Sperm Quality in 1252 Adolescents and Young Adults (AYAs) Undergoing Fertility Preservation Due to Cancer or Nonmalignant Diseases.

Purpose: To investigate the quality of emergency-collected semen samples aimed at sperm cryopreservation provided by adolescents and young adults (AYAs) presenting with cancer or nonmalignant diseases. Methods: This is a prospective cohort study of postpubertal males referred for sperm cryopreservation who provided at least one semen sample for fertility preservation at the Reproductive Medicine Clinic of Karolinska University Hospital, Stockholm, Sweden, between January 2009 and January 2020. Sperm quality was assessed by total sperm count, concentration, and motility. Sperm quality by disease groups was compared with the reference population data of fertile men defined by the World Health Organization (WHO). Results: Among the 1252 patients who provided samples for cryopreservation, 1063 had cancer and 189 had nonmalignant diseases. The most common malignant indications included testicular cancers (n = 501) and Hodgkin lymphoma (n = 102). Among those with nonmalignant disease, 35% (n = 66) had testicular disease. Sperm quality was significantly lower in all groups of patients with cancer compared with the reference population. In total, azoospermia was found in 8% of the patients with cancer, in 9% of those with nonmalignant testicular disease, and in 3% of the remaining men with nonmalignant disease. Conclusion: Sperm quality in adult patients with cancer was significantly impaired compared with the WHO reference population standards for fertile men. For adolescent patients, standard reference values are lacking. AYAs wishing to preserve fertility should receive individualized counseling regarding sperm quality at the time of cryopreservation, and in selected cases, banking of additional samples should be recommended depending on the sperm quality parameters.

Budd Chiari Syndrome: Radiological Aspects of the Disease Pertaining to Infertility and Role of Interventional Radiology in Successful Conception.

Background/Aims: To study the association of infertility in patients with Budd Chiari syndrome, radiological aspects of the disease determining infertility and to see if there are improved chances of conception following radiological intervention. Methods: Retrospective search of the hospital records was done and patients with Budd Chiari syndrome, who underwent radiological intervention between January 2016 till October 2021 were initially included. Patients outside the reproductive age group, unmarried patients, patients who did not attempt conception or attempted for less than 1 year and patients having other causes of infertility were excluded. 90 patients were assessed for presence of primary or secondary infertility using infertility questionnaire. In patients with infertility, conception during 1-year follow-up period following radiological intervention, was assessed. Results: 146 patients underwent radiological intervention for Budd Chiari syndrome in the study period. 56 patients meeting the exclusion criteria were excluded from the study and subsequently 90 patients were assessed for infertility. 16.7% (15/90) of our patients with Budd Chiari syndrome had infertility, of which 7 were male, and 8 were female. Infertility is more common in younger age group (mean - 28.8 ± 4.2 years) (P < 0.001). In females, presence of pelvic venous congestion on preprocedural imaging showed significant association with infertility (P < 0.001). 6 (40%) out of 15 of patients with infertility conceived during a 1-year follow-up period after radiological intervention. Conclusion: Infertility is a common in patients with Budd Chiari syndrome, with a prevalence of 16.7%. Pelvic venous congestion is associated with women having infertility. Radiological interventions play important role in management of Budd Chiari and may help to overcome infertility in these patients.

Relationship Between Lipid Profile and Body Mass Index in Patients With Polycystic Ovarian Syndrome: A Cross-Sectional Study Among Indian Women of Reproductive Age.

