 2.5 mg/kg (twice weekly) cisplatin intraperitoneally (i.p.) for 4 weeks. In Group 3, rats received oridonin (10 mg/kg/day, i.p.). At the end of the study, the ovaries were removed in all groups. Histopathologic analysis and follicle counting were performed. Plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels were measured, while ovarian transforming growth factor-beta 1 (TGF-β1), SMAD family member 3 (SMAD3), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels were evaluated. Results: Oridonin alleviated cisplatin-induced histopathological changes in the ovarian tissue. The numbers of primordial, primary, secondary, and tertiary follicles were significantly decreased, while ovarian fibrosis was significantly increased in Group 2 compared with Group 1 (p < 0.05). Co-treatment with oridonin statistically significantly increased follicle counts at all developmental stages and markedly reduced ovarian fibrosis in group 2 compared with group 3. Compared with Group 1, AMH decreased, whereas MDA, TNF-α, TGF-β1, SMAD3, and TIMP-1 increased in Group 2 (p < 0.001); these alterations were markedly attenuated in Group 3. Conclusions: These findings suggest that oridonin may exert protective effects against cisplatin-induced ovarian injury. Full article

Background/Objectives: Shift work is a form of circadian dysregulation, which has been associated with adverse reproductive health outcomes. However, the association between circadian dysregulation and ovarian reserve remains uncertain. The present study examines whether shift work is associated with lower AMH levels in women seeking fertility treatment. Methods: This retrospective cohort study includes female patients aged 20–39 years presenting between February 2023 and June 2024. Patients were excluded if they had only one ovary, a current cancer diagnosis, or past chemotherapy use. Demographic and medical data were obtained from the electronic medical record. AMH levels were compared between daytime workers and shift workers. Results: A total of 1135 patients met inclusion criteria. The median age was 35 years (IQR 32–37). Of these, 89% (n = 1014) reported daytime work, and 11% (n = 121) reported shift work, comprising 102 working rotating shifts, seven working night shifts, and 12 working evening shifts. Daytime-only workers had a median AMH of 17.20 pmol/L (9.1–30.0). Combined shift workers had a median AMH of 17.10 pmol/L (8.1–31.0). There was no statistically significant difference in AMH levels between daytime workers and shift workers (p = 0.935). Although not significant, the odds of having low AMH levels (<7 pmol/L) were 25% higher among shift workers compared to daytime workers (OR 1.246, p = 0.345). Conclusions: In this cohort, AMH levels did not significantly differ between daytime and shift workers, offering reassurance to individuals required to engage in shift work. Future research should include larger cohorts and incorporate more comprehensive measures of circadian disruption. Full article

Granulosa cells (GCs), an element of the ovarian follicle, are crucial for oocyte maturation, folliculogenesis, and steroidogenesis. Granulosa cells play a crucial role in fertilization by providing metabolic and hormonal support to the oocyte, maintaining its quality and regulating its meiotic arrest. Oocyte quality and fertilization efficiency depend on the proper activity of GCs, especially their mutual communication, providing metabolic support and protecting against oxidative stress. When interrupted, they may take part in the pathogenesis of polycystic ovary syndrome, premature ovarian failure, primary ovarian insufficiency, and diminished ovarian reserve. GCs are enclosed in the antrum where they communicate with surrounding cells, create a dynamic microenvironment, and regulate hormone biosynthesis. To analyze molecular mechanisms regulating endogenous signaling, it is important to consider the dynamic transcriptomic response of porcine GCs during in vitro culturing over 48, 96, and 144 h. Transcriptomic analysis revealed a variable and dynamic transcriptional upregulation of genes associated with cellular response to endogenous and external stimuli, chemical compound metabolism, vascular development, and GCs migration. Also, proven by Gene Ontology (GO) enrichment analysis, the following terms were highlighted: “cellular response to chemical stimulus” and “cellular response to organic substance”. Specific genes, such as HSD3B1, POSTN, LOX, SERPINB2, ITGB3, ANKRD1, SLC1A1, and SFRP2, exhibited significant expression changes, suggesting extensive GCs self-regulation and metabolism changes. Further analysis indicates improvements in cellular response to a cytokine stimulus, growth factor response, hormone response, enzyme-linked receptor protein signaling, and positive regulation of cell migration. These findings suggest interweaving of regulatory mechanisms underlying intercellular communication in GCs during in vitro culturing, despite the lack of signals from the native ovarian environment. Further investigating interplays of detecting pathways will provide a more comprehensive understanding and even insights into the potential clinical use of the knowledge about the role of GCs in folliculogenesis, oocyte maturation and ovulation. Full article

