János Zádori

Gene expression plays a fundamental role in defining the characteristics of living organisms. To deepen our understanding of tissue-specific gene expression, we analyzed transcript variant enrichment across different tissues in human and Drosophila melanogaster. Datasets are widely accessible for both of these organisms. Given the substantial volume of available information, we have focused our interest on three fundamentally distinct tissues: the brain, where both neuronal and glial cells exhibit a relatively high cellular surface area, thus requiring a large amount of lipids; the adipose tissue, which is well-known for lipid storage; and the testis, which contains a massive number of developing spermatids with high membrane requirement. These three organs have fundamental differences in their structure and function yet share some common features; they all have lipid-rich cells and have special metabolic pathways. Most studies focus on gene expression, and transcript level analyses are less common; therefore, we aimed to characterize the transcript profiles of these tissues and examine evolutionarily conserved pathways between humans and Drosophila. Additionally, we analyzed the flanking sequences of transcriptional start sites of tissue-enriched transcripts. Our findings suggest that Drosophila tissues exhibit more distinct regulation of gene expression in individual tissues (weaker correlation in expression and variable nucleotide content in core promoter), whereas human gene expression is more generalized, likely relying more heavily on distal regulatory elements for tissue-specific expression. Through network analysis, summarizing tissue specificity, physical interactions, and orthologue data, we identified shared central pathways among these tissues. A relatively large network was observable in the testis, where the ubiquitin proteasome system, various kinases and transcription factors showed central position in both organisms. Additionally, we highlighted the evolutionary potential of highly enriched testis-specific transcripts. This work provides valuable insights into the mechanisms underlying tissue-specific gene expression and evolutionary conservation.

Objectives: We aimed to develop and validate a per-cycle prediction model for in vitro fertilization (IVF) success using only preprocedural clinical variables available at the first consultation. Methods: We retrospectively analysed 1243 IVF/ICSI cycles (University of Szeged, 21 January 2022–12 December 2023). An Extreme Gradient Boosting (XGBoost version 1.7.7.1) classifier was trained on 14 baseline predictors (e.g., female age, AMH, BMI, FSH, LH, sperm concentration/motility, and infertility duration). A parsimonious 9-variable model was derived by feature importance. Model performance was assessed on the untouched test set and, as a final step, on an independent same-centre external validation cohort (n = 92) without re-fitting or recalibration. Results: The 9-variable model achieved an AUC of 0.876 on the internal test set, with an accuracy of 81.70% (95% CI 76.30–86.30%), sensitivity of 75.60%, specificity of 84.40%, PPV of 68.60%, and NPV of 88.50%. In external validation, the model maintained strong performance with an accuracy of 78.30%, confirming consistent discrimination on an independent same-centre cohort. Female age was the dominant high-impact feature, while AMH and BMI acted as “workhorse” predictors, and male factors added incremental value. Conclusions: IVF outcome can be predicted at the first visit using routinely collected preprocedural data. The model showed consistent discrimination internally and in external validation, supporting its potential utility for early, individualized counselling and treatment planning.

Objectives: Our aim is to report an uncommon pituitary activation occurring during the desensitization phase of the gonadotropin-releasing hormone agonist (GnRHa) long protocol, a cornerstone of medically assisted reproduction (MAR) therapy, in a young woman. Results: We present a case of a 33-year-old female patient with secondary infertility, who exhibited a prolonged and asynchronous follicular development during ovarian stimulation using the GnRH antagonist protocol. Therefore, during a repeat attempt, the long GnRH agonist protocol was employed. Surprisingly, rather than achieving suppression with the agonist, ultrasound detected many large follicles in both ovaries, accompanied by extremely elevated estrogen levels, indicating imminent ovarian hyperstimulation syndrome (OHSS). This unusual phenomenon was also observed during a subsequent attempt using the long protocol in another reproductive center. As part of the work-up to identify the underlying etiology, contrast-enhanced magnetic resonance imaging (MRI) of the sella turcica was performed, which revealed an 11 × 13 × 10 mm pituitary macroadenoma without evidence of pathological hormone secretion. The luteinizing hormone-releasing hormone (LHRH) stimulation test showed a normal luteinizing hormone and follicle-stimulating hormone response. Other abnormalities of the hypothalamo–hypophyseal–target-organ axis were not found. Neurosurgical intervention was deemed unnecessary; radiological follow-up of the lesion was recommended. Conclusions: In this case, the clinical presentation was markedly different from the expected suppressive effects of GnRH agonist therapy, with profoundly elevated estrogen levels and clinical signs of imminent OHSS. Notably, hypersensitivity of the adenohypophysis was not demonstrated following a single physiological LHRH stimulation test. However, the presence of a pituitary adenoma identified on MRI raises the possibility that gonadotropin receptor function was altered by the lesion—an effect revealed only after repeated GnRH agonist exposure, resulting in a paradoxical stimulatory response.