Introduction Characterized by a range of symptoms including irregular menstrual cycles, hirsutism, and infertility, polycystic ovarian syndrome (PCOS) also poses substantial metabolic challenges. Among these, dyslipidemia and obesity are particularly concerning due to their long-term implications for cardiovascular health. The present study explores the intricate relationship between lipid profile and body mass index (BMI) in patients with PCOS presenting to the Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, a tertiary care teaching hospital in Northern India. Methods The present work involves analysis of clinical characteristics of 230 premenopausal women between 18-45 years of age diagnosed with PCOS (according to Rotterdam Criteria). Patients with conditions such as congenital adrenal hyperplasia; Cushing's syndrome; uncontrolled hypertension, smoking, hypogonadism; using oral contraceptives; pregnant or lactating mothers; smoking or drug addiction; psychiatric illness; and those diagnosed with androgen-secreting tumors were excluded. For each participant, data was collected pertaining to demographics (age, marital status), clinical presentation, height, and weight (for BMI calculation), and total lipid profile comprising of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). The patients were stratified according to their BMI as per the WHO Asian classification, and Pearson's correlation coefficient was calculated to see the correlation between lipid profile and BMI. Results The final analysis was done on 228 patients, with a mean age of 25.22 (±4.82) years, and 45.6% were currently married. Among the participants, 28.1% of the participants were overweight, and 42.5% of them classified as obese, while the remaining 29.4% had a BMI in the normal range. The mean (SD) total cholesterol was 172.26 (49.55) mg/dl, and 65 patients (28.5%) had elevated serum cholesterol (≥200 mg/dl). Triglycerides were raised (≥ 150 mg/dl) in a majority of the study participants (n=160, 70.2%). While none of the patients had high VLDL-C, LDL-C was elevated in 52 patients (22.8%). HDL-C levels were lower than the threshold value of 50 mg/dl in 152 participants (66.7%). On performing correlation analysis, a significant negative correlation was noted between HDL-C and BMI in the entire study cohort (r=-0.342, p=0.003). Overweight patients exhibited a statistically significant positive correlation between triglycerides and BMI (r=2.628, p=0.002). Participants with BMI in the overweight range demonstrated statistically significant correlations with HDL-C (r=-0.497, p=0.017) and triglycerides (r=2.628, p=0.002); and BMI of obese patients significantly correlated with total cholesterol (r=0.301, p=0.037) and triglycerides (r=0.146, p=0.028). Conclusion The findings of the study underscore the multifaceted nature of PCOS, affecting reproductive health as well as metabolic components. The significant correlations between BMI and lipid parameters, specifically, HDL-C, triglycerides, and total cholesterol, highlight the importance of weight management in reducing cardiovascular risks in women with PCOS.

Comparison of Adding Sildenafil Versus Estradiol to Clomiphene Citrate on the Applebaum Score and Pregnancy Rate in Patients With Unexplained Infertility: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Both sildenafil and estradiol are seen to improve endometrial thickness in patients with infertility who are undergoing clomiphene induction cycles. However, the correlation between endometrial thickness and pregnancy rate is debatable. This study investigated the effect of adding oral sildenafil to clomiphene citrate (CC), compared to adding estradiol valerate, on the uterine biophysical profile (Applebaum score) and pregnancy rate. METHODS: This was a double-blinded, randomized controlled trial conducted in Kisangani in the Democratic Republic of the Congo from October 1, 2021, to October 31, 2023. Patients with unexplained infertility were randomly assigned to one of two groups: the interventional, which was given CC (2 x 50 mg/day from day 3 to day 7 of the menstrual cycle) + sildenafil (2 x 25 mg/day orally from day 8 to day 12) or (ii) the control group, which was given CC (similar dosage as the intervention group) + EV (2 x 2 mg/day orally from day 8 to day 12), for a maximum of three cycles. Applebaum scores and clinical pregnancy rates were measured. RESULTS: Patients in the sildenafil and EV groups were similar in mean age (29.04 versus 28.89 years). Of the 74 patients enrolled in each group, 71 in the sildenafil group and 72 in the EV group received treatment and were followed to completion. The Applebaum scores were significantly higher in the sildenafil group than in the EV group (17.05 versus 15.14, respectively, P=0.000). In the sildenafil group, the clinical pregnancy rate was also significantly higher, at 28.92% versus 20.83% in the EV group (P = 0.04). CONCLUSION: As compared to EV, the oral addition of sildenafil to CC is associated with a good Applebaum score and a high rate of clinical pregnancy in patients with unexplained infertility.

Association of rs4588 polymorphism in vitamin D binding protein gene with polycystic ovarian syndrome in Iranian women: a case-control study.

OBJECTIVE: Vitamin D deficiency and variations in the vitamin D binding protein (VDBP) gene may play a role in the development of Polycystic ovary syndrome (PCOS). This study aims to investigate the association of the rs4588 polymorphism with PCOS in Iranian women, as well as its association with infertility and recurrent pregnancy loss (RPL) in these patients. RESULTS: The analysis revealed statistically significant differences in the distributions of genotypes and alleles of the rs4588 polymorphism among the three groups (p < 0.0001). The AC genotype and A allele showed an association with an elevated risk of PCOS and infertility. In this study, no association was found between genotypes and alleles of the rs4588 polymorphism and the risk of RPL in women with PCOS. Subjects with the AA or AC genotype exhibited significantly higher levels of LDL compared to those with the CC genotype.