Leptin (LEP) is an adipocyte-derived cytokine that integrates nutritional status, metabolism, and reproduction in cattle, with particular relevance for modern high-producing dairy cows. In ruminants, LEP and its receptors are widely expressed in metabolic and reproductive tissues, including adipose tissue, liver, hypothalamus, pituitary, ovary, uterus, and placenta, where LEP modulates energy homeostasis, neuroendocrine function, and local tissue responses. Changes in circulating LEP concentrations during the transition period reflect changes in body fat reserve, insulin and GH-IGF-1 dynamics, thyroid hormones, and inflammation and contribute to coordinated metabolic adaptations supporting the onset of lactation. At the reproductive level, LEP influences the hypothalamic–pituitary–gonadal axis, affects the pulsatility of luteinizing hormone (LH) under nutritional stress, and exerts direct effects on ovarian steroidogenesis, folliculogenesis, oocyte competence, embryo development, and uterine immune function. New evidence also links LEP profiles to major peripartum disorders, including subclinical ketosis, insulin resistance, postpartum ovarian inactivity, and uterine inflammatory diseases, and emphasises its potential as part of a panel evaluating the risk of metabolic and reproductive disorders. Furthermore, polymorphisms within the bovine LEP gene and its signalling network have been associated with milk production, feed efficiency, body condition, and fertility traits, suggesting opportunities to incorporate markers into genomic selection schemes aimed at improving robustness and reproductive performance. This review summarises current knowledge on LEP biology in cattle, with an emphasis on dairy cows, and discusses perspectives on translating this information into practical tools for nutritional management, health monitoring, and genetic improvement in bovine production systems. Full article

Advanced maternal age is a significant social and clinical issue associated with the natural decline in a woman’s ovarian reserve. This prospective, single-center study included women with primary infertility who presented to the Gyncentrum Clinic in Katowice and analyzed 77 ovarian follicles. The study group consisted of patients of advanced reproductive age with diminished ovarian reserve, who underwent hormonal stimulation in preparation for oocyte retrieval. Each metaphase II (MII) oocyte was fertilized in vitro and cultured individually in a time-lapse incubator. Follicular fluid obtained during oocyte retrieval was collected separately from each follicle and used for non-invasive biochemical analysis of prognostic factors using a Multiplex assay. The concentrations of interleukin 10 (IL-10), granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF), and C-type natriuretic peptide (CNP) were evaluated. The analysis showed that lower concentrations of GM-CSF and CNP were associated with an increased probability of oocyte fertilization, whereas higher levels of IL-10 and G-CSF had the greatest impact on blastocyst formation. This model was supported by continuous embryo monitoring. An eightfold increase in the likelihood of blastocyst formation was observed when early embryo cleavage occurred between 25 and 27 h after insemination. Furthermore, prolonged duration of the first cytokinesis reduced the probability of blastocyst development, while an extended cell cycle at the two-blastomere stage significantly affected further embryo development. These findings may support non-invasive embryo selection strategies. Full article

Background: Spermidine is involved in a wide range of cellular processes, including mammalian oocyte development. Wheat germ is a natural source of polyamines and contains high concentrations of spermidine. However, no studies have evaluated the effects of wheat germ-derived spermidine on the regulation of mammalian ovarian function. The present study aimed to investigate the effect and underlying mechanism of wheat germ-derived spermidine on mammalian ovarian function. Methods: A feeding trial was carried out on mice with diets supplemented with varying concentrations of spermidine. The underlying mechanism by which spermidine exerts its beneficial effects on ovarian function and fertility in mice was explored through the integration of serum metabolomics and intestinal microbiomics analyses. Results: The results showed that dietary spermidine-rich feed significantly increased spermidine absorption and affected the metabolism of spermine and putrescine in the intestines. Dietary intake of low-concentration spermidine significantly increased the number of pups per litter and the secretion levels of estradiol (E2), progesterone (P4), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Furthermore, compared with a normal diet, spermidine supplementation resulted in significantly higher ovarian reserves and fewer atretic follicles. Correspondingly, metabolomics analysis revealed that spermidine primarily affected lipid metabolism and endocrine functions related to reproduction. In addition, dietary spermidine significantly altered the structural composition of the gut microbiota. Correlation analysis demonstrated that the abundance of Oceanisphaera, Atopostipes, and Actinobacteriota was significantly positively correlated with the secretion of E2, P4, and LH. Conclusions: Overall, these findings yield phenotypic insights into spermidine’s mediation of mammalian reproductive performance and offer a potential therapeutic strategy for individuals with reproductive dysfunction. Full article