Background: Thyroid disorders, particularly thyroid autoimmunity, are increasingly prevalent among women of reproductive age and have been linked to fertility outcomes. While current endocrinology guidelines define distinct thyroid-stimulating hormone (TSH) target values for women undergoing assisted reproductive technology (ART), the optimal preconception TSH range for in vitro fertilization (IVF) success remains a topic of debate. Objectives: This study aimed to assess the impact of baseline TSH levels within the recommended normal range on IVF outcomes, specifically clinical pregnancy and live birth rates. Additionally, we assessed the predictive value of procedural and preprocedural factors, including maternal body mass index (BMI) and TSH, using machine learning models. Methods: We conducted a retrospective, single-center cohort study at the Institute of Reproductive Medicine, University of Szeged, involving 996 women who underwent IVF, with or without intracytoplasmic sperm injection. Biometric, medical history, laboratory, and procedural factors were analyzed. Pregnancy and live birth predictions were modeled using support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost) algorithms. The significance of features in the RF and XGBoost models was assessed. Results: SVM models achieved a mean accuracy of 72.26% in predicting pregnancy but were less effective for live birth classification. RF and XGBoost models demonstrated an area under the receiver operating characteristic curve of 0.76 and 0.74 for pregnancy and 0.67 and 0.61, respectively, for live birth. Key predictors included embryo score, maternal age, BMI, and specific hormone levels. Notably, male factors also contributed to outcome prediction. Analysis suggested that variations in maternal TSH within the normal range (0.3–4.0 mIU/L) had no significant impact on IVF success. Conclusions: Our study suggests that preconception TSH levels within the reference range do not significantly influence IVF success, which indirectly supports the validity of the current recommendations on this matter. While machine learning models demonstrated promising predictive performance, larger prospective studies are needed to refine thyroid function targets in ART, with a separate analysis of women with thyroid autoimmunity.

Introduction: While tubal occlusion is a prevalent cause of infertility, accounting for 11–35% of infertility cases among women, there remains a limited understanding of the factors influencing clinical pregnancy following in vitro fertilization (IVF). Methods: In our retrospective, cross-sectional cohort study conducted at a single tertiary center, medical records of women aged 19 to 43 years were analyzed. Logistic regression models were employed to identify the prognostic factors associated with clinical pregnancy after IVF in patients with tubal factor infertility, excluding cases with hydrosalpinx. Results: Data from 219 women diagnosed with tubal occlusion were compared to 1140 cases with non-tubal indication, covering a total of 1359 IVF cycles. A lower maternal age (adjusted odds ratio [AOR]: 0.89, p = 0.001) and a higher embryo quality (AOR: 1.26, p = 0.01) emerged as important factors in clinical pregnancy in the tubal infertility group. Moreover, a lower maternal (AOR:0.91, p < 0.01) and paternal age (p = 0.001), and favorable semen quality (AOR: 1.32, p = 0.03) were critical determinants in the non-tubal infertility group. BMI was generally higher in tubal infertility patients (p = 0.01). Furthermore, FSH level (AOR: 0.93, p = 0.004), AMH level (p < 0.04), number of embryos transferred (AOR: 2.04, p < 0.001), and embryo quality (AOR: 1.26, p < 0.001) came into prominence only in the non-tubal infertility group. The clinical pregnancy rate (34.2%) of women with tubal occlusion did not differ significantly from those in other forms of infertility undergoing IVF (35.4%). Conclusions: Although tubal infertility is typically anticipated to yield the highest clinical pregnancy rates following IVF, it is crucial to acknowledge that both maternal and paternal characteristics can also significantly impact the outcomes.

Numerous diseases can arise as a consequence of mitochondrial malfunction. Hence, there is a significant focus on studying the role of mitochondria in cancer, ageing, neurodegenerative diseases, and the field of developmental biology. Mitochondria could exist as discrete organelles in the cell; however, they have the ability to fuse, resulting in the formation of interconnected reticular structures. The dynamic changes between these forms correlate with mitochondrial function and mitochondrial health, and consequently, there is a significant scientific interest in uncovering the specific molecular constituents that govern these transitions. Moreover, the specialized mitochondria display a wide array of variable morphologies in their cristae formations. These inner mitochondrial structures are closely associated with the specific functions performed by the mitochondria. In multiple cases, the presence of mitochondrial dysfunction has been linked to male sterility, as it has been observed to cause a range of abnormal spermatogenesis and sperm phenotypes in different species. This review aims to elucidate the dynamic alterations and functions of mitochondria in germ cell development during the spermatogenesis of Drosophila melanogaster.