The effect of supportive counseling on self-esteem of infertile women after in vitro fertilization (IVF) failure: a randomized controlled trial study.

BACKGROUND: The unsuccessful treatment of infertility can lead to heightened levels of negative emotions, which are often associated with various psychological consequences. These consequences may include a decrease in self-confidence, feelings of loneliness, reduced self-esteem, and even discontinuation of treatment. Therefore, it is crucial to implement interventions that can help improve these consequences for women who have experienced IVF failure. The present study aimed to examine the effect of supportive counseling on self-esteem of infertile women after IVF failure. METHODS: this randomized clinical trial study was conducted on 63 infertile women after IVF failure, referred to Milad Infertility Center in Mashhad in 2021. In the intervention group, the researcher provided individual supportive counseling sessions. These sessions took place over a span of four weeks, with each session lasting 60 min (One session every week). Data collection was conducted both before and one month after the study using Eysenck self-esteem Questionnaire. Data were analyzed using SPSS25, as well as statistical tests such as chi-square, independent t-test, Paired t-test and Mann-Whitney tests. A significance level of less than 5% was considered. RESULTS: The study found no significant difference in mean scores of self-esteem between the two groups before the study (p = 0.823). However, after one month, the intervention group had significantly higher self-esteem scores (24.3 ± 18.55) compared to the control group (21.74 ± 5.62) (p = 0.043) Moreover, Based on the Within-group comparison, there was a 2.43 ± 3.24 point increase in self-esteem scores of the intervention group after one month, while the control group showed a -0.33 ± 3.72 point decrease. CONCLUSION: Supportive counseling was found to be effective in improving self-esteem following IVF failure. As a result, it can be recommended as an effective, affordable, and low-risk counseling approach for women who have experienced IVF failure. By offering supportive counseling, it is possible to help prevent and alleviate the psychological consequences associated with IVF failure. TRIAL REGISTRATION: This research project was registered at the Iranian Registry of Clinical Trials with code IRCT20210407050883N1- Date of registration 2021-05-25.

In Vitro Generation of Haploid Germ Cells from Human XY and XXY Immature Testes in a 3D Organoid System.

Increasing survival rates of children following cancer treatment have resulted in a significant population of adult survivors with the common side effect of infertility. Additionally, the availability of genetic testing has identified Klinefelter syndrome (classic 47,XXY) as the cause of future male infertility for a significant number of prepubertal patients. This study explores new spermatogonia stem cell (SSC)-based fertility therapies to meet the needs of these patients. Testicular cells were isolated from cryopreserved human testes tissue stored from XY and XXY prepubertal patients and propagated in a two-dimensional culture. Cells were then incorporated into a 3D human testicular organoid (HTO) system. During a 3-week culture period, HTOs maintained their structure, viability, and metabolic activity. Cell-specific PCR and flow cytometry markers identified undifferentiated spermatogonia, Sertoli, Leydig, and peritubular cells within the HTOs. Testosterone was produced by the HTOs both with and without hCG stimulation. Upregulation of postmeiotic germ cell markers was detected after 23 days in culture. Fluorescence in situ hybridization (FISH) of chromosomes X, Y, and 18 identified haploid cells in the in vitro differentiated HTOs. Thus, 3D HTOs were successfully generated from isolated immature human testicular cells from both euploid (XY) and Klinefelter (XXY) patients, supporting androgen production and germ cell differentiation in vitro.

Elucidating the Transcriptional States of Spermatogenesis-Joint Analysis of Germline and Supporting Cell, Mice and Human, Normal and Perturbed, Bulk and Single-Cell RNA-Seq.