Introduction: Breast cancer is the most common malignancy in women of reproductive age, and treatment advances have heightened the importance of fertility preservation (FP) for young patients. Despite heterogeneity across subtypes—hormone receptor-positive (HR+), HER2-positive, triple-negative (TNBC), and BRCA1/2-associated—existing guidelines lack subtype-specific FP guidance. Methods: This systematic review compared FP strategies across subtypes, identified subtype-specific challenges, and proposed pathways toward precision oncofertility care. PubMed, Scopus, and Web of Science were searched following PRISMA guidelines for English-language studies from 2004 to 2024. Results: After screening 1837 records, 19 studies met eligibility criteria (2 RCTs, 17 cohort studies); 11 of 17 non-randomized studies were at low overall risk of bias, and 6 at moderate risk due to confounding. Discussion: COS using letrozole- or tamoxifen-modified protocols was feasible, yielding 8–14 mature oocytes per cycle with reduced estradiol exposure suitable for HR+ disease. Evidence was strongest for HR+ patients; TNBC and HER2+ data were more limited, with some studies noting reduced ovarian reserve. GnRH agonists during chemotherapy reduced ovarian failure rates and improved post-treatment recovery, most consistently in hormone receptor-negative disease. BRCA1/2 carriers showed broadly comparable FP outcomes to non-carriers, though BRCA1-positive patients had modestly reduced oocyte yields in some studies with inconsistent results. Conclusions: Among studies with medium-term follow-up (3–5.5 years), no significant increase in recurrence or mortality attributable to FP was identified; long-term data beyond 5 years remain sparse. Substantial heterogeneity precluded meta-analysis; all synthesis is narrative. Standardized outco reporting and larger prospective subtype-stratified studies are required to establish precision oncofertility recommendations. Full article

Background and Objectives: Numerous risk factors for both female and male fertility have been established including age, ovarian reserve, infertility cause, occupational and lifestyle factors. The objective of our study was to determine the influence of occupational and lifestyle factors on assisted reproduction (ART) outcomes at a Serbian referral tertiary center. Materials and Methods: The study included all consecutive infertile couples undergoing ART at the Clinic for Ob/Gyn University Clinical Center Belgrade, from January 2019 to January 2022. Inclusion criteria comprised primary and unexplained infertility, age ≤ 45 years, body mass index ≤ 30 kg/m² and undergoing fresh autologous ART cycles. All patients filled in the socio-epidemiological questionnaire that analyzed their lifestyle and habits. Medical history data and data regarding the current ART cycle were taken from patient records. The primary outcome was clinical pregnancy. Results: Our study included 501 couples (women and men) with infertility undergoing ART. Clinical pregnancy was achieved in 22.2% of examined patients. Achieving clinical pregnancy in the ART cycle for women was associated with younger age and use of vitamins, minerals, and trace elements, whereas younger age and absence of chronic illnesses were the most important factors for male partners. When women and men were assessed together as couples, achieving clinical pregnancy correlated only with the use of vitamins, minerals and trace-elements by both partners. Conclusions: This study confirmed that some occupational and lifestyle factors were associated with clinical pregnancy after ART in patients with unexplained primary infertility and normal BMI. Full article

Background and Objectives: The optimal oocyte yield in gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles remains debated, and data specific to antagonist protocols are limited. This study evaluated the discriminative and independent predictive performance of oocyte count for clinical pregnancy in GnRH antagonist IVF cycles. Materials and Methods: This retrospective cohort included 1171 women undergoing their first GnRH antagonist IVF cycle with fresh embryo transfer at a single tertiary center (September 2007–December 2021). The primary outcome was an institutional composite pregnancy outcome (sustained β-hCG positivity with subsequent ongoing intrauterine pregnancy or live birth; biochemical and ectopic pregnancies were negative). Patients were grouped by oocytes retrieved (1–5, 6–10, 11–15, ≥16). Performance was assessed with logistic regression, ROC with 2000-iteration bootstrap, integrated discrimination improvement (IDI), continuous net reclassification improvement (NRI), and restricted cubic spline. Predefined subgroup analyses by age, regimen, and antral follicle count tertile were performed. Results: A positive outcome occurred in 430 patients (36.7%). After adjustment, oocyte count was not an independent predictor (adjusted odds ratio 0.999, 95% CI 0.979–1.020; p = 0.96). The full model (AUC 0.564, 95% CI 0.529–0.598) did not outperform oocyte count alone (AUC 0.532; bootstrap p = 0.11). IDI (0.011) and NRI (0.135) were statistically detectable but clinically trivial. Spline regression showed no non-linearity (p = 0.47). Findings were consistent across subgroups, and the narrow confidence interval excluded per-oocyte effects ≥1.10. Conclusions: In GnRH antagonist IVF cycles, oocyte count showed weak discriminatory performance and was not independently associated with fresh-cycle pregnancy. Oocyte yield should be interpreted alongside—rather than as a substitute for—established parameters such as age and ovarian reserve. The principal clinical value of a higher oocyte response may lie in cumulative rather than fresh-cycle success. Live-birth outcomes were not available, and the source institution was permanently closed in 2025; these limitations define the boundary of inference. Full article