In studying the molecular underpinning of spermatogenesis, we expect to understand the fundamental biological processes better and potentially identify genes that may lead to novel diagnostic and therapeutic strategies toward precision medicine in male infertility. In this review, we emphasized our perspective that the path forward necessitates integrative studies that rely on complementary approaches and types of data. To comprehensively analyze spermatogenesis, this review proposes four axes of integration. First, spanning the analysis of spermatogenesis in the healthy state alongside pathologies. Second, the experimental analysis of model systems (in which we can deploy treatments and perturbations) alongside human data. Third, the phenotype is measured alongside its underlying molecular profiles using known markers augmented with unbiased profiles. Finally, the testicular cells are studied as ecosystems, analyzing the germ cells alongside the states observed in the supporting somatic cells. Recently, the study of spermatogenesis has been advancing using single-cell RNA sequencing, where scientists have uncovered the unique stages of germ cell development in mice, revealing new regulators of spermatogenesis and previously unknown cell subtypes in the testis. An in-depth analysis of meiotic and postmeiotic stages led to the discovery of marker genes for spermatogonia, Sertoli and Leydig cells and further elucidated all the other germline and somatic cells in the testis microenvironment in normal and pathogenic conditions. The outcome of an integrative analysis of spermatogenesis using advanced molecular profiling technologies such as scRNA-seq has already propelled our biological understanding, with additional studies expected to have clinical implications for the study of male fertility. By uncovering new genes and pathways involved in abnormal spermatogenesis, we may gain insights into subfertility or sterility.

Effects of Systolic Blood Pressure Elevation on Internal Sperm Artery Identification During Microsurgical Subinguinal Varicocelectomy.

Microsurgical subinguinal varicocelectomy (MSV) is the gold standard for treating varicoceles. Preservation of the internal spermatic arteries (ISAs) during MSV is important for sperm production. This study aimed to evaluate the safety and efficacy of elevating systolic blood pressure (SBP) using MSV. Data from 252 consecutive adult male patients were retrospectively reviewed. The patients were divided into two groups: a traditional group that underwent conventional MSV (n = 134) and a modified group that underwent MSV with a transiently elevated SBP of 140-160 mm Hg (n = 118). Arterial identification time, unilateral operative time, number of ISAs, arterial injury rate, and other postoperative indicators, including postoperative complications and sperm parameters, were compared between the groups. All the procedures were successful. The arterial identification and unilateral operative times were significantly shorter in the modified group (31.34 ± 10.44 vs. 42.94 ± 12.39 min and 61.48 ± 8.78 vs. 76.35 ± 12.33 min, p < .01, respectively). Intraoperatively, the number of preserved ISAs was significantly higher in the modified group (1.92 ± 0.53 vs. 1.45 ± 0.32, p < .01). The arterial injury rate did not differ significantly between the groups (2.74% vs. 0%, respectively). Compared with preoperative values, sperm parameters improved significantly 6 months postoperatively. Significant differences in semen parameters or postoperative complications were not observed between the groups. Elevated intraoperative SBP can be used to rapidly, safely, and effectively identify ISAs, increase the number of retained spermatic arteries, and markedly reduce the operative time for MSV.

KIT in oocytes: a key factor for oocyte survival and reproductive lifespan.

BACKGROUND: The KITL-KIT interaction is known as an important initiator in oocyte activation through the downstream pathway of PI3K-AKT-FOXO3 signalling. Previous studies utilising germ cell-specific Kit mutant knockin and kinase domain knockout models with Vasa-Cre suggested the crucial role of KIT in oocyte activation at the primordial follicle stage. METHODS: We utilised mice with complete postnatal deletion of KIT expression in oocytes via Gdf9-iCre and conducted analyses on ovarian follicle development, specific markers, hormone assays, and fertility outcomes. FINDINGS: Our findings reveal contrasting phenotypes compared to previous mouse models with prenatal deletion of Kit. Specifically, postnatal deletion of Kit exhibit no defects in germ cell nest breakdown, follicle activation, and folliculogenesis during development. Remarkably, upon reaching full maturity, mice with postnatal deletion of Kit experience a complete loss of ovarian reserve, growing follicles, and ovarian function. Furthermore, mice display smaller ovarian size and weight, delayed folliculogenesis, and phenotypes indicative of primary ovarian insufficiency (POI), including elevated serum levels of FSH, reduced AMH, and absence of ovarian follicles, ultimately resulting in infertility. Additionally, the ovaries exhibit randomly distributed expression of granulosa and theca cell markers such as Inhibin α, ACVR2B, and LHR. Notably, there is the uncontrolled expression of p-SMAD3 and Ki67 throughout the ovarian sections, along with the widespread presence of luteinised stroma cells and cleaved Caspase-3-positive dying cells. INTERPRETATION: These genetic studies underscore the indispensable role of KIT in oocytes for maintaining the survival of ovarian follicles and ensuring the reproductive lifespan. FUNDING: This work was supported by National Institutes of Health grant R01HD096042 and startup funds from UNMC (S.Y.K.).

Female Reproductive Endocrine Disorders.

This article is a summary of normal menstrual bleeding and how to recognize abnormalities based on patient's symptoms as well as identify possible causes in order to direct treatment. This article discusses abnormal uterine bleeding including the definition, etiology, evaluation, and treatment. It also discusses primary ovarian insufficiency, transgender medicine, and menopause.

The influence of assisted reproductive technologies-related stressors and social support on perceived stress and depression.

BACKGROUND: While assisted reproductive technologies (ART) have helped many people experiencing infertility become pregnant, the ART process can take a psychological toll. This study examined whether and how perceived stress- and depression-related symptoms vary among individuals at different stages of the infertility and ART process, and whether ART-specific stressors and emotional support are associated with mental health symptomatology. METHODS: Data were collected using an online REDCap survey administered between July 2021 and March 2022. The survey was administered to 240 participants who had experienced infertility, including those who had not yet accessed ART, those undergoing ART but who were not yet pregnant, those currently pregnant through ART, and those who had given birth in the last year through ART. Each participant completed the Cohen Perceived Stress Scale (range 0-40) and the Edinburgh Depression Scale (range 0-30). Participants who had undergone ART were asked about their experience of ART-specific stressors and how helpful partner and provider support had been during the ART process. Survey data were analyzed using ANOVA and multivariate linear regressions. RESULTS: 88% of participants reported medium or high levels of perceived stress, and 43.8% of respondents showed probable indications of depression. Perceived stress and depression symptoms were significantly higher for individuals currently undergoing, but not yet pregnant from, ART treatments. These effect sizes were substantial; for example, depression scores in this group were five points higher than among currently pregnant individuals and nine points higher than among postpartum individuals. For the subset of participants who had used or were currently undergoing ART (N = 221), perceived social stigma and the physical and time demands of ART were significantly associated with higher stress and depression symptoms, while partner emotional support was associated with lower perceived stress. CONCLUSIONS: The ART process exacerbates perceived stress and depression symptoms among individuals experiencing infertility. Given the potential long-term impacts on both parent and child wellbeing, clinicians and policymaking groups, including the American Society for Reproductive Medicine (ASRM), should consider making access to mental health services a standard of care during infertility treatment.

Clusterin expression and distribution in spermatozoa as predictor of male fertility.

Clusterin (CLU), one of the main glycoproteins in mammalian semen and the male reproductive tract, plays a role in spermatogenesis and sperm maturation. Given the poor reliability of classic seminal studies in determining male-fertilizing capacity and the differences in CLU abundance between normal and abnormal spermatozoa, we investigated the potential value of mRNA-CLU levels and protein distribution in spermatozoa as markers of sperm quality and predictors of male fertility. This multicenter study included 90 patients undergoing in vitro fertilization (IVF) treatment with their partners, and a control group of 36 fertile males with normal seminograms. We assessed the relationship between IVF treatment outcomes, seminogram variables, mRNA-CLU levels by quantitative real-time-PCR and CLU distribution by immunostaining in spermatozoa. Our study reveals CLU staining in the acrosome (p = 0.002, OR 14.8, 95% CI: 2.7-79.3) and mRNA-CLU levels (p = 0.005, OR 10.85, 95% CI: 2.0-57.4) as independent risk factors for pregnancy failure, irrespective of traditional seminogram variables. Additionally, our results suggest that CLU, and specially its secreted isoform, constitutes a component of the protein pool that human spermatozoa can produce during its maturation process, exhibiting a variable abundance and distribution in spermatozoa from fertile men compared to those in patients with altered seminograms and infertile patients with normal seminograms. Our study is the first to identify mRNA-CLU levels and CLU immunostaining in the spermatozoa acrosome as independent risk factors for pregnancy failure, with distribution patterns correlating with sperm maturity and seminogram alterations.

Behind the Genetics: The Role of Epigenetics in Infertility-Related Testicular Dysfunction.