Background/Objective: Phoenixin (PNX), a recently identified neuropeptide, has been shown to regulate the hypothalamic–pituitary–gonadal axis and play a role in folliculogenesis and oocyte maturation. However, its clinical relevance in ovarian reserve remains unclear. This study aimed to evaluate the association between serum PNX-14 and PNX-20 levels and ovarian reserve and to determine whether these peptides provide additional information regarding ovarian reserve status in women with diminished ovarian reserve (DOR). Methods: This prospective case–control study included 160 women of reproductive age. Participants were categorized according to anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). Serum PNX-14 and PNX-20 levels were measured using ELISA. Statistical analyses included group comparisons, Spearman correlation, receiver operating characteristic (ROC) analysis, and logistic regression. Results: PNX-14 levels differed significantly across AMH-defined groups (p < 0.001), with higher levels observed in women with DOR. In contrast, PNX-20 levels showed no significant differences (p = 0.305). PNX-14 demonstrated excellent diagnostic performance for identifying DOR (AUC = 0.921), with a sensitivity of 78.7% and a specificity of 95.3% at a cut-off value of 183 pg/mL. A significant negative correlation was found between AMH and PNX-14 (r = −0.639, p < 0.001), whereas PNX-20 showed no significant correlation. In logistic regression analysis, PNX-14 was significantly associated with DOR in unadjusted and partially adjusted models; however, this association was attenuated after adjustment for AFC. Conclusions: PNX-14 is significantly associated with ovarian reserve status and may provide complementary information regarding DOR when interpreted alongside established ovarian reserve markers. In contrast, PNX-20 does not appear to have clinical utility in this context. Full article

In the female organism, Anti-Müllerian hormone (AMH) is produced exclusively by granulosa cells, particularly in secondary and early tertiary follicles. The amount of AMH released into the blood is proportional to the total number of follicles present in the ovaries and is therefore used to estimate the ovarian functional reserve. In both cattle and mares, a strong and highly repeatable association has also been demonstrated between AMH concentrations and antral follicle count. Therefore, AMH may serve as a biomarker with broad diagnostic utility in reproductive medicine in these species, as it reflects the functional ovarian reserve through its association with viable antral and preantral follicles. While AMH is already being used for clinical diagnostics in human reproductive medicine and has been extensively investigated, it has received little attention in applied veterinary practice so far. This review explores the applications of AMH for reproductive medicine in cattle and horses, monoovulatory farm animals in which assisted reproductive technologies are widely used. The objectives of this review are to (I) provide clinically relevant background information and a comparative discussion of (II) the role of AMH in follicular development, (III) its value as a fertility indicator, and (IV) its significance for embryo production in vivo and in vitro in cows and mares, with particular emphasis on practical relevance and potential applications. Full article

Background/Objectives: Bone and soft tissue sarcomas frequently affect children, adolescents, and young adults, yet data on chemotherapy-related ovarian reserve decline in this population remain limited. We aimed to characterize anti-Müllerian hormone (AMH) dynamics during treatment and identify factors associated with post-neoadjuvant chemotherapy (post-NACT) ovarian reserve. Methods: We conducted a retrospective, single-center, longitudinal cohort study of 85 female patients with bone and soft tissue sarcoma who underwent serial serum AMH testing during treatment. In the paired cohort with complete baseline and post-NACT AMH measurements (n = 75), post-NACT AMH was defined as the value obtained at the surgery/post-neoadjuvant time point after completion of NACT. Log-transformed multivariable linear modeling and left-censored Tobit regression sensitivity analysis were performed. Results: Median AMH declined from 3.46 ng/mL at baseline to 0.39 ng/mL after the first NACT cycle and to 0.15 ng/mL after the second cycle, corresponding to reductions of 88.7% and 95.7%, respectively. In the paired cohort, median AMH declined from 3.81 ng/mL to 0.19 ng/mL post NACT, with a median absolute decline of 2.75 ng/mL and a median percent decline of 94.4%. In the log-transformed multivariable linear model, log(baseline AMH) was the sole independent predictor of log(post-NACT AMH) (β = 0.735, 95% CI 0.357–1.114, p < 0.001). In Tobit sensitivity analysis, 4 post-NACT AMH values were treated as left-censored at 0.05 ng/mL, and the pattern remained consistent. Conclusions: Ovarian reserve depletion in female sarcoma patients occurred predominantly within the first one to two cycles of NACT. These findings support early, individualized fertility preservation counseling in this population. Full article