In recent decades, we have witnessed a progressive decline in male fertility. This is partly related to the increased prevalence of chronic diseases (e.g., obesity and diabetes mellitus) and risky lifestyle behaviors. These conditions alter male fertility through various non-genetic mechanisms. However, there is increasing evidence that they are also capable of causing sperm epigenetic alterations, which, in turn, can cause infertility. Furthermore, these modifications could be transmitted to offspring, altering their general and reproductive health. Therefore, these epigenetic modifications could represent one of the causes of the progressive decline in sperm count recorded in recent decades. This review focuses on highlighting epigenetic modifications at the sperm level induced by non-genetic causes of infertility. In detail, the effects on DNA methylation, histone modifications, and the expression profiles of non-coding RNAs are evaluated. Finally, a focus on the risk of transgenerational inheritance is presented. Our narrative review aims to demonstrate how certain conditions can alter gene expression, potentially leading to the transmission of anomalies to future generations. It emphasizes the importance of the early detection and treatment of reversible conditions (such as obesity and varicocele) and the modification of risky lifestyle behaviors. Addressing these issues is crucial for individual health, in preserving fertility, and in ensuring the well-being of future generations.

Reply to Abid et al. Comment on "Asir et al. Investigation of Vitamin D Levels in Men with Suspected Infertility. Life 2024, 14, 273".

In response to the insightful comments made by Dr. Abid et al. on our article "Investigation of Vitamin D Levels in Men with Suspected Infertility", we address several key points concerning the generalizability and methodology of our study. Dr. Abid et al.'s critique primarily focused on the single-center nature of our research, regional variations in ultraviolet (UV) exposure, dietary factors affecting vitamin D levels, and the sample size of our study. We discuss the inherent value and controlled environment of single-center studies while acknowledging the need for multi-center validation. Additionally, we explain our consideration of sun exposure and dietary intake in our analysis, and recognize the importance of larger, more diverse studies to strengthen our findings. Our response aims to clarify these aspects and emphasize the significance of vitamin D in male infertility, encouraging further research in this field.

Advanced Sperm Selection Techniques for Assisted Reproduction.

Male infertility accounts for approximately 40% of infertility cases. There are many causes of male infertility, including environmental factors, age, lifestyle, infections, varicocele, and cancerous pathologies. Severe oligozoospermia, cryptozoospermia, and azoospermia (obstructive and non-obstructive) are identified as severe male factor infertility, once considered conditions of sterility. Today, in vitro fertilization (IVF) techniques are the only treatment strategy in cases of male factor infertility for which new methodologies have been developed in the manipulation of spermatozoa to achieve fertilization and increase success rates. This review is an update of in vitro manipulation techniques, in particular sperm selection, emphasizing clinical case-specific methodology. The success of an IVF process is related to infertility diagnosis, appropriate choice of treatment, and effective sperm preparation and selection. In fact, selecting the best spermatozoa to guarantee an optimal paternal heritage means increasing the blastulation, implantation, ongoing pregnancy and live birth rates, resulting in the greater success of IVF techniques.

Robotic Living Donor Hysterectomy for Uterus Transplantation: An Update on Donor and Recipient Outcomes.

Background/Objectives: Uterus transplantation (UTx) has evolved into a clinical reality for women with absolute uterine infertility. The international experience with UTx has predominantly utilized living donor grafts-and strategies to minimize harm to donors remain paramount. Robotic living donor hysterectomy represents a minimally invasive approach to facilitate rapid donor recovery, improve pelvic visualization and operative access, and maintain UTx recipient outcomes. The aim of this study is to describe donor, recipient, graft, and pregnancy outcomes after adoption of a robotic living donor hysterectomy program. Methods: The Dallas UtErus Transplant Study (DUETS) incorporated a robotic living donor hysterectomy operative protocol, including transvaginal extraction, from April 2019. Prospectively collected data were analyzed, and a case series presented, to describe donor intra- and post-operative outcomes and recipient intra-operative outcomes, graft viability, established pregnancies, and live births. Early cases were compared to later cases to better describe the learning curve associated with the technique. Results: Sixteen robotic living donor hysterectomies were performed with 100% graft viability after implantation demonstrated by myometrial flow and onset of menses. Early experience (eight cases) demonstrated two cases of ureteric injury. Later experience (eight cases) demonstrated a reduction in operative time (11 h 10 min vs. 6 h 38 min), with no ureteric injuries and a reduction in major operative morbidity from 25% to 12.5% (Clavien-Dindo grade ≥3). At the time of reporting, nine successful live births have occurred, with six ongoing pregnancies. Conclusions: Robotic living donor hysterectomy represents a safe approach to minimize donor harm without compromising UTx recipient, graft, and pregnancy-related outcomes. A learning curve is demonstrated with the adoption of the novel technique-with particularly care required to prevent ureteric injuries, and ongoing vigilance and reporting necessary given the small case numbers of robotic living donor hysterectomy reported internationally.

Metabolic Dysfunction-Associated Steatotic Liver Disease and Polycystic Ovary Syndrome: A Complex Interplay.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) are prevalent conditions that have been correlated with infertility through overlapped pathophysiological mechanisms. MASLD is associated with metabolic syndrome and is considered among the major causes of chronic liver disease, while PCOS, which is characterized by ovulatory dysfunction and hyperandrogenism, is one of the leading causes of female infertility. The pathophysiological links between PCOS and MASLD have not yet been fully elucidated, with insulin resistance, hyperandrogenemia, obesity, and dyslipidemia being among the key pathways that contribute to liver lipid accumulation, inflammation, and fibrosis, aggravating liver dysfunction. On the other hand, MASLD exacerbates insulin resistance and metabolic dysregulation in women with PCOS, creating a vicious cycle of disease progression. Understanding the intricate relationship between MASLD and PCOS is crucial to improving clinical management, while collaborative efforts between different medical specialties are essential to optimize fertility and liver health outcomes in individuals with MASLD and PCOS. In this review, we summarize the complex interplay between MASLD and PCOS, highlighting the importance of increasing clinical attention to the prevention, diagnosis, and treatment of both entities.

Genetic Insights into Azoospermia and Severe Oligozoospermia: Discovering Seven SNPs through GWAS and In Silico Analysis.

Azoospermia and severe oligozoospermia represent the most extreme forms of male infertility. Despite their prevalence, the genetic foundations of these conditions are not well understood, with only a limited number of genetic factors identified so far. This study aimed to identify single-nucleotide polymorphisms (SNPs) linked to both azoospermia and severe oligozoospermia. We conducted a genome-wide association study (GWAS) involving 280 Greek males with normal semen parameters and 85 Greek males diagnosed with either azoospermia or severe oligozoospermia. Following rigorous quality control measures, our analysis identified seven SNPs associated with azoospermia/severe oligozoospermia. An in silico functional annotation was subsequently used to further investigate their role. These SNPs, found in regions not previously associated with male reproductive disorders, suggest novel genetic pathways that may contribute to these forms of infertility and pave the way for future studies. Additionally, this study sheds light on the significant role of noncoding RNAs in the pathogenesis of male infertility, with three of the identified SNPs situated in long intergenic non-coding RNAs (lincRNAs). Our findings highlight the intricate genetic landscape of azoospermia and severe oligozoospermia, underlining the necessity for more detailed studies to fully grasp the underlying mechanisms and their potential for informing diagnostic and therapeutic strategies.

Assessing the Efficacy of Acanthoic Acid Isolated from Acanthopanax koreanum Nakai in Male Infertility: An In Vivo and In Silico Approach.

Acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum Nakai, possesses diverse pharmacological activities, including anti-inflammatory, anti-diabetic, gastrointestinal protection, and cardiovascular protection. This study is the first to investigate the egg-hatching rates of Drosophila melanogaster affected by acanthoic acid. Notably, male flies supplemented with 10 µM acanthoic acid exhibited a strong increase in hatching rates compared with controls under adverse temperature conditions, suggesting a potential protective effect against environmental stressors. Molecular docking simulations revealed the binding affinities and specific interactions between acanthoic acid and proteins related to male infertility, including SHBG, ADAM17, and DNase I, with binding affinity values of -10.2, -6.8, and -5.8 kcal/mol, respectively. Following the docking studies, molecular dynamic simulations were conducted for a duration of 100 ns to examine the stability of these interactions. Additionally, a total binding energy analysis and decomposition analysis offered insights into the underlying energetic components and identified key contributing residues.